CN105131026B - A kind of dual-component catalyst synthesizes N, the method for O-bis- (trimethylsilyl) acetamide - Google Patents
A kind of dual-component catalyst synthesizes N, the method for O-bis- (trimethylsilyl) acetamide Download PDFInfo
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- CN105131026B CN105131026B CN201510614597.3A CN201510614597A CN105131026B CN 105131026 B CN105131026 B CN 105131026B CN 201510614597 A CN201510614597 A CN 201510614597A CN 105131026 B CN105131026 B CN 105131026B
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- ethylchlorosilane
- acetamide
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- 239000003054 catalyst Substances 0.000 title claims abstract description 30
- 238000000034 method Methods 0.000 title claims abstract description 23
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 91
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 86
- 238000006243 chemical reaction Methods 0.000 claims abstract description 61
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims abstract description 51
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 35
- 150000002460 imidazoles Chemical class 0.000 claims abstract description 15
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 claims abstract description 7
- 238000003756 stirring Methods 0.000 claims description 15
- 239000002994 raw material Substances 0.000 claims description 8
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 claims 2
- 239000005051 trimethylchlorosilane Substances 0.000 claims 1
- 239000000047 product Substances 0.000 description 80
- 239000003039 volatile agent Substances 0.000 description 56
- 239000007788 liquid Substances 0.000 description 40
- 239000000463 material Substances 0.000 description 39
- 238000004821 distillation Methods 0.000 description 34
- 238000003860 storage Methods 0.000 description 22
- 239000007789 gas Substances 0.000 description 17
- 239000003921 oil Substances 0.000 description 16
- 238000004519 manufacturing process Methods 0.000 description 12
- 238000012856 packing Methods 0.000 description 10
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 9
- 230000035484 reaction time Effects 0.000 description 8
- 239000012535 impurity Substances 0.000 description 7
- 238000007086 side reaction Methods 0.000 description 7
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 description 6
- 239000005046 Chlorosilane Substances 0.000 description 6
- 150000003869 acetamides Chemical class 0.000 description 6
- KOPOQZFJUQMUML-UHFFFAOYSA-N chlorosilane Chemical compound Cl[SiH3] KOPOQZFJUQMUML-UHFFFAOYSA-N 0.000 description 6
- 230000001351 cycling effect Effects 0.000 description 6
- 239000012530 fluid Substances 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- -1 sulfidomethyl Chemical group 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 238000009833 condensation Methods 0.000 description 5
- 230000005494 condensation Effects 0.000 description 5
- 239000000945 filler Substances 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000003223 protective agent Substances 0.000 description 4
- 230000036632 reaction speed Effects 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 229930186147 Cephalosporin Natural products 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 229940124587 cephalosporin Drugs 0.000 description 3
- 150000001780 cephalosporins Chemical class 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 229920000548 poly(silane) polymer Polymers 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- YKFRUJSEPGHZFJ-UHFFFAOYSA-N N-trimethylsilylimidazole Chemical compound C[Si](C)(C)N1C=CN=C1 YKFRUJSEPGHZFJ-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- VVAKEQGKZNKUSU-UHFFFAOYSA-N 2,3-dimethylaniline Chemical class CC1=CC=CC(N)=C1C VVAKEQGKZNKUSU-UHFFFAOYSA-N 0.000 description 1
- VOWZNBNDMFLQGM-UHFFFAOYSA-N 2,5-dimethylaniline Chemical class CC1=CC=C(C)C(N)=C1 VOWZNBNDMFLQGM-UHFFFAOYSA-N 0.000 description 1
- UFFBMTHBGFGIHF-UHFFFAOYSA-N 2,6-dimethylaniline Chemical class CC1=CC=CC(C)=C1N UFFBMTHBGFGIHF-UHFFFAOYSA-N 0.000 description 1
- DOLQYFPDPKPQSS-UHFFFAOYSA-N 3,4-dimethylaniline Chemical class CC1=CC=C(N)C=C1C DOLQYFPDPKPQSS-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 229940122502 Cholesterol absorption inhibitor Drugs 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- AYDQIZKZTQHYIY-UHFFFAOYSA-N OC(=O)C1(C)CC(C(O)=O)=CC=C1 Chemical compound OC(=O)C1(C)CC(C(O)=O)=CC=C1 AYDQIZKZTQHYIY-UHFFFAOYSA-N 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229910000062 azane Inorganic materials 0.000 description 1
- AAMATCKFMHVIDO-UHFFFAOYSA-N azane;1h-pyrrole Chemical class N.C=1C=CNC=1 AAMATCKFMHVIDO-UHFFFAOYSA-N 0.000 description 1
- 150000003851 azoles Chemical class 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- ACXMTAJLYQCRGF-PBFPGSCMSA-N cefatrizine Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)[C@H](N)C=2C=CC(O)=CC=2)CC=1CSC1=CN=N[N]1 ACXMTAJLYQCRGF-PBFPGSCMSA-N 0.000 description 1
- 229960002420 cefatrizine Drugs 0.000 description 1
- YGBFLZPYDUKSPT-MRVPVSSYSA-N cephalosporanic acid Chemical compound S1CC(COC(=O)C)=C(C(O)=O)N2C(=O)C[C@H]21 YGBFLZPYDUKSPT-MRVPVSSYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000013070 direct material Substances 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 description 1
- 229960000815 ezetimibe Drugs 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000003961 organosilicon compounds Chemical class 0.000 description 1
- 238000002161 passivation Methods 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- ULWHHBHJGPPBCO-UHFFFAOYSA-N propane-1,1-diol Chemical compound CCC(O)O ULWHHBHJGPPBCO-UHFFFAOYSA-N 0.000 description 1
- 238000004451 qualitative analysis Methods 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 238000000066 reactive distillation Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 150000004756 silanes Chemical class 0.000 description 1
- 238000002444 silanisation Methods 0.000 description 1
- 238000006884 silylation reaction Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/10—Compounds having one or more C—Si linkages containing nitrogen having a Si-N linkage
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0235—Nitrogen containing compounds
- B01J31/0244—Nitrogen containing compounds with nitrogen contained as ring member in aromatic compounds or moieties, e.g. pyridine
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
Abstract
The present invention provides a kind of dual-component catalyst synthesis N, the method for O-bis- (trimethylsilyl) acetamide, including trim,ethylchlorosilane charging, synthesis reactor charging, regulation trim,ethylchlorosilane rate of addition, temperature, reaction.The synthesis reactor charging, synthesis reactor is added by acetamide, triethylamine, catalyst dimethylaniline and catalyst imidazoles；The acetamide is 1 with triethylamine weight ratio:3.60‑3.94；The catalyst dimethylaniline consumption is the 0.1 0.5% of acetamide weight；The catalyst imidazoles consumption is the 0.08 0.6% of acetamide weight；The trim,ethylchlorosilane charging, the addition of trim,ethylchlorosilane and the weight ratio of acetamide are 3.77 4.03：1.Finished product prepared by the present invention, purity is 99.51 99.62%, and once through yield is 91.33 93.66%.
Description
Technical field
N is synthesized the present invention relates to a kind of dual-component catalyst, the method for O-bis- (trimethylsilyl) acetamide belongs to organic
Synthesis technical field.
Background technology
N, O-bis- (trimethylsilyls) acetamide (hereinafter referred to as BSA) are important organosilyl protective agents.Organosilicon is protected
Agent refers to be used for a kind of organic-silylation reagent for protecting various organo-functional groups in organic synthesis.In organic synthesis, if point
Several positions or functional group may react in son, if only wanting to react on a certain position or functional group, Er Qieyou
Selective reaction condition or reagent is can not find, the position that can now would not want to react is protected, and is waited and is achieved the goal
Recover original functional group again afterwards.Organosilyl protective agents generally can be divided into trimethyl silicon type, simple function steric hindrance type, difunctionality position
Resistance type and the major class of Special type four.BSA is the most frequently used trimethyl silicon type protective agent, is mainly used in amino acid, completes acid, alcohol and acid amides
Silanization protection, be neutral silanes protective agent, with low toxicity, easily reaction, the property such as easily remove, in analytical chemistry, organic
Synthesis, medicine and it is natural substance modified in terms of application be increasingly subject to pay attention to.
BSA products are as important medicine intermediate, for preparing cephalosporins medicine and its intermediate, such as synthesis cephalo
Amino acid, synthesizing propanediol cefatrizine, the ammonia azoles sulfidomethyl cephalosporanic acid diformazan of synthesis 7- Α methoxyl group -7- amino -3- methyl four
Base ester, synthesis 7-7 α of beta-amino-methoxyl group-3- [（1- methyl isophthalic acid H- tetrazolium -5- bases）Sulfidomethyl] -3- cephem -4- carboxylic acids two
Benzene methyl etc.；Synthesis of selective cholesterol absorption inhibitor bulk drug ezetimibe；Passivation and sample as chromosorb
The modifying agent of polar group, is analyzed the compound that a variety of use conventional chromatography evaluations can not carry out qualitative and quantitative analysis
Obtain satisfied result.In recent years with the rapid perfect, development of China's organosilicon chemistry technology, make organo-silicon compound conduct
The correlation research of pharmaceutical synthesis reagent and intermediate has obtained most attention.BSA is increasingly obtained extensively in organic synthesis
Using, particularly in compound structure containing unsaturated bond, hydroxyl, carbonyl, carboxyl, amino and the protection of other functional groups, BSA
Play and more importantly acted on.
Existing BSA synthetic methods mainly have：
Chinese patent（Application number：200410044929.0）BSA production technologies are proposed, its primary operational is：During synthesis
Triethylamine and acetamide are put into reactor, is stirred 1 hour, then in N2Under the protection of gas, front three is added dropwise into reactor
Base chlorosilane, control temperature has been filled in the range of 50 DEG C of ＜ in 2-6 hours, then protection reaction 8-16 in 40-65 DEG C
Hour, reaction is cooled to less than 35 DEG C, discharging after terminating；The material reacted is added in closing centrifuge and carries out solid-liquid point
From mother liquor send in concentration kettle and concentrated, and the mother liquor after concentration is at 60-100 DEG C, and pressure is -0.2 to -0.998 atmospheric pressure, tower
The colourless transparent liquid that rectifying is obtained is carried out under the conditions of high 6-15 meters.The main deficiency of the technique is：（1）Reaction time is long, reaction
Time was more than 10 hours；(2) reaction is carried out at ambient pressure, although using N2The protection of gas, reaction system unavoidably enters
Air simultaneously brings moisture into, it may occur that other side reactions；（3）It is 0.2 to 0.998 atmospheric pressure, 6-15 meters of conditions of tower height in vacuum
Lower carry out rectifying, power consumption is big, high energy consumption, especially to reach the condition that vacuum is 0.998 atmospheric pressure, and power consumption is too big.
Chinese patent（Application number：200810120760.0）Propose be using TSIM and acetamide as raw material,
Using sulfhydryl compound as catalyst, the method that BSA is synthesized by reactive distillation.In a band constant pressure funnel, thermometer, magnetic force
Stirring and with 33.6g (0.24mol) trimethyl silicon based imidazoles and 1.5g are added in 250 milliliters of there-necked flasks of 1 meter of rectifying column
(0.01mol) 2- mercaptobenzothiazolers, and by 12g (0.2mol) acetamides and 33.6g (0.24mol) trimethyl silicon substrate miaow
The mixed liquor of azoles is added to constant pressure funnel.Then heat, open magnetic agitation, depressurize, it is vacuum to control reaction pressure
Mixed liquor is slowly added dropwise at 160 DEG C or so in 0.08MPa, control temperature of reaction kettle from constant pressure funnel, and side border ring rectifying is received
The cut of less than 90 DEG C of collection is BSA crude products, and it is 5 hours to control the reaction time.Then, crude product is rectifying to obtain high content
BSA sterlings, yield 85%, content 99.2%.The main deficiency of the technique is：（1）Accessory substance acetonitrile and silicon ether are produced, and then
Can occur some other side reaction；（2）Reaction temperature is high, and temperature of reaction kettle is controlled at 160 DEG C or so, consumes energy larger, easily causes
BSA loses；（3）Under the conditions of vacuum 0.08MPa, the reaction time is also up to 5 hours；（4）Production cost is high, to raw material
TSIM quality requirement is high.
French Patent (FRP)（The patent No.：FR2574079）Synthesis BSA route is proposed, this method is with the silicon of hexamethyl two
Azane is raw material, elder generation and acetic anhydride, then generates BSA with trim,ethylchlorosilane and triethylamine react.The technique is mainly not enough
It is：（1）Although this reaction only produces the triethylamine hydrochloride of half amount in acetamide and trim,ethylchlorosilane reaction, it
Generate the acetate of trimethyl silicone hydride again, easily blocking pipeline, have a strong impact on reaction and carry out；（2）Side reaction increase, by-product
Thing increases, and production cost is high；（3）Finished product purity is low, and amount of impurities and content are higher.
United States Patent (USP)（The patent No.:US4276423）Propose using trimethyl silicon based imidazole and N- trimethyl silicon substrate acetyl
The method that amine prepares BSA.Temperature of reaction system regulation is in 120-170 DEG C, vacuum 65mmHg posts, the distillation of side border ring, reaction
Yield more than 90%.The main deficiency of the technique is：（1）Trimethyl silicon based imidazole can occur reversible with N- trimethyl silicanes yl acetamide
Reaction, reaction temperature is high；（2）Because side reaction is more, in product, amount of impurities is more, content is high：（3）Work is distilled using side border ring
Skill, industrialized production enforcement difficulty is big.
In recent years, with the research and development and the success of Clinical practice of the new cephalosporin analog antibiotic of the third generation, in pharmaceutical synthesis
To BSA purity requirement more and more highers, conventional purity 99.0 (GC) % can not meet requirement；In addition, utilizing MEMS (micro-electro-mechanical systems
System) for technical backstopping be used for separate and detect that the MEMS cell captures chip of cancer cell must use purity 99.5 in use
(GC) more than % BSA, otherwise testing result is without in all senses；Other several injection cephalosporin analog antibiotic synthesis must make
With purity 99.5 (GC) more than % BSA, otherwise side reaction especially severe side reaction occurs even to occur again and again after human body injection
It is dead.To there is reaction time length, production cost height, product purity in domestic and international existing BSA production technologies left in 99.0 (GC) % mostly
The right side, product stability is poor（A period of time product is placed its colour changed into yellow occur, have floccule etc.）.Therefore, one kind is developed to carry simultaneously
High BSA purity and the production method of yield, to promoting industry development, there is important economic implications and social benefit.
The content of the invention
For reaction temperature height, reaction time length, product purity low impurity content present in domestic existing BSA productions
It is high, improve yield and cost the problems such as raise, the present invention provides a kind of dual-component catalyst synthesis N, O-bis- (trimethylsilyl)
The method of acetamide, using domestic trim,ethylchlorosilane, triethylamine and the acetamide being easy to get as raw material, adds other organic base conduct
Acid binding agent plays catalytic action simultaneously, is reacted under rough vacuum, with circulating pump forced circulation except promoting reaction to carry out
Outside, the hydrochloride for reacting generation is removed from reaction system in time, greatly accelerates reaction speed；Using smart under vacuum condition
Evaporate, product quality is stable and the holding time is long.
The goal of the invention that the present invention is realized is：
（1）Shorten the reaction time；
（2）Reaction temperature is reduced, reaction temperature is reduced to less than 40 DEG C；
（3）Product BSA purity is brought up to more than 99.5% (GC)；
（4）Amount of impurities is reduced, impurity content is reduced, the complexity knot such as polysilane in product, polyoxy silane is especially reduced
Structure compounds content；
（5）Reduce amine content in product；
（6）While improving yield, production cost is reduced；
（7）Product excellent storage stability.
The reaction principle of the present invention is as follows：
In BSA synthetic reactions, trim,ethylchlorosilane and acetamide are reacted as direct material, and triethylamine is as tiing up
Sour agent neutralizes the HCl of trim,ethylchlorosilane and acetamide generation, medium is kept neutral or alkalescent, to improve acylation reaction
Yield, reaction equation shows as follows：
To solve above technical problem, the technical solution adopted by the present invention is as follows：
A kind of dual-component catalyst synthesize N, the method for O-bis- (trimethylsilyl) acetamide, including trim,ethylchlorosilane plus
Material, synthesis reactor charging, regulation trim,ethylchlorosilane rate of addition, temperature, reaction.
The following is the further improvement to above-mentioned technical proposal：
The synthesis reactor charging, acetamide, triethylamine, catalyst dimethylaniline and catalyst imidazoles are added and synthesized
Kettle；The acetamide is 1 with triethylamine weight ratio:3.60-3.94.
The catalyst dimethylaniline consumption is the 0.1-0.5% of acetamide weight.
The catalyst imidazoles consumption is the 0.08-0. 6% of acetamide weight.
The trim,ethylchlorosilane charging, the addition of trim,ethylchlorosilane and the weight ratio of acetamide are 3.77-4.03：
1。
The synthesis reactor charging, after raw material is added, starts stirring, agitator speed is set as 85-100RPM, stirs 45-
After 55 minutes, adjustment synthesis reactor vacuum is 0.01-0.025MPa.
The regulation trim,ethylchlorosilane rate of addition, temperature, control 33-39 DEG C of dropping temperature, trim,ethylchlorosilane control
System was added in 90-110 minutes.
The reaction, trim,ethylchlorosilane completion of dropping continues to keep reaction temperature to be 33-39 DEG C, keeps synthesis reactor true
Reciprocal of duty cycle is 0.01-0.025MPa, and circulating pump is continued cycling through 120-150 minutes, and reaction terminates.
Finished product prepared by the present invention, purity is 99.51-99.62%, and once through yield is 91.33-93.66%.
The suitable catalyst of present invention selection, based on Lewis alkali, accelerates the reaction speed of trim,ethylchlorosilane and acetamide
Degree, makes acetamide carbonyl increased activity, so as to improve its reactivity；Reduce BSA and hydrogen chloride touch opportunity.
The present invention is while reaction, while the triethylamine hydrochloride of generation is removed into reaction system, maintains essentially in reaction
Under homogeneous phase condition carry out, in time remove generation triethylamine hydrochloride, be also beneficial to accelerate reaction speed, reduce finished product BSA with
Hydrogen chloride deep reaction generates other compounds.
The selection of catalyst of the present invention, by test of many times, it is determined that it is major catalyst to use dimethylaniline, wherein 2,
6- dimethylanilines are other as 2,5- dimethylanilines, 3,4- dimethylanilines, 2,3- dimethylanilines also may be used to preferably use
Use；Meanwhile, imidazoles is selected as cocatalyst, imidazoles boiling point is higher, easily divide away from big with BSA boiling-point differences when finished product is separated
From.
Beneficial effects of the present invention are：
（1）Dual-component catalyst catalyst dimethyl benzene is used in trim,ethylchlorosilane and acetamide synthetic reaction of the present invention
Amine and imidazoles, react under the conditions of low vacuum, and reaction speed is accelerated,
Reaction time of the invention (finishes) from starting to be fed to reaction, is 4-4.5 hours, in the prior art industrialized production
Technique is generally 8-18 hours.
（2）Reaction temperature is reduced to as 33-39 DEG C by present 40-65 DEG C；Rectification temperature, receives finished product condensate temperature
73 DEG C are reduced to by 90 DEG C, other side reactions such as finished product BSA decomposition, polymerization are significantly reduced.
（3）Product BSA prepared by the present invention, is initially operated under vacuum during distillation, and rear distillation uses Gao Zhen
Empty, low-temperature operation, product purity brings up to 99.51-99.62%.
（4）Product BSA prepared by the present invention, amount of impurities and impurity content are few, and polysilane, polyoxy silane etc. are multiple in product
Miscellaneous structural compounds content is low, polysilane content≤0.1%, polyoxy silane contents≤0.1% in control product.
（5）In product prepared by the present invention, amine content is low, and amine content is 0.21-0.35%.
（6）The inventive method, while improving yield, reduces production cost, BSA once through yield is domestic up to 93.66%
Existing yield is no more than 90%, product cost reduction by more than 2%.
（7）Solve the problem of product bin stability is poor；
Product prepared by the present invention, excellent storage stability, product purity is 99.40-99.53% (GC) after storing 1 year, outside
See as colourless transparent liquid, no floccule.Domestic like product bin stability is poor, and purity declines 3%, and production after storing 1 year
Product arrive faint yellow for micro- Huang, or even floccule occur.
（8）When trim,ethylchlorosilane is added dropwise into kettle, trim,ethylchlorosilane charge door is immersed in below synthesis reactor liquid level；Follow
The entrance synthesis reactor circulation line charging aperture of the circulation fluid of ring pump must be immersed in below synthesis reactor liquid level.Plus synthesis reactor in negative pressure
Under state, raw material trim,ethylchlorosilane hardly with air contact, moisture weakens significantly to the Hydrolysis of trim,ethylchlorosilane,
The conversion ratio of raw material trim,ethylchlorosilane is improved, conversion ratio improves more than 3%.
（9）In reactor bottom outlet connection circulating pump, the i.e. open the circulation pump after starting to be added dropwise trim,ethylchlorosilane, with
Reactor agitator acts synergistically, and enhances the degree of material mixing, promotes heat and mass；Two filterings are followed by circulating pump
Device, one is used for coarse filtration（Filtering accuracy 100-200 mesh）, one is used to carefully filter（Filtering accuracy 300-400 mesh）, filter out life
Into triethylamine hydrochloride, system reacts under homogeneous phase condition, and material contact is more abundant, and reaction effect is good.
Brief description of the drawings
Technological process and equipment below in conjunction with accompanying drawing and implementation to the present invention are further described.
Fig. 1 is BSA synthesis technique schematic flow sheets；
In figure：1- trim,ethylchlorosilane head tanks；The pipelines of 2- first regard cup；3- synthesis reactors；4- circulating pumps；5- first is filtered
Device；The filters of 6- second；7- distillation stills；8- packed towers；9- condensers；10- front-end volatiles receiving tanks；11- finished product receiving tanks；12-
Water-jet vavuum pump；13- oil seal type oil-sealed rotary pumps；14- first pressures（Vacuum）Instruction device on the spot；The temperature of 15- first
Spend instruction device on the spot；16- second temperatures instruction device on the spot；The pipelines of 17- second regard cup.18- second pressures（Vacuum）Just
Ground instruction device；The pressure of 19- the 3rd（Vacuum）Instruction device on the spot.
Embodiment
The preferred embodiments of the present invention are illustrated below, it will be appreciated that preferred embodiment described herein is only used
In the description and interpretation present invention, it is not intended to limit the present invention.
A kind of dual-component catalyst of embodiment 1 synthesizes N, the method for O-bis- (trimethylsilyl) acetamide
Reaction is carried out in 1000L kettles, and synthesis step is as follows：
（1）Trim,ethylchlorosilane feeds
350kg trim,ethylchlorosilanes are extracted into trim,ethylchlorosilane head tank 1 with vacuum, start to keep trimethyl before feeding
The tiny structure of chlorosilane head tank 1, keeps vacuum 0.001-0.005
MPa。
（2）Synthesis reactor 3 feeds
By 90kg acetamides, 345kg triethylamines, 0.15kg2,6- dimethylanilines add synthesis reactor 3 with 0.25kg imidazoles,
Stirring is opened, agitator speed is set as 85RPM, after stirring 45 minutes, adjustment synthesis reactor 3 vacuum is 0.01-0.015MPa.
（3）Start that trim,ethylchlorosilane is added dropwise
Trim,ethylchlorosilane head tank 1 is adjusted to normal pressure, trim,ethylchlorosilane is added dropwise into kettle, trim,ethylchlorosilane adds
Material mouth must be submerged in below the liquid level of synthesis reactor 3 at 20-35mm, starts trim,ethylchlorosilane i.e. unlatching is added dropwise to synthesis reactor 3 and follows
Ring pump 4, material sequentially passes through circulating pump 4, the first filter 5, the second filter 6 and enters synthesis reactor 3, in the first filter 5, the
The triethylamine hydrochloride of generation is filtered out in tow filtrator 6；The circulation line charging aperture of entrance synthesis reactor 3 of circulation fluid must be submerged in
Below the liquid level of synthesis reactor 3 at 20-35mm.
（4）Adjust trim,ethylchlorosilane rate of addition, temperature
Trim,ethylchlorosilane rate of addition is adjusted, 33-35 DEG C of dropping temperature is controlled, trim,ethylchlorosilane was controlled at 90 minutes
Inside add.
（5）Reaction
Trim,ethylchlorosilane completion of dropping, continues to keep reaction temperature to be 33-35 DEG C, and the holding vacuum of synthesis reactor 3 is
0.01-0.015MPa, circulating pump 4 is continued cycling through 120 minutes, and reaction terminates.
（6）Material sends into distillation still 7
The material valve for leading to synthesis reactor 3 is closed, the valve for leading to distillation still 7, open the circulation pump 4, by synthesis reactor 3 is opened
Interior material feeding distillation still 7 is distilled.
（7）Distill to obtain front-end volatiles
Distillation destilling tower used is packed tower 8,4 meters of tower height, built-in tetrafluoro filler.
A, the first front-end volatiles collection
Hydraulic jet pump 12 is first opened, when vacuum reaches 0.082-0.086MPa, steam is passed through to the chuck of distillation still 3 and adds
Material in hot kettle, regards cup 17 by the second pipeline, examines material and steam situation.Work as second pressure（Vacuum）Indicate on the spot
After the vacustat that device 18 is shown, before 68 DEG C（That is temperature<68℃）Condensate liquid as front-end volatiles, and by front-end volatiles
Access in front-end volatiles receiving tank 10, obtain the first front-end volatiles；
B, the second front-end volatiles collection
When gas phase temperature is stepped up to 68.1 DEG C, first steam off valve, then switch vacuum system, by water-jet
Vavuum pump 12 is switched to oil seal type oil-sealed rotary pump 13；Oil seal type oil-sealed rotary pump 13 is stable, after vacustat, observation
The second temperature gas phase temperature situation of change of instruction device 16 on the spot, keep vacuum and intercept vacuum for 0.096~
0.099MPa, is again turned on after steam valve, and the condensate liquid of 68.1-70 DEG C of gained also serves as front-end volatiles access front-end volatiles receiving tank
In 10, the second front-end volatiles are obtained.
（8）Distill to obtain finished product
When gas phase temperature is stepped up to 70.1 DEG C, close the valve of front-end volatiles receiving tank 10 and open finished product receiving tank 11
Valve, intercepts 70.1-73 DEG C, gained condensate liquid is as finished product and is linked into finished product receiving tank 11.
（9）Close Distallation systm, finished product packing storage, low temperature storage
When observing the second temperature temperature rise that instruction device 16 is shown on the spot and seen depending on cup 17 by the second pipeline
Observe from the condensation flow quantity that condenser 9 comes out reduce when, the heating steam of distillation still 7 is first closed, when observing that the second pipeline regards
When the liquid of cup 17 is almost without dropping down, oil seal type oil-sealed rotary pump 13, finished product packing storage, the low temperature under the conditions of nitrogen-sealed are closed
Storage.
The BSA products of preparation, once through yield 91.33%, purity (GC) 99.51%.It is shown in Table 1
BSA product quality indicators made from table 1
Product purity is 99.42% (GC) after product is stored 1 year, and outward appearance is colourless transparent liquid, no floccule.
A kind of dual-component catalyst of embodiment 2 synthesizes N, the method for O-bis- (trimethylsilyl) acetamide
Reaction is carried out in 1000L kettles.Synthesis step is as follows：
（1）Trim,ethylchlorosilane feeds
380kg trim,ethylchlorosilanes are extracted into trim,ethylchlorosilane head tank 1 with vacuum, start to keep trimethyl before feeding
The tiny structure of chlorosilane head tank 1, keeps vacuum 0.001-0.005MPa.
（2）Synthesis reactor 3 feeds
By 100kg acetamides, 365kg triethylamines, 0.2kg2,6- dimethylanilines add synthesis reactor 3 with 0.2kg imidazoles,
Stirring is opened, agitator speed is set as 85RPM, after stirring 50 minutes, adjustment synthesis reactor 3 vacuum is 0.01-0.015MPa.
（3）Start that trim,ethylchlorosilane is added dropwise
Trim,ethylchlorosilane head tank 1 is adjusted to normal pressure, trim,ethylchlorosilane is added dropwise into kettle, trim,ethylchlorosilane adds
Material mouth must be submerged in 20-35cm below the liquid level of synthesis reactor 3；Start that trim,ethylchlorosilane i.e. ON cycle is added dropwise to synthesis reactor 3
Pump 4, material sequentially passes through circulating pump 4, the first filter 5, the second filter 6 and enters synthesis reactor 3, in the first filter 5, second
The triethylamine hydrochloride of generation is filtered out in filter 6；The circulation line charging aperture of entrance synthesis reactor 3 of circulation fluid must be submerged in conjunction
20-35cm below into the liquid level of kettle 3.
（4）Adjust trim,ethylchlorosilane rate of addition, temperature
Trim,ethylchlorosilane rate of addition is adjusted, 33-35 DEG C of dropping temperature is controlled, trim,ethylchlorosilane is controlled at 100 points
Added in clock.
（5）Reaction
Trim,ethylchlorosilane completion of dropping, continues to keep reaction temperature to be 33-35 DEG C, and the holding vacuum of synthesis reactor 3 is
0.01-0.015MPa, circulating pump 4 is continued cycling through 130 minutes, and reaction terminates.
（6）Material sends into distillation still 7
The material valve for leading to synthesis reactor 3 is closed, the valve for leading to distillation still 7 is opened；Open the circulation pump 4, by synthesis reactor 3
Interior material is sent into distillation still 7, and adds the front-end volatiles of embodiment 1.
（7）Distill to obtain front-end volatiles
Distillation destilling tower used is packed tower 8,4 meters of tower height, built-in tetrafluoro filler.
A, the first front-end volatiles collection
Hydraulic jet pump 12 is first opened, when vacuum reaches 0.082-0.086MPa, steam is passed through to the chuck of distillation still 7 and adds
Material in hot kettle, examines material depending on cup 17 by the second pipeline and steams situation.Work as second pressure（Vacuum）Indicate on the spot
After the vacustat that device 18 is shown, before 68 DEG C of gained（<68℃）Condensate liquid accessed as front-end volatiles, and by front-end volatiles
In front-end volatiles receiving tank 10, the first front-end volatiles are obtained；
B, the second front-end volatiles collection
When gas phase temperature is stepped up to 68.1 DEG C, first steam off valve, then switch vacuum system, by water-jet
Vavuum pump 12 is switched to oil seal type oil-sealed rotary pump 13.Oil seal type oil-sealed rotary pump 13 is stable, after vacustat, observation
The second temperature gas phase temperature situation of change of instruction device 16 on the spot, keep vacuum and intercept vacuum for 0.096~
0.099MPa；It is again turned on after steam valve, the condensate liquid of 68.1-70 DEG C of gained also serves as front-end volatiles access front-end volatiles receiving tank
In 10, the second front-end volatiles are obtained.
（8）Distill to obtain finished product
When gas phase temperature is stepped up to 70.1 DEG C, close the valve of front-end volatiles receiving tank 10 and open finished product receiving tank 11
Valve, intercepts 70.1-73 DEG C, gained condensate liquid is as finished product and is linked into finished product receiving tank 11.
（9）Close Distallation systm, finished product packing storage, low temperature storage
When observing the second temperature temperature rise that instruction device 16 is shown on the spot and seen depending on cup 17 by the second pipeline
Observe from the condensation flow quantity that condenser 9 comes out reduce when, the heating steam of distillation still 7 is first closed, when observing that the second pipeline regards
When the liquid of cup 17 is almost without dropping down, oil seal type oil-sealed rotary pump 13, finished product packing storage, the low temperature under the conditions of nitrogen-sealed are closed
Storage.The product of preparation：Once through yield 92.46%, purity (GC) 99.55%.It is shown in Table 2
Product quality indicator made from table 2
Product purity is 99.43% (GC) after product is stored 1 year, and outward appearance is colourless transparent liquid, no floccule.
A kind of dual-component catalyst of embodiment 3 synthesizes N, the method for O-bis- (trimethylsilyl) acetamide
Reaction is carried out in 1000L kettles, and synthesis step is as follows：
（1）Trim,ethylchlorosilane feeds
420kg trim,ethylchlorosilanes are extracted into trim,ethylchlorosilane head tank 1 with vacuum, start to keep trimethyl before feeding
The tiny structure of chlorosilane head tank 1, keeps vacuum 0.001-0.005MPa.
（2）Synthesis reactor 3 feeds
By 110kg acetamides, 400kg triethylamines, 0.3kg2,6- dimethylanilines add synthesis reactor 3 with 0.2kg imidazoles,
Stirring is opened, agitator speed is set as 90RPM.After stirring 50 minutes, adjustment synthesis reactor 3 vacuum is 0.01-0.015MPa.
（3）Start that trim,ethylchlorosilane is added dropwise
Trim,ethylchlorosilane head tank 1 is adjusted to normal pressure.Trim,ethylchlorosilane is added dropwise into kettle, trim,ethylchlorosilane adds
Material mouth must be submerged in 20-35cm below the liquid level of synthesis reactor 3；Start that trim,ethylchlorosilane i.e. ON cycle is added dropwise to synthesis reactor 3
Pump 4, material sequentially passes through circulating pump 4, the first filter 5, the second filter 6 and enters synthesis reactor 3, in the first filter 5, second
The triethylamine hydrochloride of generation is filtered out in filter 6；The circulation line charging aperture of entrance synthesis reactor 3 of circulation fluid must be submerged in conjunction
20-35cm below into the liquid level of kettle 3.
（4）Adjust trim,ethylchlorosilane rate of addition, temperature
Trim,ethylchlorosilane rate of addition is adjusted, 33-35 DEG C of dropping temperature is controlled, trim,ethylchlorosilane is controlled at 100 points
Added in clock.
（5）Reaction
Trim,ethylchlorosilane completion of dropping, continues to keep reaction temperature to be 33-35 DEG C, and the holding vacuum of synthesis reactor 3 is
0.01-0.015MPa, circulating pump 4 is continued cycling through 130 minutes, and reaction terminates.
（6）Material sends into distillation still
The material valve for leading to synthesis reactor 3 is closed, the valve for leading to distillation still 7, open the circulation pump 4, by synthesis reactor 3 is opened
Interior material is sent into distillation still 7, and adds the front-end volatiles of embodiment 2.
（7）Distill to obtain front-end volatiles
Distillation destilling tower used is packed tower 8,4 meters of tower height, built-in tetrafluoro filler.
A, the first front-end volatiles collection
Hydraulic jet pump 12 is first opened, when vacuum reaches 0.082-0.086MPa, steam is passed through to the chuck of distillation still 7 and adds
Material in hot kettle, examines material depending on cup 17 by the second pipeline and steams situation；Work as second pressure（Vacuum）Indicate on the spot
After the vacustat that device 18 is shown, before 68 DEG C of gained condensate liquid（<68℃）Accessed as front-end volatiles, and by front-end volatiles
In front-end volatiles receiving tank 10, the first front-end volatiles are obtained；
B, the second front-end volatiles collection
When gas phase temperature is stepped up to 68.1 DEG C, first steam off valve, then switch vacuum system, by water-jet
Vavuum pump 12 is switched to oil seal type oil-sealed rotary pump 13.Oil seal type oil-sealed rotary pump 13 is stable, after vacustat, observation
The second temperature gas phase temperature situation of change of instruction device 16 on the spot, keep vacuum and intercept vacuum for 0.096~
0.099MPa；It is again turned on after steam valve, the condensate liquid of 68.1-70 DEG C of gained also serves as front-end volatiles access front-end volatiles receiving tank
In 10, the second front-end volatiles are obtained.
（8）Distill to obtain finished product
When gas phase temperature is stepped up to 70.1 DEG C, close the valve of front-end volatiles receiving tank 10 and open finished product receiving tank 11
Valve, intercepts 70.1-73 DEG C, gained condensate liquid is as finished product and is linked into finished product receiving tank 11.
（9）Close Distallation systm, finished product packing storage, low temperature storage
When observing the second temperature temperature rise that instruction device 16 is shown on the spot and seen depending on cup 17 by the second pipeline
Observe from the condensation flow quantity that condenser 9 comes out reduce when, the heating steam of distillation still 7 is first closed, when observing that the second pipeline regards
When the liquid of cup 17 is almost without dropping down, oil seal type oil-sealed rotary pump 13, finished product packing storage, the low temperature under the conditions of nitrogen-sealed are closed
Storage.The product of preparation, once through yield 92.96%, purity (GC) 99.52%.It is shown in Table 3
Product quality indicator made from table 3
Product purity is 99.40% (GC) after product is stored 1 year, and outward appearance is colourless transparent liquid, no floccule.
A kind of dual-component catalyst of embodiment 4 synthesizes N, the method for O-bis- (trimethylsilyl) acetamide
Reaction is carried out in 1000L kettles, and synthesis step is as follows：
（1）Trim,ethylchlorosilane feeds
460kg trim,ethylchlorosilanes are extracted into trim,ethylchlorosilane head tank 1 with vacuum, start to keep trimethyl before feeding
The tiny structure of chlorosilane head tank 1, keeps vacuum 0.001-0.005MPa.
（2）Synthesis reactor 3 feeds
By 120kg acetamides, 440kg triethylamines, 0.3kg2,6- dimethylanilines add synthesis reactor 3 with 0.3kg imidazoles,
Stirring is opened, agitator speed is set as 90RPM.After stirring 50 minutes, adjustment synthesis reactor 3 vacuum is 0.015-0.02MPa.
（3）Start that trim,ethylchlorosilane is added dropwise
Trim,ethylchlorosilane head tank 1 is adjusted to normal pressure.Trim,ethylchlorosilane is added dropwise into kettle, trim,ethylchlorosilane adds
Material mouth must be submerged in 20-35cm below the liquid level of synthesis reactor 3；Start that trim,ethylchlorosilane i.e. ON cycle is added dropwise to synthesis reactor 3
Pump 4, material sequentially passes through circulating pump 4, the first filter 5, the second filter 6 and enters synthesis reactor 3, in the first filter 5, second
The triethylamine hydrochloride of generation is filtered out in filter 6；The circulation line charging aperture of entrance synthesis reactor 3 of circulation fluid must be submerged in conjunction
20-35cm below into the liquid level of kettle 3.
（4）Adjust trim,ethylchlorosilane rate of addition, temperature
Trim,ethylchlorosilane rate of addition is adjusted, 36-39 DEG C of dropping temperature is controlled, trim,ethylchlorosilane is controlled at 110 points
Added in clock.
（5）Reaction
Trim,ethylchlorosilane completion of dropping, continues to keep reaction temperature to be 36-39 DEG C, and the holding vacuum of synthesis reactor 3 is
0.015-0.02MPa, circulating pump 4 is continued cycling through 150 minutes, and reaction terminates.
（6）Material sends into distillation still 7
The material valve for leading to synthesis reactor 3 is closed, the valve for leading to distillation still 7 is opened.Open the circulation pump 4, by synthesis reactor 3
Interior material is sent into distillation still 7, and adds the front-end volatiles of embodiment 3.
（7）Distill to obtain front-end volatiles
Distillation destilling tower used is packed tower 8,4 meters of tower height, built-in tetrafluoro filler.
A, the first front-end volatiles collection
Hydraulic jet pump 12 is first opened, when vacuum reaches 0.082-0.086MPa, steam is passed through to the chuck of distillation still 7 and adds
Material in hot kettle, examines material depending on cup 17 by the second pipeline and steams situation.Work as second pressure（Vacuum）Indicate on the spot
After the vacustat that device 18 is shown, before 68 DEG C of gained condensate liquid（<68℃）Accessed as front-end volatiles, and by front-end volatiles
In front-end volatiles receiving tank 10；
B, the second front-end volatiles collection
When gas phase temperature is stepped up to 68.1 DEG C, first steam off valve, then switch vacuum system, by water-jet
Vavuum pump 12 is switched to oil seal type oil-sealed rotary pump 13.Oil seal type oil-sealed rotary pump 13 is stable, after vacustat, observation
The second temperature gas phase temperature situation of change of instruction device 16 on the spot, keep vacuum and intercept vacuum for 0.096~
0.099MPa.It is again turned on after steam valve, the condensate liquid of 68.1-70 DEG C of gained also serves as front-end volatiles access front-end volatiles receiving tank
In 10.
（8）Distill to obtain finished product
When gas phase temperature is stepped up to 70.1 DEG C, close the valve of front-end volatiles receiving tank 10 and open finished product receiving tank 11
Valve, gained condensate liquid intercepts 70.1-73 DEG C, as finished product and is linked into finished product receiving tank 11.
（9）Close Distallation systm, finished product packing storage, low temperature storage
When observing the second temperature temperature rise that instruction device 16 is shown on the spot and seen depending on cup 17 by the second pipeline
Observe from the condensation flow quantity that condenser 9 comes out reduce when, the heating steam of distillation still 7 is first closed, when observing that the second pipeline regards
When the liquid of cup 17 is almost without dropping down, oil seal type oil-sealed rotary pump 13, finished product packing storage, the low temperature under the conditions of nitrogen-sealed are closed
Storage.The product of preparation, once through yield 93.28%, purity (GC) 99.60%.It is shown in Table 4
Product quality indicator made from table 4
Product purity is 99.50% (GC) after product is stored 1 year, and outward appearance is colourless transparent liquid, no floccule.
A kind of dual-component catalyst of embodiment 5 synthesizes N, the method for O-bis- (trimethylsilyl) acetamide
Reaction is carried out in 1000L kettles, and synthesis step is as follows：
（1）Trim,ethylchlorosilane feeds
470kg trim,ethylchlorosilanes are extracted into trim,ethylchlorosilane head tank 1 with vacuum, start to keep trimethyl before feeding
The tiny structure of chlorosilane head tank 1, keeps vacuum 0.001-0.005MPa.
（2）Synthesis reactor 3 feeds
120kg acetamides, 460kg triethylamines, 0.45kg2,6- dimethylanilines and 0.4kg imidazoles are added into synthesis reactor
3, stirring is opened, agitator speed is set as 100RPM.After stirring 55 minutes, adjustment synthesis reactor 3 vacuum is 0.02-
0.025MPa。
（3）Start that trim,ethylchlorosilane is added dropwise
Trim,ethylchlorosilane head tank 1 is adjusted to normal pressure, trim,ethylchlorosilane is added dropwise into kettle, trim,ethylchlorosilane adds
Material mouth must be submerged in 20-35cm below the liquid level of synthesis reactor 3；Start that trim,ethylchlorosilane i.e. ON cycle is added dropwise to synthesis reactor 3
Pump 4, material sequentially passes through circulating pump 4, the first filter 5, the second filter 6 and enters synthesis reactor 3, in the first filter 5, second
The triethylamine hydrochloride of generation is filtered out in filter 6；The circulation line charging aperture of entrance synthesis reactor 3 of circulation fluid must be submerged in conjunction
20-35cm below into the liquid level of kettle 3.
（4）Adjust trim,ethylchlorosilane rate of addition, temperature
Trim,ethylchlorosilane rate of addition is adjusted, 36-39 DEG C of dropping temperature is controlled, trim,ethylchlorosilane is controlled at 110 points
Added in clock.
（5）Reaction
Trim,ethylchlorosilane completion of dropping, continues to keep reaction temperature to be 36-39 DEG C, and the holding vacuum of synthesis reactor 3 is
0.02-0.025MPa, circulating pump 4 is continued cycling through 150 minutes, and reaction terminates.
（6）Material sends into distillation still 7
The material valve for leading to synthesis reactor 3 is closed, the valve for leading to distillation still 7 is opened.Open the circulation pump 4, by synthesis reactor
Material is sent into distillation still 7 in 3, and adds the front-end volatiles of embodiment 4.
（7）Distill to obtain front-end volatiles
Distillation destilling tower used is packed tower 8,4 meters of tower height, built-in tetrafluoro filler.
A, the first front-end volatiles collection
Hydraulic jet pump 12 is first opened, when vacuum reaches 0.082-0.086MPa, steam is passed through to the chuck of distillation still 7 and adds
Material in hot kettle, examines material depending on cup 17 by the second pipeline and steams situation.Work as second pressure（Vacuum）Indicate on the spot
After the vacustat that device 18 is shown, before 68 DEG C of gained condensate liquid（<68℃）Accessed as front-end volatiles, and by front-end volatiles
In front-end volatiles receiving tank 10；
B, the second front-end volatiles collection
When gas phase temperature is stepped up to 68.1 DEG C, first steam off valve, then switch vacuum system, by water-jet
Vavuum pump 12 is switched to oil seal type oil-sealed rotary pump 13.Oil seal type oil-sealed rotary pump 13 is stable, after vacustat, observation
The second temperature gas phase temperature situation of change of instruction device 16 on the spot, keep vacuum and intercept vacuum for 0.096~
0.099MPa.It is again turned on after steam valve, the condensate liquid of 68.1-70 DEG C of gained also serves as front-end volatiles access front-end volatiles receiving tank
In 10.
（8）Distill to obtain finished product
When gas phase temperature is stepped up to 70.1 DEG C, close the valve of front-end volatiles receiving tank 10 and open finished product receiving tank 11
Valve, gained condensate liquid intercepts 70.1-73 DEG C, as finished product and is linked into finished product receiving tank 11.
（9）Close Distallation systm, finished product packing storage, low temperature storage
When observing the second temperature temperature rise that instruction device 16 is shown on the spot and seen depending on cup 17 by the second pipeline
Observe from the condensation flow quantity that condenser 9 comes out reduce when, the heating steam of distillation still 7 is first closed, when observing that the second pipeline regards
When cup liquid is almost without dropping down, oil seal type oil-sealed rotary pump 13 is closed, finished product packing is put in storage, and low temperature is deposited under the conditions of nitrogen-sealed
Storage.
The product prepared, once through yield 93.66%, purity (GC) 99.62%.It is shown in Table 5
Product quality indicator made from table 5
Product purity is 99.53% (GC) after product is stored 1 year, and outward appearance is colourless transparent liquid, no floccule.
Unless otherwise indicated, the percentage employed in the present invention is percetage by weight, ratio of the present invention,
For mass ratio.
Finally it should be noted that：The preferred embodiments of the present invention are the foregoing is only, are not intended to limit the invention,
Although the present invention is described in detail with reference to the foregoing embodiments, for those skilled in the art, it still may be used
To be modified to the technical scheme described in foregoing embodiments, or equivalent substitution is carried out to which part technical characteristic.
Within the spirit and principles of the invention, any modification, equivalent substitution and improvements made etc., should be included in the present invention's
Within protection domain.
Claims (1)
1. a kind of dual-component catalyst synthesizes N, the method for O-bis- (trimethylsilyl) acetamide, it is characterised in that：Including trimethyl
Chlorosilane feeds, synthesis reactor charging, regulation trim,ethylchlorosilane rate of addition, temperature, reaction；
The synthesis reactor charging, synthesis reactor is added by acetamide, triethylamine, catalyst dimethylaniline and catalyst imidazoles；Institute
It is 1 that acetamide, which is stated, with triethylamine weight ratio:3.60-3.94；
The synthesis reactor charging, after raw material is added, starts stirring, agitator speed is set as 85-100RPM, 45-55 points of stirring
Zhong Hou, adjustment synthesis reactor vacuum is 0.01-0.025MPa；
The catalyst dimethylaniline consumption is the 0.1-0.5% of acetamide weight；
The catalyst imidazoles consumption is the 0.08-0. 6% of acetamide weight.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510614597.3A CN105131026B (en) | 2015-09-24 | 2015-09-24 | A kind of dual-component catalyst synthesizes N, the method for O-bis- (trimethylsilyl) acetamide |
| CN201710677090.1A CN107383083A (en) | 2015-09-24 | 2015-09-24 | A kind of production method for improving organosilicon medicine intermediate BSA purity |
| CN201710677089.9A CN107383082A (en) | 2015-09-24 | 2015-09-24 | A kind of composite catalyzing produces high purity N, the method for O-bis- (trimethylsilyl) acetamide |
| CN201710675934.9A CN107365325A (en) | 2015-09-24 | 2015-09-24 | A kind of purity is high, the production method of the N of high income, O-bis- (trimethylsilyls) acetamide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510614597.3A CN105131026B (en) | 2015-09-24 | 2015-09-24 | A kind of dual-component catalyst synthesizes N, the method for O-bis- (trimethylsilyl) acetamide |
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|---|---|---|---|
| CN201710677089.9A Division CN107383082A (en) | 2015-09-24 | 2015-09-24 | A kind of composite catalyzing produces high purity N, the method for O-bis- (trimethylsilyl) acetamide |
| CN201710675934.9A Division CN107365325A (en) | 2015-09-24 | 2015-09-24 | A kind of purity is high, the production method of the N of high income, O-bis- (trimethylsilyls) acetamide |
| CN201710677090.1A Division CN107383083A (en) | 2015-09-24 | 2015-09-24 | A kind of production method for improving organosilicon medicine intermediate BSA purity |
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| CN105131026A CN105131026A (en) | 2015-12-09 |
| CN105131026B true CN105131026B (en) | 2017-10-03 |
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| CN201710677090.1A Withdrawn CN107383083A (en) | 2015-09-24 | 2015-09-24 | A kind of production method for improving organosilicon medicine intermediate BSA purity |
| CN201510614597.3A Expired - Fee Related CN105131026B (en) | 2015-09-24 | 2015-09-24 | A kind of dual-component catalyst synthesizes N, the method for O-bis- (trimethylsilyl) acetamide |
| CN201710675934.9A Withdrawn CN107365325A (en) | 2015-09-24 | 2015-09-24 | A kind of purity is high, the production method of the N of high income, O-bis- (trimethylsilyls) acetamide |
| CN201710677089.9A Withdrawn CN107383082A (en) | 2015-09-24 | 2015-09-24 | A kind of composite catalyzing produces high purity N, the method for O-bis- (trimethylsilyl) acetamide |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201710677090.1A Withdrawn CN107383083A (en) | 2015-09-24 | 2015-09-24 | A kind of production method for improving organosilicon medicine intermediate BSA purity |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201710675934.9A Withdrawn CN107365325A (en) | 2015-09-24 | 2015-09-24 | A kind of purity is high, the production method of the N of high income, O-bis- (trimethylsilyls) acetamide |
| CN201710677089.9A Withdrawn CN107383082A (en) | 2015-09-24 | 2015-09-24 | A kind of composite catalyzing produces high purity N, the method for O-bis- (trimethylsilyl) acetamide |
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| CN (4) | CN107383083A (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1793307U (en) * | 1959-04-30 | 1959-08-13 | Georg Westphal | DEVICE FOR MALT CRUSHING. |
| EP0937730A2 (en) * | 1998-02-19 | 1999-08-25 | Wacker Siltronic Gesellschaft für Halbleitermaterialien Aktiengesellschaft | Process for preparing silylated carboxylic acid amides |
| GB2361477A (en) * | 2000-03-29 | 2001-10-24 | Atofina | Semi-continuous process for preparing bis-silyl carboxamides |
| CN1699375A (en) * | 2004-05-20 | 2005-11-23 | 孙友璋 | Process for preparing N,O-bis tri silicyl trifluoroacetamide |
| CN1699308A (en) * | 2004-05-20 | 2005-11-23 | 孙友璋 | Process for preparing N,O-bis(trimethylsilyl)acetamide |
-
2015
- 2015-09-24 CN CN201710677090.1A patent/CN107383083A/en not_active Withdrawn
- 2015-09-24 CN CN201510614597.3A patent/CN105131026B/en not_active Expired - Fee Related
- 2015-09-24 CN CN201710675934.9A patent/CN107365325A/en not_active Withdrawn
- 2015-09-24 CN CN201710677089.9A patent/CN107383082A/en not_active Withdrawn
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1793307U (en) * | 1959-04-30 | 1959-08-13 | Georg Westphal | DEVICE FOR MALT CRUSHING. |
| EP0937730A2 (en) * | 1998-02-19 | 1999-08-25 | Wacker Siltronic Gesellschaft für Halbleitermaterialien Aktiengesellschaft | Process for preparing silylated carboxylic acid amides |
| GB2361477A (en) * | 2000-03-29 | 2001-10-24 | Atofina | Semi-continuous process for preparing bis-silyl carboxamides |
| CN1699375A (en) * | 2004-05-20 | 2005-11-23 | 孙友璋 | Process for preparing N,O-bis tri silicyl trifluoroacetamide |
| CN1699308A (en) * | 2004-05-20 | 2005-11-23 | 孙友璋 | Process for preparing N,O-bis(trimethylsilyl)acetamide |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105131026A (en) | 2015-12-09 |
| CN107383082A (en) | 2017-11-24 |
| CN107383083A (en) | 2017-11-24 |
| CN107365325A (en) | 2017-11-21 |
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