Organic Syntheses, Coll. Vol. 5, p.277 (1973); Vol. 48, p.56 (1968).
靛红的合成
Organic Syntheses, Coll. Vol. 1, p.327 (1941); Vol. 5, p.71 (1925).ISATINSubmitted by C. S. Marvel and G. S. Hiers.Checked by J. B. Conant1. Procedure(A) Isonitrosoacetanilide.—In a 5-l. round-bottomed flask are placed 90 g. (0.54 mole) of chloral hydrate and 1200 cc. of water. To this solution are then added, in order: 1300 g. of crystallized sodium sulfate(Note 1); a solution of 46.5 g. (0.5 mole) of aniline(Note 2) in 300 cc. of water to which 51.2 g.(43 cc., 0.52 mole) of concentrated hydrochloric acid (sp. gr. 1.19) has been added to dissolve the amine (Note 3); and, finally, a solution of 110 g. (1.58 moles) of hydroxylamine hydrochloride(Note 4) in 500 cc. of water. The flask is heated over a wire gauze by a Meker burner so that vigorous boiling begins in about forty to forty-five minutes. After one to two minutes (Note 5) of vigorous boiling the reaction is complete. During the heating period, some crystals of isonitrosoacetanilide separate. On cooling the solution in running water the remainder crystallizes, is filtered with suction, and air-dried. The yield is 65–75 g. (80–91 per cent of the theoretical amount) of a product melting at 175°.(B) Isatin.—Six hundred grams (326 cc.) of concentrated sulfuric acid (sp. gr. 1.84) is warmed to 50° in a 1-l. round-bottomed flask fitted with an efficient mechanical stirrer, and, to this, 75 g. (0.46 mole) of dry (Note 6)isonitrosoacetanilide is added at such a rate as to keep the temperature between 60° and 70° but not higher (Note 7). External cooling should be applied at this stage so that the reaction can be carried out more rapidly. After the addition of the isonitroso compound is finished, the solution is heated to 80° and kept at this temperature for about ten minutes to complete the reaction. Then the reaction mixture is cooled to room temperature and poured upon ten to twelve times its volume of cracked ice. After standing for about one-half hour, the isatin is filtered with suction, washed several times with cold water to remove the sulfuric acid, and then dried in the air. The yield of crude isatin, which melts at 189–192°, is 47–52 g. (71–78 per cent of the theoretical amount). This product is pure enough for many purposes (Note 8).For purification, 200 g. of the crude product is suspended in 1 l. of hot water and treated with a solution of 88 g. of sodium hydroxide in 200 cc. of water. The solution is stirred mechanically and the isatin passes into solution. Dilute hydrochloric acid is then added, with stirring, until a slight precipitate appears. This requires about 290–300 cc. of an acid made by diluting one volume of concentrated hydrochloric acid (sp. gr. 1.19) with two volumes of water (Note 9). The mixture is then filtered at once, the precipitate is rejected, and the filtrate is made acid to Congo red paper with hydrochloric acid. The solution is then cooled rapidly, and the isatin which separates is filtered with suction and dried in the air. The pure product thus obtained weighs 150–170 g. (Note 10) and (Note 11) and melts at 197–200° (corr.).Isatin may also be crystallized from three times its weight of glacial acetic acid. In this case it isobtained in large brown-red crystals which melt at 196–197°.2. Notes1. Several runs were made in which the amounts of water and sodium sulfate were varied over a considerable range, and this concentration was found to give the best yield of product of good quality. The sodium sulfate seems to have more than a salting-out effect. If a saturated solution of sodium chloride is used no product is obtained.2. Redistilled aniline boiling over a 2° range was used in these experiments. The ordinary "pure" grade gives slightly lower yields.3. If the aniline is not in solution, a considerable quantity of tarry material is formed during the heating period. No tar is formed when the method described is used.4. The hydroxylamine hydrochloride used was the crude material prepared as described on p. 318. Preliminary experiments showed that this reagent must be present in considerable excess. Equally good results were obtained by using a solution of crude hydroxylamine sulfate which also contained sodium sulfate and ammonium sulfate with a little excess sulfuric acid. The hydroxylamine content was determined in this solution by titration with potassium permanganate solution. When this crude solution is used, the addition of sodium sulfate is not always necessary.5. Longer heating of the reaction mixture gives a lower yield of dark-colored product.6. If too much moisture is left in the isonitrosoacetanilide it is not easy to control the reaction with sulfuric acid.7. The reaction does not start below 45–50° but becomes too violent above 75–80°. If the temperature becomes too high, the entire run is lost by charring. Stirring is needed to prevent local overheating.8. In some smaller preparations when the sulfuric acid solution was poured on ice a yellow compound precipitated, which was shown to be the oxime of isatin. It has also been isolated from the acid mother liquors from which the isatin has separated. The oxime probably owes its formation to the hydrolysis of some unaltered isonitrosoacetanilide (J. P. Wibaut,1 private communication).9. The correct amount of acid that must be added to precipitate the impurities but not the isatin will vary with different samples of crude isatin. If too much acid is added, some isatin comes down with the impurities. This may be saved and added to a subsequent run.10. The yield of isatin is lower than for some of its derivatives. The explanation given in the literature is that some sulfonation occurs during the treatment with sulfuric acid, with corresponding loss of product.11. This method can be applied successfully to other isatin derivatives. Thus, under the same conditions, 54 g. of p-toluidine gives 75–77 g. (83–86 per cent of the theoretical amount) of isonitrosoaceto-p-toluidine melting at 162°. Eighty grams of this isonitroso compound treated as described under isonitrosoacetanilide gives 65–68 g. (90–94 per cent of the theoretical amount) of crude 5-methyl isatin melting at 179–183°. This is purified as described under isatin by solution in sodium hydroxide and partial neutralization to throw out the impurities or by recrystallization from three parts of glacial acetic acid. The purified 5-methyl isatin melts at 187°.3. DiscussionIsatin can be prepared by the oxidation of indigo;2 and the condensation of aniline, chloral hydrate, and hydroxylamine salts, followed by the action of sulfuric acid.3 The latter method by Sandmeyer3 seemed most promising and has been studied in detail. The procedure described differs from it in the use of hydroxylamine hydrochloride itself instead of a crude solution of hydroxylamine sulfate, and in the use of sodium sulfate to salt out the isonitroso compound.This preparation is referenced from:z Org. Syn. Coll. Vol. 5, 635References and Notes1.Wibaut and Geerling, Rec. trav. chim. 50, 41 (1931).2.Erdmann, J. prakt. Chem. 24, 11 (1841); Laurent, ibid. 25, 434 (1842); Gericke, ibid. 95, 177(1865); Knop, ibid. 97, 86 (1866); Knape, ibid. (2) 43, 211 (1891); Hofmann, Ann. 53, 10 (1845); Sommaruga, Ann. 190, 369 (1878); Gericke, Jahresber. 580 (1865); Forrer, Ber. 17, 976 (1884); Diez and Co., Ger. pat. 229,815 [Frdl. 10, 353 (1910–12)]; Rabinovich and Dzirkal, Khim. Farm. Prom. 1933, 190 [C. A. 28, 475 (1934)]; Henesy, J. Soc. Dyers Colourists, 53, 345, 347 (1937).3.Sandmeyer, Helvetica Chim. Acta 2, 237, 239 (1919); Geigy, Brit. pat. 128,122 [C. A. 13, 2375(1919)].AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)isonitroso compoundindigohydroxylamine saltssulfuric acid (7664-93-9)hydrochloric acid (7647-01-0)acetic acid (64-19-7)aniline (62-53-3)sodium hydroxide (1310-73-2)potassium permanganate (7722-64-7)sodium chloride (7647-14-5)sodium sulfate (7757-82-6)Hydroxylamine hydrochloride (5470-11-1)ammonium sulfate (7783-20-2)hydroxylamine (7803-49-8)Isatin (91-56-5)chloral hydrate (302-17-0)isonitrosoacetanilide (1769-41-1)hydroxylamine sulfate (10046-00-1)5-methyl isatin(608-05-9)p-toluidine (106-49-0)isonitrosoaceto-p-toluidine Copyright © 1921-2005, Organic Syntheses, Inc. All Rights Reserved。
Organic Syntheses, Coll. Vol. 5, p.157 (1973); Vol. 44, p.15 (1964).
Organic Syntheses, Coll. Vol. 5, p.157 (1973); Vol. 44, p.15 (1964).t-BUTYL AZIDOFORMATE[Formic acid, azido-, tert-butyl ester]Submitted by Louis A. Carpino, Barbara A. Carpino, Paul J. Crowley, Chester A. Giza, and PaulH. Terry1.Checked by Virgil Boekelheide and S. J. Cross.1. ProcedureIn a 1-l. round-bottomed flask fitted with a mechanical stirrer are placed 82 g. (0.62 mole) of t-butyl carbazate,2 72 g. of glacial acetic acid, and 100 ml. of water. The solution is cooled in an ice bath, and 47.0 g. (0.68 mole) of solid sodium nitrite is added over a period of 40–50 minutes, the temperature being kept at 10–15° (Note 1). The mixture is allowed to stand in the ice bath for 30 minutes, 100 ml. of water is added, and the floating oil is extracted into four 40-ml. portions of ether. The combined ether extracts are washed twice with 50-ml. portions of water and with 40-ml. portions of 1M sodium bicarbonate solution until no longer acidic (about three washings are required). The solution is dried over magnesium sulfate, and the ether is removed by distillation from a water bath maintained at 40–45°; water aspirator pressure of 140–150 mm. is used. The pressure is then lowered to 70 mm., and the water bath temperature is raised to 90–95°. The azide is distilled (Caution! (Note 2)) using a Claisen flask and is collected at 73–74° (70 mm.), n24D 1.4227, after a few drops of fore-run. The yield is 57–72.8 g. (64–82%) (Note 3) and (Note 4).2. Notes1. The sodium nitrite may be added as a concentrated aqueous solution.2. It is recommended that the distillation be carried out behind a safety shield. The submitters have distilled this compound several hundred times without incident under the conditions given on a scale up to 300–400 g. per run. On the other hand, Prof. P. G. Katsoyannis (University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania) has reported that an explosion took place in the receiving flask while the compound was being distilled under conditions previously used without incident. The reason for the explosion could not be traced. According to Prof. R. Schwyzer (Ciba, Ltd., Basel, Switzerland) tests at a Swiss Federal Institute showed that the compound could not be exploded by mere heating: it simply decomposes. For explosion, one must apply a primary explosive such as lead azide or silver azide. An attempt by the submitters to distil the azide at atmospheric pressure resulted in vigorous carbonization, but no explosion occurred. In view of the potential hazard some investigators prefer not to distil the azide; they use the crude material after removal of solvent. High yields of carbo-t-butoxy derivatives may be obtained in this way.3. When freshly distilled, the azide is water-white. When the azide is allowed to stand for several weeks, it slowly develops a light yellow color; however, this does not appear to affect its reactivity as an acylating agent.34. The azide should be handled with adequate ventilation. Careless inhalation of the substance was accompanied by development of a painful throbbing headache or a sensation of giddiness or both. These effects disappeared within several hours upon exposure to fresh air.3. Discussiont-Butyl azidoformate has been prepared by a variety of procedures,3,4,5,6,7,8,9,10,11,12 of which the present procedure and that described elsewhere in this series12appear most satisfactory.Because of the instability of t-butyl chloroformate a number of carbonic acid derivatives have been prepared and studied as reagents for the introduction of the carbo-t-butoxy group. A listing of these reagents and references to their preparation may be found in reference 13. In spite of some disadvantages the most widely used reagent is still t-butyl azidoformate, although t-butyl 2,4,5-trichlorophenyl-carbonate appears to be another potentially useful reagent. t-Butyl azidoformate is a convenient reagent for the acylation of amines, hydrazines, and similar compounds.3The acylation product of hydroxylamine, t-butyl N-hydroxycarbamate,5 is a valuable intermediate in the synthesis of O-substituted hydroxylamines such as O-acyl- and O-sulfonylhydroxylamines, many of which are valuable aminating agents and have not be obtained in any other way.14,15 This preparation is referenced from:z Org. Syn. Coll. Vol. 5, 160z Org. Syn. Coll. Vol. 6, 199z Org. Syn. Coll. Vol. 6, 203z Org. Syn. Coll. Vol. 6, 207z Org. Syn. Coll. Vol. 6, 418z Org. Syn. Coll. Vol. 7, 70References and Notes1.Department of Chemistry, University of Massachusetts, Amherst, Massachusetts.2.L. A. Carpino, D. Collins, and S. Göwecke, this volume, p. 166.3.L. A. Carpino, J. Am. Chem. Soc., 79, 4427 (1957).4.L. A. Carpino, J. Am. Chem. Soc., 79, 98 (1957).5.L. A. Carpino, C. A. Giza, and B. A. Carpino, J. Am. Chem. Soc., 81, 955 (1959).6.K. P. Polzhofer, Chimia (Aarau), 23, 298 (1969).7.H. Yajima and H. Kawatani, Chem. Pharm. Bull. (Tokyo), 16, 182 (1968).8.M. Itoh and D. Morino, Experientia, 24, 101 (1968).9.Y. A. Kiryushkin and A. I. Miroshnikov, Experientia, 21, 418 (1965).10.K. Inouye, M. Kanayama, and H. Otsuka, Nippon Kagaku Zasshi, 85, 599 (1964).11. D. S. Tarbell, Accounts Chem. Res., 2, 296 (1969).12.M. A. Insalaco and D. S. Tarbell, Org. Syntheses, 50, 9 (1970).13.L. A. Carpino, K. N. Parameswaran, R. K. Kirkley, J. W. Spiewak, and E. Schmitz, J. Org.Chem., 35, 3291 (1970).14.L. A. Carpino, J. Am. Chem. Soc., 82, 3133 (1960).15.L. A. Carpino, J. Am. Chem. Soc., 85, 2144 (1963).AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)acetic acid (64-19-7)ether (60-29-7)sodium bicarbonate (144-55-8)sodium nitrite(7632-00-0)hydroxylamine (7803-49-8)magnesium sulfate (7487-88-9)silver azidet-BUTYL AZIDOFORMATE,Formic acid, azido-, tert-butyl ester (1070-19-5)t-butyl carbazate (870-46-2)t-butyl chloroformatet-butyl 2,4,5-trichlorophenyl-carbonate (16965-08-5)t-butyl N-hydroxycarbamate (36016-38-3)lead azideCopyright © 1921-2005, Organic Syntheses, Inc. All Rights Reserved。
钯碳 水合肼 还原 硝基
Organic Syntheses, Coll. Vol. 5, p.30 (1973); Vol. 40, p.5 (1960).2-AMINOFLUORENE[2-Flurenylamine]Submitted by P. M. G. Bavin1Checked by John C. Sheehan and Roger E. Chandler..1. ProcedureIn a 2-l. three-necked round-bottomed flask, equipped with a mechanical stirrer (Note 1), reflux condenser, and dropping funnel, are placed 30 g. of pure 2-nitrofluorene, m.p. 157° [Org. Syntheses, Coll. Vol. 2, 447 (1943)], and 250 ml. of 95% ethanol. After warming to 50° on a steam bath, 0.1 g. of palladized charcoal catalyst (previously moistened with alcohol) is added (Note 2) and the stirrer is started. About 15 ml. of hydrazine hydrate is added from the dropping funnel during 30 minutes (Note 3). At this point an additional 0.1 g. of catalyst (previously moistened with alcohol) is added and the mixture is heated until the alcohol refluxes gently. After 1 hour the nitrofluorene has dissolved completely and the supernatant liquor is almost colorless.The catalyst is removed by filtration with gentle suction through a thin layer of Celite (Note 4). The flask is rinsed with 30 ml. of hot alcohol which is then used to wash the catalyst and Celite. The combined filtrates are concentrated under reduced pressure to about 50 ml. (Note 5) and then heated to boiling at atmospheric pressure. When 250 ml. of hot water is added slowly, 2-aminofluorene is precipitated as a colorless, crystalline powder. After cooling in an ice bath, the 2-aminofluorene is collected, washed with water, and dried in the dark in a vacuum desiccator. The product melts at 127.8–128.8° (Note 6) and amounts to 24–25 g. (93–96%).2. Notes1. If the stirring is omitted, the nitrofluorene takes longer to dissolve.2. A suitable catalyst is 10% palladium-on-charcoal, such as is supplied by Baker and Company, Inc., 113 Astor Street, Newark 5, New Jersey.3. The reaction is exothermic, and too rapid addition of the hydrazine may cause the mixture to foam out of the condenser.4. Caution! The catalyst is often pyrophoric and should be kept moistened with alcohol. Celite is a diatomaceous earth filter aid.5. A rotary evaporator is very convenient for the concentration since some of the amine invariably crystallizes toward the end.6. The melting point is that reported in Organic Syntheses, Coll. Vol. 2, 448 (1943), for a recrystallized sample.3. DiscussionThe preparation of 2-aminofluorene reported previously in Organic Syntheses[Coll. Vol. 2, 448 (1943)] we based on the method of Diels.2The present procedure illustrates a general method for the reduction of aromatic nitro compounds to aromatic amines using hydrazine and a hydrogenation catalyst such as palladium, platinum, nickel, iron, or rethenium. The literature on this procedure up to 1963 has been reviewed.3 In many instances the catalytic hydrazine reductions give yields of amine equal to or better than those obtained by directcatalytic hydrogenation or other reduction methods. Both the apparatus and the procedure are simple. Under appropriate conditions the method may be used for the dehalogenation of aliphatic and aromatic halides,3 a reaction for which palladium appears to be a specific catalyst. The method has also been used for the reduction of azobenzene and azoxybenzene to hydrazobenzene (80–90%),4 as well as for the synthesis of steroid aziridines by reduction of mesylate esters by vicinal azido alcohols (using Raney nickel).5References and Notes1.National Research Council of Canada Post-doctorate Fellow, 1954-56, at the University ofOttawa, Ottawa, Ontario.2.O. Diels, Ber., 34, 1758 (1901).3. A. Furst, R. C. Berlo, and S. Hooton, Chem. Rev., 65, 51 (1965).4.P. M. G. Bavin, Can. J. Chem., 36, 238 (1958).5.K. Ponsold, Ber., 97, 3524 (1964).AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)2-Flurenylaminepalladized charcoal catalystpalladium-on-charcoalethanol (64-17-5)iron (7439-89-6)platinum (7440-06-4)nickel,Raney nickel (7440-02-0)palladium (7440-05-3)hydrazine hydrate (7803-57-8)hydrazine (302-01-2)Azoxybenzene (495-48-7)Azobenzene (103-33-3)2-Nitrofluorene (607-57-8)2-Aminofluorene(153-78-6)Nitrofluoreneretheniumhydrazobenzene (122-66-7) Copyright © 1921-2005, Organic Syntheses, Inc. All Rights Reserved。
重氮化反应 氨基变卤素
Organic Syntheses, Coll. Vol. 2, p.351 (1943); Vol. 19, p.55 (1939).IODOBENZENE[Benzene, iodo-]Submitted by H. J. Lucas and E. R. Kennedy.Checked by John R. Johnson and P. L. Barrick.1. ProcedureIn a 3- or 5-gallon stoneware crock are placed 950 cc. (1130 g., 11.7 moles) of concentrated hydrochloric acid (sp. gr. 1.19), 950 cc. of water, 200 g. (196 cc., 2.15 moles) of aniline, and 2 kg. of ice (Note 1). The mixture is agitated by a mechanical stirrer, and, as soon as the temperature drops below 5°, a chilled solution of 156 g. (2.26 moles) of sodium nitrite in a measured volume (700–1000 cc.) of water is introduced fairly rapidly from a separatory funnel, the stem of which projects below the surface of the reaction mixture. The addition should not be fast enough to cause the temperature to rise to 10° or to cause evolution of oxides of nitrogen. The last 5 per cent of the nitrite solution is added more slowly, and the reaction mixture is tested with starch-iodide paper at intervals until an excess of nitrous acid is indicated.Stirring is continued for ten minutes, and if necessary the solution is filtered rapidly through a loose cotton plug in a large funnel. An aqueous solution of 358 g. (2.16 moles) of potassium iodide is added and the reaction mixture allowed to stand overnight. The mixture is transferred to a large flask (or two smaller flasks) and heated on a steam bath, using an air-cooled reflux condenser, until no more gas is evolved, then allowed to cool and stand undisturbed until the heavy organic layer has settled thoroughly.A large part of the upper aqueous layer is siphoned off, and discarded (Note 2). The residual aqueous and organic layers are made alkaline by the cautious addition of strong sodium hydroxide solution (100–125 g. of solid technical sodium hydroxide is usually required) and steam-distilled at once. The last one-third of the steam distillate is collected separately and combined with the aqueous layer separated from the earlier portions of the distillate. This mixture is acidified with 5–10 cc. of concentrated sulfuric acid and steam-distilled again. The iodobenzene from this operation is combined with the main portion and dried with 10–15 g. of calcium chloride(Note 3) and (Note 4). Distillation under reduced pressure gives 327–335 g. (74–76 per cent of the theoretical amount) of iodobenzene, b.p. 77–78°/20 mm. or 63–64°/8 mm. (Note 5).2. Notes1. If more ice is used a portion remains unmelted after the diazotization is completed.2. If a good separation has been made not more than 1–2 g. of iodobenzene is lost with the upper layer.3. An appreciable amount of iodobenzene is retained by the solid calcium chloride. By treating the spent drying agent with water 8–12 g. of iodobenzene can be recovered.4. The crude iodobenzene weighs 350–355 g. (80 per cent of the theoretical amount) and is pure enough for many purposes without redistillation.5. If the distillation is carried too far, the distillate will be colored.3. DiscussionThe preparation of iodobenzene by iodination of benzene, with iodine and nitric acid, and a survey of preparative methods have been given in an earlier volume.1 The present procedure, based upon the method of Gattermann,2 gives a purer product.This preparation is referenced from:z Org. Syn. Coll. Vol. 5, 660z Org. Syn. Coll. Vol. 5, 665References and Notes. Syn. Coll. Vol. I, 1941, 323.2.Gattermann-Wieland, "Laboratory Methods of Organic Chemistry," p. 283. Translated from thetwenty-fourth German edition by W. McCartney, The Macmillan Company, New York, 1937.AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)oxides of nitrogencalcium chloride (10043-52-4)sulfuric acid (7664-93-9)hydrochloric acid (7647-01-0)Benzene (71-43-2)aniline (62-53-3)sodium hydroxide (1310-73-2)nitric acid (7697-37-2)potassium iodide (7681-11-0)sodium nitrite (7632-00-0)nitrous acid (7782-77-6)iodine (7553-56-2)Iodobenzene,Benzene, iodo-(591-50-4)Copyright © 1921-2005, Organic Syntheses, Inc. All Rights Reserved。
Organic Syntheses有机合成
Organic Syntheses(有机合成手册), John Wiley & Sons (免费)/Named Organic Reactions Collection from the University ofOxford (有机合成中的命名反应库) (免费)http://www.chem.ox.ac. ... rganicReac...有机化学资源导航Organic Chemistry Resources Worldwide/有机合成文献综述数据库Synthesis Reviews (免费)/srev/srev.htmCAMEO (预测有机化学反应产物的软件)http://zarbi.chem.yale ... o/index.shtmlCarbohydrate Letters (免费,摘要)/Carbohydrate_Letters/Carbohydrate Research (免费,摘要)/locate/carresCurrent Organic Chemistry (免费,摘要)/coc/index.htmlElectronic Encyclopedia of Reagents for Organic Synthesis (有机合成试剂百科全书e-EROS)/eros/European Journal of Organic Chemistry (免费,摘要)http://www.interscienc ... es/1434-193X/Methods in Organic Synthesis (MOS,有机合成方法)/is/database/mosabou.htmOrganic Letters (免费,目录)/jo ... f7/index.htmlOrganometallics (免费,目录)/jo ... d7/index.htmlRussian Journal of Bioorganic Chemistry (Bioorganicheskaya Khimiya) (免费,摘要) http://www.wkap.nl/journalhome.htm/1068-1620Russian Journal of Organic Chemistry (Zhurnal Organicheskoi Khimii) (免费,摘要) http://www.maik.rssi.ru/journals/orgchem.htmScience of Synthesis: Houben-Weyl Methods of Molecular Transformation/Solid-Phase Synthesis database (固相有机合成)/chem_db/sps.htmlSynthetic Communications (免费,摘要)/ ... productid/SCCSyntheticPages (合成化学数据库) (免费)/The Complex Carbohydrate Research Center (复杂碳水化合物研究中心)/合成材料老化与应用(免费,目录)http://hccllhyyy.perio ... /default.html金属卡宾络合物催化的烯烃复分解反应(免费) ... 02/2.6%20.htm上海化学试剂研究所/英国化学数据服务中心CDS (Chemical Database Service)/cds/cds.html英国皇家化学会碳水化合物研究组织(Carbohydrate Group of the Royal Society of Chemistry)/lap/rsccom/dab/perk002.htm有机反应催化学会(ORCS, Organic Reaction Catalysis Society)/有机合成练习(免费)/中国科学院成都有机化学研究所：催化与环境工程研究发展中心/MainIndex.htm金属有机及元素有机化学：CASREACT - Chemical Reactions Database(CAS的化学反应数据库)/CASFILES/casreact.html日本丰桥大学Jinno实验室的研究数据库(液相色谱、多环芳烃/药物/杀虫剂的紫外谱、物性) (免费)http://chrom.tutms.tut ... H/research...A New Framework for Porous Chemistry (金属有机骨架) (免费) ... 83432324.htmlActa Crystallographica Section B (免费,摘要)http://journals.iucr.o ... homepage.htmlActa Crystallographica Section E (免费,摘要)http://journals.iucr.o ... homepage.htmlBibliographic Notebooks for Organometallic Chemistryhttp://www.ensc-lille. ... bco/bnoc.htmlBiological Trace Element Research (生物痕量元素研究杂志) (免费,摘要)http://www.humanapress ... =0163-4984...Journal of Organometallic Chemistry (免费,摘要)/locate/jnlabr/jomOrganic Letters (免费,目录)/jo ... f7/index.htmlOrganometallics (免费,目录)/jo ... d7/index.htmlSyntheticPages (合成化学数据库) (免费)/金属卡宾络合物催化的烯烃复分解反应(免费) ... 02/2.6%20.htm金属有机参考读物：The Organometallic HyperTextBook by Rob Toreki/organomet/index.html金属有机化学国家重点实验室，中国科学院上海有机所/元素有机化学国家重点实验室（南开大学）/在线网络课程：有机金属反应和均相催化机理(Dermot O'Hare 主讲)http://www.chem.ox.ac. ... ot/organomet/药物化学：Fisher Scientific/PubMed: MEDLINE和PREMEDLINE (免费)/PubMed/生物医药:BioMedNet: The World Wide Club for the Biological and Medical Community /AIDSDRUGS (艾滋病药物) (免费) ... aidsinfs.htmlautodock (分子对接软件) (免费) ... doc/autodock/DIRLINE (卫生与生物医药信息源库) (免费)/HISTLINE (医药史库) (免费)/TOXNET (化合物毒性相关数据库系列) (免费)/日本药典，第14版(免费)http://jpdb.nihs.go.jp/jp14e/index.html小分子生物活性数据库ChemBank (免费)/Ashley Abstracts Database (药物研发、市场文献摘要) (免费) ... ey/search.aspBIOSIS/BIOSIS/ONLINE/DBSS/biosisss.html从检索药物交易信息库PharmaDeals (部分免费)/从ChemWeb检索有机药物用途及别名库Negwer: organic-chemical drugs and their synonyms (部分免费)http://cwgen.chemweb.c ... ersearch.html美国常用药品索引库RxList (免费)/美国国家医学图书馆NLM的免费在线数据库(免费)/ho ... internet.html制药公司目录(Pharmaceutical Companies on Virtual Library: Pharmacy Page)/company.html37℃医学网/AAPS PharmSci (免费,全文)/Abcam Ltd.有关抗体、试剂的销售，抗体的搜索)/Acta Pharmaceutica (免费,摘要)http://public.srce.hr/acphee/Advanced Drug Delivery Reviews (免费,摘要)http://www.elsevier.nl/locate/drugdelivAmerican Journal of Drug and Alcohol Abuse (免费,摘要)/ ... productid/ADAAmerican Journal of Pharmaceutical Education (AJPE) (免费,全文)/Amgen Inc. (医药)/Anita's web picks (药学与药物化学信息导航)http://wwwcmc.pharm.uu.nl/oyen/webpicks.htmlAnnals of Clinical Microbiology and Antimicrobials (免费,全文)/Annual Review of Pharmacology and Toxicology (免费,摘要)/Anti-Cancer Drug Design (免费,摘要)/antcan/生物有机化学：ScienceDirect: 在线访问Elsevier的1100种期刊全文(免费目录) (免费)/生命、环境科学综合性资源TheScientificWorld (sciBASE)/生物医药:BioMedNet: The World Wide Club for the Biological and Medical Community /BIOETHICSLINE (BIOETHICS onLINE) (免费)/BIOME (生命科学资源导航)/browse/Directory of P450-containing Systems(P450酶系目录)http://p450.abc.hu/DIRLINE (卫生与生物医药信息源库) (免费)/百名最佳生物技术网站列表(Top 100 Biotechnology WWW Sites)/top100.asp从ChemWeb检索《化学工程与生物技术文摘》库CEABA (部分免费)/课程材料：MIT生物学超文本教材 ... 7001main.html生物材料网(Biomaterials Network)/生物信息学资源导航，上海生物化学所/bio/index.htm小分子生物活性数据库ChemBank (免费)/英国剑桥医学研究委员会：分子生物学实验室LMB/biology site of the network./BIOSIS/BIOSIS/ONLINE/DBSS/biosisss.htmlCATH Protein Structure Classification (蛋白质结构分类) (免费)/bsm/cath/Databases and Tools for 3-D Protein Structure Comparison and Alignment (三维蛋白质结构对比) (免费)/ce.htmlLos Alamos National Laboratory Bioscience Division/Protein Data Bank (PDB, 蛋白质数据库) (免费)/pdb/计算分子生物学:Computational Molecular Biology at NIH/molbio/酶命名数据库(ENZYME-Enzyme nomenclature database) (免费) /enzyme/Access Excellence (有关生物、生命等的科学教育网站)/Acta Biochimica Polonica (免费,全文)http://www.actabp.pl/Acta Biotechnologica (生物技术学报) (免费,摘要)http://www.wiley-vch.d ... eticIndex/...American Institute of Biological Sciences (AIBS)/American Journal of Medical Genetics Part A (免费,摘要) http://www3.interscien ... jtoc?ID=33129Amos' WWW links page (生物大分子网络资源导航)/alinks.htmlAmersham International (英国，生物技术供应商)/。
有机化学常用期刊网址
1． ScienceDirect (SD)网址：/(1) Catalysis Communications （催化通讯）(2) Journal of Molecular Catalysis A: Chemical （分子催化A：化学）(3) Tetrahedron (T) （四面体）(4) Tetrahedron: Asymmetry (TA) （四面体：不对称）(5) Tetrahedron Letters (TL) （四面体快报）(6) Applied Catalysis A: General （应用催化A）2． EBSCOhost数据库网址：/(1) Synthetic Communcations （合成通讯）(2) Letters in Organic Chemistry (LOC)(3) Current Organic Synthesis(4) Current Organic Chemistry3. Springer数据库网址：http:// /(1) Molecules （分子）(2) Monatshefte für Ch emie / Chemical Monthly （化学月报）(3) Science in China Series B: Chemistry （中国科学B）(4) Catalysis Letts （催化快报）4. ACS Publications (美国化学会)网址：/(1) Journal of the American Chemical Society (JACS) （美国化学会志）(2) Organic Letters (OL) （有机快报）(3) The Journal of Organic Chemistry (JOC) （美国有机化学）(4) Journal of Medicinal Chemistry (JMC) （美国药物化学）(5) Chemical Reiew （化学评论）5. Royal Society of Chemistry (RSC) (英国皇家化学会)网址：/Publishing/Journals/Index.asp(1) Green Chemistry （绿色化学）(2) Chemical Communications (CC) （化学通讯）(3) Chemical Society Reviews （化学会评论）(4) Journal of the Chemical Society （化学会志）Journal of the Chemical Society, Perkin Transactions 1 (1972-2002) Journal of the Chemical Society, Perkin Transactions 2 (1972-2002) Journal of the Chemical Society B: Physical Organic (1966-1971) Journal of the Chemical Society C: Organic (1966-1971)(5) Organic & Biomolecular Chemistry (OBC) （有机生物化学）/publishing/jo ... p?type=CurrentIssue6. Wiley网址：/(1) Advanced Synthesis & Catalysis (ASC) （先进合成催化）(2) Angewandte Chemie International Edition （德国应用化学）(3) Chemistry - A European Journal （欧洲化学）(4) Chinese Journal of Chemistry （中国化学）(5) European Journal of Organic Chemistry （欧洲有机化学）(6) Helvetica Chimica Acta （瑞士化学）(7) Heteroatom Chemistry （杂原子化学）7. Ingent网址：/(1) Journal of Chemical Research (JCR) （化学研究杂志）(2) Canadian Journal of Chemistry （加拿大化学）(3) Current Organic Chemistry(4) Mini-Reviews in Organic Chemistry(5) Phosphorus, Sulfur, and Silicon and the Related Elements （磷、硫、硅和相关元素）(6) Letters in Organic Chemistry8. Taylor & Francis数据库网址：http://www.journalsonline.tandf. ... sp?referrer=default(1) Synthetic Communications(2) Journal of Sulfur Chemistry（硫化学杂志）(3) Phosphorus, Sulfur, and Silicon and the Related Elements 9. Thieme数据库网址：/(1) Synlett （合成快报）(2) Synthesis （合成）10. 日本化学会网址：(1) Chem. Lett. (CL) （化学快报）http://www.jstage.jst.go.jp/browse/cl/_vols(2) Bull. Chem. Soc. Jpn. http://www.csj.jp/journals/bcsj/index.html11. 澳大利亚化学会（Australian Journal of Chemistry）http://www.publish.csiro.au/nid/52.htm12．巴西化学会.br/13．Molecules/molecules/14．韩国化学会http://journal.kcsnet.or.kr/15．印度化学会http://www.niscair.res.in/Scienc ... hin.htm&d=test816．国际有机制备和程序（Organic Preparations and Procedures International，OPPI）/17．有机化学/index.htm有机合成：Organic Syntheses(有机合成手册), John Wiley & Sons (免费)/Named Organic Reactions Collection from the University ofOxford (有机合成中的命名反应库) (免费)/thirdyearcomputing/NamedOrganicReac...有机化学资源导航Organic Chemistry Resources Worldwide/有机合成文献综述数据库Synthesis Reviews (免费)/srev/srev.htmCAMEO (预测有机化学反应产物的软件)/products/cameo/index.shtmlCarbohydrate Letters (免费,摘要)/Carbohydrate_Letters/Carbohydrate Research (免费,摘要)/locate/carresCurrent Organic Chemistry (免费,摘要)/coc/index.htmlElectronic Encyclopedia of Reagents for Organic Synthesis (有机合成试剂百科全书e-EROS)/eros/European Journal of Organic Chemistry (免费,摘要)/jpages/1434-193X/Methods in Organic Synthesis (MOS,有机合成方法)/is/database/mosabou.htmOrganic Letters (免费,目录)/journals/orlef7/index.htmlOrganometallics (免费,目录)/journals/orgnd7/index.htmlRussian Journal of Bioorganic Chemistry (Bioorganicheskaya Khimiya) (免费,摘要)http://www.wkap.nl/journalhome.htm/1068-1620Russian Journal of Organic Chemistry (Zhurnal Organicheskoi Khimii) (免费,摘要)http://www.maik.rssi.ru/journals/orgchem.htmScience of Synthesis: Houben-Weyl Methods of Molecular Transformation /Solid-Phase Synthesis database (固相有机合成)/chem_db/sps.htmlSynthetic Communications (免费,摘要)/servlet/product/productid/SCCSyntheticPages (合成化学数据库) (免费)/The Complex Carbohydrate Research Center (复杂碳水化合物研究中心) /合成材料老化与应用 (免费,目录)/default.html金属卡宾络合物催化的烯烃复分解反应 (免费)/html/books/O61BG/b1/2002/2.6%20.htm上海化学试剂研究所/英国化学数据服务中心CDS (Chemical Database Service)/cds/cds.html英国皇家化学会碳水化合物研究组织 (Carbohydrate Group of the Royal Society of Chemistry)/lap/rsccom/dab/perk002.htm有机反应催化学会 (ORCS, Organic Reaction Catalysis Society)/有机合成练习 (免费)/中国科学院成都有机化学研究所：催化与环境工程研究发展中心/MainIndex.htm金属有机及元素有机化学：CASREACT - Chemical Reactions Database(CAS的化学反应数据库)/CASFILES/casreact.html日本丰桥大学 Jinno实验室的研究数据库(液相色谱、多环芳烃/药物/杀虫剂的紫外谱、物性) (免费)http://chrom.tutms.tut.ac.jp/JINNO/ENGLISH/RESEARCH/research...A New Framework for Porous Chemistry (金属有机骨架) (免费)/alchem/articles/1056983432324.htmlActa Crystallographica Section B (免费,摘要)/b/journalhomepage.htmlActa Crystallographica Section E (免费,摘要)/e/journalhomepage.htmlBibliographic Notebooks for Organometallic Chemistryhttp://www.ensc-lille.fr/recherche/cbco/bnoc.htmlBiological Trace Element Research (生物痕量元素研究杂志) (免费,摘要) /JournalDetail.pasp?issn=0163-4984... Journal of Organometallic Chemistry (免费,摘要)/locate/jnlabr/jomOrganic Letters (免费,目录)/journals/orlef7/index.htmlOrganometallics (免费,目录)/journals/orgnd7/index.htmlSyntheticPages (合成化学数据库) (免费)/金属卡宾络合物催化的烯烃复分解反应 (免费)/html/books/O61BG/b1/2002/2.6%20.htm金属有机参考读物：The Organometallic HyperTextBook by Rob Toreki /organomet/index.html金属有机化学国家重点实验室，中国科学院上海有机所/元素有机化学国家重点实验室（南开大学）/在线网络课程：有机金属反应和均相催化机理 (Dermot O'Hare 主讲)/icl/dermot/organomet/药物化学：Fisher Scientific/PubMed: MEDLINE和PREMEDLINE (免费)/PubMed/生物医药:BioMedNet: The World Wide Club for the Biological and Medical Community/AIDSDRUGS (艾滋病药物) (免费)/pubs/factsheets/aidsinfs.htmlautodock (分子对接软件) (免费)/pub/olson-web/doc/autodock/DIRLINE (卫生与生物医药信息源库) (免费)/HISTLINE (医药史库) (免费)/TOXNET (化合物毒性相关数据库系列) (免费)/日本药典，第14版 (免费)http://jpdb.nihs.go.jp/jp14e/index.html小分子生物活性数据库ChemBank (免费)/Ashley Abstracts Database (药物研发、市场文献摘要) (免费)/databases/ashley/search.aspBIOSIS/BIOSIS/ONLINE/DBSS/biosisss.html从检索药物交易信息库PharmaDeals (部分免费)/从ChemWeb检索有机药物用途及别名库Negwer: organic-chemical drugs and their synonyms (部分免费)/negwer/negwersearch.html美国常用药品索引库RxList (免费)/美国国家医学图书馆NLM的免费在线数据库 (免费)/hotartcl/chemtech/99/tour/internet.html制药公司目录(Pharmaceutical Companies on Virtual Library: Pharmacy Page) /company.html37℃医学网/AAPS PharmSci (免费,全文)/Abcam Ltd.有关抗体、试剂的销售，抗体的搜索)/Acta Pharmaceutica (免费,摘要)http://public.srce.hr/acphee/Advanced Drug Delivery Reviews (免费,摘要)http://www.elsevier.nl/locate/drugdelivAmerican Journal of Drug and Alcohol Abuse (免费,摘要)/servlet/product/productid/ADAAmerican Journal of Pharmaceutical Education (AJPE) (免费,全文)/Amgen Inc. (医药)/Anita's web picks (药学与药物化学信息导航)http://wwwcmc.pharm.uu.nl/oyen/webpicks.htmlAnnals of Clinical Microbiology and Antimicrobials (免费,全文)/Annual Review of Pharmacology and Toxicology (免费,摘要)/Anti-Cancer Drug Design (免费,摘要)/antcan/生物有机化学：ScienceDirect: 在线访问Elsevier的1100种期刊全文 (免费目录) (免费) /生命、环境科学综合性资源TheScientificWorld (sciBASE)/生物医药:BioMedNet: The World Wide Club for the Biological and MedicalCommunity/BIOETHICSLINE (BIOETHICS onLINE) (免费)/BIOME (生命科学资源导航)/browse/Directory of P450-containing Systems(P450酶系目录)http://p450.abc.hu/DIRLINE (卫生与生物医药信息源库) (免费)/百名最佳生物技术网站列表 (Top 100 Biotechnology WWW Sites)/top100.asp从ChemWeb检索《化学工程与生物技术文摘》库CEABA (部分免费)/课程材料：MIT生物学超文本教材:8001/esgbio/7001main.html生物材料网 (Biomaterials Network)/生物信息学资源导航，上海生物化学所/bio/index.htm小分子生物活性数据库ChemBank (免费)/英国剑桥医学研究委员会：分子生物学实验室LMB/biology site of the network./生物有机化学：ScienceDirect: 在线访问Elsevier的1100种期刊全文 (免费目录) (免费) /生命、环境科学综合性资源TheScientificWorld (sciBASE)/生物医药:BioMedNet: The World Wide Club for the Biological and Medical Community/BIOETHICSLINE (BIOETHICS onLINE) (免费)/BIOME (生命科学资源导航)/browse/Directory of P450-containing Systems(P450酶系目录)http://p450.abc.hu/DIRLINE (卫生与生物医药信息源库) (免费)/百名最佳生物技术网站列表 (Top 100 Biotechnology WWW Sites) /top100.asp从ChemWeb检索《化学工程与生物技术文摘》库CEABA (部分免费) /课程材料：MIT生物学超文本教材:8001/esgbio/7001main.html生物材料网(Biomaterials Network)/生物信息学资源导航，上海生物化学所/bio/index.htm小分子生物活性数据库ChemBank (免费)/英国剑桥医学研究委员会：分子生物学实验室LMB/biology site of the network./。
Organic Syntheses, Coll. Vol. 6, p.967 (1988); Vol. 51, p.53 (1971).
Organic Syntheses, Coll. Vol. 6, p.967 (1988); Vol. 51, p.53 (1971).AZIRIDINES FROM β-IODOCARBAMATES: 1,2,3,4-TETRAHYDRONAPHTHALENE(1,2)IMINE[1H -Naphth[1,2-b ]azirine, 1a,2,3,7b-tetrahydro-]Submitted by C. H. Heathcock 1 and A. Hassner 2.Checked by William G. Kenyon and Richard E. Benson. 1. ProcedureA 500-ml., round-bottomed flask equipped with a reflux condenser is charged with a solution of 25 g. of potassium hydroxide in 250 ml. of 95% ethanol , to which is added 16.6 g. (0.0498 mole) of methyl (trans -2-iodo-1-tetralin)carbamate (Note 1). The resulting mixture is heated under reflux on a stream bath for 2 hours, cooled, and added to 500 ml. of water. The clear, yellow solution is shaken three times with 100-ml. portions of diethyl ether . The ether layers are combined, washed three times with 125-ml. portions of water and once with 125 ml. of a saturated sodium chloride , dried over 5 g. of anhydrous potassium carbonate , and filtered. The ether is removed by distillation on a steam bath, giving the crude imine as a yellow-brown oil (Note 2). The oil is transferred to a small flask, the container is rinsed with ether , and the rinse is added to the distillation flask. The product is collected by distillation through a small Vigreux column with warm water circulating through the condenser to prevent crystallization of the product. The fraction boiling at 80–82° (0.15–0.25 mm.) is collected as a solid that forms in the receiver, yielding 4.9–5.1 g. (68–70%) of the imine, m.p. 54–56° (Note 2); the IR spectrum has a band at 3205 cm.−1 (NH) (Note 3).2. Notes1. The methylcarbamate may be prepared by the procedure in Org. Synth., Coll. Vol. 6, 795 (1988).2. The submitters state that product, m.p. 49–51°, can be obtained by direct crystallization of the oil. The oil from a run conducted on a scale twice that described above is cooled to −15° and 30 ml. of pentane is added. Upon scratching the flask, the product crystallizes, is collected by filtration, and washed with a little cold pentane , yielding 9–10 g. (62–69%), m.p. 49–51°.3. The 1H NMR spectrum (CCl 4) shows a broad singlet centered at δ 0.7 (1H) and complex multiplets at 1.1–3.05 (6H) and 6.76–7.30 (4H).3. DiscussionThe procedure reported here, that of Hassner and Heathcock,3 is more convenient than the Wenker synthesis of aziridines 4 and appears to be more general.5 It represents a simple route from olefins to aziridines (via β-iodocarbamates).3,5,6 Aziridines are also useful as intermediates in the synthesis of amino alcohols and heterocyclic systems.5,7,8,9This preparation is referenced from:z Org. Syn. Coll. Vol. 6, 795 References and Notes1.Department of Chemistry, University of California, Berkeley, California 94720.2.Present address: Department of Chemistry, State University of New York, Binghamton, NewYork 13901.3. A. Hassner and C. Heathcock, Tetrahedron, 20, 1037 (1964).4.O. E. Paris and P. E. Fanta, J. Am. Chem. Soc., 74, 3007 (1952).5. A. Hassner and C. Heathcock, J. Org. Chem., 30, 1748 (1965).6.G. Drefahl and K. Ponsold, Chem. Ber., 93, 519 (1960).7.H. W. Heine, Angew. Chem., 74, 772 (1962) [Angew. Chem. Int. Ed. Engl., 1, 528 (1962)].8. A. Hassner, M. E. Lorber, and C. Heathcock, J. Org. Chem., 32, 540 (1967).9.L. A. Paquette and D. E. Kuhla, Tetrahedron Lett., 4517 (1967).AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)β-IODOCARBAMATESethanol (64-17-5)potassium carbonate (584-08-7)ether,diethyl ether (60-29-7)sodium chloride (7647-14-5)potassium hydroxide (1310-58-3)Pentane (109-66-0)methylcarbamate1,2,3,4-Tetrahydronaphthalene(1,2)imine,1H-Naphth[1,2-b]azirine, 1a,2,3,7b-tetrahydro- (1196-87-8)Methyl (trans-2-iodo-1-tetralin)carbamate (1210-13-5)Copyright © 1921-2005, Organic Syntheses, Inc. All Rights Reserved。
Organic Syntheses, Coll. Vol. 2, p.464 (1943); Vol. 13, p.84 (1933).
Organic Syntheses, Coll. Vol. 2, p.464 (1943); Vol. 13, p.84 (1933).NITROSOMETHYLURETHANE[Carbamic acid, methylnitroso-, ethyl ester]Submitted by W. W. Hartman and Ross Phillips.Checked by Louis F. Fieser and J. T. Walker.1. ProcedureTo 206 g. (2 moles) of ethyl N-methylcarbamate(p. 278) and 600 cc. of ordinary ethyl ether in a 5-l. flask is added, along with 200 g. of ice, 650 g. (9 moles) of 96 per cent sodium nitrite(Note 1) dissolved in 1 l. of cold water. The flask is provided with a stopper carrying a thermometer, a tube to lead off evolved nitric oxide, and a separatory funnel with an extension tube reaching to the bottom of the flask. A solution of 1.2 kg. (6.7 moles) of cold 35 per cent nitric acid, prepared by pouring 600 g. (426 cc.) of concentrated acid onto 600 g. of ice, is then cautiously added through the funnel in the course of one and one-half hours. The flask is given an occasional swirl to ensure some mixing, but most of the stirring is done by the evolved gases. Ice is added as required to keep the temperature below 15°. The ether layer first becomes pale red and gradually changes to a blue-green. As soon as the color has changed to green, the ether layer is separated (Note 2), washed twice with cold water, and then with cold potassium carbonate solution until carbon dioxide is no longer evolved. The solution is dried with solid potassium carbonate, and the ether is distilled from a water bath using a 1-l. flask with a 30-cm. column arranged for vacuum distillation. The vacuum is applied as soon as most of the ether has been removed, and the flask is heated gently so that the temperature of the liquid does not exceed 45–50° (Note 3) until the pressure has been reduced below 20 mm. The yield of nitrosomethylurethane boiling at 59–61/10 mm. is 200 g. (76 per cent of the theoretical amount). The density is 1.133 at 20°.2. Notes1. A large excess of sodium nitrite is required to give a satisfactory yield. This may be due to reaction according to the following equations: Nitric oxide (NO) is lost during the reaction. It is not thought advisable to use this by passing in oxygen because of the danger of an explosion, or by passing in air because of the loss of material by evaporation.2. Nitrosomethylurethane irritates the skin.3. According to the literature, nitrosomethylurethane explodes when attempts are made to distil it at normal pressure.3. DiscussionNitrosomethylurethane has been prepared by treating ethyl methylcarbamate with sodium nitrite and sulfuric acid,1 and by passing the gases generated from arsenious oxide and nitric acid into an ethereal solution of ethyl methylcarbamate.2This preparation is referenced from:z Org. Syn. Coll. Vol. 3, 119z Org. Syn. Coll. Vol. 4, 780z Org. Syn. Coll. Vol. 5, 842References and Notes1.Klobbie, Rec. trav. chim. 9, 139 (1890).2.v. Pechmann, Ber. 28, 856 (1895); Schmidt, ibid. 36, 2477 (1903); Brühl, ibid. 36, 3635 (1903).AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)arsenious oxideNitric oxide (NO)potassium carbonate (584-08-7)sulfuric acid (7664-93-9)ether,ethyl ether (60-29-7)nitric acid (7697-37-2)oxygen (7782-44-7)sodium nitrite (7632-00-0)carbon dioxide (124-38-9)nitric oxideNitrosomethylurethaneEthyl N-methylcarbamate,ethyl methylcarbamate (105-40-8)Carbamic acid, methylnitroso-, ethyl ester (615-53-2)Copyright © 1921-2005, Organic Syntheses, Inc. All Rights Reserved。
Organic Syntheses, Coll. Vol. 2, p.165 (1943); Vol. 15, p.3 (1935).
Organic Syntheses, Coll. Vol. 2, p.165 (1943); Vol. 15, p.3 (1935).DIAZOMETHANE[Methane, diazo-]Submitted by F. ArndtChecked by C. R. Noller and I. Bergsteinsson.1. ProcedureDiazomethane is highly toxic. The utmost care is essential in the preparation and use of this material.In a 500-cc. round-bottomed flask are placed 60 cc. of 50 per cent aqueous potassium hydroxide solution and 200 cc. of ether. The mixture is cooled to 5°, and 20.6 g. (0.2 mole) of nitrosomethylurea (p. 461) is added with shaking. The flask is fitted with a condenser set for distillation. The lower end of the condenser carries an adapter passing through a two-holed rubber stopper and dipping below the surface of 40 cc. of ether contained in a 300-cc. Erlenmeyer flask and cooled in an ice-salt mixture. The exit gases are passed through a second 40-cc. portion of ether likewise cooled below 0°. The reaction flask is placed in a water bath at 50° and brought to the boiling point of the ether with occasional shaking. The ether is distilled until it comes over colorless, which is usually the case after two-thirds of the ether has been distilled. Under no circumstances should all the ether be distilled. The combined ether solutions in the receiving flasks contain from 5.3 to 5.9 g. of diazomethane (63–70 per cent of the theoretical amount) (Note 1) and (Note 2), which is sufficiently dry for most purposes (Note 3).If a dry solution of diazomethane is required, the ether solution is allowed to stand for three hours over pellets of pure potassium hydroxide(Note 4). For extremely dry solutions, further drying is effected with sodium wire.2. Notes1. For analysis an aliquot portion (about one-twentieth) of the solution is allowed to react at 0° with a solution of an accurately weighed sample of about 1.3 g. of pure benzoic acid in 50 cc. of absolute ether. The benzoic acid must be in excess as evidenced by the complete decolorization of the diazomethane solution. The unreacted benzoic acid is titrated with standard 0.2 N alkali.2. The same procedure may be used for preparing two or three times the quantity obtained here.3. The ether solution does not contain ammonia or methyl alcohol. It does contain traces of methylamine, but this is also present when diazomethane is prepared from nitrosomethylurethane.If one does not require a pure, water-free solution, as is frequently the case when carrying out tests with small amounts of material, a simplified procedure may be used. To 100 cc. of ether is added 30 cc. of 40 per cent potassium hydroxide, and the mixture is cooled to 5°. To this, with continued cooling and shaking, is added 10 g. of finely powdered nitrosomethylurea in small portions over a period of one to two minutes. The deep yellow ether layer can be decanted readily; it contains about 2.8 g. of diazomethane, together with some dissolved impurities and water. The water may be removed by drying for three hours over pellets of pure potassium hydroxide. Solutions of diazomethane in benzene and other water-immiscible organic solvents may be prepared in the same way.4. Broken sticks should not be used as the sharp corners facilitate the decomposition of the diazomethane.3. DiscussionThere are four methods of practical importance for the preparation of diazomethane: the action of alcoholic potassium hydroxide1 or sodium dissolved in glycol2 on nitrosomethylurethane; heating a mixture of potassium hydroxide, chloroform, hydrazine hydrate, and absolute alcohol;3 the action of potassium hydroxide on nitrosomethylurea,4 the method described above; and the action of alkoxides on the nitroso derivative of β-methylaminoisobutyl methyl ketone.5 The choice of a method will usually depend upon the availability of the starting material. Directions for the preparation of the starting materials used in the first three methods are given in this volume; directions for preparing the nitroso derivative of β-methylaminoisobutyl methyl ketone and from it diazomethane will appear in a forthcoming volume of Organic Syntheses.Arndt, Loewe, and Avan have discussed the merits of the various methods of preparing diazomethane,6 as has Eistert.7This preparation is referenced from:z Org. Syn. Coll. Vol. 3, 244z Org. Syn. Coll. Vol. 4, 250z Org. Syn. Coll. Vol. 5, 231z Org. Syn. Coll. Vol. 5, 245z Org. Syn. Coll. Vol. 5, 351z Org. Syn. Coll. Vol. 5, 877z Org. Syn. Coll. Vol. 5, 1099z Org. Syn. Coll. Vol. 6, 432z Org. Syn. Coll. Vol. 6, 613z Org. Syn. Coll. Vol. 8, 196z Org. Syn. Coll. Vol. 9, 300References and Notes1.v. Pechmann, Ber. 27, 1888 (1894); 28, 855 (1895).2.Meerwein and Burneleit, ibid. 61, 1845 (1928).3.Staudinger and Kupfer, ibid. 45, 505 (1912).4.Arndt and Amende, Angew. Chem. 43, 444 (1930); Arndt and Scholz, ibid. 46, 47 (1933).5.Adamson and Kenner, J. Chem. Soc. 1935, 286; 1937, 1551.6.Arndt, Loewe, and Avan, Ber. 73, 606 (1940).7.Eistert, Angew. Chem. 54, 99, 124 (1941).AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)nitroso derivative of β-methylaminoisobutyl methyl ketonealcohol (64-17-5)ammonia (7664-41-7)Benzene(71-43-2)methyl alcohol (67-56-1)ether (60-29-7)chloroform (67-66-3)Benzoic acid (65-85-0)potassium hydroxide (1310-58-3)sodium,sodium wire (13966-32-0)hydrazine hydrate (7803-57-8)methylamine (74-89-5)Diazomethane,Methane, diazo- (334-88-3)NitrosomethylureaNitrosomethylurethane Copyright © 1921-2005, Organic Syntheses, Inc. All Rights Reserved。
organic synthesis
Organic Syntheses, Coll. Vol. 4, p.755 (1963); Vol. 33, p.68 (1953).4-PENTYN-1-OLSubmitted by E. R. H. Jones, Geoffrey Eglinton, and M. C. Whiting 1.Checked by Arthur C. Cope and Ronald M. Pike. 1. ProcedureCaution! This preparation should be conducted in a hood to avoid exposure to ammonia .A solution of sodium amide in liquid ammonia is prepared according to a procedure previously described (Note 1) in a 3-l. three-necked round-bottomed flask equipped with a cold-finger condenser (cooled with Dry Ice) attached through a soda-lime tower to a gas-absorption trap,2 a mercury-sealed stirrer, and an inlet tube. Anhydrous liquid ammonia (1 l.) is introduced from a commercial cylinder through the inlet tube, and 1 g. of hydrated ferric nitrate is added, followed by 80.5 g. (3.5 g. atoms) of clean, freshly cut sodium (Note 1) and (Note 2). The inlet tube is replaced with a 250-ml. dropping funnel, and the mixture is stirred until all the sodium is converted into sodium amide , after which 120.5 g. (1 mole) of tetrahydrofurfuryl chloride 3 (Note 3) is added over a period of 25 to 30 minutes. The mixture is stirred for an additional period of 1 hour, after which 177 g. (3.3 moles) of solid ammonium chloride is added in portions at a rate that permits control of the exothermic reaction. The flask is allowed to stand overnight in the hood while the ammonia evaporates. The residue is extracted thoroughly with ten 250-ml. portions of ether , which are decanted through a Büchner funnel (Note 4). The ether is distilled, and the residue is fractionated at a reflux ratio of about 5 to 1, through a column containing a 20-cm. section packed with glass helices yielding 63–71 g. (75–85%) of 4-pentyn-1-ol , b.p. 70–71° /29 mm., n D1.4443 (Note 5).2. Notes1. Procedures for converting sodium to sodium amide are given on p. 763 and in a previous volume.42. More liquid ammonia should be added through the inlet tube if vaporization reduces the liquid volume to less than 750 ml.3. Freshly distilled tetrahydrofurfuryl alcohol should be used in the preparation of tetrahydrofurfuryl chloride according to the procedure of Organic Syntheses.34. Ether extraction of the solid must be thorough or the yield will be reduced. A large Soxhlet extractor may be used if desired.5. Others have reported b.p. 154–155°, n D 1.4432;5 b.p. 154–155°, n D 1.4450.6 A sample purified through the silver derivative had b.p. 77° /37 mm., n D 1.4464. The α-naphthylurethan of 4-pentyn-1-ol crystallized as needles from 60–80° petroleum ether; m.p. 79–80°. 3. Discussion4-Pentyn-1-ol has been prepared from 4-penten-1-ol 3 by bromination followed by dehydrobromination with alkali;6 by the reaction of 3-bromodihydropyran or 3,4-dihydro-2H-pyran with n -butylsodium , n -butyllithium , or n -butylpotassium ;5,7 by the reaction of dihydropyran or 2-methylenetetrahydrofuran with n -amylsodium or n -butyllithium ;7 by the reduction of ethyl 4-pentynoate with lithium aluminum hydride ;8and by the method used in this preparation.9251922.515References and Notes1.Victoria University of Manchester, Manchester, England.. Syntheses Coll. Vol.2, 4 (1943).. Syntheses Coll. Vol.3, 698 (1955).. Syntheses Coll. Vol.3, 219 (1955).5.Paul and Tchelitcheff, Compt. rend., 230, 1473 (1950); Paul, Angew. Chem., 63, 304 (1951);Paul, Bull. soc. chim. France, 18, 109 (1951).6.Lespieau, Compt. rend., 194, 287 (1932).7.Paul and Tchelitcheff, Bull. soc. chim. France, 19, 808 (1952).8.Colonge and Gelin, Bull. soc. chim. France, 1954, 799.9.Eglinton, Jones, and Whiting, J. Chem. Soc., 1952, 2873.AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)petroleum etherα-naphthylurethan of 4-pentyn-1-olammonia (7664-41-7)ether (60-29-7)ammonium chloride (12125-02-9)sodium (13966-32-0)tetrahydrofurfuryl alcohol (97-99-4)sodium amide (7782-92-5)n-butyllithium (109-72-8)ferric nitratelithium aluminum hydride (16853-85-3)dihydropyran2-methylenetetrahydrofurann-amylsodium4-Penten-1-ol (821-09-0)Tetrahydrofurfuryl chloride(3003-84-7)4-Pentyn-1-ol (5390-04-5)3-bromodihydropyran3,4-dihydro-2H-pyran (110-87-2)ethyl 4-pentynoate (63093-41-4)n-butylsodiumn-butylpotassium Copyright © 1921-2005, Organic Syntheses, Inc. All Rights Reserved。
Organic Syntheses, Coll. Vol. 4, p.218 (1963); Vol. 36, p.14 (1956).
Organic Syntheses, Coll. Vol. 4, p.218 (1963); Vol. 36, p.14 (1956).CYCLODECANONESubmitted by Arthur C. Cope, John W. Barthel, and Ronald Dean Smith 1.Checked by N. J. Leonard and J. C. Little. 1. ProcedureA 1-l. round-bottomed three-necked flask is fitted with a sealed stirrer (Note 1), a dropping funnel, and a reflux condenser, through which a thermometer extends nearly to the bottom of the flask. In the flask are thoroughly mixed 40.5 g. (0.62 g. atom) of zinc dust (Note 2) and 100 ml. of glacial acetic acid , and to this mixture is added 42.5 g. (0.25 mole) of sebacoin (p.840) (Note 3). The mixture is stirred rapidly, and 90 ml. of concentrated C.P. hydrochloric acid is added dropwise during a period of 5 to 10 minutes, or as fast as control of foaming and temperature permits. The temperature must be kept between 75 and 80° (Note 4), and cooling by a water bath may be necessary during the addition of the hydrochloric acid . Stirring is continued for 1.5 hours at 75–80°. Thirty minutes after the initial addition of hydrochloric acid , and again 30 minutes later, 90-ml. portions of concentrated hydrochloric acid are added to the mixture while the temperature is maintained at 75–80°. After the reaction is complete, the remaining zinc is separated from the cooled mixture by decantation (Note 5). The liquid phase is diluted with 700 ml. of saturated aqueous sodium chloride solution and extracted with four 250-ml. portions of ether , each of which is first used to wash the residual zinc (Note 6). The ether extracts are combined and washed with 250 ml. of saturated sodium chloride solution, three 250-ml. portions of 10% sodium carbonate solution (foaming!), and finally 250 ml. of saturated sodium chloride solution. The ethereal solution is dried over anhydrous magnesium sulfate (about 25 g. is needed). After the drying agent has been removed by filtration and the solvent by distillation, the residue is distilled at reduced pressure through an efficient column (Note 7). After a small fore-run consisting mostly of cyclodecane ,cyclodecanone is collected at 99–101°/8 mm. The yield is 29–30 g. (75–78%), n 25 1.4808–1.4810 (Note 8).2. Notes1. A metal stirrer must not be used. A simple glass stirrer with a ball-joint seal is satisfactory.2. Mallinckrodt technical grade may be used.2 If Mallinckrodt analytical reagent zinc dust is used, the reaction temperature must be maintained at 50–55° instead of 75–80°.3. Pure sebacoin gives a colorless product. A sebacoin-sebacil mixture must first be purified by recrystallization from pentane as described (p.841). The sebacil apparently is not reduced completely according to the accompanying directions and thus may contaminate the product (Note 7).4. The reaction temperature is important. At temperatures below 75° some sebacoin remains unreduced, while at temperatures above 80° considerable cyclodecane is formed. The submitters report that the reaction run at the reflux temperature gives cyclodecanone in 27% yield and cyclodecane in 32% yield.5. The product should be isolated and distilled as quickly as possible inasmuch as the unreacted sebacoin is readily oxidized to sebacil , which cannot be separated from the cyclodecanone by simple distillation.6. The residual zinc may be pyrophoric.7. For efficient separation of cyclodecanone from cyclodecane , a 60-cm. column of the simple Podbielniak type 3 may be used. Removal of sebacil cannot be accomplished readily by fractional distillation, since cyclodecanone and sebacil have virtually identical boiling points.8. Cyclodecanone regenerated from its semicarbazone, m.p. 203.5–205.5°, has n 25 1.4806.3. DiscussionD DThe procedure described is a modification of the directions of Prelog, Frenkiel, Kobelt, and Barman.4Cyclodecanone has been prepared by the dehydration of sebacoin followed by catalytic hydrogenation,5 by the pyrolysis of the thorium or yttrium salt of nonane-1,9-dicarboxylic acid,6 and by the ring enlargement of cyclononanone,7 as well as by the reduction of sebacoin.8This preparation is referenced from:z Org. Syn. Coll. Vol. 5, 277References and Notes1.Massachusetts Institute of Technology, Cambridge 39, Massachusetts.2.Brown and Borkowski, J. Am. Chem. Soc., 74, 1901 (1952).3.Cason and Rapoport, Laboratory Text in Organic Chemistry, 2nd ed., p. 294, Prentice-Hall,Englewood Cliffs, New Jersey, 1962.4.Prelog, Frenkiel, Kobelt, and Barman, Helv. Chim. Acta, 30, 1741 (1947).5.Stoll, Helv. Chim. Acta, 30, 1837 (1947).6.Ruzicka, Stoll, and Schinz, Helv. Chim. Acta, 9, 249 (1926); 11, 670 (1928).7.Kohler, Tishler, Potter, and Thompson, J. Am. Chem. Soc., 61, 1057 (1939).8.Blomquist, Burge, and Sucsy, J. Am. Chem. Soc., 74, 3636 (1952).AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)Sebacoinsebacoin-sebacilthorium or yttrium salt of nonane-1,9-dicarboxylic acidhydrochloric acid (7647-01-0)acetic acid (64-19-7)ether (60-29-7)sodium chloride (7647-14-5)sodium carbonate (497-19-8)zinc (7440-66-6)Pentane (109-66-0)magnesium sulfate (7487-88-9)Cyclodecanone(1502-06-3)cyclodecane (293-96-9)cyclononanone (3350-30-9)Sebacil (96-01-5) Copyright © 1921-2005, Organic Syntheses, Inc. All Rights Reserved。
Organic Syntheses, Coll. Vol. 10, p.613 (2004); Vol. 76, p.86 (1999).
Organic Syntheses, Coll. Vol. 10, p.613 (2004); Vol. 76, p.86 (1999).(2S,3S)-(+)-(3-PHENYLCYCLOPROPYL)METHANOL[ Cyclopropanemethanol, 2-phenyl-, (1S-trans)- ]Submitted by André B. Charette and Hélène Lebel1 .Checked by Kevin Minbiole, Patrick Verhoest, and Amos B. Smith, III.1. ProcedureA.Butylmagnesium bromide. To a 500-mL, three-necked, round-bottomed flask equipped with an egg-shaped magnetic stirrer, 125-mL pressure-equalizing addition funnel, reflux condenser and a glass stopper (Note 1), is added 17.0 g (0.70 mol) of magnesium turnings(Note 2). Stirring is started, and the system is flame-dried for 2 min. The flask is cooled to room temperature under a flow of argon, and 30 mL of ether(Note 3) is introduced to cover the magnesium. A solution of 24 mL (0.22 mol) of bromobutane(Note 4) in 70 mL of ether is placed in the pressure-equalizing addition funnel. Then, 1 mL (0.01 mol) of bromobutane is added to the suspension of magnesium in ether. The mixture is heated gently to initiate the reaction (Note 5). When the reaction has started, the solution of bromide in ether is added dropwise at a rate sufficient to maintain a gentle reflux (Note 6). After completion of the addition, the funnel is rinsed with 5 mL of ether . The gray solution is stirred for 15 min and then transferred to a dry flask under argon via cannula. The Grignard reagent is titrated with a solution of isopropyl alcohol in benzene using 1,10-phenanthroline as the indicator (Note 7).2 A 1.90-2.10 M solution of Grignard reagent is obtained.B.Butylboronic acid. To a 1-L, one-necked, round-bottomed flask equipped with an egg-shaped magnetic stirrer (Note 1) and an internal thermocouple probe (Note 11) is added 220 mL of ether(Note 3), followed by 10 mL (89.2 mmol) of trimethyl borate(Note 12). The clear solution is cooled to −75°C (internal temperature) and stirred vigorously, then 45 mL (87.8 mmol) of a 1.95 M solution of butylmagnesium bromide in ether(Note 13) is added dropwise via cannula at such a rate that the internal temperature does not exceed −65°C (Note 14). After the addition is complete, the resulting white slurry is stirred for an additional 2 hr at −75°C under argon. The cooling bath is removed, and thereaction mixture is allowed to warm to room temperature (Note 15). Hydrolysis is carried out by the dropwise addition of 100 mL of an aqueous 10% solution of hydrochloric acid . The white precipitate is dissolved, and the resulting clear biphasic mixture is stirred for 15 min, at which time the two layers are separated. The aqueous layer is extracted with ether (2 × 50 mL), and the combined extracts are dried over magnesium sulfate . After concentration of the ethereal solution under reduced pressure, the residual white solid is purified by recrystallization as follows: After dissolution in hot water (25 mL), the resulting biphasic solution is cooled to 0°C to induce recrystallization of the boronic acid. The solid is collected on a Büchner funnel, washed with 50 mL of hexanes and placed under vacuum (0.2 mm) for 60 min (Note 16) and (Note 17). Between 5.0-6.5 g (55-72% yield) of the boronic acid is produced as a white solid (Note 18).C.[(2-)-N,O,O'[2,2'-Iminobis[ethanolato]]]-2-butylboron,1. A 250-mL, one-necked, round-bottomed flask equipped with an egg-shaped magnetic stirrer (Note 1) is charged with 5.15 g (50.5 mmol) of butylboronic acid and 5.31 g (50.5 mmol) of diethanolamine(Note 19). Ether, 100 mL (Note 3) and 50 mL of dichloromethane(Note 20) are added, followed by about 10 g of molecular sieves 3Å (Note 21). The resulting heterogeneous solution (Note 22) is stirred for 2 hr under argon. The solid is triturated with dichloromethane (50 mL), filtered through a medium fritted disk funnel and washed with dichloromethane (2 × 50 mL). The filtrate is concentrated under reduced pressure to produce the crude desired complex. The diethanolamine complex is purified by recrystallization as follows: the white solid is dissolved in hot dichloromethane (20 mL), then ether (50 mL) is added to induce recrystallization of the complex. The mixture is cooled to 0°C and the solid is collected on a Büchner funnel and washed with ether (2 × 30 mL). The product is dried under reduced pressure (0.2 mm) to afford 7.70 g (89%) of the title compound as a white crystalline solid (Note 23).D.(4R-trans)-2-Butyl-N,N,N',N'-tetramethyl[1,3,2]dioxaborolane-4,5-dicarboxamide3. A 500-mL, one-necked, round-bottomed flask equipped with an egg-shaped magnetic stirrer, under argon is charged with 7.70 g (45.0 mmol) of the butylboronate diethanolamine complex and 11.9 g (58.3 mmol) of (R,R)-(+)-N,N,N',N'-tetramethyltartaric acid diamide(Note 24). The solids dissolve upon the addition of 225 mL of dichloromethane . Brine (70 mL) is added, and the resulting biphasic solution is stirred for 30 min under argon. The two layers are separated, and the aqueous layer is extracted with dichloromethane (50 mL). The combined organic layers are washed with brine (50 mL), dried over magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure and dried under reduced pressure (0.2 mm) to give 11.3 g (93%) of the title compound as a pale yellow oil (Note 25).E.(2S,3S)-(+)-(3-Phenylcyclopropyl)methanol. A 250-mL, one-necked, round-bottomed flask equipped with an egg-shaped magnetic stirrer (Note 26) and an internal thermocouple probe (Note 11), is charged with 45 mL of dichloromethane(Note 20) and 1.60 mL (14.9 mmol) of 1,2-dimethoxyethane (DME) (Note 27). The solution is cooled to −10°C (internal temperature) with an acetone/ice bath, and 1.50 mL (14.9 mmol) of diethylzinc is added (Note 28). To this stirred solution is added 2.40 mL (29.8 mmol) of diiodomethane(Note 29) over a 15-20 min period while maintaining the internal temperature between −8°C and −12°C. After the addition is complete, the resulting clear solution is stirred for 10 min at −10°C. A solution of 2.41 g (8.94 mmol) of the dioxaborolane ligand in 10 mL of dichloromethane is added via cannula under argon over a 5-6 min period while maintaining the internal temperature below −5°C. A solution of 1.00 g (7.45 mmol) of cinnamyl alcohol(Note 30) in 10 mL of dichloromethane is immediately added via cannula under argon over a 5-6 min period while maintaining the internal temperature under −5°C. The cooling bath is removed, and the reaction mixture is allowed to warm to room temperature and stirred for 8 hr at that temperature (Note 31).Workup.Method A. The reaction is quenched with aqueous saturated ammonium chloride (10 mL) and aqueous 10% hydrochloric acid (40 mL). The mixture is then diluted with ether (60 mL) and transferred to a separatory funnel. The reaction flask is rinsed with ether (15 mL), and aqueous 10% hydrochloric acid (10 mL) and both solutions are transferred to the separatory funnel. The two layers are separated, and the aqueous layer is washed with ether (20 mL). The combined organic layers are transferred to an Erlenmeyer flask, and a solution containing 60 mL of aqueous 2 N sodium hydroxide and 10 mL of aqueous 30% hydrogen peroxide is added in one portion (Note 32). The resulting biphasic solution is stirred vigorously for 5 min. The two layers are separated and the organic layer is washed successively with aqueous 10% hydrochloric acid(50 mL), aqueous saturated sodium sulfite(50 mL),aqueous saturated sodium bicarbonate (50 mL), and brine (50 mL). The organic layer is dried over magnesium sulfate and filtered, and the filtrate is concentrated under reduced pressure. The crude product is left under reduced pressure (0.2 mm) overnight (12-16 hr) to remove the butanol produced in this oxidative work-up. The product is purified by a Kugelrohr distillation (90°C, 0.8 mm) to afford 1.05 g (95%) of (2S,3S)-(+)-(3-phenylcyclopropyl)methanol as a colorless oil (Note 33) and (Note 34). Workup . Method B [with recovery of (R,R)-(+)-N,N,N',N'-tetramethyltartaric acid diamide ]. The mixture is quenched with aqueous saturated ammonium chloride (80 mL), and the resulting biphasic mixture is stirred for 5 min. The two clear layers are separated, and the aqueous layer is washed with dichloromethane (20 mL) (Note 35). The combined organic layers are dried over magnesium sulfate and filtered, and the filtrate is concentrated under reduced pressure. The residual oil is dissolved in ether (75 mL) and water (50 mL). The resulting biphasic mixture is stirred for 1 hr. The layers are separated, and the aqueous layer is washed with ether (20 mL). This aqueous layer is kept for tetramethyltartaric acid diamide recovery (see below). The combined organic layers are treated with 60 mL of aqueous 2 N sodium hydroxide and 10 mL of aqueous 30% hydrogen peroxide (Note 32). The resulting biphasic mixture is stirred for 5 min. The two layers are separated and the organic layer is washed successively with aqueous 10% hydrochloric acid (50 mL), saturated aqueous sodium sulfite (50 mL), saturated aqueous sodium bicarbonate (50 mL), and brine (50 mL). The organic layer is dried over magnesium sulfate and filtered, and the filtrate is concentrated under reduced pressure. The crude product is left under reduced pressure (0.2 mm) overnight (12-16 hr) to remove butanol produced in this oxidative work-up. The product is purified by a Kugelrohr distillation (90°C, 0.8 mm) to afford 1.02 g (93%) of (2S ,3S )-(+)-(3-phenylcyclopropyl)methanol as a colorless oil.Recovery of (R,R)-(+)-N,N,N',N'-tetramethyltartaric acid diamide . The aqueous layer from the above extraction is concentrated under reduced pressure, and the crude product is recrystallized by an initial dissolution in hot dichloromethane (5 mL) followed by the addition of ethyl acetate (10 mL) to afford between 600 mg to 750 mg (33-41% yield) of the (R,R)-(+)-N,N,N',N'-tetramethyltartaric acid diamide (Note 36) and (Note 37).2. Notes1. All glassware was dried in an oven (110°C) and after assembly was allowed to cool under an atmosphere of argon .2. Magnesium turnings were purchased from Sigma-Aldrich Fine Chemicals Company Inc. and were used without further purification.3. Ether was freshly distilled from sodium/benzophenone.4. Bromobutane was purchased from Fisher Scientific Company and was freshly distilled from phosphorus pentoxide (P 2O 5) (bp 100-104°C).5. The formation of a gray cloudy suspension indicates that the reaction has started. Furthermore, the reaction is sufficiently exothermic to induce the ether to reflux even when the reaction flask is not heated. If the reaction does not start within 2 to 3 min, repeat the heating procedure.6. Between 1.5 hr and 2 hr are needed for addition.7. A dried 10-mL, one-necked, round-bottomed flask is charged with 1 mL of Grignard, some drops of THF (Note 8) and a crystal of 1,10-phenanthroline (Note 9). The slightly pink solution is titrated with a 0.5 M solution of isopropyl alcohol in benzene (Note 10). Between 3.8 and 4.2 mL (±0.2 mL) is obtained to give a clear colorless solution (three titrations).8. THF was freshly distilled from sodium/benzophenone.9. 1,10-Phenanthroline was purchased from Sigma-Aldrich Fine Chemicals Company Inc. and was used without further purification. 10. Isopropyl alcohol was freshly distilled from calcium hydride (CaH 2) and benzene was freshly distilled from sodium . 11. A Barnant 100, Type T Thermo-Couple Thermometer was used to monitor the internal temperature of the reaction solution. 12. Anhydrous trimethyl borate (with <5% of methanol ) was purchased from Sigma-Aldrich Fine Chemicals Company Inc. and was used without further purification. Alternatively, a non anhydrous reagent can be dried by distillation from calcium hydride (bp 68-69°C). 13. Commercially available (Sigma-Aldrich Fine Chemicals Company Inc.), butylmagnesium chloride ,2.0 M in ether , can be used and a similar yield is observed.14. Between 20 and 30 min are needed for the addition. 15. Between 1 hr and 1.5 hr are needed. 16. The amount of the boroxine significantly increases if the solid is left under reduced pressure for a longer period of time. The boroxine is always a contaminant of the boronic acid (see discussion). 17. Sometimes a second recrystallization is needed to obtain pure boronic acid by removing by-products resulting from autooxidation. 18. The physical properties are as follows: mp 95-97°C; 1H NMR (400 MHz, DMSO) δ: 0.56 (t, 2 H, J = 7.6), 0.83 (t, 3 H, J = 7.2), 1.31-1.19 (m, 4 H), 7.34 (br s, 2 H) ; 13C NMR (100 MHz, DMSO) δ: 13.9, 15.3 (br), 25.1, 26.5 ; 11B NMR (128.4 MHz, DMSO) δ: 32.7 . 19. Diethanolamine was purchased from Fisher Scientific Company and was used without further purification. 20. Dichloromethane was freshly distilled from CaH 2. 21. Molecular sieves, 3Å, powder, average particle size 3-5 μ were purchased from Sigma-Aldrich Fine Chemicals Company Inc. and dried under vacuum at 250°C for 24 hr, before using. 22. A few minutes after the addition of the molecular sieves, a white precipitate forms and sometimes maintaining stirring becomes difficult. 23. The physical properties are as follows: mp 145-148°C; 1H NMR (400 MHz, CDCl 3) δ: 0.44-0.48 (m, 2 H), 0.88 (t, 3 H, J = 7.1), 1.21-1.37 (m, 4 H), 2.79 (br s, 2 H), 3.26 (br s, 2 H), 3.88 (br s, 2 H), 3.98 (br s, 2 H),4.80-4.98 (m, 1 H) ; 13C NMR (100 MHz, CDCl 3) δ: 14.1, 18.4 (br), 26.5, 28.1, 51.4, 62.5 ; 11B NMR (128.4 MHz, CDCl 3) δ: 13.1, 32.7 . Anal. Calcd for C 8H 18BNO 2: C, 56.18; H, 10.61; N, 8.19. Found: C, 56.15; H, 10.86; N, 8.07. 24. (R,R)-(+)-N,N,N',N'-Tetramethyltartaric acid diamide was prepared from diethyl tartrate and dimethylamine and was freshly recrystallized with methanol and ethyl acetate .3 The physical properties are as follows: mp 186-187°C [lit.2 189-190°C]; 1H NMR (400 MHz, CDCl 3) δ: 3.01 (s, 6 H), 3.13 (s, 6 H), 4.21 (br s, 2 H), 4.65 (s, 2 H) ; 13C NMR (100 MHz, CDCl 3) δ: 36.1, 36.9, 69.8, 170.8 ; [α]20 D +43° (EtOH, c 2.03) [lit.2 [α]20 D +43° (EtOH, c 3.0)]. This product is also commercially available from Sigma-Aldrich Fine Chemicals Company Inc. 25. The physical properties are as follows: 1H NMR (400 MHz, CDCl 3) δ: 0.85 (t, 2 H, J = 7.7); 0.87 (t, 3 H, J = 7.2), 1.29-1.41 (m, 4 H), 2.98 (s, 6 H), 3.20 (s, 6 H), 5.53 (s, 2 H) ; 13C NMR (100 MHz, CDCl 3) δ: 9.9 (br), 13.6, 25.0, 25.7, 35.7, 36.9, 75.6, 168.23 ; 11B NMR (128.4 MHz, CDCl 3) δ: 34.2 ; [α]20 D −104.4° (CHCl 3, c 1.70). HRMS Calcd for C 12H 23BN 2O 4: 270.1751. Found: 270.1746. Anal. Calcd for C 12H 23BN 2O 4: C, 53.35; H, 8.58; N, 10.37. Found: C, 53.67; H, 9.07; N, 10.21. 26. All glassware was flame dried, then cooled under a flow of dry argon . 27. DME was freshly distilled from sodium/benzophenone. 28. Diethylzinc is a moisture sensitive and pyrophoric liquid and must be manipulated in an inert atmosphere with gas-tight syringes. Neat diethylzinc was purchased from Akzo Nobel Chemicals Company Inc. and was used without further purification. 29. Diiodomethane was purchased from Acros-Fisher Scientific Company and used without further purification. If necessary, diiodomethane can be purified if it shows any signs of slight decomposition (orange or red color develops over time): diiodomethane is washed with aqueous saturated sodium sulfite , dried over sodium sulfate (Na 2SO 4), and distilled from copper (40°C, 1.0 mm). The pale yellow liquid is collected on copper . 30. Cinnamyl alcohol was purchased from Sigma-Aldrich Fine Chemicals Company Inc. and was freshly purified by Kugelrohr distillation: a first fraction boiling at <70°C (1.0 mm) was discarded, and the alcohol was collected as a white solid at 80°C (1.0 mm). 31. A similar yield is obtained when the submitters stirred this mixture for 14 hr. No noticeable decomposition and side reactions are observed after slightly longer periods of time. 32. Hydrogen peroxide was purchased from ACP Chemicals Company Inc. and used without further purification. 33. Alternatively, the product can be purified by flash chromatography on silica gel (78.5 g, 4 cm × 16 cm) using 30% ethyl acetate in hexanes as the mobile phase (800 ml) to afford 1.06 g (96%) of the title compound. 34. The physical properties are as follows: bp 90°C, 0.8 mm; IR (film) cm −1: 3350, 3050, 3000, 2950, 2900, 1600, 1500, 1450, 1100, 1050, 1000, 750, 700 ; 1H NMR (400 MHz, CDCl 3) δ: 0.92-1.01 (m, 2 H), 1.43-1.51 (m, 1 H), 1.75 (br s, 1 H), 1.82-1.86 (m, 1 H), 3.59-3.67 (m, 2 H), 7.07-7.10 (m, 2 H),7.15-7.20 (m, 1 H), 7.25-7.30 (m, 2 H) ; 13C NMR (100 MHz, CDCl 3) δ: 13.8, 21.2, 25.2, 66.3, 125.6, 125.8, 128.3, 142.5 ; [α]20 D +82° (EtOH, c 1.74) [lit.4 (2R,3R)-cyclopropylmethanol >99% ee [α]20 D −92° (EtOH, c 1.23)]. Anal. Calcd for C 10H 12O: C, 81.04 H, 8.16. Found: C, 81.15; H, 8.30. The enantiomeric excess of the product is determined precisely by GC analylsis of the corresponding trifluoroacetate ester derivative: To a solution of 10 mg of the crude alcohol in 0.75 mL of pyridine is added 0.25 mL of trifluoroacetic anhydride (TFAA). After 30 min at room temperature, an additional 0.25 mL of TFAA is added. After 30 min, the reaction mixture is diluted with 5 mL of ether . This solution was injected directly into the GC (0.5 μL) with the following conditions: Cyclodex G-TA, 0.32 × 30 m; pressure 25 psi; isotherm: 110°C, T r (minor) 11.5 min, T r (major) 12.0 min; enantiomeric ratio: 29:1 (93% ee). 35. If the resulting organic layers are not clear, the combined organic layers should be washed with an additional 50 mL of aqueous saturated ammonium chloride . 36. An additional 10-15% of the diol can be recovered from the first aqueous saturated ammonium chloride extract (Note 38): the layer is concentrated on a rotatory evaporator and the white solid is triturated with cold methanol (30 mL), the mixture is filtered on a Büchner funnel, and the solid is washed with cold methanol (20 mL). The filtrate is concentrated to ca. 25 mL and treated with 2.5 g of sodium sulfide (Note 39). The resulting mixture is stirred for 30 min and then filtered on Celite (6 g, 1 cm × 4 cm). The filtrate is concentrated by rotary evaporation, and the residue is purified by flash chromatography on silica gel (75 g, 3.5 cm × 14.5 cm) by dissolving it in 10 mL of 10% methanol in chloroform and eluting with 10% methanol in chloroform . A recrystallization with dichloromethane and ethyl acetate give pure material. 37. The physical properties are identical to those of (Note 24). 38. The diol decomposes after a few hours at room temperature in this layer. 39. Sodium sulfide was purchased from Anachemia Science and was used without further purification.Waste Disposal InformationAll toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.3. DiscussionParts A-D. The preparation of boronic acids by the addition of a Grignard reagent to a trialkyl borate is one of the most convenient and well-established methods involving relatively inexpensive starting materials.5 6 The carefully monitored addition of butylmagnesium bromide to trimethyl borate avoids any complications resulting from overaddition, and relatively good yields of the butylboronic acid are obtained after acid hydrolysis. Usually, alkylboronic acids are relatively difficult to characterize and to obtain analytically pure,7 8 because they readily tend to form boroxines (anhydrides) under dehydrating conditions (when heated or when left under reduced pressure). The white solid (butylboronic acid ) is transformed into a colorless oil (tributylboroxine) if dehydration is pushed to completion. Conversely, butylboronic acid and its boroxine are also readily oxidized by air to generate 1-butanol and boric acid .9 10 For these reasons, it is almost impossible to isolate butylboronic acid without any traces of water, its boroxine or oxidation by-products.In order to avoid these complications, butylboronic acid is quickly converted to its air-stable and more robust diethanolamine derivative 1.11 Complex 1 could be contaminated with some unseparable diethanolamine if a small excess of diethanolamine is used in its preparation. However, this has no effect on the efficiency of the synthesis of the chiral dioxaborolane ligand 3. Diethanolamine complex 1 reacts quantitatively with a slight excess of tetramethyltartramide 2 under biphasic conditions to produce the desired chiral dioxaborolane ligand 3. Ligand 3 is relatively stable, and is neither excessively hygroscopic nor oxygen-sensitive. It must be stored under argon for longer periods of time. However, the submitters have shown that the enantioselectivities are directly related to the ligand purity.Consequently, it is generally preferable to use freshly prepared ligand for obtaining optimal results.Part E. The enantioselective cyclopropanation of allylic alcohols using the chiral dioxaborolane ligand 3 and Zn(CH 2I)2·DME is a powerful tool for synthesizing three-membered rings. This method is much simpler and produces superior enantiomeric excesses compared to those using other stoichiometric chiral ligands.12 13 14 The scope of the reaction is wide and a variety of allylic alcohols have been converted into their cyclopropane derivatives in excellent enantiomeric excesses (88-94%).15 16 It was also shown that polyenes can be cyclopropanated at the allylic alcohol position with excellent chemo- and enantioselectivities.17 Recently, this reaction has been used in the synthesis of cyclopropane containing natural products.18 19 20 21Caution! The previously reported preparation of Zn(CH 2I)2 without a complexing additive 22 is highly exothermic, and a violent decomposition sometimes occurred. For safety reasons, the use of the Zn(CH 2I)2·DME as reported here is mandatory if this reaction is carried out on a =8 mmole scale.23 If the internal temperature during the formation of the reagent is carefully monitored, the procedure reported here is extremely safe even on larger scales.Note that the structure of Zn(CH 2I)2·DME is derived from the stoichiometry of the reactants (Et 2Zn, CH 2I 2, DME). Substantial quantities of IZnCH 2I·DME are necessarily formed at the reaction temperature and as a by-product of the cyclopropanation. Another improvement was made in this procedure: the number of equivalents of the reagent has been decreased to 2.0 equiv (vs 5 equiv in the original paper). However, under these conditions that minimize the amount of Et 2Zn used but require longer reaction times, the yield of the diol recovery dropped to ca. 50%.The cyclopropanation of cinnamyl alcohol is a good example of the use of dioxaborolane ligand 3 as chiral additive to synthesize chiral cyclopropanes.References and Notes1.Departement de Chimie, Université de Montréal, P.O. Box 6128, Station Downtown, Montréal(Québec) Canada, H3C 3J7.2.Soai, K.; Machida, H.; Yokota, N. J. Chem. Soc. Perkin Trans. I 1987, 1909.3.Seebach, D.; Kalinowski, H.-O.; Langer, W.; Crass, G.; Wilka, E.-M. Org. Synth., Coll. Vol. VII1990, 41.4.Evans, D. A.; Woerpel, K. A.; Hinman, M. M.; Faul, M. M. J. Am. Chem. Soc. 1991, 113, 726.5.Srebnik, M.; Cole, T. E.; Ramachandran, V.; Brown, H. C. J. Org. Chem. 1989, 54, 6085;6.Washburn, R. M.; Levens, E.; Albright, C. F.; Billig, F. A. Org. Synth., Coll. Vol. IV 1963, 68and references cited therein.7.Martichonok, V.; Jones, J. B. J. Am. Chem. Soc. 1996, 118, 950;8.Mathre, D. J.; Jones, T. K.; Xavier, L. C.; Blacklock, T. J.; Reamer, R. A.; Mohan, J. J.; Jones, E.T. T.; Hoogsteen, K.; Baum, M. W.; Grabowski, E. J. J. J. Org. Chem. 1991, 56, 751. 9.Korcek, S.; Watts, G. B.; Ingold, K. U. J. Chem. Soc., Perkin Trans. 2 1972, 242;10.Johnson, J. R.; Van Campen, Jr., M. G. J. Am. Chem. Soc. 1938, 60, 121.11.Brown, H. C.; Vara Prasad, J. V. N. J. Org. Chem. 1986, 51, 4526.aji, Y.; Nishimura, M.; Fujisawa, T. Chem. Lett. 1992, 61;aji, Y.; Sada, K.; Inomata, K. Chem. Lett. 1993, 1227;14.Kitajima, H.; Aoki, Y.; Ito, K.; Katsuki, T. Chem. Lett. 1995, 1113.15.Charette, A. B.; Juteau, H. J. Am. Chem. Soc. 1994, 116, 2651;16.Charette, A. B.; Lemay J., Angew. Chem., Int. Ed. Engl. 1997, 36, 1090.17.Charette, A. B.; Juteau, H.; Lebel, H.; Deschênes, D. Tetrahedron Lett. 1996, 37, 7925.18.For selected examples, see: (a) White, J. D.; Kim, T.-S.; Nambu, M. J. Am. Chem. Soc. 1997,119, 103;19.Barrett, A. G. M.; Kasdorf, K. J. Chem. Soc., Chem. Comm. 1996, 325;20.Falck, J. R.; Mekonnen, B.; Yu, J.; Lai, J.-Y. J. Am. Chem. Soc. 1996, 118, 6096;21.Charette, A. B.; Lebel, H. J. Am. Chem. Soc. 1996, 118, 10327.22.Denmark, S. E.; Edwards, J. P. J. Org. Chem.1991, 56, 6974.23.Charette, A. B.; Prescott, S.; Brochu, C. J. Org. Chem.1995, 60, 1081.AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)(2S,3S)-(+)-(3-Phenycyclopropyl)methanol:Cyclopropanemethanol, 2-phenyl-,(1S-trans)- (12); (110659-58-0)Butylmagnesium bromide:Magnesium, bromobutyl- (8,9); (693-03-8)Magnesium (8,9); (7439-95-4)1-Bromobutane:Butane, 1-bromo- (8,9); (109-65-9)Isopropyl alcohol:2-Propanol (8,9); (67-63-0)1,10-Phenanthroline (8,9); (66-71-7)Butylboronic acid:1-Butaneboronic acid (8);Boronic acid, butyl- (9); (4426-47-5)Trimethyl borate:Boric acid, trimethyl ester (8,9); (121-43-7)Diethanolamine:Ethanol, 2,2'-iminodi- (8);Ethanol, 2,2'-iminobis- (9): (111-42-2)(4R-trans)-2-Butyl-N,N,N',N'-tetramethyl[1,3,2]dioxaborolane-4,5-dicarboxamide:1,3,2-Dioxaborolane-4,5-dicarboxamide, 2-butyl-N,N,N'N'-tetramethyl-, (4R-trans)- (13); (161344-85-0)(R,R)-(+)-N,N,N',N'-Tetramethyltartaric acid diamide:Tartramide, N,N,N'N'-tetramethyl-, (+)- (8);Butanediamide, 2,3-dihydroxy-N,N,N'N'-tetramethyl-, [R-(R,R)]- (9); (26549-65-5)Dimethoxyethane:Ethane, 1,2-dimethoxy- (8,9); (110-71-4)Diethylzinc:Zinc, diethyl- (8,9); (557-20-0)Diiodomethane:Methane,diiodo-(8,9); (75-11-6)Cinnamyl alcohol (8);2-Propen-1-ol, 3-phenyl- (9); (104-54-1)Hydrogen peroxide (8,9); (7722-84-1)Sodium sulfite:Sulfurous acid, disodium salt (8,9); (7757-83-7)Copper (8,9); (7440-50-8)Trifluoroacetic anhydride:Acetic acid, trifluoro-, anhydride (8,9); (407-25-0)Sodium sulfide (8,9); (1313-82-2) Copyright © 1921-2005, Organic Syntheses, Inc. 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Organic Syntheses, Coll. Vol. 10, p.382 (2004); Vol. 75, p.31 (1998).
Organic Syntheses, Coll. Vol. 10, p.382 (2004); Vol. 75, p.31 (1998).ETHYL (R)-2-AZIDOPROPIONATE[ Propanoic acid, 2-azido-, ethyl ester, (R)- ]Submitted by Andrew S. Thompson, Frederick W. Hartner, Jr., and Edward J. J. Grabowski 1 .Checked by Christopher L. Lynch and Stephen F. Martin. 1. ProcedureEthyl (R)-2-azidopropionate . An oven-dried, 500-mL, three-necked flask is equipped with an overhead stirrer, nitrogen inlet, and an immersion thermometer (Note 1). The flask is charged with ethyl S-(−)-lactate (19.2 mL, 0.169 mol) (Note 2), tetrahydrofuran (175 mL) (Note 3), and diphenylphosphoryl azide (40 mL, 0.185 mol) (Note 4). The mixture is cooled to 2°C in an ice-water bath. To the mixture is added 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (24 mL, 0.157 mol) (Note 5) dropwise via syringe. (Caution: The DBU addition causes an exotherm. The reaction temperature is maintained below 5°C by carefully controlling the rate of addition. For this reaction the addition required 35 min). A thick white precipitate forms during the DBU charge. The reaction is stirred at 1°C for 1 hr, and then it is warmed to room temperature and stirred under nitrogen for 24 hr (Note 6). The resulting homogeneous reaction is diluted with methyl tert-butyl ether (MTBE, 170 mL), and water (100 mL) is added. After the water layer is removed, the organic phase is washed with water (100 mL) and 0.5 M citric acid monohydrate (100 mL). The organic layer is dried ( Na 2SO 4 ) and concentrated under reduced pressure to ca. 40-50 g of a pale yellow oil (Note 7). The product is purified by simple distillation to afford 12.84 g (57%) of a clear, colorless oil, bp 83−88°C/50mm (Note 8), (Note 9) and (Note 10).2. Notes1. A Teflon-coated thermocouple of the J-type attached to an Omega model 650 digital thermometer can be substituted for the immersion thermometer.2. Ethyl lactate was purchased from Aldrich Chemical Company, Inc. , and used without further purification. The water content was 0.8 mg/mL by Karl Fisher titration (Metrohm model 684 KF coulometer).3. Tetrahydrofuran was purchased from Fisher Scientific Company and dried over 4 Å molecular sieves for 18 hr prior to use. The water content was less than 0.05 mg/mL by Karl Fisher titration.4. Diphenylphosphoryl azide was 98% as purchased from Aldrich Chemical Company, Inc. , and the water content was less than 0.01 mg/mL by Karl Fisher titration.5. DBU was 98% as purchased from Aldrich Chemical Company, Inc. , and the water content was 0.5 mg/mL by Karl Fisher titration. The amount of DBU was calculated to be 0.93 equiv of the ethyl lactate charge by assuming a purity of 98% for DBU and 100% purity for ethyl lactate . Amounts of base over 1 equiv resulted in product epimerization.6. The reaction typically requires 16-24 hr. The progress of the reaction was monitored by capillary GC after diluting a 0.1-mL sample with 1 mL of methyl tert-butyl ether . GC conditions: Hewlett-Packard 5890 series II GC using an Alltech Econo-cap column (30 M × 0.32 mm × 0.25 μM, catalog # 19646). [The submitters used an HP-5 column (25 M × 0.32 mm × 0.52 mm, HP part # 19091J-112)]. Start oven at 50°C, then increase to 250°C at 10°C per min. The reaction was considered complete after 90% conversion; starting material R t 4.3 min, product R t7.0 min. 7. The vacuum was deliberately bled to maintain 120-130 mm to minimize product losses due to volatility.8. The yield was based on the DBU charge. The product was contaminated with 4-8% of starting material that codistilled with the product. The following characterization data was obtained: ethyl (R)-(+)-2-azidopropionate : [α] D 25 +14.8° ( hexane , c 1.00); 1H NMR (250 MHz, CDCl 3) δ: 1.28 (t, 3 H, J = 7.2), 1.43 (d, 3 H, J = 7.1), 3.89 (q, 1 H, J = 7.1), 4.21 (q, 2 H, J = 7.2) ; 13C NMR (75 MHz, CDCl 3) δ: 14.1, 16.7, 57.3, 61.8, 170.9 ; IR (thin film) cm −1: 2120, 1743 . 9. Optical purity can be quantitatively assayed by HPLC after reducing a sample to the amine with triphenylphosphine . A 50-mg sample was diluted with 10:1 THF:water (1 mL in a screw cap vial) and treated with triphenylphosphine (190 mg). Gas evolution begins within 5 min; once this subsides the reaction is sealed and placed in an oil bath at 50°C for 30 min. The mixture is diluted with HClO 4 (pH 1.0, 1 mL) and washed with dichloromethane (2 × 1 mL). The acidic water phase contains the salt of the amine. A 200-μL sample was diluted to 1 mL and assayed by HPLC using a Crownpak CR(+) column (Diacel Chemical Industries): HPLC conditions; aqueous pH 1.0 HClO 4 , flow 0.5 mL/min, UV detection at 210 nm. The product had an enantiomeric excess of 96%, major enantiomer, R t 3.4 min, and minor enantiomer, R t 5.0 min. 10. The product from the distillation was analyzed by drop weight testing and differential scanning calorimetry (DSC). The drop weight test indicated that the product was not shock sensitive. By DSC, there was a 400 cal/g release of energy which initiated at 135°C. The pot residue showed a slow release of energy which was estimated to be ca. 100 cal/g and initiated at 150°C.Waste Disposal InformationAll toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.3. DiscussionAsymmetric introduction of azide to the α-position of a carbonyl has been achieved by several methods. These include amine to azide conversion by diazo transfer,2 chiral enolate azidation,3 4 and displacement of optically active trifluoromethanesulfonates,5 p-nitrobenzenesulfonates,6 or halides.7 8 Alkyl 2-azidopropionates have been prepared in optically active form by diazo transfer,2 p-nitrobenzenesulfonate displacement,6 and the Mitsunobu displacement using zinc azide .9 The method presented here is the simplest of the displacement methods since alcohol activation and displacement steps occur in the same operation. In cases where the α-hydroxy esters are available, this would be the simplest method to introduce azide.In addition to α-hydroxy carbonyl compounds, the method can be generally applied for alcohol to azide displacements. This method has been successfully demonstrated on fourteen optically active alcohols.10 Mechanistically, this reaction proceeds in two stages. The first is alcohol activation via formation of the corresponding phosphate, and the second stage is the azide displacement step. The method is most useful for azide displacements of alcohols which tend to racemize using highly reactive groups for activation (e.g., sulfonate formation or Mitsunobu conditions 11). When diphenylphosphoryl azide and DBU are used, the alcohol is only mildly activated for displacement as a phosphate. Use of the phosphate thus provides access to azide displacements of alcohols that are too sensitive using standard activation techniques. However, since the phosphate is only mildly activating, the alcohol undergoing displacement should be benzylic, allylic, or as in the present case, α to a carbonyl.Certain classes of compounds are too reactive for the present method. Ethyl mandelate produced a racemic, protected phenyl glycine derivative. Benzylic alcohols with two methoxy groups (directly conjugating in the 2 and 4 positions) gave azide of 50% e.e.Other classes of alcohols are unreactive. Ethyl 3-hydroxybutyrate (a β-hydroxy ester) went to the phosphate stage, but would not undergo azide displacement. In this example about 30% of the crotonate was formed because of β-elimination.References and Notes1.Department of Process Research, Merck Research Laboratories, Rahway, NJ 07065.2.Zaloom, J.; Roberts, D. C. J. Org. Chem.1981, 46, 5173.3.Evans, D. A.; Britton, T. C. J. Am. Chem. Soc.1987, 109, 6881;4.Evans, D. A.; Britton, T. C.; Ellman, J. A.; Dorow, R. L. J. Am. Chem. Soc.1990, 112, 4011.5.Effenberger, F.; Burkard, U.; Willfahrt, J. Angew. Chem., Int. Ed. Engl.1983, 22, 65. Thetrifluoromethanesulfonate displacements were demonstrated with amines (not azide).6.Hoffman, R. V.; Kim, H. O. Tetrahedron1992, 48, 3007.7.Evans, D. A.; Ellman, J. A.; Dorow, R. L. Tetrahedron Lett.1987, 28, 1123;8.Durst, T.; Koh, K. Tetrahedron Lett.1992, 33, 6799.9.Viaud, M. C.; Rollin, P. Synthesis1990, 130.10.Thompson, A. S.; Humphrey, G. R.; DeMarco, A. M.; Mathre, D. J.; Grabowski, E. J. J. J. Org.Chem.1993, 58, 5886.11.Mitsunobu, O.; Wada, M.; Sano, T. J. Am. Chem. Soc.1972, 94, 679; Lal, B.; Pramanik, B. N.;Manhas, M. S.; Bose, A. K. Tetrahedron Lett.1977, 1977; Fabiano, E.; Golding, B. T.; Sadeghi, M. M. Synthesis1987, 190; Chen, C.-P.; Prasad, K.; Repic, O. Tetrahedron Lett.1991, 32, 7175;Hughes, D. L. Org. React.1992, 42, 335.AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)Ethyl (R)-2-azidopropionate:Propanoic acid, 2-azido-, ethyl ester, (R)- (12); (124988-44-9)Ethyl (S)-(−)-lactate:Lactic acid, ethyl ester, L- (8);Propanoic acid, 2-hydroxy-, ethyl ester, (S)- (9); (687-47-8)Diphenylphosphoryl azide:Phosphorazidic acid, diphenyl ester (8, 9); (26386-88-9)1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU):Pyrimido[1,2-a]azepine, 2,3,4,6,7,8,9,10-octahydro- (8, 9); (6674-22-2)Methyl tert-butyl ether:Ether, tert-butyl methyl (8);Propane, 2-methoxy-2-methyl- (9); (1634-04-4)Citric acid monohydrate (8);1, 2, 3-Propanetricarboxylic acid, 2-hydroxy-, monohydrate (9); (5949-29-1)Copyright © 1921-2005, Organic Syntheses, Inc. All Rights Reserved。
Organic Syntheses, Coll. Vol. 5, p.699 (1973); Vol. 45, p.64 (1965).
Organic Syntheses, Coll. Vol. 5, p.699 (1973); Vol. 45, p.64 (1965).LEVOPIMARIC ACIDSubmitted by Winston D. Lloyd and Glen W. Hedrick 1.Checked by William G. Dauben and Robert M. Coates. 1. ProcedurePine oleoresin [1 kg. containing 260 g. (0.86 mole) of levopimaric acid] (Note 1) and (Note 2) is dissolved in 2 l. of acetone in a 4-l. beaker. A solution of 200 g. (2.2 moles) of 2-amino-2-methyl-1-propanol (Note 3) in 200 ml. of acetone is added as rapidly as possible with stirring. The pasty precipitate which forms almost immediately is collected by suction filtration and is pressed as dry as possible using a rubber dam (Note 4). The crude moist precipitate is returned to a 2-l. beaker and is dissolved in the minimum volume ( 1 l.) of boiling methanol . The methanolic solution is cooled to 5° in a refrigerator and stirred occasionally to expedite crystallization. When the crystallization is completed, the solid is collected by suction filtration. The precipitate is redissolved in a minimum volume of boiling methanol (1 l.)(Note 5), the solution concentrated to two-thirds its original volume (Note 6), cooled to 5°, and the amine salt allowed to crystallize. The solid is filtered by suction, and the filter cake is air-dried to yield 68–78 g. (20–23% of the available levopimaric acid) of the 2-amino-2-methyl-1-propanol salt of levopimaric acid, [α]25D −202° (Note 7) and (Note 8). The recrystallization is repeated; approximately 0.8 l. of boiling methanol is used and then concentrated, the yield of amine salt is 41–46 g. (12–14% of the available levopimaric acid), [α]25D −210° (Note 9).In a 1-l. separatory funnel there are first placed 400 ml. of ether and 75 ml. of 10% phosphoric acid (Note 10), and then the above amine salt is added (Note 11). The mixture is shaken vigorously for a few minutes, an additional 50 ml. of 10% phosphoric acid added, and the vigorous shaking continued until all the solid has disappeared. The ether layer is separated, washed twice with 100-ml. portions of water, and dried over anhydrous sodium sulfate . The drying agent is separated by filtration, the ether is removed at room temperature under reduced pressure using a rotary evaporator, and the residue dissolved in 40–60 ml. of boiling ethanol . The levopimaric acid is collected by suction filtration, yield 26–31 g. (10–12%), m.p. 147–150°, [α]25D −265° (Note 12), (Note 13), and (Note 14).2. Notes1. The longleaf pine (Pinus palustris ) oleoresin used was analyzed by the method of Lloyd and Hedrick 2 and was found to contain a total resin acid content of 660 g. The oleoresin used by the checkers was obtained from Shelton Naval Stores Co., Valdosta, Georgia. The oleoresin can also be obtained from thefollowing sources: K. S. Varn and Co., Hoboken, Georgia; The Langdale Co., Valdosta, Georgia; Vidalia Gum Turpentine Co., Vidalia, Georgia; Stallworth Pine Products Co., Mobile, Alabama;Filtered Rosin Products Company, Baxley, Georgia; Taylor-Lowenstein and Co., Mobile, Alabama; and Nelio Chemicals, Inc., Jacksonville, Florida.2. If any woody material remains undissolved, it should be removed by filtration of the acetone solution.3. The 2-amino-2-methyl-1-propanol, m.p. 25–29°, N.E. 88.5–99.0, was obtained from the Commercial Solvents Corporation and was used without further purification. The checkers obtained their material from Matheson Coleman and Bell Co.4. The use of a rubber dam is essential in this step to effect the separation of the residual acetone. It is also beneficial to use a rubber dam in the other suction filtrations in this process.5. If a clear solution is not obtained, the undissolved material should be removed by filtration.6. Concentration of the solution at this point gives a major improvement in yield. Crystallization does not occur during this concentration step unless the solution is seeded.7. All rotations were taken with a 2% methanolic solution.8. If the rotation is −210° or more negative, the next recrystallization may be omitted and the levopimaric acid generated directly.9. The maximum observed rotation for the 2-amino-2-methyl-1-propanol salt of levopimaric acid is [α] 24D−218°.3Methanol and ethanol solutions give the same specific rotations, but methanol is the preferred solvent because the time required to effect solution in ethanol is longer. If pure levopimaric acid, m.p. 151–153°, [α]24D−276° is desired, the salt with −210° rotation should be dissolved in 8 parts of boiling methanol, the solution concentrated to the point of incipient crystallization, cooled, and filtered. The yield in this recrystallization is about 70%.10. The submitters find phosphoric acid more convenient than boric acid3 or acetic acid.4 Acid isomerization to abietic acid3,5 did not occur under the conditions used here.11. After an induction period of approximately 1 week, the amine salt begins to be oxidized by air and the salt should be converted to levopimaric acid as soon as possible after it has been isolated.12. The checkers found that their material with [α]25D−260° had a melting point at 125–150°. The melting point is very sensitive to impurities, and a few percent of impurities can lower it drastically. 13. The yields obtained using this procedure can vary with the source of the oleoresin; the submitters report a yield of 29–34% of levopimaric acid.14. Using slash pine (Pinus elliotti) oleoresin containing approximately 16% of levopimaric acid,6,7 the submitters found yields consistently less than their reported 29–34%. Pine "scrape," a material which crystallizes on the surface of the pine tree, has been used in a similar process4 but gives highly variable yields and, owing to interference by oxidation products, may fail to give the desired material. To avoid the deleterious effects of oxidized materials, the use of fresh oleoresin is recommended.3. DiscussionThe described process of isolating levopimaric acid is based on the method of Summers, Lloyd, and Hedrick.8 The procedure, a modification of the process devised by Harris and Sanderson3 and Loeblich, Baldwin, O'Connor, and Lawrence,4 is more convenient and gives improved yields.4. Merits of the PreparationIn pine oleoresin, many resin acids occur. This procedure illustrates how, by the use of a specific amine, it is possible to get a specific precipitation of one resin acid from a mixture of acids.References and Notes1.Contribution of the Naval Stores Laboratory, Olustee, Florida, one of the laboratories of theSouthern Utilization Research and Development Division, Agricultural Research Service, U.S.Department of Agriculture.2.W. D. Lloyd and G. W. Hedrick, J. Org. Chem., 26, 2029 (1961).3.G. C. Harris and T. F. Sanderson, J. Am. Chem. Soc., 70, 334 (1948).4.V. M. Loeblich, D. E. Baldwin, R. T. O'Connor, and R. V. Lawrence, J. Am. Chem. Soc., 77,6311 (1955).5. D. E. Baldwin, V. M. Loeblich, and R. V. Lawrence, J. Am. Chem. Soc., 78, 2015 (1956).6. B. L. Davis and E. E. Fleck, Ind. Eng. Chem., 35, 171 (1943).7. D. E. Baldwin, V. M. Loeblich, and R. V. Lawrence, J. Chem. Eng. Data, 3, 342 (1958).8.H. B. Summers, Jr., W. D. Lloyd, and G. W. Hedrick, Ind. Eng. Chem., Prod. Res. Develop., 2,143 (1963).AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)LEVOPIMARIC ACID2-amino-2-methyl-1-propanol salt of levopimaric acidethanol (64-17-5)acetic acid (64-19-7)methanol (67-56-1)ether (60-29-7)sodium sulfate (7757-82-6)acetone (67-64-1)phosphoric acid (7664-38-2)boric acid (10043-35-3)2-amino-2-methyl-1-propanol (124-68-5)ABIETIC ACID (514-10-3)Copyright © 1921-2005, Organic Syntheses, Inc. All Rights Reserved。
氰基水解酯化
Organic Syntheses, Coll. Vol. 1, p.270 (1941); Vol. 2, p.27 (1922).ETHYL PHENYLACETATE[α-Toluic acid, ethyl ester]Submitted by Roger Adams and A. F. Thal.Checked by Oliver Kamm1. ProcedureIn a 3-l. round-bottomed flask, fitted with an efficient reflux condenser, are mixed 750 g. (918 cc.) of 95 per cent alcohol, 750 g. (408 cc.) of concentrated sulfuric acid and 450 g. (3.85 moles) of benzyl cyanide(Note 1). The mixture, which soon separates into two layers, is heated to boiling over a low flame, for six to seven hours, cooled, and poured into 2 l. of water, and the upper layer is separated. This is washed with a little 10 per cent sodium carbonate solution (Note 2) to remove small amounts of phenylacetic acid which may have been formed, and then distilled under reduced pressure. A small amount of water goes over first and then a pure product boiling 132–138°/32 mm. (120–125°/17–18 mm.) (Note 3). The yield is 525–550 g. (83–87 per cent of the theoretical amount).2. Notes1. The benzyl cyanide can be prepared according to the directions on p. 107; the product which boils over a 5° range should be used.2. In washing the layer of ethyl phenylacetate with sodium carbonate it is sometimes advisable to add a certain amount of sodium chloride so that the ester will separate more readily.3. The product obtained is water-clear and practically colorless. Although the product is collected over a 5° range, most of the liquid is found to boil over a 1° range, if distilled slowly without superheating. The boiling point of ethyl phenylacetate is near that of benzyl cyanide. However, a Kjeldahl analysis of the product shows that only a trace of nitrogen compounds is present.3. DiscussionEthyl phenylacetate can be prepared by the esterification of phenylacetic acid and alcohol by hydrochloric1 or sulfuric acid;2 and by the treatment of benzyl cyanide with alcohol and hydrogen chloride3 or sulfuric acid, which is much more convenient in the laboratory.This preparation is referenced from:z Org. Syn. Coll. Vol. 1, 107z Org. Syn. Coll. Vol. 2, 288References and Notes1.Radziszewski, Ber. 2, 208 (1869).2.Volhard, Ann. 296, 2 (footnote) (1897); Senderens and Aboulenc, Compt. rend. 152, 1855(1911).3.Wislicenus, Ber. 20, 592 (1887); Ann. 296, 361 (1897).AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)hydrochloricalcohol (64-17-5)sulfuric acid (7664-93-9)hydrogen chloride (7647-01-0)sodium chloride (7647-14-5)sodium carbonate (497-19-8)Benzyl cyanide (140-29-4)Phenylacetic acid (103-82-2)α-Toluic acid, ethyl ester (93-89-0)Ethyl phenylacetate (101-97-3)Copyright © 1921-2005, Organic Syntheses, Inc. All Rights Reserved。
Organic Syntheses, Coll. Vol. 4, p.68 (1963); Vol. 39, p.3 (1959).
Organic Syntheses, Coll. Vol. 4, p.68 (1963); Vol. 39, p.3 (1959).BENZENEBORONIC ANHYDRIDE[Boroxin, triphenyl-]Submitted by Robert M. Washburn, Ernest Levens, Charles F. Albright, and Franklin A. Billig1.Checked by B. C. McKusick and H. C. Miller.1. ProcedureCaution! Benzeneboronic acid and its anhydride are toxic substances and may irritate mucous tissues such as those of the eyes. In case of contact, carefully wash exposed parts of the body with soap and water (Note 1).The apparatus consists of a four-necked 5-l. round-bottomed Morton flask2 fitted with a 500-ml. graduated dropping funnel with a pressure-equalizing side arm, a 1-l. graduated dropping funnel of the same type, a thermometer, an efficient mechanical stirrer (Note 2), and an inlet for dry nitrogen. The apparatus is thoroughly swept with dry nitrogen, and the reaction flask is charged with 1.5 l. of anhydrous ether, dry nitrogen(Note 3) being used for pressure transfer.Three hundred thirty-six milliliters (312 g., 3 moles) of methyl borate is distilled directly into the 500-ml. dropping funnel shortly before starting the reaction (Note 4). One liter (544 g., 3 moles) of a 3M ethereal solution of phenylmagnesium bromide is pressure-transferred with dry nitrogen to the 1-l. dropping funnel (Note 5). During subsequent operations until the hydrolysis step, a positive pressure of 10–20 mm. of nitrogen is maintained in the closed system by means of a mercury bubbler to prevent access of atmospheric moisture. The ether is cooled to below −60° by a bath of Dry Ice and acetone and is kept below −60° all during the reaction (Note 6). The reactants are added to the well-stirred reaction mixture alternately in small portions, first 10 ml. of methyl borate and then 30 ml. of phenylmagnesium bromide, the rate of addition being as rapid as is possible without the temperature of the mixture rising above −60° (Note 7). Stirring is continued for an additional 20 minutes below −60° after the addition of the reagents is completed.The stirred mixture, maintained at or below 0°, is hydrolyzed by the addition of 200 ml. of distilled water during 5 minutes. It is then neutralized by addition of a solution of 84 ml. of concentrated sulfuric acid in 1.7 l. of distilled water during 15 minutes. The mixture is transferred to a 5-l. separatory funnel, the ether layer is separated, and the aqueous layer is extracted with three 250-ml. portions of ether.The combined ether layer and extracts are transferred to a 5-l. round-bottomed flask equipped with a Hershberg stirrer,3 a dropping funnel, a Claisen head with a water-cooled condenser, an electric heating mantle, and an ice-cooled receiver (Note 8). After approximately one-half of the ether has been removed by distillation from the stirred mixture, 1.5 l. of distilled water is added slowly while the distillation is continued until a head temperature of 100°is reached (Note 9).While stirring is continued, the aqueous distilland is cooled in an ice bath (Note 10). The benzeneboronic acid, which separates as small white crystals, is collected on a Büchner funnel and washed with petroleum ether. The petroleum ether removes traces of dibenzeneborinic acid, which are seen in the hot mother liquor as globules of brown oil and which may color the product. The acid is dehydrated to benzeneboronic anhydride by heating it in an oven at 110° and atmospheric pressure for 6 hours (Note 11). Benzeneboronic anhydride is obtained as a colorless solid, weight 240–247 g. (77–79%) (Note 12), m.p. 214–216°.2. Notes1. A summary of the physiological activity of benzeneboronic acid may be found in reference 4.2. The submitters found that for a preparation of this size a 1-inch Duplex Dispersator (Premier Mill Corp., Geneva, New York) operating at 7500 r.p.m. provided excellent agitation of the heterogeneous reaction mixture. For smaller preparations (1-l. flask) they found that a Stir-O-Vac (Labline, Inc., 217 N. Desplainer St., Chicago 6, Illinois) operating at 5000 r.p.m. was satisfactory. The type of agitation is very important for, whereas the submitters obtained yields of around 91%, the checkers obtained yields of only 77–80% with either a Morton stirrer2 (excessive splashing deposited some of the reaction mixture on the warm upper walls of the flask) or a Polytron dispersion mill type of stirrer (there was too much hold-up in the stirrer housing).3. Tank nitrogen was dried with phosphorus pentoxide.4. Methyl borate (b.p. 68°) forms a 1:1 azeotrope (b.p. 54.6°) with methanol (b.p. 64°).5 Since the presence of even a small amount of methanol reduces the yield considerably more than would be expected from the stoichiometry, 46,7methyl borate stocks should be freshly distilled through a good column to remove as fore-run any methyl borate-methanol azeotrope which may have been formed by hydrolysis during storage.5. Mallinckrodt analytical reagent grade ether, dried over sodium, was used. The methyl borate was the commercial product of American Potash and Chemical Corporation containing 99% ester as received. The phenylmagnesium bromide was purchased as a 3.0M solution in ether from Arapahoe Special Products, Inc., Boulder, Colorado.6. The yield of benzeneboronic anhydride is highly dependent upon the reaction temperature, as the following data of the submitters show. At a reaction temperature of 15° the yield was 49%; at 0°, 76%; −15°, 86%; −30°, 92%; −45°, 92%; −60°, 99%. The yields are based on the combined first and second crops of benzeneboronic acid.7. At a given temperature, the maximum yield of benzeneboronic acid and the minimum amount of by-product dibenzeneborinic acid are obtained when neither reagent is present in excess. The addition of small increments of reactants is a convenient approximation imposed by the difficulty of adjusting stopcocks to small rates of flow. Alternatively, the Hershberg dropping funnel8 or other metering device may be used to maintain the stoichiometry. Addition times, which depend upon the efficiency of stirring and heat transfer, vary from about 1 hour at −60° to 15 minutes at 0°.8. Stirring is helpful during the ether distillation to prevent superheating.9. Small amounts of benzene, phenol, and biphenyl, which may be formed in the reaction, are removed by the steam distillation. Enough water has been added to ensure solution of all of the product.10. The product crystallizes at 43° with a temperature rise to 45°. The solubility of benzeneboronic acid in water (g./100 g. of water) is approximately 1.1 at 0° and 2.5 at 25°; the solubility-temperature relationship is linear to at least 45°.11. If benzeneboronic acid rather than its anhydride is desired, it can be obtained by air-drying the moist acid in a slow stream of air nearly saturated with water. The yield of acid is 282–332 g. One can readily convert the anhydride to the acid by recrystallizing it from water. Benzeneboronic acid gradually dehydrates to the anhydride if left open to the atmosphere at room temperature and 30–40% relative humidity. The melting point observed is that of the anhydride because the acid dehydrates before it melts.12. The submitters report a yield of 91% and state that an additional 27 g. (9%) of acid can be obtained from the aqueous mother liquor.3. DiscussionThe procedure described4,6 is a modification of the method of Khotinsky and Melamed,9who firstreported the preparation of boronic acids from Grignard reagents and borate esters. Benzeneboronic acid and the corresponding anhydride also have been prepared by reaction of phenylmagnesium bromide with boron trifluoride;10 by the reaction of phenyllithium with butyl borate;11 by the reaction of diphenylmercury with boron trichloride;12 by the reaction of benzene with boron trichloride in the presence of aluminum chloride;13 and by the reaction of triphenylborane with boric oxide.14 The present procedure is also applicable to the synthesis of substituted benzeneboronic acids.4 Benzeneboronic acid and its anhydride are of use as starting materials for the synthesis of phenylboron dichloride15 and of various substituted boronic and borinic acids and esters.7,16This preparation is referenced from:z Org. Syn. Coll. Vol. 10, 613References and Notes1.American Potash and Chemical Corporation, Whittier, California.2.Morton, Ind. Eng. Chem., Anal. Ed., 11, 170 (1939); Morton and Redman, Ind. Eng. Chem., 40,1190 (1948).. Syntheses Coll. Vol.2, 117 (1943).4.Washburn, Levens, Albright, Billig, and Cernak, Advances in Chem. Ser., 23, 102 (1959);5.Schlesinger, Brown, Mayfield, and Gilbreath, J. Am. Chem. Soc., 75, 213 (1953).6.Washburn, Billig, Bloom, Albright, and Levens, Advances in Chem. Ser., 32, 208 (1961).7.Seaman and Johnson, J. Am. Chem. Soc., 53, 711 (1931).. Syntheses Coll. Vol.2, 129 (1943).9.Khotinsky and Melamed, Ber., 42, 3090 (1909).10.Krause and Nitsche, Ber., 55B, 1261 (1922); Krause, German pat. 371,467 (1923) [C. A., 18, 992(1924)].11.Brindley, Gerrard, and Lappert, J. Chem. Soc., 1955, 2956.12.Michaelis and Becker, Ber., 15, 180 (1882).13.Muetterties, J. Am. Chem. Soc., 82, 4163 (1960).14.McCusker, Hennion, Ashby, and Rutowski, J. Am. Chem. Soc., 79, 5194 (1957).15.Dandegaonker, Gerrard, and Lappert, J. Chem. Soc., 1957, 2893.ppert, Chem. Revs., 56, 987, 1013 (1956).AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)petroleum etherboric oxidesulfuric acid (7664-93-9)Benzene (71-43-2)methanol (67-56-1)ether(60-29-7)phenol (108-95-2)nitrogen (7727-37-9)aluminum chloride (3495-54-3)sodium (13966-32-0)Biphenyl (92-52-4)Phenylmagnesium bromide (100-58-3)Diphenylmercury (587-85-9)Phenyllithium (591-51-5)boron trifluoride (7637-07-2)Benzeneboronic anhydrideBoroxin, triphenyl- (3262-89-3)Benzeneboronic acid (98-80-6)methyl boratedibenzeneborinic acidmethyl borate-methanolButyl borate (688-74-4)boron trichloride (10294-34-5)triphenylborane (960-71-4)phenylboron dichloride (873-51-8)phosphorus pentoxide (1314-56-3) Copyright © 1921-2005, Organic Syntheses, Inc. All Rights Reserved。
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Organic Syntheses, Coll. Vol. 5, p.277 (1973); Vol. 48, p.56 (1968).CYCLODECANONESubmitted by R. D. Burpitt and J. G. Thweatt1.Checked by William G. Dauben, Michael H. McGann, and Noel Vietmeyer.1. ProcedureTo a 500-ml. round-bottomed flask fitted with a 25- to 30-cm. column packed with glass helices to which is attached a water separator2 filled with hexane(Note 1) are added 126 g. (1.00 mole) of cyclooctanone(Note 2), 100 g. (1.4 moles) of pyrrolidine, 100 ml. of xylene, and 0.5 g. of p-toluenesulfonic acid. The solution is heated under reflux until the separation of water ceases (Note 3). The water separator is replaced by a distillation head, and the reaction mixture is distilled through the column under reduced pressure to remove solvent and unreacted starting materials. When the head temperature reaches 50° (1 mm.), distillation is stopped, and the residue of almost pure N-(1-cycloocten-1-yl)pyrrolidine (152–161 g.) is used in the next step without further purification (Note 4).The crude enamine is dissolved in 450 ml. of ether, and the solution is transferred to a 1-l. three-necked flask equipped with a sealed stirrer, a 250-ml. dropping funnel, and a two-necked adapter fitted with a calcium chloride tube and a thermometer immersed in the solution. A solution of 71–76 g. (0.85–0.90 mole) (Note 5) of methyl propiolate(Caution! Methyl propiolate is a severe lachrymator and should be handled only in the hood.) in 150 ml. of ether is added dropwise. During the addition the temperature of the mixture is maintained at 25–30° by periodic cooling of the reaction flask in a dry ice-acetone bath. When the addition is almost complete, a white solid begins to separate. The mixture is stirred at 25–30° for an additional hour, cooled to 0°, and filtered to remove the solid. This is dissolved in 700 ml. of 6% hydrochloric acid(Note 6), the acidic solution is warmed at 55–60° for 1 hour, and the mixture is cooled and extracted with two 100-ml. portions of ether. The ether is removed on a steam bath, and the residue of crude methyl 10-oxocyclodec-2-ene-1-carboxylate is dissolved in 300 ml. of methanol and hydrogenated over 5 g. of 5% palladium-on-alumina catalyst at 40 p.s.i. pressure and room temperature.The catalyst is filtered, 200 g. (155 ml.) of 25% aqueous sodium hydroxide is added to the filtrate, and the mixture is heated under reflux for 1 hour. The condenser is replaced by a short Vigreux column and distillation head, and the heating is continued until most of the methanol has distilled. The two-phase residue is cooled and extracted with two 100-ml. portions of ether. The ether is removed on a steam bath, and the residue is distilled through a 20-cm. Vigreux column to yield 68–77 g. (44–50%) of cyclodecanone, b.p. 94–98° (10 mm.), m.p. 20–22° (Note 7).2. Notes1. If hexane is not used in the trap, an excessive amount of pyrrolidine is lost in the aqueous layer.2. Cyclooctanone from Aldrich Chemical Co., methyl propiolate from Farchan Research Laboratories, and pyrrolidine from Eastman Organic Chemicals were used as received.3. The reaction is usually complete after 3–6 hours at reflux. Owing to dissolved pyrrolidine, the aqueous layer amounts to 35–45 ml., and thus its volume is not a good measure of the extent of reaction.4. Pure N-(1-cycloocten-1-yl)pyrrolidine, b.p. 76–78° (1 mm.), may be isolated by distillation through a Vigreux column.5. The amount used should be adjusted to be equimolar with the amount of crude enamine.6. This solid intermediate is reasonably stable to storage under nitrogen; however, the yield in the acid hydrolysis step is better when freshly prepared material is hydrolyzed immediately.7. The same reaction sequence may be used to convert cyclododecanone to cyclotetradecanone. Preparation of the pyrrolidine enamine of cyclododecanone requires 2–3 days at reflux, and reaction of the enamine with methyl propiolate is best carried out in refluxing hexane. The enamine-propiolate reaction may also be used to convert cycloheptanone to cyclononanone. In this case the procedure must be modified to provide for partial hydrogenation of the intermediate amino ester without prior hydrolysis.3 The reduced intermediate is saponified as described in the present procedure.3. DiscussionCyclodecanone has been obtained together with other products in the pyrolysis of the thorium or yttrium salts of nonanedioic acid.4 It has also been prepared by reduction of sebacoin with zinc and hydrochloric acid,5,6 by dehydration of sebacoin followed by catalytic hydrogenation,7 by ring enlargement of cyclononanone with diazomethane8,9 and of cyclooctanone with diazomethane in the presence of a Lewis acid catalyst,9 by hydroboration of 1,2-cyclodecadiene followed by oxidation of the organoborane,10 and by the present procedure.34. Merits of the PreparationThe chief merits of this preparation are its simplicity and the high purity of the product. Although the synthesis involves several steps, each step is a simple operation, and all intermediates may be used in the subsequent steps without purification. The purity of even the crude product is high, and any impurities which may be present are readily removed by a simple distillation.The overall yield of cyclodecanone is comparable to the overall yield obtained by conversion ofdimethyl sebacate to sebacoin11 and subsequent reduction to cyclodecanone.6 In addition, the present procedure does not require the use of a high-speed stirrer, the rigorous exclusion of air, and the high dilution that are necessary in preparing sebacoin.References and Notes1.Research Laboratories, Tennessee Eastman Company, Division of Eastman Kodak Company,Kingsport, Tennessee 37662.2.S. Natelson and S. Gottfried, Org. Syntheses, Coll. Vol. 3, 381 (1955).3.K. C. Brannock, R. D. Burpitt, V. W. Goodlett, and J. G. Thweatt, J. Org. Chem., 29, 818 (1964).4.L. Ruzicka, M. Stoll, and H. Schinz, Helv. Chim. Acta, 9, 249 (1926); 11, 670 (1928).5.V. Prelog, L. Frenkiel, M. Kobelt, and P. Barman, Helv. Chim. Acta, 30, 1741 (1947).6. A. C. Cope, J. W. Barthel, and R. D. Smith, Org. Syntheses, Coll. Vol. 4, 218 (1963).7.M. Stoll, Helv. Chim. Acta, 30, 1837 (1947).8. E. P. Kohler, M. Tishler, H. Potter, and H. T. Thompson, J. Am. Chem. Soc., 61, 1057 (1939).9. E. Muller, M. Bauer, and W. Rundel, Tetrahedron Lett., No. 13, 30 (1960).10. D. Devaprabhakara and P. D. Gardner, J. Am. Chem. Soc., 85, 1458 (1963).11.N. L. Allinger, Org. Syntheses, Coll. Vol. 4, 840 (1963).AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)Sebacoinpalladium-on-aluminaenamine-propiolatethorium or yttrium salts of nonanedioic acidhydrochloric acid (7647-01-0)methanol (67-56-1)ether (60-29-7)sodium hydroxide (1310-73-2)nitrogen (7727-37-9)zinc (7440-66-6)xylene (106-42-3)Diazomethane (334-88-3)pyrrolidine(123-75-1)hexane (110-54-3)Cyclodecanone (1502-06-3)cyclononanone (3350-30-9)Cycloheptanone (502-42-1)dimethyl sebacate (106-79-6)Cyclooctanone (502-49-8)cyclododecanone (830-13-7)methyl propiolate (922-67-8)N-(1-cycloocten-1-yl)pyrrolidinemethyl 10-oxocyclodec-2-ene-1-carboxylatecyclotetradecanone (3603-99-4)pyrrolidine enamine1,2-cyclodecadienep-toluenesulfonic acid (104-15-4) Copyright © 1921-2005, Organic Syntheses, Inc. All Rights Reserved。