脂肪卤代物的合成

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卤代化合物(Cl 综述

浓 HCl/ZnCl2Fra bibliotek4h, heat
yield:66%
[3]
在某些仲醇、叔醇和β位具有叔碳取代基的伯醇的反应中，若反应温度过高，会产生重排、异构化和脱卤等副反应。例如，巴豆醇(1)用48%氢溴酸于-15℃反应，或者用饱和溴化氢气体于0℃反应，除主要得到正常卤代物(2)外，还有不同比例的双键异构化副产物(3)。
H+ OH 1 -H 2 O Br Br Br 48% HBr/-15o C 2 (86%) (79%) 3 (14%) (21%)
6
Br
饱和 HBr/0oC
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2. 醇和卤化氢或氢卤酸的反应
2.1 醇和氯化氢反应的方法示例
(100%)
[6]
10
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3. 醇和卤化亚砜的反应
醇用溴化亚砜的溴置换反应，类似于氯化亚砜。溴化亚砜可以由SOCl2和溴化氢气体在0℃反应得到。
3.1 醇和二氯亚砜反应的方法示例
S Cl N 2
S HO N 1
SOCl2
Confidential
OH PBr3 Et2O,R.t.,1h (82%) Br [7]
三卤化磷和醇进行反应时，首先生成亚磷酸的单、双或三酯的混合（9）和卤化氢，然后，由于倾向于形成磷酰基（P=O）而使（9）中烷氧键发生断裂，于是卤素负离子对酯分子中亲电性烷基作亲核取代反应，生成卤化物。
R OH + PX3 -HX P O R 9
OH PBr3(0.28mol)/20C,22h(19%) PBr3(0.75mol)/150C,24h(64%) PBr3(0.28mol)/20C,24h(1%) (60%) (63%) (54%)

脂肪族和环状酮的合成和反应

脂肪族和环状酮的合成和反应脂肪族和环状酮是有机化学中两种重要的化合物类别。

它们在生物学、药物学和合成化学等领域中具有广泛的应用价值。

本文将探讨脂肪族和环状酮的合成和反应方法，为读者提供相关知识和实践指导。

一、脂肪族的合成和反应方法脂肪族化合物是由碳和氢元素构成的，其分子结构为线性的或支链状的碳链。

常见的脂肪族化合物包括烷烃、烯烃和炔烃等。

脂肪族的合成和反应方法主要有以下几种：1. 烃类合成：烃类是由碳和氢元素组成的最简单的有机化合物。

烷烃是一类只含有碳和氢原子的饱和烃，可以通过烷化反应、脱氢反应等方法合成。

烯烃和炔烃则可以通过卤代烃的脱氢反应、乙炔和烯烃的加成反应等方法合成。

2. 氧化反应：脂肪族化合物可通过氧化反应转化为醇、醚和酮等功能性化合物。

常见的氧化试剂包括酸性高锰酸钾、过氧化氢和氧气等，它们可将脂肪族化合物中的氢原子氧化成羟基、醚基或酮基。

3. 反应衍生：脂肪族化合物可以通过取代反应、加成反应和消除反应等方法进行进一步衍生。

其中取代反应是最常见的方法，例如烷基化反应、卤素化反应、硝化反应等。

二、环状酮的合成和反应方法环状酮是由羰基（C=O）功能团存在于环状结构中的有机化合物。

环状酮具有广泛的生物活性，并广泛应用于药物开发和天然产物合成等领域。

环状酮的合成和反应方法主要有以下几种：1. 羰基化合：羰基化合是合成环状酮的一种重要方法。

它主要通过酸催化或酸催化的缩合反应实现。

常用的羰基化合试剂包括柯斯雷儿试剂、亚硝化钠和格氏试剂等。

2. 酮的环化：酮的环化反应是一种将直链酮转化为环状酮的方法。

其中较常用的方法是酸催化的环化反应和金属催化的环化反应。

酸性条件下，直链酮可以通过高斯曼环化反应形成内酯。

而金属催化剂如铂或钯催化条件下，直链酮可以发生羟酮异构化反应，生成环状酮。

3. 环状亲核试剂攻击：环状酮可被亲核试剂进攻，发生环上位阻取代、开环加成等反应。

这些反应通常是在碱性条件下进行，常用试剂有醇、胺和硫醇等。

大学有机化学之脂肪族卤代烃

SN1反应进程与能量关系图：
T1 T2
能量
C
+ Br
C Br + OH
C OH + Br
反应进程
SN1反应的化学特征 :
CH3 HO C CH3 CH3
HO
CH3 C H3C CH3
H3C
OH
H3C H3C
C
OH
1）外消旋化（构型翻转 + 构型保持）因：SN1反应第一步生成的碳正离子为平面构型（正电荷的碳原子为sp2杂化的）。第二步亲核试剂向平面任何一面进攻的几率相等。
1．按分子中所含卤原子的数目，分为一卤代烃和多卤代烃。
一元卤代烃
二元卤代烃
多元卤代烃
CH3I
CH2 CH2 Br Br
CHI3
2．按卤素所连的碳原子的类型，分为：
伯卤代烃
仲卤代烃
叔卤代烃
R-CH2-X
R CH-X R
R R C-X R
卤代烃的命名：
与脂肪烃或脂环烃类似，卤原子作为取代基。
编号一般从离取代基近的一端开始，取代基的列出按“顺序规则”小的基团先列出
R-X一般为1°RX，（仲、叔卤代烷与醇钠反应时，主要发生消除反应生成烯烃）。
这是制备醚、尤其是混醚的一种常用方法
（丙）与氰化钠反应
BrCH2(CH2)5Br + 2KCN
C2H5OH, H2O Reflux 8h, 75%
NCCH2(CH2)5CN + 2KBr
RCH2X + NaCN
醇
RCH2CN + 腈
C2H5ONa C2H5OH, 55℃
CH2
CH CH3 + NaBr + C2H5OH

脂肪族偶氮化合物的合成过程

脂肪族偶氮化合物的合成过程脂肪族偶氮化合物是一类含有两个氮原子的有机化合物，其合成过程可以分为以下几个步骤：醚化反应、硝基化反应、还原反应和偶氮化反应。

一、醚化反应1. 选择一种适当的醇和卤代烷进行醚化反应。

常用的醇包括甲醇、乙醇等，而卤代烷则可以是氯代烷或溴代烷。

2. 将适量的醇和卤代烷加入一个干净干燥的圆底烧瓶中，并加入适量的碱催化剂（如氢氧化钠或碳酸钾）。

3. 在室温下搅拌混合物，使其充分反应。

此时，会观察到生成了相对较稳定的醚类产物。

4. 将混合物加入一个分液漏斗中，并加入足够的水来萃取产物。

重复此步骤多次，直到有机层不再呈现白色。

5. 将有机层收集并用无水盐（如硫酸镁）除去水分。

通过蒸馏或其他纯化方法得到纯净的醚化产物。

二、硝基化反应1. 将醚化产物溶解在无水的硫酸中，生成相应的硫酸酯。

2. 加入适量的浓硝酸，并在低温条件下搅拌混合物。

此时，会观察到产生了硝基化合物。

3. 将混合物加入冰水中，使其充分冷却。

硝基化合物会从有机层转移到水相中。

4. 用氢氧化钠溶液调节pH值，使其碱性。

此时，硝基化合物会以游离态存在于水相中。

5. 用氯仿或其他有机溶剂提取游离态的硝基化合物。

重复此步骤多次，直到有机层不再呈现黄色。

6. 将有机层收集并用无水盐除去水分。

通过蒸馏或其他纯化方法得到纯净的硝基化合物。

三、还原反应1. 将硝基化合物溶解在无水乙醇中，并加入适量的金属还原剂（如锌粉）和催化剂（如盐酸）。

2. 在室温下搅拌混合物，使其充分反应。

此时，硝基基团会被还原成氨基基团。

3. 将混合物加热至沸腾，并继续搅拌。

通过蒸馏或其他纯化方法得到纯净的还原产物。

四、偶氮化反应1. 将还原产物溶解在适量的无水醇中，并加入亚硝酸钠溶液。

2. 在低温条件下搅拌混合物，并逐渐加入稀酸（如盐酸）。

此时，会观察到生成了偶氮化合物。

3. 继续搅拌混合物，并用冰水冷却。

偶氮化合物会从有机层转移到水相中。

4. 用氯仿或其他有机溶剂提取偶氮化合物。

脂肪族卤代烃氨解反应的研究进展

脂肪族卤代烃氨解反应的研究进展明文勇;梅苏宁;段琦;杨建明;吕剑【摘要】脂肪胺是人类生活和化学工业中重要的中间体,醇的氨解是制备脂肪胺的主要方法,当脂肪族卤代烃廉价易得时,也可以使用脂肪卤代烃的氨解反应来制备各种脂肪胺.综述了近年来脂肪族卤代烃与氨、胺和其它含氮化合物的氨解反应的研究进展,并对德尔宾反应和盖布瑞尔反应进行了简介.【期刊名称】《化学工程师》【年(卷),期】2016(030)011【总页数】5页(P52-56)【关键词】脂肪胺;脂肪族卤代烃;氨解;进展【作者】明文勇;梅苏宁;段琦;杨建明;吕剑【作者单位】山东华安新材料有限公司,山东淄博255300;氟氮化工资源高效开发与利用国家重点实验室,陕西西安710065;氟氮化工资源高效开发与利用国家重点实验室,陕西西安710065;西安近代化学研究所,陕西西安710065;山东华安新材料有限公司,山东淄博255300;氟氮化工资源高效开发与利用国家重点实验室,陕西西安710065;西安近代化学研究所,陕西西安710065;氟氮化工资源高效开发与利用国家重点实验室,陕西西安710065;西安近代化学研究所,陕西西安710065【正文语种】中文【中图分类】O625.63脂肪胺是非常重要的有机合成中间体，其中低级脂肪胺，如乙胺、丙胺、异丙胺、丁胺、环戊胺等是医药、农药、染料、食品添加剂等许多化学品的重要原料或中间体，高级脂肪胺则很容易衍生成阳离子或非离子型表面活性剂，这些表面活性剂广泛用于合成织物柔软剂、农药乳化剂、石油破乳剂、杀菌剂、缓蚀剂和固化剂等。

制备脂肪胺主要采用氨基化法，其中最主要的是醇的氨基化，当脂肪族卤代烃廉价易得时，也可以使用卤代烃的氨解反应[1-4]来制备各种脂肪族伯、仲、叔胺及季铵盐等。

氨解反应是指氨或胺与有机化合物发生复分解生成胺的反应，利用该反应可以制备多种含氮化合物，其反应方程式如式（1）所示，该反应属于亲核取代反应。

在脂肪族卤代烃的氨解反应中，卤原子比较容易被氨基取代，例如氯代烷在一定压力下用NH3·H2O处理就可以得到相应伯胺。

药物合成卤化反应

第一章卤化反应
Halogenation Reaction
定义：有机化合物分子中引入
卤素原子(X)的反应称卤化反应。用途：作为特定活性化合物作官能团转化的中间体
如：制备药物中间体糖皮质激素醋酸可的松
O CH3 C O OH
I2/CaO CH3OH/CaCl2
CH2 I C O OH
CH2 OCCH3 C O OH
R2
C
C O SMe2
H
H2O
Br C H R1 C OH H R2 Br C R1 C O H
R2
-消除 (在燥 MSO中干 D )
第一节不饱和烃的卤加成反应
▲三、不饱和烃和【次卤酸（酯）】、【N-卤代酰胺】的反应
OAc NBS/DMSO AcOCH2 O OgluAc4 OAc Br O AcOCH2 O OgluAc4 r.t
Cl2/CH2Cl2
h
降冰片烷
Cl
外向型(exo) 70~95%
第二节烃类的卤代反应
▲一、脂肪烃的卤取代反应
苄位、烯丙位的卤取代：
X2
h 或他其引剂发
X
(X=Cl, Br)
O N +X O
O h N X 或由自基引剂发 O
第二节烃类的卤代反应
▲一、脂肪烃的卤取代反应
C
R2
C
R4
X-OH
R1 R2
OH
R3 R4
C
X
C
H2O
R1 R2
OH
R3
C
C
X R4
HClO HBrO
Cl--OH Br--OH
第一节不饱和烃的卤加成反应

脂肪族卤代烃

(甲) 水解
在H2O或H2O／OH－中进行，得醇。
RX
+
H2O
ROH
可逆反应！
+
HX
OH-
反应活性：RI＞RBr＞RCl＞RF(难) 加碱的原因：①亲核性：OH－＞H2O；
②OH－可中和反应生成的HX。
H2O + X-
C5H11Cl NaOH/H2O
自由基氯化得
C5H11OH + NaCl 杂醇油，
(2) 相对密度
分子中卤素原子数目↑，其相对密度↑。一元卤代烷中RF、RCl的d＜1；RBr、RI的d＞1；多卤代烃的d＞1。
(3) 光谱性质
a. 红外光谱
化学键 νC－X/cm-1
C－F 1000～1400
C－Cl 600～800
C-Br 500～600
C-I ～500
b. 核磁共振谱由于电负性：X＞C(饱和)，所以α-H、β-H的δ有明显的去屏蔽效
Cl 3-氯环己烯
CH2 CH2 Br Br 1,2-二溴乙烷
二元卤代烃
CHI3 三碘甲烷
三元卤代烃
Cl
CH2=C-CH=CH2 2-氯1,3-丁二烯
F2C=CF2 四氟乙烯
一元卤代烃
多元卤代烃
第一节卤代烷
(一) 卤代烷的分类和命名 (二) 卤代烃的制法 (三) 卤代烷的物理性质 (四) 卤代烷的化学性质 (五) 亲核取代反应机理 (六) 影响亲核取代反应的因素 (七) 消除反应的机理 (八) 影响消除和取代反应的因素
(甲) 普通命名法
烷基名＋卤素名
例：
CH3CH2CH2CH2Cl 正丁基氯
CH3 H3C C Br
CH3

卤代反应2011

卤化03
亲电加成（大多数不饱和烃的卤加成反应）亲电取代（芳烃和羰基α位的卤取代反应）
卤化反应机理
亲核取代（醇羟基、羧羟基和其他官能团的卤置换反应）自由基反应（饱和烃、苄位和烯丙位的卤取代反应、某些不饱和烃的卤加成反应、羧基和重氮基的卤置换反应）
卤化04
卤化反应的类型
不饱和烃的卤加成反应
CH2(COOC2H5)2 Br2/CCl4 1h BrCH(COOC2H5)2 75%
Halogenation of 1,3-dicarbonyl compounds
羰基的卤取代17
醇酚醚卤置换01
第四节醇、酚、醚的卤置换反应
醇的卤置换反应酚的卤置换反应醚的卤置换反应
一、醇的卤置换反应
醇酚醚卤置换03
卤化氢（氢卤酸）置换
可逆平衡反应羟基的活性顺序：叔>仲>伯，苄位和烯丙位也很活泼活性大的叔、苄位反应倾向于SN1机理，其他为SN2 卤化氢的活性顺序：HI>HBr>HCl>HF
卤化亚砜置换
醇酚醚卤置换04
亚硫酰卤（氯化亚砜、溴化亚砜）与醇反应生成卤代烷和二氧化硫与卤化氢，易分离，在醇的卤化中应用较广。醇与氯化亚砜作用先是生成氯代亚硫酸酯和氯化氢，接着氯代亚硫酸酯发生分解。
烃类的卤取代08
NO2 Cl2O/(CF3SO2)2O 0 /POCl3 Cl
CH3 Br N
+
NO2
CH3 NO2 Br
O Br conc.H2SO4 rt 3.5h O N H O N
O NO2
+
H N N N H
Br
98% COOH
O
O
COOH

脂肪族醛的合成方法研究

脂肪族醛的合成方法研究脂肪族醛是一种重要的有机化合物，具有广泛的应用领域，如医药、香料、涂料等。

因此，脂肪族醛的合成方法研究具有重要意义。

本文将介绍几种主要的脂肪族醛合成方法，并探讨其原理和优缺点。

一、卤代脂肪醇的氧化法卤代脂肪醇的氧化法是合成脂肪族醛的传统方法之一。

该方法通过将卤代脂肪醇与氧化剂反应，将醇基氧化成醛基，得到脂肪族醛。

常用的氧化剂有氧，过氧化氢等。

这种方法具有简单、操作方便的优点，但也存在一些不足之处。

首先，该方法需要较高的反应温度和长时间的反应时间，反应条件相对苛刻。

其次，反应产物的纯度不高，需要经过多次提纯才能得到纯度较高的脂肪族醛。

二、脂肪酸的脱羧法脂肪酸的脱羧法是另一种常用的脂肪族醛合成方法。

该方法通过将脂肪酸与还原剂（如碱金属、强还原剂）反应，将羧基脱除，得到脂肪族醛。

这种方法具有高收率、简单纯洁的优点，但也存在一些问题。

首先，该方法的反应过程比较慢，需要较长的反应时间。

其次，部分杂质难以完全去除，会影响反应产物的纯度。

三、醛的还原法醛的还原法是合成醇的常用方法，但反过来也可以通过此法合成脂肪族醛。

该方法通过将醛与还原剂（如氢气、金属氢化物）反应，将醛基还原成醇基，得到脂肪族醛。

该方法具有反应条件温和、反应速度较快的特点。

然而，它也存在一些局限性。

首先，该方法需要较高的反应温度和压力，不利于大规模工业应用。

其次，反应中会伴随一定程度的氧化反应，降低了产物的选择性和收率。

四、醇的氧化法醇的氧化法是合成脂肪族醛的常用方法之一。

该方法通过将醇与氧化剂（如高价金属氧化物催化剂、过氧化物）反应，将醇基氧化为醛基，得到脂肪族醛。

该方法具有高产率、反应速度快、操作简便的优点。

然而，醇的氧化过程中常伴随酯的生成，需要经过一系列的分离纯化步骤才能得到目标产物。

另外，一些催化剂在反应过程中会产生氧化副产物，影响产物的纯度。

综上所述，脂肪族醛的合成方法有多种选择，每种方法都有其独特的优势和局限性。

脂肪族卤代烃类物质毒理学资料

脂肪族卤代烃类是指开链烃中的氢原子被卤族元素取代的衍生物，即氟代、氯代、溴代或碘代衍生物。

根据烃基结构可分为饱和卤代烃(卤代烷烃)和不饱和卤代烃(如卤代烯烃)。

根据分子中所含卤原子数目而分为一卤代物、二卤代物和多卤代物。

各衍生物的理化性质差别很大。

在常温下，一般低级卤代烃(C1～C4)是气体，高级卤代烃(>C16)是固体，中间的是液体。

卤代烃分子中如烃基相同，则以氯代烃的比重和沸点最低，碘代烃最高。

如卤素相同，沸点则随分子量的增加而增高。

绝大多数的卤代烃都不溶于水，易溶于有机溶剂中。

卤素是卤代烃的功能团，其化学活性主要由卤原子决定。

一般碳-卤键比碳-碳键或碳-氢键活泼，易断裂，有亲核试剂的性质。

此外，卤代烃中卤原子的活性还与其直接相连的基团结构有很大的关系。

卤代烷烃是相当活泼的化合物。

卤代烯烃中的卤原子有些是非常活泼的，有些则不活泼，它们的活性取决于卤素与双键的位置。

就生物活性而言，溴代烃和碘代烃的毒性大于氯代烃：氟代烃化学性质稳定，毒性也较小，但也有例外。

工业上常用的卤代烃大多数是易挥发的液体。

多数卤代烃不易燃，不易爆。

常用作溶剂、化工原料或中间体，并广泛用于农业、医药和轻工业。

氟代烃类有饱和的和不饱和的单氟烃、多氟烃、卤氟烃及其聚合物等。

用作致冷剂和合成橡胶及塑料的主要原料。

绝大多数氟代烃化合物在毒理学上属于“惰性物质”，但是少数品种由于经体内生物转化等因素影响，毒性很大，如六(全)氟环丁烯和八(全)氟异丁烯具有相当于或高于光气的高毒性。

易挥发的氟代烃化合物具有轻度麻醉作用。

多氟烷烃或氟卤烷烃对中枢神经更具抑制作用。

某些氟烷烃及氟卤烷烃，如氟里昂能提高心肌对肾上腺素或去甲肾上腺素的感受性，使心肌应激性增强，诱发心律紊乱，甚至心动骤停。

此外，还能兴奋迷走神经，抑制心脏传导系统和心血管运动中枢，引起心动过缓，心电图上表现出房室传导阻滞和T波改变。

吸入三氯氟甲烷、二氯二氟甲烷等氟烷烃气雾剂时，可造成致命性心律紊乱和心动骤停。

经典合成反应标准操作

经典化学合成反应标准操作药明康德新药开发有限公司化学合成部编写前言有机合成研究人员在做化学反应经常碰到常规的反应手边没有现成的标准操作步骤而要去查文献，在试同一类反应时，为了寻找各种反应条件方法也得去查资料。

为了提高大家的工作效率，因此化学合成部需要一份《经典合成反应标准操作》。

在这份材料中，我们精选药物化学中各类经典的合成反应，每类反应有什么方法，并通过实际经验对每类反应的各种条件进行点评，供大家在摸索合成条件时进行比较。

同时每种反应的标准操作，均可作为模板套用于书写客户的final report，这样可以大大节省研究人员书写final report的时间，也相应减少在报告中的文法错误。

另外本版是初版，在今后的工作中我们将根据需要修订这份材料。

药明康德新药开发有限公司化学合成部2005-6-28目录1.胺的合成a)还原胺化b)直接烷基化c)腈的还原d)酰胺的还原e)硝基的还原f)叠氮的还原g)Hoffman降解h)羧酸通过Cris 重排2.羧酸衍生物的合成a)酰胺化的反应b)酯化反应c)腈转化为酯和酰胺d)钯催化的插羰反应e)酯交换为酰氨3.羧酸的合成a)醇氧化b)酯水解c)酰胺的水解d)腈的水解e)有机金属试剂的羰基化反应f)芳香甲基的氧化4.醛酮的合成a)Weinreb 酰胺合成醛酮b)醇氧化c)酯的直接还原d)有机金属试剂对腈加成合成酮5.脂肪卤代物的合成a)醇转化为脂肪溴代物通过PBr3 转化通过PPh3 与CBr4 转化HBr直接交换通过相应的氯代物或磺酸酯与LiBr交换、b)醇转化为脂肪氯代物通过SOCl2转化通过PPh3 与CCl4 转化HCl直接交换c)醇转化为脂肪碘代物通过PPh3 与I2 转化通过相应的氯代物或磺酸酯与NaI交换6.芳香卤代物的合成a)Sandermyyer 重氮化卤代b)直接卤代c)杂环的酚羟基或醚的卤代7.醇的合成a)羧酸或酯的还原b)醛酮的还原c)卤代烃的水解.d)吡啶的氧化转位8.酚的合成a)Sandermayer 重氮化反应b)醚的水解c)Bayer-vigerlar 氧化d)硼酸的氧化9.腈的合成a)磺酸酯或卤代烃的取代b)酰胺的脱水c)芳卤代烃的氰基取代10.硝化反应11.醚的合成a)芳香醚的合成酚与烷基卤代烃的直接烷基化Mitsunobu 芳香醚化Buckwald芳香醚化b)脂肪醚的合成醇的醚化12.脲的合成a)胺与异腈酸酯的反应b)用三光气合成脲c)羰基二咪唑（CDI）合成脲d)对硝基苯酚碳酰胺合成脲.13.烯烃的合成a)Wittig 反应b)羟基的消除c)Wittig-Horner 反应合成α,β-不饱和酯14.磺酸及磺酰氯的合成a)氯磺化反应合成磺酰氯b)从硫醇合成磺酰氯c)磺化反应15.氨基酸的合成a)Streck 反应合成b)手性氨基酸的合成16.偶联反应a)Suzuki Couplingb)Buckwald 芳胺化，芳酰胺化、c)Heck 反应17.Mitsunobu 反应a)醇的反转b)胺的取代18.脱羟基反应19.酮还原为亚甲基.20.氨的保护及脱保护策略a)用碳酰胺作保护基b)苄基保护21.醇的保护及脱保护策略a)用硅醚进行保护b)其他醚类保护22.羧基的保护Boc脱保护-------------------------------------------------------------------------------------------------------1格氏反应---------------------------------------------------------------------------------------------------------1 还原胺化---------------------------------------------------------------------------------------------------------2卤化反应---------------------------------------------------------------------------------------------------------2 Suzuki coupling-------------------------------------------------------------------------------------------------2 磺化反应---------------------------------------------------------------------------------------------------------3 酯化反应---------------------------------------------------------------------------------------------------------3 水解反应---------------------------------------------------------------------------------------------------------3 硝化反应---------------------------------------------------------------------------------------------------------4 n-BuLi------------------------------------------------------------------------------------------------------------4 LiAlH4还原-----------------------------------------------------------------------------------------------------4 POCl3的杂环氯代----------------------------------------------------------------------------------------------5 NaH---------------------------------------------------------------------------------------------------------------5 NBS---------------------------------------------------------------------------------------------------------------5 氢化反应---------------------------------------------------------------------------------------------------------6 m-CPBA----------------------------------------------------------------------------------------------------------6 EDC---------------------------------------------------------------------------------------------------------------6 用三光气成脲---------------------------------------------------------------------------------------------------7 芳卤用n-BuLi处理后与Weinreb酰胺成酮-----------------------------------------------------------------7Boc 上保护OHH 2NHO OOO OOO OHN HO OHO O A BTo a solution of A (2.72 g, 13.9 mmol) and tetramethylammonium hydroxide pentahydrate (5.62 g, 31.0 mmol) in acetonitrile (270 mL) was added di-tert-butyldicarbonate (3.79 g; 17.4 mmol) and the resulting solution was allowed to stir 18 h at rt and concentrated. The residue was partitioned between Et2O/H2O; the phases were separated and the aqueous phase extracted twice more with Et2O. The aqueous phase was brought to pH 4 with solid citric acid and extracted with CHCl3 (3.x.100 mL). The organic extracts were combined, dried (Na2SO4) and concentrated to afford 2.58 g (63 percent) B as a white foam.ReturnBoc 脱保护OON HOO OOH 2NTert-Butyl 2-(2-methoxyphenoxy)ethylcarbamate (23.8 g, 89 mmol) in dichloromethane (10 ml) was cooled to 0 deg C and stirred as a mixture of trifluoroacetic acid: dichloromethane (1:1, 40 ml) was added dropwise. The mixture was allowed to warm to rt, stirred for 2 hours and concentrated in vacuo. The residue was taken back up in dichloromethane (100 ml) and the solution was washed with saturated aqueous sodium hydrogen carbonate (3*20 ml) and aqueous sodium hydroxide (10percent, 3*20 ml), dried (Na2SO4), filtered and concentrated in vacuo to provide 2-(2-methoxyphenoxy)ethylamine (13 g, 88percent yield) as a light yellow solid.Return格氏反应NCNNOA stirred mixture of magnesium turnings (23.6 g, 0.98 mol) and Et2O (200 mL) under nitrogen is treated with a crystal of iodine and about 5percent of a solution of bromoethane (56.3 ml, 0.75 mol) in Et2O (375 mL). When the reaction starts, the remainder of the bromoethane solution is added, dropwise at a rate sufficient to maintain a gentle reflux. After the addition, stirring is continued for 1 hour. To this solution ofethylmagnesium bromide was slowly added a solution of 4-cyanopyridine (39 g, 0.375 mol) in Et2O (750 ml). The reaction mixture was warmed at reflux for 12 hours, treated with concentrated H2SO4 (125 ml)/H2O (125 ml), and then washed three times with Et2O (250 ml). The aqueous portion was made basic (PH 9) with 15percent NaOH solution and extracted five times with 250 ml portions of Et2O. The combined Et2O extracts were dried (MgSO4), and the solvent was removed under reduced pressure to afford a brown oil (48.4 g, 95percent).Return还原胺化OHO H 2N+HON HA solution of 2-amino-4-ethylphenol (1.00 g. 7.28 mmol), 2-naphthaldehyde (1.13 g, 7.28 mmol), and p-toluenesulfonic acid (0.05 g) in methanol (50 ML) was stirred at room temp for 24 h. To the resultant solution, sodium borohydride (0.82 g, 22 mmol) was added in small portions. After addition was completed, the mixture was stirred at room temperature for 30 min and concentrated under vacuum. The residue was then subjected to column chromatography on silica gel eluted with 10percent ethyl acetate in hexane and followed by recrystallization (aqueous methanol) yielded 450 mg (22percent) of analytically pure product.Return卤化反应O 2NO 2NBrTo a stirred solution of 8-methyl-1-nitro-naphthalene (10.6g, 56.32 mmol) and iron (III) chloride (0.45 g, 2.77 mmo) in CCl4 (150 ml) heated to 60°C was added dropwise (3.0 ml, 58.23 mmol) of bromine. After one hour, the reaction mixture was poured into saturated NaHCO3 solution, and the layers were separated. The aqueous layer was re-extracted with CH2Cl2. The combined organic layers were dried (MgSO4) and the solvent was removed under reduced pressure. The crude residue was recrystallized from ethanol and the mother liquors were concentrated and then flash chromatographed on silica, eluding hexanes:ethyl acetate (12: 1).Return Suzuki couplingBrBOO NH+NH To a mixture of 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-indole (2 g, 8.2 mnmol) and3-bromobenzene (0.87 ml, 8.3 mmol) in THF (28 ml) were added palladium catalyst Pd(PPh3)4 (284 mg, 0.25 mmol) and the freshly prepared sodium hydroxide solution (984 mg in 9 ml of water).The system was degassed and then charged with nitrogen for three times. The mixture was stirred under nitrogen at 70 °C oil bath for 6 hours. The reaction solution was cooled to room temperature, diluted with ethyl acetate and separated from water layer. The ethyl acetate solution was washed by brine, dried over Na2SO4 and concentrated. The residue was purified on a silica gel column eluding with hexanes: EtOAc 9:1 to give 1.38 g (78%yield) of 4-phenyl-1H-indole as a colorless liquid.Return 磺化反应NOFFFNOFFFSOClOChlorosulfonic acid (4.66g, 40 mmol) is added dropwise to a cold (0°C) solution of2,3-dihydro-2-trifluoroacetyl-1H-Benz[de]isoquinoline (2.9g, 8 mmol) in chloroform (800 ml). The resulting solution is stirred at 0°C for 30 minutes. The cold bath is then removed and the solution is stirred at room temperature for 1 hour then cautiously poured into ice water. The organic layer is separated, dried over magnesium sulfate and concentrated to afford the title compound. The crude product is purified by column chromatography eluted with 10% acetic ether in petroleum ether (2.36 g, 81% yield).Return酯化反应HOHO O HOOOA mixture of 4-hydroxymethylnaphthoic acid (10 g, 50 mmol), methanol (300 ml), and concentrate H2SO4 (2 ml) was refluxed overnight. The insolubles were filtered off and the filtrate was concentrated. The residue was taken up in ethyl acetate and washed with aqueous NaHCO3 (2*), brine, dried over MgSO4, and concentrated to give a yellow oil. Silica gel column chromatography using ethyl acetate/hexane (1/3) gave the desired product as a yellow oil (3.3 g, 35%yield).Return水解反应OO OHOA solution of 1-Methyl-naphthalene-2-carboxylic acid methyl ester (7.20g, 35mmol) and 2N sodium hydroxide (35ml) in tetrahydrofuran (130ml) was stirred under reflux for 18 hours. The mixture was neutralised using 2N hydrochloric acid, and extracted with dichloromethane (3x). The combined organic solutions were dried (MgSO4), and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gelusing an elution gradient of dichloromethane: methanol (100:0 to 97:3) to afford the title compound as a solid (3.11g, 47.8%yield).Return硝化反应2To a cold (0°C) suspension of 1-methylnaphthalene (5 g, 35.2 mmol) in HNO3 was added H2SO4 (5 ml)dropwise. After stirring the reaction for one hour, the solution was diluted with ethyl acetate and washed with water (3*), aqueous saturated NaHCO3 (2*) and brine, dried over MgSO4, and concentrated. The product was purified by silica gel column chromatography using ethyl acetate: hexane (5: 95) and recrystallized from methanol to give yellow needles (0.22g, 33% yield).Returnn-BuLiEtOCF 3O CF 3O NCTo a dry three-necked round-bottomed flask with an addition funnel and at -78°C under inert atmosphere was charged with anhydrous THF (500 ml). A solution of n-butyllithium (2.5 M in hexane, 88 ml, 220 mmol) was added dropwise followed by addition of a solution of acetonitrile (10.43 ml, 200 mmol) in anhydrous THF (100 ml). The internal temperature was maintained below -70°C during the entire addition process. After 2 hr at -78°C a solution of Trifluoro-acetic acid ethyl ester (14.2 g, 100 mmol) in anhydrous THF (30 ml) was added dropwise and the mixture was stirred for 1.5 hr. To the mixture was added acetic anhydride to quench the reaction. The reaction mixture was allowed to warm up to rt. A precipitate was filtered and the filtrate was concentrated to give a brown oil, which was used in the next step without purification.ReturnLiAlH4还原HOHO O HOHOA solution of 2,3-naphthalenedicarboxylic acid (4.6 g, 0.023 mole) in dry THF (135 ml, warmed to 50° to maintain solution) is added dropwise over 15 minutes to a 1.15 M lithium aluminum hydride solution in THF (45 ml, 0.052 mole). The solution is stirred 3 hours after which TLC indicated consumption of diacid and formation of a new major product. The reaction is quenched carefully with THF-water, then 2N hydrochloric acid (40 ml) is added, and the resulting mixture is extracted 3 times with ether. The combined ether extracts are washed with water (2 times), with saturated sodium bicarbonate solution (1 time), with water, and are dried (sodium sulfate), filtered, and concentrated to give a tan solid (3.67 g). The solid isrecrystallized from ethyl acetate giving the title compound (2.91 g, 67.3%yield) as a light tan crystalline material.ReturnPOCl3的杂环氯代NNHOOH NClClTo a suspension of 2,4-dihydroxy-5,6-dimethylpyrimidine (6.2 g, 0.044 mol) in POCl3 (25 ml) was slowly added N,N-dimethylaniline (6.18 ml, 0.049 mol). The mixture was then refluxed at 125 °C for 3 hours. After this time, the starting material completely dissolved indicating that the reaction was completed.The reaction mixture was cooled and then poured slowly onto ice to quench the POCl3(caution[exothermic]). A precipitate formed, which was filtered and washed with ice-cold water. The precipitate was dried under high vacuum overnight to yield 2,4-dichloro-5,6-dimethyl-pyrimidine (7.2 g, 0.041 mol, 92%yield) as a yellow solid.ReturnNaHHSH 2N Cl+SNH 2Sodium hydride (50% in mineral oil, 5.5 g, 0.11 mol) was added portionwise at 0 °C under a nitrogen atmosphere to a solution of 2-aminobenzenethiol (12 ml, 0.1 mol) in DMF (120 ml). After 0.5 h, benzyl chloride (11.5 ml, 0.1 mol) in DMF (80 ml) was added in 0.5 h. The solution was stirred for 3 h while the temperature was allowed to rise to rt, then it was poured into ice/water (1000 g). The precipitate was filtered, dissolved in ethyl acetate and washed with brine. The organic layer was dried over Na2SO4 and evaporated. The solid obtained was ground in pentane (19.3 g, 90% yield).ReturnNBSN NFClCl NBSNNFClClBrA mixture of 2,4-Dichloro-6-ethyl-5-fluoro-pyrimidine (27.46 g，0.14mol), AIBN (1.32 g) and n-bromosuccinimide (27.02 g，0.152mol) in CH2Cl2 (170 ml) was refluxed under a nitrogen atmosphere for 36 h. Then washed by water, the aqueous was extracted by CH2Cl2. The combined organic layer was washed by saturated Na2S2O3 and brine, dried over Na2SO4, and evaporated to give a white solid which was purified by column chromatography eluted with 50% acetic ether in petroleum ether (34 g, 88.6% yield).Return 氢化反应O ONH OONH2Cl ClA mixture of ethyl 3-(N-benzylamino)-3-methylbutyrate hydrochloride (25g, 0.1 mol) and 10percent Pd-C (2g) in 250 ml of dried alcohol was hydrogenated under 55 psi H2 for four days. The reaction medium was then filtered and evaporated under reduced pressure to provide an amber oil which gradually crystallized upon standing (18 g, 100% yield).Returnm-CPBAS NH2SNH2OA solution of 85% m-chloroperoxybenzoic acid (19 g, 94 mmol) in CH2Cl2 (350 ml)was added at –5 –0 °C to a solution of 2-Benzylsulfanyl-phenylamine (19 g, 88 mmol) in CH2Cl2 (400 ml). The mixture wasallowed to warm to rt in 3 h, then it was washed with a 5% Na2S2O3 solution, 10% NaHCO3 solution and brine. The organic layer was dried over Na2SO4, and evaporated. The solid was ground in pentane (19 g, 95% yield).ReturnEDCNH 2O+H OTo a 0°C mixture of Boc-L-tyrosine (2.04 g, 7.26 mmol) and amylamine (0.63 gl, 7.26 mmol) in methylene chloride (30 ml) is added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) (1.53 g, 9.9 mmol). The white mixture is stirred at 0°C for 5 min and at room temp for 23 hrs. The resulting solution is diluted with methylene chloride (30 ml) and washed successively with 0.5 M HCl (40 ml), water (20 ml) and sat aq sodium bicarbonate (25 ml). The organic phase is dried over magnesium sulfate and concentrated to a foam (1.84 g, 72.4%yield), sufficiently pure to carry into the next step. An analytical sample is obtained by HPLC.Return三光气成脲NH 2ONO 2Si O Cl ClO Cl ClO 2NHN H NOHOHNO 2+To a solution of 2-(tert-butyldimethylsilyloxy)-4-nitroaniline (200 mg, 0.75 mmol) in toluene (10 ml) triethylamine (0.13 ml, 1.64 mmol) and triphosgene (88.4 mg, 0.3 mmol) were added. The reaction mixturewas stirred at 70 °C for 2 hours, then cooled to room temperature. Then more 2-(tert-butyldimethylsilyloxy)-4-nitroaniline (200 mg, 0.75 mmol) was added. The resulting mixture was allowed to stir at 70 °C for 48 hours then cooled to room temperature. The reaction mixture was partitioned between water and ethyl acetate. The combined organic phase was washed with brine, dried over MgSO4 and filtered. Removal of solvent at reduced pressure and chromatography of the resulting oil on silica gel (hexane: ethyl acetate, 10:1) gave 1,3-Bis-(2-hydroxy-4-nitro-phenyl)-urea (130 mg, 31%yield).Return芳卤用n-BuLi 处理后与Weinreb 酰胺成酮N F FFN O O+F FF ONFTo a solution of diisopropylamine (17.69 ml, 0.135 mole) in THF (200 ml) at –78°C under argon wasadded n-butyllithium (54.0 ml, 2.5M in hexane, 0.135 mole), followed after 5 min by dropwise a solution of 2-fluoro-4-methylpyridine (10 g, 0.090 mole) in THF (20 ml). After stirring for 15 min at –78°C, a solution of N-methoxy-N-methyl-3-trifluoromethylbenzamide (23.08 g, 0.099 mole) in THF (10 ml) was added dropwise. After stirring for more 5 min, the reaction was allowed to warm to 0°C and quenched by pouring into water (400 ml) and ethyl acetate (400 ml). The layers were separated, and the aqueous layer washed with ethyl acetate (200 ml). The ethyl acetate extracts were combined, dried over anhydrous sodium sulfate, filtered, and concentrated to an oil which was chromatographed on silica gel with 20percent ethyl acetate in hexane to give 21.6 g of 2-(2-Fluoro-pyridin-4-yl)-1-(3-trifluoromethyl-phenyl)-ethanone (84.8%yield).Return。

脂肪卤化反应

脂肪卤化反应
脂肪卤化反应是一种将脂肪分子中碳氢键的饱和度降低的反应。

它涉及脂肪分子和卤素（如氯和溴）的化学反应，以产生卤代脂肪和氢卤酸。

脂肪分子是由长链碳氢化合物组成的，因此它们具有高度饱和度。

通过卤化反应，脂肪分子中的一些碳氢键会被卤素取代，产生卤代脂肪。

这降低了脂肪分子的饱和度，使其更易于消化和吸收。

脂肪卤化反应常用于食品加工中，例如生产黄油和酥油等食品。

在这些食品生产过程中，卤素通常会被亚硝酸盐代替，以达到相似的效果。

然而，在高温下进行脂肪卤化反应会产生一些有害的化合物，如多环芳烃和氯化丙烯等，因此需要注意控制反应条件。

卤代化合物(Cl+..

dioxane O O O C O S Cl O C O S Cl ¹ÐÍ¹ ·×ª -SO 2 Cl C Cl C Cl + SO2 + dioxane
构型保留
Cl + SO2 + Cl
OH
SOCl2 -HCl
O C O S Cl 4
pyridine Cl
外消旋混合物
Confidential We Are Determined To Serve You Better 8
Me2 NOCH SOCl2 Me2 N=CHCl Cl 7 SOCl2, DMF heat, 15 min (Me 2N)3 PO SOCl2 (Me 2N)2 PCl=NMe2 Cl 8
C 8H 7C 6H 4 (OCH 2CH2 )5 OH
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C 8H 7C 6H 4 (OCH 2CH2 )5 Cl
H+ OH 1 -H 2 O Br Br Br 48% HBr/-15o C 2 (86%) (79%) 3 (14%) (21%)
6
Br
饱和 HBr/0oC
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2. 醇和卤化氢或氢卤酸的反应
2.1 醇和氯化氢反应的方法示例
OH 5 5.6 mol SOCl2/Et 2O 0.7 mol SOCl2/Et 2O
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Cl (24%) (1%)
+ (76%) (99%)
9
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3. 醇和卤化亚砜的反应
在氯化亚砜的反应中，若加入有机碱（如吡啶）作为催化剂，或者醇本身分子内存在氨基等碱性基团，因能与反应中生成的氯化氢结合，故有利于提高卤代反应速率。此外，该反应也适宜于一些对酸敏感的醇类的氯置换反应。例如，2-羟甲基四氢呋喃(6)用二氯亚砜和吡啶在室温下反应，可得到预期的2-氯甲基四氢呋喃，而不影响酯环醚结构.

经典合成反应标准操作

为了提高大家的工作效率，因此化学合成部需要一份《经典合成反应标准操作》。

另外本版是初版，在今后的工作中我们将根据需要修订这份材料。

药明康德新药开发有限公司化学合成部2005-6-28目录1.胺的合成a)还原胺化b)直接烷基化c)腈的还原d)酰胺的还原e)硝基的还原f)叠氮的还原g)Hoffman降解h)羧酸通过Cris 重排2.羧酸衍生物的合成a)酰胺化的反应b)酯化反应c)腈转化为酯和酰胺d)钯催化的插羰反应e)酯交换为酰氨3.羧酸的合成a)醇氧化b)酯水解c)酰胺的水解d)腈的水解e)有机金属试剂的羰基化反应f)芳香甲基的氧化4.醛酮的合成a)Weinreb 酰胺合成醛酮b)醇氧化c)酯的直接还原d)有机金属试剂对腈加成合成酮5.脂肪卤代物的合成a)醇转化为脂肪溴代物通过PBr3 转化通过PPh3 与CBr4 转化HBr直接交换通过相应的氯代物或磺酸酯与LiBr交换、b)醇转化为脂肪氯代物通过SOCl2转化通过PPh3 与CCl4 转化HCl直接交换c)醇转化为脂肪碘代物通过PPh3 与I2 转化通过相应的氯代物或磺酸酯与NaI交换6.芳香卤代物的合成a)Sandermyyer 重氮化卤代b)直接卤代c)杂环的酚羟基或醚的卤代7.醇的合成a)羧酸或酯的还原b)醛酮的还原c)卤代烃的水解d)吡啶的氧化转位8.酚的合成a)Sandermayer 重氮化反应b)醚的水解c)Bayer-vigerlar 氧化d)硼酸的氧化9.腈的合成a)磺酸酯或卤代烃的取代b)酰胺的脱水c)芳卤代烃的氰基取代10.硝化反应11.醚的合成a)芳香醚的合成酚与烷基卤代烃的直接烷基化Mitsunobu 芳香醚化Buckwald芳香醚化b)脂肪醚的合成醇的醚化12.脲的合成a)胺与异腈酸酯的反应b)用三光气合成脲c)羰基二咪唑（CDI）合成脲d)对硝基苯酚碳酰胺合成脲13.烯烃的合成a)Wittig 反应b)羟基的消除c)Wittig-Horner 反应合成,-不饱和酯14.磺酸及磺酰氯的合成a)氯磺化反应合成磺酰氯b)从硫醇合成磺酰氯c)磺化反应15.氨基酸的合成a)Streck 反应合成b)手性氨基酸的合成16.偶联反应a)Suzuki Couplingb)Buckwald 芳胺化，芳酰胺化、c)Heck 反应17.Mitsunobu 反应a)醇的反转b)胺的取代18.脱羟基反应19.酮还原为亚甲基20.氨的保护及脱保护策略a)用碳酰胺作保护基b)苄基保护21.醇的保护及脱保护策略a)用硅醚进行保护b)其他醚类保护22.羧基的保护Boc脱保护-------------------------------------------------------------------------------------------------------1 格氏反应---------------------------------------------------------------------------------------------------------1还原胺化---------------------------------------------------------------------------------------------------------2卤化反应---------------------------------------------------------------------------------------------------------2S u z u k i coupling------------------------------------------------------------------------------------------------- 2 磺化反应---------------------------------------------------------------------------------------------------------3酯化反应---------------------------------------------------------------------------------------------------------3水解反应---------------------------------------------------------------------------------------------------------3硝化反应---------------------------------------------------------------------------------------------------------4n-BuLi------------------------------------------------------------------------------------------------------------ 4 L i A l H4还原-----------------------------------------------------------------------------------------------------4 P O C l3的杂环氯代----------------------------------------------------------------------------------------------5 NaH--------------------------------------------------------------------------------------------------------------- 5 NBS--------------------------------------------------------------------------------------------------------------- 5 氢化反应---------------------------------------------------------------------------------------------------------6m-CPBA---------------------------------------------------------------------------------------------------------- 6 EDC--------------------------------------------------------------------------------------------------------------- 6用三光气成脲---------------------------------------------------------------------------------------------------7 芳卤用n-BuLi 处理后与Wei nr eb酰胺成酮-----------------------------------------------------------------7Boc 上保护OHH 2NHO OOO OOO OHN HO OHO O A BTo a solution of A (2.72 g, 13.9 mmol) and tetramethylammonium hydroxide pentahydrate (5.62 g, 31.0 mmol) in acetonitrile (270 mL) was added di-tert-butyldicarbonate (3.79 g; 17.4 mmol) and the resulting solution was allowed to stir 18 h at rt and concentrated. The residue was partitioned between Et2O/H2O; the phases were separated and the aqueous phase extracted twice more with Et2O. The aqueous phase was brought to pH 4 with solid citric acid and extracted with CHCl3 (3.x.100 mL). The organic extracts were combined, dried (Na2SO4) and concentrated to afford 2.58 g (63 percent) B as a white foam.ReturnBoc 脱保护OON HOO OOH 2NTert-Butyl 2-(2-methoxyphenoxy)ethylcarbamate (23.8 g, 89 mmol) in dichloromethane (10 ml) was cooled to 0 deg C and stirred as a mixture of trifluoroacetic acid: dichloromethane (1:1, 40 ml) was added dropwise. The mixture was allowed to warm to rt, stirred for 2 hours and concentrated in vacuo. The residue was taken back up in dichloromethane (100 ml) and the solution was washed with saturated aqueous sodium hydrogen carbonate (3*20 ml) and aqueous sodium hydroxide (10percent, 3*20 ml), dried (Na2SO4), filtered and concentrated in vacuo to provide 2-(2-methoxyphenoxy)ethylamine (13 g, 88percent yield) as a light yellow solid.Return格氏反应NCNNOA stirred mixture of magnesium turnings (23.6 g, 0.98 mol) and Et2O (200 mL) under nitrogen is treated with a crystal of iodine and about 5percent of a solution of bromoethane (56.3 ml, 0.75 mol) in Et2O (375 mL). When the reaction starts, the remainder of the bromoethane solution is added, dropwise at a rate sufficient to maintain a gentle reflux. After the addition, stirring is continued for 1 hour. T o this solution of ethylmagnesium bromide was slowly added a solution of 4-cyanopyridine (39 g, 0.375 mol) in Et2O (750 ml). The reaction mixture was warmed at reflux for 12 hours, treated with concentrated H2SO4 (125 ml)/H2O (125 ml), and then washed three times with Et2O (250 ml). The aqueous portion was made basic (PH 9) with 15percent NaOHsolution and extracted five times with 250 ml portions of Et2O. The combined Et2O extracts were dried (MgSO4), and the solvent was removed under reduced pressure to afford a brown oil (48.4 g, 95percent).Return还原胺化OHO H 2N+HON HA solution of 2-amino-4-ethylphenol (1.00 g. 7.28 mmol), 2-naphthaldehyde (1.13 g, 7.28 mmol), and p-toluenesulfonic acid (0.05 g) in methanol (50 ML) was stirred at room temp for 24 h. To the resultant solution, sodium borohydride (0.82 g, 22 mmol) was added in small portions. After addition was completed, the mixture was stirred at room temperature for 30 min and concentrated under vacuum. The residue was then subjected to column chromatography on silica gel eluted with 10percent ethyl acetate in hexane and followed by recrystallization (aqueous methanol) yielded 450 mg (22percent) of analytically pure product.Return卤化反应O 2NO 2NBrTo a stirred solution of 8-methyl-1-nitro-naphthalene (10.6g, 56.32 mmol) and iron (III) chloride (0.45 g, 2.77 mmo) in CCl4 (150 ml) heated to 60°C was added dropwise (3.0 ml, 58.23 mmol) of bromine. After one hour, the reaction mixture was poured into saturated NaHCO3 solution, andthe layers were separated. The aqueous layer was re-extracted with CH2Cl2. The combined organic layers were dried (MgSO4) and the solvent was removed under reduced pressure. The crude residue was recrystallized from ethanol and the mother liquors were concentrated and then flash chromatographed on silica, eluding hexanes:ethyl acetate (12: 1).ReturnSuzuki couplingBrBOO NH+NH To a mixture of 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-indole (2 g, 8.2 mnmol) and 3-bromobenzene (0.87 ml, 8.3 mmol) in THF (28 ml) were added palladium catalystPd(PPh3)4 (284 mg, 0.25 mmol) and the freshly prepared sodium hydroxide solution (984 mg in 9 ml of water).The system was degassed and then charged with nitrogen for three times. The mixture was stirred under nitrogen at 70 °C oil bath for 6 hours. The reaction solution was cooled to room temperature, diluted with ethyl acetate and separated from water layer. The ethyl acetate solution was washed by brine, dried over Na2SO4 and concentrated. The residue was purified on a silica gel column eluding with hexanes: EtOAc 9:1 to give 1.38 g (78%yield) of4-phenyl-1H-indole as a colorless liquid.Return磺化反应NOFFFNOFFFSOClOChlorosulfonic acid (4.66g, 40 mmol) is added dropwise to a cold (0°C) solution of2,3-dihydro-2-trifluoroacetyl-1H-Benz[de]isoquinoline (2.9g, 8 mmol) in chloroform (800 ml). The resulting solution is stirred at 0°C for 30 minutes. The cold bath is then removed and the solution is stirred at room temperature for 1 hour then cautiously poured into ice water. The organic layer is separated, dried over magnesium sulfate and concentrated to afford the title compound. The crude product is purified by column chromatography eluted with 10% acetic ether in petroleum ether (2.36 g, 81% yield).Return 酯化反应HOHO O HOO OA mixture of 4-hydroxymethylnaphthoic acid (10 g, 50 mmol), methanol (300 ml), and concentrate H2SO4 (2 ml) was refluxed overnight. The insolubles were filtered off and the filtrate was concentrated. The residue was taken up in ethyl acetate and washed with aqueous NaHCO3 (2*), brine, dried over MgSO4, and concentrated to give a yellow oil. Silica gel column chromatography using ethyl acetate/hexane (1/3) gave the desired product as a yellow oil (3.3 g, 35%yield).Return水解反应OO OHOA solution of 1-Methyl-naphthalene-2-carboxylic acid methyl ester (7.20g, 35mmol) and 2N sodium hydroxide (35ml) in tetrahydrofuran (130ml) was stirred under reflux for 18 hours. The mixture was neutralised using 2N hydrochloric acid, and extracted with dichloromethane (3x). The combined organic solutions were dried (MgSO4), and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gelusing an elution gradient of dichloromethane: methanol (100:0 to 97:3) to afford the title compound as a solid (3.11g, 47.8%yield).Return硝化反应2To a cold (0°C) suspension of 1-methylnaphthalene (5 g, 35.2 mmol) in HNO3 was added H2SO4 (5 ml) dropwise. After stirring the reaction for one hour, the solution was diluted with ethyl acetate and washed with water (3*), aqueous saturated NaHCO3 (2*) and brine, dried over MgSO4, and concentrated. The product was purified by silica gel column chromatography usingethyl acetate: hexane (5: 95) and recrystallized from methanol to give yellow needles (0.22g, 33% yield).Returnn-BuLiEtOCF 3O CF 3O NCTo a dry three-necked round-bottomed flask with an addition funnel and at -78°C under inert atmosphere was charged with anhydrous THF (500 ml). A solution of n-butyllithium (2.5 M in hexane, 88 ml, 220 mmol) was added dropwise followed by addition of a solution of acetonitrile (10.43 ml, 200 mmol) in anhydrous THF (100 ml). The internal temperature was maintained below -70°C during the entire addition process. After 2 hr at -78°C a solution of Trifluoro-acetic acid ethyl ester (14.2 g, 100 mmol) in anhydrous THF (30 ml) was added dropwise and the mixture was stirred for 1.5 hr. T o the mixture was added acetic anhydride to quench the reaction. The reaction mixture was allowed to warm up to rt. A precipitate was filtered and the filtrate was concentrated to give a brown oil, which was used in the next step without purification.ReturnLiAlH4还原HOHO O HOHOA solution of 2,3-naphthalenedicarboxylic acid (4.6 g, 0.023 mole) in dry THF (135 ml, warmed to50° to maintain solution) is added dropwise over 15 minutes to a 1.15 M lithium aluminum hydride solution in THF (45 ml, 0.052 mole). The solution is stirred 3 hours after which TLC indicated consumption of diacid and formation of a new major product. The reaction is quenched carefully with THF-water, then 2N hydrochloric acid (40 ml) is added, and the resulting mixture is extracted 3 times with ether. The combined ether extracts are washed with water (2 times), with saturated sodium bicarbonate solution (1 time), with water, and are dried (sodium sulfate), filtered, and concentrated to give a tan solid (3.67 g). The solid is recrystallized from ethyl acetate giving the title compound (2.91 g, 67.3%yield) as a light tan crystalline material.ReturnPOCl3的杂环氯代NN HO OHNClClTo a suspension of 2,4-dihydroxy-5,6-dimethylpyrimidine (6.2 g, 0.044 mol) in POCl3 (25 ml) was slowly added N,N-dimethylaniline (6.18 ml, 0.049 mol). The mixture was then refluxed at 125 °C for 3 hours. After this time, the starting material completely dissolved indicating that the reaction was completed. The reaction mixture was cooled and then poured slowly onto ice to quench the POCl3 (caution[exothermic]). A precipitate formed, which was filtered and washed with ice-cold water. The precipitate was dried under high vacuum overnight to yield2,4-dichloro-5,6-dimethyl-pyrimidine (7.2 g, 0.041 mol, 92%yield) as a yellow solid.ReturnNaHHSH 2N Cl+SNH 2Sodium hydride (50% in mineral oil, 5.5 g, 0.11 mol) was added portionwise at 0 °C under a nitrogen atmosphere to a solution of 2-aminobenzenethiol (12 ml, 0.1 mol) in DMF (120 ml). After 0.5 h, benzyl chloride (11.5 ml, 0.1 mol) in DMF (80 ml) was added in 0.5 h. The solution was stirred for 3 h while the temperature was allowed to rise to rt, then it was poured into ice/water (1000 g). The precipitate was filtered, dissolved in ethyl acetate and washed with brine. The organic layer was dried over Na2SO4 and evaporated. The solid obtained was ground in pentane (19.3 g, 90% yield).ReturnNBSNN FCl ClN N FCl ClBrA mixture of 2,4-Dichloro-6-ethyl-5-fluoro-pyrimidine (27.46 g ， 0.14mol), AIBN (1.32 g) and n-bromosuccinimide (27.02 g ， 0.152mol) in CH2Cl2 (170 ml) was refluxed under a nitrogen atmosphere for 36 h. Then washed by water, the aqueous was extracted by CH2Cl2. The combined organic layer was washed by saturated Na2S2O3 and brine, dried over Na2SO4, and evaporated to give a white solid which was purified by column chromatography eluted with 50% acetic ether in petroleum ether (34 g, 88.6% yield).Return 氢化反应O ONH OONH2Cl ClA mixture of ethyl 3-(N-benzylamino)-3-methylbutyrate hydrochloride (25g, 0.1 mol) and10percent Pd-C (2g) in 250 ml of dried alcohol was hydrogenated under 55 psi H2 for four days. The reaction medium was then filtered and evaporated under reduced pressure to provide an amber oil which gradually crystallized upon standing (18 g, 100% yield).Returnm-CPBAS NH2SNH2OA solution of 85% m-chloroperoxybenzoic acid (19 g, 94 mmol) in CH2Cl2 (350 ml)was added at –5 – 0 °C to a solution of 2-Benzylsulfanyl-phenylamine (19 g, 88 mmol) in CH2Cl2 (400 ml). The mixture was allowed to warm to rt in 3 h, then it was washed with a 5% Na2S2O3 solution, 10% NaHCO3 solution and brine. The organic layer was dried over Na2SO4, and evaporated. The solid was ground in pentane (19 g, 95% yield).ReturnEDCNH 2O+H OTo a 0°C mixture of Boc -L-tyrosine (2.04 g, 7.26 mmol) and amylamine (0.63 gl, 7.26 mmol) in methylene chloride (30 ml) is added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) (1.53 g, 9.9 mmol ). The white mixture is stirred at 0°C for 5 min and at room temp for 23 hrs. The resulting solution is diluted with methylene chloride (30 ml) and washed successively with 0.5 M HCl (40 ml), water (20 ml) and sat aq sodium bicarbonate (25 ml). The organic phase is dried over magnesium sulfate and concentrated to a foam (1.84 g, 72.4%yield), sufficiently pure to carry into the next step. An analytical sample is obtained by HPLC.Return三光气成脲NH 2ONO 2Si O Cl ClO Cl ClO 2NH N H NOHOHNO 2+To a solution of 2-(tert-butyldimethylsilyloxy)-4-nitroaniline (200 mg, 0.75 mmol) in toluene (10 ml) triethylamine (0.13 ml, 1.64 mmol) and triphosgene (88.4 mg, 0.3 mmol) were added. The reaction mixture was stirred at 70 °C for 2 hours, then cooled to room temperature. Then more 2-(tert -butyldimethylsilyloxy)-4-nitroaniline (200 mg, 0.75 mmol) was added. The resulting mixture was allowed to stir at 70 °C for 48 hours then cooled to room temperature. The reaction mixture was partitioned between water and ethyl acetate. The combined organic phase was washed with brine, dried over MgSO4 and filtered. Removal of solvent at reduced pressure and chromatography of the resulting oil on silica gel (hexane: ethyl acetate, 10:1) gave 1,3-Bis-(2-hydroxy-4-nitro-phenyl)-urea (130 mg, 31%yield).Return芳卤用n-BuLi 处理后与Weinreb 酰胺成酮N FF FFN O O+F FF ONFTo a solution of diisopropylamine (17.69 ml, 0.135 mole) in THF (200 ml) at –78°C underargon was added n-butyllithium (54.0 ml, 2.5M in hexane, 0.135 mole), followed after 5 min by dropwise a solution of 2-fluoro-4-methylpyridine (10 g, 0.090 mole) in THF (20 ml). After stirring for 15 min at –78°C, a solution of N -methoxy-N-methyl-3-trifluoromethylbenzamide (23.08 g, 0.099 mole) in THF (10 ml) was added dropwise. After stirring for more 5 min, the reaction wasallowed to warm to 0°C and quenched by pouring into wate r (400 ml) and ethyl acetate (400 ml). The layers were separated, and the aqueous layer washed with ethyl acetate (200 ml). The ethyl acetate extracts were combined, dried over anhydrous sodium sulfate, filtered, and concentrated to an oil which was chromatographed on silica gel with 20percent ethyl acetate in hexane to give 21.6 g of 2-(2-Fluoro-pyridin-4-yl)-1-(3-trifluoromethyl-phenyl)-ethanone (84.8%yield).Return。

脂肪替代物的应用概述

脂肪替代物主要有两大类型，代脂肪（Ｆａｔｓｕｂｓｔｉｔｕｔｅｓ）和模拟脂肪（Ｆａｔｍｉｍｉｃｓ）。

代脂肪是以脂肪酸为基础的酯化产品，具有类似油脂的物理性质，其酯键能抵抗人体内脂肪酶的催化水解，因此不参与能量代谢。

模拟脂肪以碳水化合物或蛋白质为基础成分，原料经过物理方法处理，能以水状液体系的物理特性模拟出脂肪润滑细腻的口感特性，但是不能耐高温处理。

以碳水化合物为基本组分的脂肪替代物，可分为全消化、部分消化和不消化３种，所提供的热量为０￣１６．８ｋＪ／ｇ。

与脂肪相比，热量的供给减少了１６．８￣３７．８ｋＪ／ｇ；以蛋白质为基本组分的脂肪代替物，一般亦可降低热量供给。

代脂肪更接近传统食用油脂。

１代脂肪１．１蔗糖聚酯（Ｓｕｃｒｏｓｅｆａｔｔｙａｃｉｄｐｏｌｙｅｓｔｅｒｓ）蔗糖聚酯全称蔗糖脂肪酸聚酯，是脂肪酸或脂肪酸低级烷基酯（如甲基酯、乙基酯）与蔗糖的直接酯化或酯交换反应产物。

蔗糖代替甘油在酯化反应中提供羟基。

常见的脂肪酸为１２个或１２个以上碳原子的饱和与不饱和脂肪酸。

蔗糖聚酯属于高酯产品，其感官特性和加工性能决定于其分子中脂肪酸的种类和酯化度。

酯化度６￣８的蔗糖聚酯成油状，具有轻微的油脂香味，口味微甜，其粘度在常见植物油的粘度范围之内，比甘油三酯要高。

具备传统油脂为食品提供的组织特性和风味特性，可应用于焙烤或油炸食品的加工中。

蔗糖聚酯具有不吸收性。

这是因为蔗糖聚酯的分子体积很大，且其脂肪酸为非极性分子，其中的酯键被严密包裹而隐藏起来，使脂肪酶分子由于立体位阻而无法对其进行分解，故在代谢中不会被肠道吸收，不提供热量。

蔗糖聚酯也具有传统脂肪的亲脂性，可以溶解一定量的胆固醇，再加上蔗糖聚酯的不吸收性，从而降低了对胆固醇的吸收。

临床试验表明：在７５０ｍｇ／天高胆固醇食品中加入１４ｇ／天的蔗糖聚酯，就足以阻碍人体对胆固醇的吸收，同时却不影响胆汁酸的排出量，也不影响血清中高密度酯蛋白的含量。

这无疑是受高血脂和心血管病患者欢迎的产品。

α-卤代化合物的合成研究进展

α-卤代化合物的合成研究进展何雪（乐山师范学院，乐山614000）摘要：卤代反应是一个重要而又特殊的反应，本文讲述有机化学中常涉及的羰基α-位、烯丙位及苄基位碳原子上的卤代反应等，对α-卤代化合物的合成进行研究。

同时对反应原理、原因以及优缺点作出理论分析，简述了它们在合成上的应用。

关键词：α-卤代化合物、卤代反应、绿色卤化试剂、化学合成Research Progress on Synthesis of α-halogenated compoundHe Xue(Leshan Normal University, Leshan 614000)Abstract: halogenating reaction is an important and special reaction, this article tells the carbonly– often involved in organic chemistry, allylic and benzylic carbon atoms of halogenated reaction, study on the synthesis of α-halogenated compounds. At the same time, make a theoretical analysis of the reaction principle, the reason and the advantages and disadvantages, their application in the synthesis are described in this paper.Keywords: α- halogenated hydrocarbons, halogenated reaction，green halogenating reagent, chemical synthesi.一、引言卤代反应是一类重要的有机反应，广泛应用于医药中间体、农药中间体等精细化学品合成领域。

脂肪族烯烃的卤代反应方程式汇总

脂肪族烯烃的卤代反应方程式汇总脂肪族烯烃是一类碳链上含有一个或多个双键的有机化合物。

它们具有广泛的应用领域，包括化学合成、聚合反应、生物医药等。

卤代反应是脂肪族烯烃中常见的一种官能团转化反应，通过与卤素反应，可以将烯烃上的双键转化为卤代烃。

本文将汇总脂肪族烯烃的卤代反应方程式，以帮助读者更好地理解和应用这些反应。

1. 溴代反应脂肪族烯烃与溴气反应，可以生成溴代烃。

反应通常需要在惰性溶剂中进行，如氯仿、乙醚等。

以下是一些常见的脂肪族烯烃溴代反应方程式：(1) 以乙烯为例：CH₂=CH₂ + Br₂→ CH₂Br-CH₂Br(2) 以丙烯为例：CH₂=CH-CH₃ + Br₂ → CH₂Br-CH₂CH₃2. 氯代反应类似于溴代反应，脂肪族烯烃也可以与氯化剂反应生成氯代烃。

以下是一些常见的脂肪族烯烃氯代反应方程式：(1) 以乙烯为例：CH₂=CH₂ + Cl₂ → CH₂Cl-CH₂Cl(2) 以丙烯为例：CH₂=CH-CH₃ + Cl₂ → CH₂Cl-CH₂CH₃3. 碘代反应脂肪族烯烃与碘反应生成碘代烃的反应速度较慢，常需加热或使用催化剂。

以下是一些常见的脂肪族烯烃碘代反应方程式：(1) 以乙烯为例：CH₂=CH₂ + I₂ → CH₂I-CH₂I(2) 以丙烯为例：CH₂=CH-CH₃ + I₂ → CH₂I-CH₂CH₃4. 溴代瑞捷反应溴代瑞捷反应是脂肪族烯烃的重要官能团转化反应之一。

该反应通过使用过量的溴水在酸性条件下进行，将烯烃中的一个或多个双键同时转化为卤代基。

以下是一些常见的脂肪族烯烃溴代瑞捷反应方程式：(1) 以丙烯为例：CH₂=CH-CH₃ + Br₂ + H₂O → CH₂Br-CHBr-CH₃(2) 以戊二烯为例：CH₂=CH-CH=CH-CH₃ + Br₂ + H₂O → CH₂Br-CHBr-CHBr-CH₃总结：脂肪族烯烃的卤代反应是有机化学中重要的反应类型之一。

这些反应可以通过与溴、氯、碘等卤素进行反应，将烯烃上的双键转化为卤代基。

有机化学基础知识点整理脂肪族化合物的合成与反应

有机化学基础知识点整理脂肪族化合物的合成与反应脂肪族化合物是有机化学中重要的类别之一。

它们是由碳原子链构成的化合物，通常是疏水性的，并且在许多生物和工业过程中都扮演着重要的角色。

本文将对脂肪族化合物的合成与反应进行整理。

合成脂肪族化合物的合成主要有两个途径：自然合成和人工合成。

1. 自然合成脂肪族化合物可以通过生物体内的代谢途径经过一系列的酶催化反应来进行合成。

例如，人体内产生的甘油三酯就是通过脂肪酸和甘油的酯化反应得到的。

此外，一些维生素和植物中的油脂也是通过自然合成得到的。

2. 人工合成人工合成脂肪族化合物通常需要使用化学合成方法。

这些方法包括取代反应、加成反应、还原反应等。

取代反应是通过将一个或多个原子或基团替换为其他原子或基团来合成脂肪族化合物。

常见的取代反应有卤代烷与碳酸酯的醇解反应、硫酸酯的酯交换反应等。

加成反应是将两个或多个分子叠加在一起形成新的分子。

常见的加成反应有醛酮的加成反应、烯烃与氢气的加成反应等。

还原反应是通过还原剂将一个化合物还原成另一种化合物。

常见的还原反应有氢化反应、金属还原反应等。

反应脂肪族化合物有许多重要的反应。

以下是一些常见的反应。

1. 氧化反应脂肪族化合物可以发生氧化反应，生成含有氧原子的化合物。

例如，醇可以通过氧化反应生成醛和酮。

常见的氧化剂有酸性高锰酸钾（KMnO₄）、过氧化氢（H₂O₂）等。

2. 烷基化反应烷基化反应是将一种化合物中的氢原子替换为烷基基团。

常见的烷基化试剂有碱金属（如钠、钾）和有机卤化物。

烷基化反应常用于合成脂肪族化合物的衍生物。

3. 反应物加成脂肪族化合物可以与其他化合物进行加成反应，生成新的化合物。

例如，两分子醛可以发生加成反应生成一个醇。

这种反应常由酸或碱催化。

4. 消除反应消除反应是指两个化合物中的一部分原子或基团相互结合形成一个小分子而脱去。

例如，脂肪族化合物的烯烃可以通过消除反应生成烃。

总结脂肪族化合物的合成与反应是有机化学中的重要内容。

脂肪酸a卤代的催化剂

脂肪酸a卤代的催化剂a 卤代脂肪酸是一类具有多重催化性能的物质，在精细化工领域应用普遍。

它可用于制备烷烃、烯烃、烷烯烃和仲烯的氧化剂、烷基化学变换、便携式燃料电池，以及光催化剂等。

1、特性a 卤代脂肪酸具有良好的抗氧化性，高温安全性和抗污染性，为多种工业应用提供了有效保护。

它们可以抗氧化剂，可以有效地阻止脂肪分解，降低氧化产物和不饱和盐的产生。

2、应用a 卤代脂肪酸可广泛应用于制汽油、柴油、航空煤油和粗油的分子重结构。

它还可用于制备润滑油添加剂、氧化剂、羰基化剂和烷基化剂等，其中可以促进烷烃在有机溶剂中的氧化，以及改变烯烃的分子结构，使烯烃更为稳定。

此外它还可以被用作燃料电池中的活性组件，以及光催化剂之间反应的催化剂。

3、成分a 卤代脂肪酸是由烯烃和烷烃组成的有机化合物，最常用的卤代脂肪酸类型是芳基烷烃卤代脂肪酸（arylalkanes），该类卤代脂肪酸构成的分子中一个烷烃和一个烯烃分别受到芳基表面的维系，通常用多种类型的碳、氮官能团替代这些芳基。

4、分类a 卤代脂肪酸有许多种，根据其结构类型可以分为三大类：顺取基卤代脂肪酸（alkylbenzyltri-alkylbenzyltrihydroxyalkanes），逆取基卤代脂肪酸（arylalkylbenzyltrihydroxyalkanes）及其衍生物，以及不可分解卤代脂肪酸（non-decompondable）。

按其结构类型又可分为三大类：顺取基卤代脂肪酸、逆取基卤代脂肪酸及其衍生物、不可分解卤代脂肪酸。

5、性质a 卤代脂肪酸具有极低的溶解性，但特性非常稳定，易溶于水和有机溶剂，不容易分解，且不与水反应。

它们可以有效地抑制脂肪的氧化和分解，防止氧化产物和不饱和盐的产生，进而保护有机物免受氧化破坏。

有机物经过处理后，可以赋予其具有良好的抗氧化性和抗污染性，使之更加可靠。

有机合成化学反应之脂肪卤代物的合成

有机合成化学反应之脂肪卤代物的合成1. 前言卤代烃是不仅是很多工业生产的重要产品，也是合成其他化合物的重要中间体，通过不同的反应可以将卤原子转变成各种其他官能团，也可以进行碳链的增长。

除了由烃基氢直接卤代可得到卤代烃外，还有很多种方法将其他的官能团转变成卤代烃，如醇羟基卤代，醛酮卤代，羧酸脱羧后卤代，磺酸酯的卤素交换，有机金属化合物卤代。

其中醇羟基的卤置换反应是制备卤化物的重要方法，常用的卤化试剂有氢卤酸、含磷卤化物和含硫卤化物等，极大多数属于醇羟基被卤素负离子亲核取代的机理。

以下按照氯化物，溴化物，碘化物的制备分别加以讨论。

氟代烃的制备容以后讨论2脂肪族氯化物的制备2.1 醇的氯代2.1.1醇与氯化氢反应在亲核取代反应中，醇羟基的活性顺序为叔羟基〉仲羟基〉伯羟基，苄位和烯丙位的羟基也很活波，这是由于碳正离子稳定性差别的结果。

同样理由，活性较大的叔醇、苄醇的氯置换反应倾向于S N 1机理，而其他醇的反应，大多数以S N 2反应机理为主。

醇和HCl 的反应属于可逆性平衡反应，其反应难易程度取决于醇和HCl 的浓度以及平衡点的移动方向。

若增加醇和HCl 的浓度，以及能够不断移去产物和反应生成的水，则均有利于加速氯置换反应和提高收率。

ROH +HX RX H 2O +在醇的氯置换反应中，活性较大的叔醇、苄醇等可以直接用浓盐酸或氯化氢气体，而伯醇常用卢卡斯试剂（浓烟酸-氯化锌）进行氯置换反应。

OH gas HClCl OH 2Cl yield:97%yield:66%[2][3]在某些仲醇、叔醇和β位具有叔碳取代基的伯醇的反应中，若反应温度过高，会产生重排、异构化和脱氯等副反应。

Example A: the preparation of t-Butyl Chloride (2-Chloro-2-Methylpropane) OH HCl ClIn a 250 ml of separatory funnel place 25 g (0.34 mol) of 2-methylpropan-2-ol and 85 ml ofconcentrated hydrochloric acid and shake the mixture from time to time during 20 min. After each shaking, loosen the stopper to relieve any internal pressure. Allow the mixture to stand for a few minutes until the layers have separated sharply; draw off and discard the lower acid layer. Wash the halide with 20 ml of 5% sodium hydrogen carbonate solution and then with 20 ml of water. Dry the preparation with 5 g of anhydrous calcium chloride or anhydrous calcium sulphate. Decant the dried liquid through a funnel supporting a fluted filter paper into a 100 ml distilling flask and distil. Collect the fraction boiling at 49-51℃. The yield of t-butyl-chloride is 28 g (90%).Ref: Practical Organic Chemistry, 4th edition, 556 Example B: the preparation of Butyl Chloride (1-Chlorobutane)OH HCl/ZnCl2ClFit a 250 ml of round-bottomed flask with a reflux condenser, the top of which is connected to a device for absorbing hydrogen chloride. Place 68 g (0.5 mol) of anhydrous zinc chloride and 40 ml (47.5 g) of concentrated hydrochloric acid in the flask, add 18.5 g (23 ml, 0.25 mol) of butane-1-ol and reflux the mixture gently for 2 hours. Arrange the condenser for downward distillation, and distil the reaction product, collecting the material which boils below 115℃. Separate the upper layer of the distillate, mix it with an equal volume of concentrated sulphuric aced and transfer the mixture to a 250 ml of flask fitted with a reflux condenser. Reflux gently for 15-30 min, and then distil the chloride from the acid; it will pass over at 76-79℃. Wash the distillate successively with 25 ml of water, 10 ml of 5% sodium hydroxide solution and 25 ml if water, dry over 1-2 g of anhydrous calcium chloride, filter and distil from a small distilling flask. Collect the butyl chloride at 75-78℃. The yield is 15-16 g (65-69%).Ref : Practical Organic Chemistry, 4th edition, 5572.1.2 醇和氯化亚砜的反应氯化亚砜是醇的氯置换反应中一种常用的良好试剂，主要是反应中生成的氯化氢和二氧化硫均为气体，易挥发除去而无残留物，经直接蒸馏可得到纯净的氯代烃。

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