2-甲基THF
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B. Comanita; D. Aycock, Industrie Pharma Magazine, No.17, 2005, 54-56 D. Aycock, OPRD, submitted for publication
MeTHF: Higher Yield in Grignard Formation
15%
98%
78%
19%
MeTHF 4 o-chlorobenzyl chloride THF
97% 20%
66%
5 allyl chloride
MeTHF THF MeTHF
86% 73% 89%
16%
•Dimerization of benzyl and allyl substrates is suppressed
MeTHF is not only an innovative product but at the same time it is an innovation enabler for the fine chemicals and pharmaceutical industry.
I hope that our presentation will convince you that this is in fact the case.
2-METHYLTETRAHYDROFURAN
2-Methyltetrahydrofuran: Simply Better than Tetrahydrofuran
Dr. Bogdan Comanita , Penn Specialty Chemicals, Inc.
Introduction
Penn Specialty Chemicals Inc. has been a leader in furan chemistry for more than 60 years,
Only 68% of IPA recovered
1.5 parts 2.82 parts toluene toluene
B. Comanita, Industrie Pharma Magazine, 22, October 2006
MeTHF: Easy solvent re-use & recycling
• Advantages from physical properties
THF Work-up has problems:
• THF is water miscible • Work-up alternatives for THF reactions:
– Add a hydrophobic solvent for phase separation
MeTHF is a furan derivative made from renewable resources with considerable advantages over THF.
MeTHF is a rapidly emerging global solvent market and Penn is spearheading the commercialization of this solvent.
MeTHF: Better Extraction Solvent in the Work-up
% IPA Recovered
100 95
94% of IPA
90 recovered 85 80 75 70 65 60 55 50
1.5 parts MeTHF
2.7 parts MeTHF
3rd extraction with toluene gave tight light phase emulsion
99.6 parts dry MeTHF
•Easy product drying and precipitation •Solvent re-use: “one pot” reactions-no product isolation •Solvent recycling: drying through simple distillation
% Energy savings for dry MeTHF vs. THF recovery
Weighted Total
BTU’s/lb of material reclaimed
Energy Savings from
Recovery/ Drying
50% MeTHF THF
966 3,16
69%
2-MeTHF Safety aspects
MeTHF Safety: Peroxide Formation
– Doesn’t work for polar compounds – Poor product recovery-second extraction needed – End-up with mixtures of solvents
Improved Process: physical properties
# Reagent
Solvent
1 benzyl chloride
THF
MeTHF
2 benzyl bromide
THF
MeTHF
3 o-methylbenzyl chloride THF
Organomagnesium MeTHF Yield
Yield
Improvement
85%
14%
99% 83%
•No specialized equipment needed
1. THF Drying Process is complex
12% water
Wet THF
water
6.7% water azeotrope
100 psi pressure
Dry THF
•Recycling is possible for dedicated capacities only
10.6% water in azeotrope
60°C decanter
0.4 parts MeTHF 5.2 parts water (recycled to next batch)
100 parts MeTHF 5.2 parts water (at start of batch distillation)
% Sol. In THF
15% 10% 15% 25%
P. Rittmeyer et al., Chemetall DE 19808570
Improved Process: chemical properties
Less impurities under acidic conditions:
– less solvent degradation @ acidic aqueous work-up – better stability to Lewis acids
Purchasing
2-MeTHF: The Value Proposition
R&D/Manufacturing
Reduced costs
Improved process
Comparable/better safety
Greener process
Safety
Environmental
Agenda
• MeTHF is the solution to THF’s shortcomings:
1. MeTHF is not miscible with water 2. Clean phase separation with no emulsions & rag layers 3. Reduced number of extraction steps 4. Easy to dry (forms azeotrope like toluene) 5. Easy to recycle and reuse
MeTHF Improves Processes
• Advantages from chemical properties
– Increased reaction yields – Increased solubility of organogrignards – Less impurities due to higher solvent stability
– Increased solvent volumes – Hard to recycle solvent mixtures (separation difficult) – Persistent emulsions and rag layers
– Add saline solution for phase separation
OHale Waihona Puke Baidu
n-BuLi
O
H
Li
H2C CH2
+
Li O H2C H
The reaction of n-butyllithium with MeTHF is considerably slower
Compound
THF MeTHF
Half life at 35°C minutes
10
70
R. Bates, J. Org. Chem. (1972) 37(4), p560.
Improved Process: chemical properties
• Advantages from chemical properties
– Increased reaction yields – Less impurities due to better solvent stability
140
160
Hours
Conditions: 50:50 THF/MeTHF: 2 N HCl at 60 C
D. Aycock, OPRD submitted for publication
Improved Process: strong base stability
THF reacts with n-butyllithium
1. MeTHF improves processes 2. MeTHF; safety aspects 3. MeTHF makes greener process 4. MeTHF cuts costs 5. Conclusions; MeTHF simply better than THF 6. Q&A session
% Water in Stream from Process
25%
10%
MeTHF THF MeTHF THF
817
3,07
771
3,04
73%
75%
6% MeTHF THF
753 2,18
66%
B. Comanita, Specialty Chemicals Magazine, October 2006
Under typical acid work up, MeTHF degrades about 6 times less than THF
% Degradation of THF and MeTHF
0.6
0.5
THF
0.4
% Degraded
0.3
0.2
MeTHF
0.1
0
0
20
40
60
80
100
120
Less impurities under basic conditions:
– more stable to n-BuLi than THF – less by-products for some organogrignard reactions
Improved process: acid degradation
• Advantages from physical properties
Improved Process: chemical properties
• MeTHF is a versatile solvent
1. Grignard 2. Lithiation 3. Hydride based reduction 4. Organopalladium 5. Organozinc 6. Biphasic reactions
P. Rittmeyer et al., Chemetall DE 19808570
MeTHF: Increased Solubility of Various Grignard Reagents
Reagents
MeMgBr EtMgBr PhMgBr EtMgCl
% Sol. In MeTHF
35% 40% 45% 30%
MeTHF: Higher Yield in Grignard Formation
15%
98%
78%
19%
MeTHF 4 o-chlorobenzyl chloride THF
97% 20%
66%
5 allyl chloride
MeTHF THF MeTHF
86% 73% 89%
16%
•Dimerization of benzyl and allyl substrates is suppressed
MeTHF is not only an innovative product but at the same time it is an innovation enabler for the fine chemicals and pharmaceutical industry.
I hope that our presentation will convince you that this is in fact the case.
2-METHYLTETRAHYDROFURAN
2-Methyltetrahydrofuran: Simply Better than Tetrahydrofuran
Dr. Bogdan Comanita , Penn Specialty Chemicals, Inc.
Introduction
Penn Specialty Chemicals Inc. has been a leader in furan chemistry for more than 60 years,
Only 68% of IPA recovered
1.5 parts 2.82 parts toluene toluene
B. Comanita, Industrie Pharma Magazine, 22, October 2006
MeTHF: Easy solvent re-use & recycling
• Advantages from physical properties
THF Work-up has problems:
• THF is water miscible • Work-up alternatives for THF reactions:
– Add a hydrophobic solvent for phase separation
MeTHF is a furan derivative made from renewable resources with considerable advantages over THF.
MeTHF is a rapidly emerging global solvent market and Penn is spearheading the commercialization of this solvent.
MeTHF: Better Extraction Solvent in the Work-up
% IPA Recovered
100 95
94% of IPA
90 recovered 85 80 75 70 65 60 55 50
1.5 parts MeTHF
2.7 parts MeTHF
3rd extraction with toluene gave tight light phase emulsion
99.6 parts dry MeTHF
•Easy product drying and precipitation •Solvent re-use: “one pot” reactions-no product isolation •Solvent recycling: drying through simple distillation
% Energy savings for dry MeTHF vs. THF recovery
Weighted Total
BTU’s/lb of material reclaimed
Energy Savings from
Recovery/ Drying
50% MeTHF THF
966 3,16
69%
2-MeTHF Safety aspects
MeTHF Safety: Peroxide Formation
– Doesn’t work for polar compounds – Poor product recovery-second extraction needed – End-up with mixtures of solvents
Improved Process: physical properties
# Reagent
Solvent
1 benzyl chloride
THF
MeTHF
2 benzyl bromide
THF
MeTHF
3 o-methylbenzyl chloride THF
Organomagnesium MeTHF Yield
Yield
Improvement
85%
14%
99% 83%
•No specialized equipment needed
1. THF Drying Process is complex
12% water
Wet THF
water
6.7% water azeotrope
100 psi pressure
Dry THF
•Recycling is possible for dedicated capacities only
10.6% water in azeotrope
60°C decanter
0.4 parts MeTHF 5.2 parts water (recycled to next batch)
100 parts MeTHF 5.2 parts water (at start of batch distillation)
% Sol. In THF
15% 10% 15% 25%
P. Rittmeyer et al., Chemetall DE 19808570
Improved Process: chemical properties
Less impurities under acidic conditions:
– less solvent degradation @ acidic aqueous work-up – better stability to Lewis acids
Purchasing
2-MeTHF: The Value Proposition
R&D/Manufacturing
Reduced costs
Improved process
Comparable/better safety
Greener process
Safety
Environmental
Agenda
• MeTHF is the solution to THF’s shortcomings:
1. MeTHF is not miscible with water 2. Clean phase separation with no emulsions & rag layers 3. Reduced number of extraction steps 4. Easy to dry (forms azeotrope like toluene) 5. Easy to recycle and reuse
MeTHF Improves Processes
• Advantages from chemical properties
– Increased reaction yields – Increased solubility of organogrignards – Less impurities due to higher solvent stability
– Increased solvent volumes – Hard to recycle solvent mixtures (separation difficult) – Persistent emulsions and rag layers
– Add saline solution for phase separation
OHale Waihona Puke Baidu
n-BuLi
O
H
Li
H2C CH2
+
Li O H2C H
The reaction of n-butyllithium with MeTHF is considerably slower
Compound
THF MeTHF
Half life at 35°C minutes
10
70
R. Bates, J. Org. Chem. (1972) 37(4), p560.
Improved Process: chemical properties
• Advantages from chemical properties
– Increased reaction yields – Less impurities due to better solvent stability
140
160
Hours
Conditions: 50:50 THF/MeTHF: 2 N HCl at 60 C
D. Aycock, OPRD submitted for publication
Improved Process: strong base stability
THF reacts with n-butyllithium
1. MeTHF improves processes 2. MeTHF; safety aspects 3. MeTHF makes greener process 4. MeTHF cuts costs 5. Conclusions; MeTHF simply better than THF 6. Q&A session
% Water in Stream from Process
25%
10%
MeTHF THF MeTHF THF
817
3,07
771
3,04
73%
75%
6% MeTHF THF
753 2,18
66%
B. Comanita, Specialty Chemicals Magazine, October 2006
Under typical acid work up, MeTHF degrades about 6 times less than THF
% Degradation of THF and MeTHF
0.6
0.5
THF
0.4
% Degraded
0.3
0.2
MeTHF
0.1
0
0
20
40
60
80
100
120
Less impurities under basic conditions:
– more stable to n-BuLi than THF – less by-products for some organogrignard reactions
Improved process: acid degradation
• Advantages from physical properties
Improved Process: chemical properties
• MeTHF is a versatile solvent
1. Grignard 2. Lithiation 3. Hydride based reduction 4. Organopalladium 5. Organozinc 6. Biphasic reactions
P. Rittmeyer et al., Chemetall DE 19808570
MeTHF: Increased Solubility of Various Grignard Reagents
Reagents
MeMgBr EtMgBr PhMgBr EtMgCl
% Sol. In MeTHF
35% 40% 45% 30%