RU1473300C - Method of synthesis of 4-benzoylamino-3-oxotetrahydrothiophene - Google Patents
Method of synthesis of 4-benzoylamino-3-oxotetrahydrothiophene Download PDFInfo
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- RU1473300C RU1473300C SU4253989A RU1473300C RU 1473300 C RU1473300 C RU 1473300C SU 4253989 A SU4253989 A SU 4253989A RU 1473300 C RU1473300 C RU 1473300C
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- RU
- Russia
- Prior art keywords
- yield
- benzoylamino
- carried out
- acetic acid
- pri
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 18
- NIXOCXSONMLYOE-UHFFFAOYSA-N n-(4-oxothiolan-3-yl)benzamide Chemical compound C=1C=CC=CC=1C(=O)NC1CSCC1=O NIXOCXSONMLYOE-UHFFFAOYSA-N 0.000 title description 6
- 230000015572 biosynthetic process Effects 0.000 title description 2
- 238000003786 synthesis reaction Methods 0.000 title description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 27
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 claims abstract description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 10
- -1 4-benzoylamino-3-hydroxy-2-methoxycarbonyl-2,5-dihydrothiophene sodium salt Chemical compound 0.000 claims abstract description 6
- 238000006114 decarboxylation reaction Methods 0.000 claims abstract description 3
- 230000007062 hydrolysis Effects 0.000 claims abstract description 3
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 3
- 159000000000 sodium salts Chemical class 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract description 4
- 239000000047 product Substances 0.000 abstract description 2
- 239000007795 chemical reaction product Substances 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 150000002391 heterocyclic compounds Chemical class 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 229930003756 Vitamin B7 Natural products 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000011735 vitamin B7 Substances 0.000 description 1
- 235000011912 vitamin B7 Nutrition 0.000 description 1
Landscapes
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
Description
Изобретение относится к органической химии, а именно к способам получения 4-бензоиламино-3-оксотетрагидротиофена (I), который является промежуточным веществом в синтезе биотина (витамина Н). The invention relates to organic chemistry, and in particular to methods for producing 4-benzoylamino-3-oxotetrahydrothiophene (I), which is an intermediate in the synthesis of biotin (vitamin H).
Целью изобретения является повышение выхода 4-бензоиламино-3-оксотетрагидротиофена. The aim of the invention is to increase the yield of 4-benzoylamino-3-oxotetrahydrothiophene.
Поставленная цель достигается путем проведения процесса гидролиза и декарбоксилирования в среде уксусной кислоты в присутствии хлористого лития и воды при соотношении уксусной кислоты, хлористого лития и воды (66,5-74,0): (8,75-9,25): (10,0-13,9) на 1 моль натриевой соли 4-бензоиламино-3-окси-2-метоксикарбонил-2,5-дигид- ротиофена при 148-150оС в течение 5-6 ч.This goal is achieved by carrying out the process of hydrolysis and decarboxylation in an acetic acid medium in the presence of lithium chloride and water with a ratio of acetic acid, lithium chloride and water (66.5-74.0): (8.75-9.25): (10 , 0-13.9) per 1 mol of the sodium salt of 4-benzoylamino-3-hydroxy-2-methoxycarbonyl-2,5-dihydrothiophene at 148-150 о С for 5-6 hours.
П р и м е р 1. 4-Бензоиламино-3-оксотетрагидротиофен (I). PRI me R 1. 4-Benzoylamino-3-oxotetrahydrothiophene (I).
К 410 мл (7,20 моль) уксусной кислоты добавляют 37,4 г (0,85 моль) хлористого лития безводного 24,0 мл (1,33 моль) воды и нагревают при перемешивании до 80оС, затем прибавляют 30 г (0,099 моль) натриевой соли 4-бензоиламино-3-окси-2-метоксикарбонил-2,5-дигидротиофена, повышают температуру обогрева до 150оС и при этой температуре размешивают 5 ч. Охлаждают, отгоняют уксусную кислоту при 50оС/100 мм рт.ст. К остатку приливают 1,0 л хлороформа и 0,3 л воды, встряхивают, отделяют водный слой и экстрагируют его хлороформом 5 раз по 100 мл. Объединеные хлороформные экстракты промывают 200 мл воды, сушат над 100 г сернокислого натрия в течение 16-18 ч. Осушитель отфильтровывают, промывают 150 мл хлороформа, хлороформ упаривают в вакууме при 35оС/100 мм рт.ст., для удаления остатков уксусной кислоты добавляют два раза по 100 мл бензола и отгоняют бензол при 40оС/100 мм рт. ст. К остатку приливают 140 мл этилового спирта, нагревают при кипении до образования раствора и выдерживают при 3-5оС в течение 16-18 ч. Выделившийся осадок отфильтровывают, промывают 50 мл диэтилового эфира. Фильтрат и промывной эфир концентрируют до 1/4 остаточного объема и выдерживают при -10оС 16-18 ч. Образовавшийся осадок отфильтровывают и промывают 30 мл диэтилового эфира. Общий выход 4-бензоиламино-3-оксотетрагидротиофена 17,6 г (85%), т.пл. 128-129оС. Смешанная проба с заведомо чистым образцом соединения I не дает депрессии температуры плавления.To 410 ml (7.20 mol) of acetic acid was added 37.4 g (0.85 mol) of anhydrous lithium chloride, 24.0 ml (1.33 mol) of water and heated with stirring to 80 ° C, then added 30 g of ( 0.099 mole) of the sodium salt of 4-benzoylamino-3-hydroxy-2-methoxycarbonyl-2,5-dihydrothiophene, increase the heating temperature to 150 ° C and stirred at this temperature for 5 hours. After cooling, acetic acid was distilled off at 50 ° C / 100 mm Hg 1.0 L of chloroform and 0.3 L of water are added to the residue, shaken, the aqueous layer is separated and extracted with chloroform 5 times in 100 ml. The combined chloroform extracts were washed with 200 ml of water, dried over 100 grams sodium sulfate for 16-18 hours. The desiccant was filtered off, washed with 150 ml of chloroform, chloroform was evaporated in vacuo at 35 ° C / 100 mm Hg, to remove the acetic acid residue was added twice with 100 ml of benzene and the benzene was distilled off at 40 ° C / 100 mm Hg. Art. To the residue is poured 140 ml of ethanol is heated under reflux to form a solution and kept at 3-5 ° C for 16-18 hours. The separated precipitate was filtered off, washed with 50 ml of diethyl ether. The filtrate and ether wash was concentrated to a residual volume of 1/4 and kept at -10 ° C 16-18 h. The resulting precipitate was filtered off and washed with 30 ml of diethyl ether. The total yield of 4-benzoylamino-3-oxotetrahydrothiophene 17.6 g (85%), so pl. 128-129 about C. A mixed sample with a knownly pure sample of compound I does not give a melting point depression.
П р и м е р 2. Процесс проводят аналогично примеру 1, но выдержка при кипении 4 ч. Выход 57%. PRI me R 2. The process is carried out analogously to example 1, but the exposure at boiling for 4 hours. Yield 57%.
П р и м е р 3. Процесс проводят аналогично примеру 1, но выдержка при кипении 8 ч. Выход 62,5%. PRI me R 3. The process is carried out analogously to example 1, but the shutter speed is 8 hours. The yield is 62.5%.
П р и м е р 4. Процесс проводят аналогично примеру 1, но при температуре 160оС. Выход 65,5%.PRI me R 4. The process is carried out analogously to example 1, but at a temperature of 160 about C. The yield of 65.5%.
П р и м е р 5. Процесс проводят аналогично примеру 1, но хлористого лития берут 45,7 г (1,08 моль). Выход 70%. PRI me R 5. The process is carried out analogously to example 1, but lithium chloride take of 45.7 g (1.08 mol). Yield 70%.
П р и м е р 6. Процесс проводят аналогично примеру 1, но воды берут 32 мл (1,76 моль). Выход 80%. PRI me R 6. The process is carried out analogously to example 1, but the water take 32 ml (1.76 mol). Yield 80%.
П р и м е р 7. Процесс проводят аналогично примеру 1, но хлористого лития берут 30 г (0,70 моль). Выход 63%. PRI me R 7. The process is carried out analogously to example 1, but lithium chloride take 30 g (0.70 mol). Yield 63%.
П р и м е р 8. Процесс проводят аналогично примеру 1, но в среде 460 мл диметилформамида. Выход 43%. PRI me R 8. The process is carried out analogously to example 1, but in the environment of 460 ml of dimethylformamide. Yield 43%.
П р и м е р 9. Процесс проводят аналогично примеру 1, но в среде 460 мл диметилсульфоксида. Выход 23%. PRI me R 9. The process is carried out analogously to example 1, but in the environment of 460 ml of dimethyl sulfoxide. Yield 23%.
П р и м е р 10. Процесс проводят аналогично примеру 1, но выдержку ведут при 135-137оС. Выход 55%.PRI me R 10. The process is carried out analogously to example 1, but the exposure is carried out at 135-137 about C. Yield 55%.
П р и м е р 11. Процесс проводят аналогично примеру 1, но воды берут 15 мл (0,83 моль). Выход 55%. PRI me R 11. The process is carried out analogously to example 1, but water is taken 15 ml (0.83 mol). Yield 55%.
П р и м е р 12. Процесс проводят аналогично примеру 1, но уксусной кислоты берут 200 мл (3,46 моль). Выход 47,5%. PRI me R 12. The process is carried out analogously to example 1, but acetic acid is taken 200 ml (3.46 mol). Yield 47.5%.
П р и м е р 13. Процесс проводят аналогично примеру 1, но уксусной кислоты берут 500 мл (8,65 моль). Выход 78%. PRI me R 13. The process is carried out analogously to example 1, but take acetic acid 500 ml (8.65 mol). Yield 78%.
Таким образом предлагаемый способ получения 4-бензоиламино-3-оксотетрагидротиофена позволяет повысить выход целевого продукта на 10-15% по сравнению с прототипом и, кроме того, отказаться от использования соляной кислоты, что упрощает аппаратурное оформление процесса. Thus, the proposed method for producing 4-benzoylamino-3-oxotetrahydrothiophene allows to increase the yield of the target product by 10-15% compared with the prototype and, in addition, to abandon the use of hydrochloric acid, which simplifies the hardware design of the process.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SU4253989 RU1473300C (en) | 1987-06-01 | 1987-06-01 | Method of synthesis of 4-benzoylamino-3-oxotetrahydrothiophene |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SU4253989 RU1473300C (en) | 1987-06-01 | 1987-06-01 | Method of synthesis of 4-benzoylamino-3-oxotetrahydrothiophene |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| RU1473300C true RU1473300C (en) | 1995-02-09 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SU4253989 RU1473300C (en) | 1987-06-01 | 1987-06-01 | Method of synthesis of 4-benzoylamino-3-oxotetrahydrothiophene |
Country Status (1)
| Country | Link |
|---|---|
| RU (1) | RU1473300C (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6294580B1 (en) | 1996-02-28 | 2001-09-25 | Glaxo Wellcome Inc. | Substituted 4-hydroxy-phenylalcanoic acid derivatives with agonist activity to PPAR-gamma |
-
1987
- 1987-06-01 RU SU4253989 patent/RU1473300C/en active
Non-Patent Citations (1)
| Title |
|---|
| Harris.S.A. et al., Biotin. IV.Synthesis oF. 4-benzamido-3-hetotetrahudrothiophene. - J.Am.Chem.Soc, 1944, vol.66, N 10, p.1757-1759. * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6294580B1 (en) | 1996-02-28 | 2001-09-25 | Glaxo Wellcome Inc. | Substituted 4-hydroxy-phenylalcanoic acid derivatives with agonist activity to PPAR-gamma |
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