US3109000A - O-benzoylthiamine bisulfide - Google Patents
O-benzoylthiamine bisulfide Download PDFInfo
- Publication number
- US3109000A US3109000A US3109000DA US3109000A US 3109000 A US3109000 A US 3109000A US 3109000D A US3109000D A US 3109000DA US 3109000 A US3109000 A US 3109000A
- Authority
- US
- United States
- Prior art keywords
- benzoylthiamine
- thiamine
- disulfide
- mixture
- percent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- SANDDEZKGWNINE-UHFFFAOYSA-M 2-[3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl]ethyl benzoate;chloride Chemical compound [Cl-].S1C=[N+](CC=2C(=NC(C)=NC=2)N)C(C)=C1CCOC(=O)C1=CC=CC=C1 SANDDEZKGWNINE-UHFFFAOYSA-M 0.000 title description 8
- RWSOTUBLDIXVET-UHFFFAOYSA-M hydrosulfide Chemical compound [SH-] RWSOTUBLDIXVET-UHFFFAOYSA-M 0.000 title 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
- IWXAZSAGYJHXPX-BCEWYCLDSA-N [(E)-4-[(4-amino-2-methylpyrimidin-5-yl)methyl-formylamino]-3-[[(E)-2-[(4-amino-2-methylpyrimidin-5-yl)methyl-formylamino]-5-benzoyloxypent-2-en-3-yl]disulfanyl]pent-3-enyl] benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC/C(SS\C(CCOC(=O)C=1C=CC=CC=1)=C(/C)N(CC=1C(=NC(C)=NC=1)N)C=O)=C(/C)N(C=O)CC1=CN=C(C)N=C1N IWXAZSAGYJHXPX-BCEWYCLDSA-N 0.000 description 30
- 239000000203 mixture Substances 0.000 description 20
- HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 14
- 229960003495 thiamine Drugs 0.000 description 14
- 235000019157 thiamine Nutrition 0.000 description 14
- 239000011721 thiamine Substances 0.000 description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical class CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 description 12
- 229960000344 Thiamine hydrochloride Drugs 0.000 description 10
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 10
- 235000019190 thiamine hydrochloride Nutrition 0.000 description 10
- 239000011747 thiamine hydrochloride Substances 0.000 description 10
- 235000019156 vitamin B Nutrition 0.000 description 10
- 239000011720 vitamin B Substances 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 229930003270 Vitamin B Natural products 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 8
- PASDCCFISLVPSO-UHFFFAOYSA-N Benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 210000000936 Intestines Anatomy 0.000 description 4
- GFEGEDUIIYDMOX-KBNZVFGVSA-N N-[(4-amino-2-methylpyrimidin-5-yl)methyl]-N-[(Z)-3-[[(E)-2-[(4-amino-2-methylpyrimidin-5-yl)methyl-formylamino]-5-hydroxypent-2-en-3-yl]disulfanyl]-5-hydroxypent-2-en-2-yl]formamide Chemical compound C=1N=C(C)N=C(N)C=1CN(C=O)C(\C)=C(CCO)/SSC(\CCO)=C(/C)N(C=O)CC1=CN=C(C)N=C1N GFEGEDUIIYDMOX-KBNZVFGVSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M NaHCO3 Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000008366 buffered solution Substances 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 230000004059 degradation Effects 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 230000002255 enzymatic Effects 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- 239000011630 iodine Substances 0.000 description 4
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 108010093489 thiaminase II Proteins 0.000 description 4
- 229960001385 thiamine disulfide Drugs 0.000 description 4
- 241000193741 Aneurinibacillus aneurinilyticus Species 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- 229960003563 Calcium Carbonate Drugs 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000227676 Paenibacillus thiaminolyticus Species 0.000 description 2
- 210000002700 Urine Anatomy 0.000 description 2
- 229940029983 VITAMINS Drugs 0.000 description 2
- 241000410737 Verasper moseri Species 0.000 description 2
- 208000007642 Vitamin B Deficiency Diseases 0.000 description 2
- 229940021016 Vitamin IV solution additives Drugs 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- CHIHQLCVLOXUJW-UHFFFAOYSA-N benzoic anhydride Chemical compound C=1C=CC=CC=1C(=O)OC(=O)C1=CC=CC=C1 CHIHQLCVLOXUJW-UHFFFAOYSA-N 0.000 description 2
- 230000036765 blood level Effects 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 235000013339 cereals Nutrition 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 150000002019 disulfides Chemical class 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L na2so4 Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000035479 physiological effects, processes and functions Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- MIMJFNVDBPUTPB-UHFFFAOYSA-N potassium hexacyanoferrate(3-) Chemical compound [K+].[K+].[K+].N#C[Fe-3](C#N)(C#N)(C#N)(C#N)C#N MIMJFNVDBPUTPB-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000001187 sodium carbonate Substances 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 150000003544 thiamines Chemical class 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229930003231 vitamins Natural products 0.000 description 2
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Definitions
- This invention relates to O-benzoylthiamiue disulfide which possesses vitamin B -like activity, and to its preparation.
- the compound of this invention possesses vitamin B -like, activity on tests on both animals and human being. Moreover, when orally administering the compound of this invention, it can be seen that blood level of total vitamin B reaches the peak more rapidly, providing longer durability as compared with thiamine hydrochloride, and a larger quantity of free vitamin B is excreted in urine as compared with thiamine hydrochloride. These mean better absorbability of the compound from the intestines than that of thiamine hydrochloride.
- the O-benzoylthiamine of our invention is useful more advantageously than thiamine hydrochloride for the treatment of vitamin B -deficiency symptoms. It is also useful as fortifying agent suitable for use in those instances where a fortifying agent of low water-solubility is desired, for instance, in the enrichment of cereals subjected to rinsing before being cooked.
- the present invention also comprises processes for preparing the O-benzoylthiamine disulfide.
- the O-benzoylthiamine disulfide may be prepared by reacting thiamine disultide with an acylating agent derived from benzoic acid such as chloride, bromide or anhydride in the presence of an acid acceptor such as sodium hydroxide,
- the oxidation mixture of thiamine in alkaline solution in which the thiamine disuliide is formed may also be used.
- the O-benzoylthiamine disuliide may also be prepared by treating O- benzoyltbiamine with an oxidizing agent such as iodine, hydrogen peroxide or potassium ferricyanide, while maintaining the pH of the reaction mixture at alkalinity.
- EXAMPLE 1 ml. of benzoyl chloride was dropped into a stirred suspension of g. of thiamine disulfide in 20 ml. of absolute pyridine at room temperature. The mixture was stirred an additional 3 hours at room temperature and was allowed to stand overnight. "The reaction mixture was concentrated under reduced pressure to remove pyridine and after adding small amounts of 20% aqueous solution of sodium hydroxide, the residue was extracted with chloroform. The extract was washed with small amounts of aqueous solution of sodium bicarbonate and water successively and 'was dried with sodium sulfate. Then the chloroform was removed by evaporation and 20 ml. of benzene was added to the residue whereby O- benzoylthiamine disulfide crystallized out.
- EXALLPLE 2 20 g. of thiamine disulfide was suspended in 200 ml. of water and 3.5 g. of concentrated hydrochloric acid was added to the suspension to dissolve the particles. The mixture was made alkaline-With sodium hydroxide. 10 ml. of benzoyl chloride was dropped into the mixture with stirring on an ice bath. 'During the period, pH of the mixture was kept in alkalinity with 20% aqueous solution of sodium hydroxide. The mixture was stirred for anadditional 3 hours at room temperature. After being adjusted to pH 7, the mixture was extracted with chloroform and the extract was treated as described in Example 1. 18 g. of O-benzoylthiamine disulfide was obtained.
- EXAMPLE 3 The procedure described in Example 1 was followed except that 20 g. of benzoic anhydride was used instead of benzoyl chloride. 16 g. of O-benzoylthiamine disulfide was obtained.
- EXAMPLE 4 24 g. of sodium hydroxide in 140 ml. of water was the mixture at room temperature with stirring. During the period, pH was held in alkalinity with sodium hydroxide. After being allowed to stand overnight,; the reaction mixture was extracted with chloroform and the extract was treated as described in Example 1. 50 g. of O-benzoylthiamine disulfide was obtained.
- EXAMPLE 5 4.5 g. of O-benzoylthiamine in 460 ml. of water was neutralized-with 7 .5 ml. of 4 N sodium hydroxide on an ice bath. Into the solution, was dropped a solution comprising 1.3 g. of iodine, 4 g. ofsodiurn iodide and ml. of water at the same temperature with stirring. As the reaction proceeds, white precipitates appeared. The mixture was stirred for an additional 10 minutes, and the precipitates were extracted with ethyl acetate.
- EXAMPLE 6 i CHa-C N-CH 3 CHzCHzOCOCaHs 2 References Cited in the file of this patent UNITED STATES PATENTS 2,458,453 Warnat Jan. 4, 1949 2,752,348 Matsukawa et a1 June 26, 1956 2,833,768 Fujiwara et a1. May 6, 1958 3,064,400 Ito et a1 Nov. 13, 1962 OTHER REFERENCES Rosenberg: Chemistry and Physiology of the Vitamins (New York, .1945), pages 120, 143-4, 134-5; 100-104. QP 801. V5 R8.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
United States Patent 3,109,000 O-BENZOYLTIHAMINE DISULFHDE Chikataro Kawasaki and Isamu Utsuini, Sakyo-ku, Kyoto,
Tadashi Fujita, Otsu, and Hiroshi Kobayashi, Nishinomiya, Japan, assignors to Tanabe Seiyaku (30., Ltd., Osaka, Japan No Drawing. Filed Aug. 30, 1961, Ser. No. 135,417 Claims priority, application Japan Oct. 5, 1960 1 Claim. (Cl. 260-2565) This invention relates to O-benzoylthiamiue disulfide which possesses vitamin B -like activity, and to its preparation.
It has been known that acid addition salts of thiamine have many deficiencies such as unpleasant odor, low stability, solubility in water or limited absorption upon oral ingestion, etc.
It has also been known that some people have thiaminase, thiamine destroying enzyme in their intestines. Therefore, no effects can be seen on such people by orally administering thiamine acid-addition salts.
According to this invention, we have found that 0 benzoylthiamine disulfide is free of the disadvantages of the above mentioned thiamine acid-addition salt, especially the hydrochloride. The O-benzoylthiamine disulfide of this invention occurs as colorless and odorless crystal melting at 146 to 147 C.
Its structural formula is as follows.
CH3 CH2CH2000C6HS 2 n has been found that O-benzoy-lthiamine disulfide is sparingly soluble in water. The solubilities in distilled water at various temperature are as follows.
TABLE I Solubilities (Percent) by weight/volume Temperature 0.)
3,109,000 Patented Oct. 729, 1963 TABLE II Residual Rate (Percent) in Aqueous Solution (2 mg./cc.) at C.
After 30 minutes After 60 minutes After minutes pH B'IDS BrHCl BTDS B11101 BTDS BiHOl (percent) (percent) (percent) (percent) (percent) (percent) pH 5.04.0: MaeElvains buffered solution. pH 8.0-9.0: Clark-Lubus bufiered solution.
TABLE III Residual Rate (Percent) in Calcium Carbonate Powder (200 mg./g.) [Relative humidity 82% at room temperaturel Substance After 5 After 25 After 40 days days days BlHCl 59 12 6 BTDS 100 94 94 It has been found that O-benzoylthiamine disulfide resists enzymatic degradation with thiaminase more strongly than thiamine hydrochloride on the test as described below.
The mixture of 1 m1. of substrate solution containing 20 of B H01 or 22.8 of BTDS (equivalent to 205 of B HCl), 1 ml. of buffered solution and 3 ml. of the enzymatic solution prepared from cultural medium of Bacillus thiaminolyticus (M.M.) or Bacillus aneurinolyticus (K.A.) was incubated for 1 hour at 37 C., and degradation rate of the substances Was assayed by thiochrorne method.
It has been also found that the compound of this invention possesses vitamin B -like, activity on tests on both animals and human being. Moreover, when orally administering the compound of this invention, it can be seen that blood level of total vitamin B reaches the peak more rapidly, providing longer durability as compared with thiamine hydrochloride, and a larger quantity of free vitamin B is excreted in urine as compared with thiamine hydrochloride. These mean better absorbability of the compound from the intestines than that of thiamine hydrochloride.
From the above facts, the O-benzoylthiamine of our invention is useful more advantageously than thiamine hydrochloride for the treatment of vitamin B -deficiency symptoms. It is also useful as fortifying agent suitable for use in those instances where a fortifying agent of low water-solubility is desired, for instance, in the enrichment of cereals subjected to rinsing before being cooked.
The present invention also comprises processes for preparing the O-benzoylthiamine disulfide. The O-benzoylthiamine disulfide may be prepared by reacting thiamine disultide with an acylating agent derived from benzoic acid such as chloride, bromide or anhydride in the presence of an acid acceptor such as sodium hydroxide,
sodium carbonate, potassium hydroxide, potassium carbonate or pyridine.
As the starting material, the oxidation mixture of thiamine in alkaline solution in which the thiamine disuliide is formed may also be used. Alternatively, the O-benzoylthiamine disuliide may also be prepared by treating O- benzoyltbiamine with an oxidizing agent such as iodine, hydrogen peroxide or potassium ferricyanide, while maintaining the pH of the reaction mixture at alkalinity.
It has been found that the reaction proceedsmost satisfactorily at a pH within the range of 10.0 to 12.0 in an aqueous medium.
The invention is further illustrated by the following examples without being limited thereto.
EXAMPLE 1 ml. of benzoyl chloride was dropped into a stirred suspension of g. of thiamine disulfide in 20 ml. of absolute pyridine at room temperature. The mixture was stirred an additional 3 hours at room temperature and was allowed to stand overnight. "The reaction mixture was concentrated under reduced pressure to remove pyridine and after adding small amounts of 20% aqueous solution of sodium hydroxide, the residue was extracted with chloroform. The extract was washed with small amounts of aqueous solution of sodium bicarbonate and water successively and 'was dried with sodium sulfate. Then the chloroform was removed by evaporation and 20 ml. of benzene was added to the residue whereby O- benzoylthiamine disulfide crystallized out.
Yield, "20 g., :colorless prisms melting at 146147 C., after recrystallizing from 99% ethanol.
Analysis-Calculated for C H OgN S C, 59.21; H, 5.49; N, 14.54. Found: C, 59.39; H, 5.79; N, 14.31.
Di-hydrochloride: Colorless prisms melting at 180"- 181" C. (decomp) Analysis.Calculated for C H OQN S -ZHCI-ZH O: C, 51.88; H, 5.50; N, 12.74. Found: C, 52.02; H, 5.57; N, 12.74. i
EXALLPLE 2 20 g. of thiamine disulfide was suspended in 200 ml. of water and 3.5 g. of concentrated hydrochloric acid was added to the suspension to dissolve the particles. The mixture was made alkaline-With sodium hydroxide. 10 ml. of benzoyl chloride was dropped into the mixture with stirring on an ice bath. 'During the period, pH of the mixture was kept in alkalinity with 20% aqueous solution of sodium hydroxide. The mixture was stirred for anadditional 3 hours at room temperature. After being adjusted to pH 7, the mixture was extracted with chloroform and the extract was treated as described in Example 1. 18 g. of O-benzoylthiamine disulfide was obtained.
EXAMPLE 3 The procedure described in Example 1 was followed except that 20 g. of benzoic anhydride was used instead of benzoyl chloride. 16 g. of O-benzoylthiamine disulfide was obtained.
EXAMPLE 4 24 g. of sodium hydroxide in 140 ml. of water was the mixture at room temperature with stirring. During the period, pH was held in alkalinity with sodium hydroxide. After being allowed to stand overnight,; the reaction mixture Was extracted with chloroform and the extract was treated as described in Example 1. 50 g. of O-benzoylthiamine disulfide was obtained.
EXAMPLE 5 4.5 g. of O-benzoylthiamine in 460 ml. of water was neutralized-with 7 .5 ml. of 4 N sodium hydroxide on an ice bath. Into the solution, was dropped a solution comprising 1.3 g. of iodine, 4 g. ofsodiurn iodide and ml. of water at the same temperature with stirring. As the reaction proceeds, white precipitates appeared. The mixture was stirred for an additional 10 minutes, and the precipitates were extracted with ethyl acetate.
After the extract was washed with water and dried, ethyl acetate was evaporated at a reduced pressure and 30 m1. of benzene was added to the residue whereby O- benzoylthiamine disulfide crystallized out.
Yield 2.9 g., 75.3% of theory.
EXAMPLE 6 i CHa-C N-CH 3 CHzCHzOCOCaHs 2 References Cited in the file of this patent UNITED STATES PATENTS 2,458,453 Warnat Jan. 4, 1949 2,752,348 Matsukawa et a1 June 26, 1956 2,833,768 Fujiwara et a1. May 6, 1958 3,064,400 Ito et a1 Nov. 13, 1962 OTHER REFERENCES Rosenberg: Chemistry and Physiology of the Vitamins (New York, .1945), pages 120, 143-4, 134-5; 100-104. QP 801. V5 R8.
Hickinbottom: Reactions of Organic Compounds (London, 1948), pages 96-99.
Williams et al.: The Biochemistry of B Vitamins (New York, 1950), pages 361-370, QP 801 V5 B6.
Zima et'al.: Die Naturwissenschaften, 41, 214 (1954).
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3109000A true US3109000A (en) | 1963-10-29 |
Family
ID=3452176
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US3109000D Expired - Lifetime US3109000A (en) | O-benzoylthiamine bisulfide |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US3109000A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3183232A (en) * | 1963-02-06 | 1965-05-11 | Shionogi & Co | O, s-disubstituted thiol-type thiamines |
| US3472735A (en) * | 1966-04-28 | 1969-10-14 | Takeda Chemical Industries Ltd | Preservation of semen |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2458453A (en) * | 1949-01-04 | Process for producing thiamin | ||
| US2752348A (en) * | 1956-06-26 | Cxnhs | ||
| US2833768A (en) * | 1958-05-06 | Compounds with vitamin brlike activity | ||
| US3064400A (en) * | 1959-11-02 | 1962-11-20 | Logan W Johnson | Model trimmer |
-
0
- US US3109000D patent/US3109000A/en not_active Expired - Lifetime
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2458453A (en) * | 1949-01-04 | Process for producing thiamin | ||
| US2752348A (en) * | 1956-06-26 | Cxnhs | ||
| US2833768A (en) * | 1958-05-06 | Compounds with vitamin brlike activity | ||
| US3064400A (en) * | 1959-11-02 | 1962-11-20 | Logan W Johnson | Model trimmer |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3183232A (en) * | 1963-02-06 | 1965-05-11 | Shionogi & Co | O, s-disubstituted thiol-type thiamines |
| US3472735A (en) * | 1966-04-28 | 1969-10-14 | Takeda Chemical Industries Ltd | Preservation of semen |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| SU1516011A3 (en) | Method of producing 5-/4-(4-acetyl-3-hydroxy-2-propylbenzyloxy)benzyl/-tetrazole | |
| CA1121825A (en) | 2-(2-thenoylthio)-propionylglycine: method for its preparation and pharmaceutical formulations containing said compound | |
| US4226861A (en) | N-Lower-alkyl 3-phenoxy-1-azetidinecarboxamides | |
| DE3500179A1 (en) | ACETYLERYTHROMYCINSTEARATE, METHOD FOR THE PRODUCTION THEREOF AND MEDICINAL PRODUCT CONTAINING THIS | |
| DE2822789A1 (en) | ANALGETIC COMPOUNDS, THE PROCESS FOR THEIR PRODUCTION AND PHARMACEUTICAL COMPOSITIONS WITH THESE ANALGETIC COMPOUNDS | |
| GB2184653A (en) | Dementia improving and therapeutic agents | |
| US3830824A (en) | Physiological organic acid silver allantoinates | |
| US3109000A (en) | O-benzoylthiamine bisulfide | |
| US3632806A (en) | Novel n - pyridylmethylidene - homo-cysteine thiolactone compound and the preparation thereof | |
| Scheindlin et al. | The action of riboflavin on folic acid | |
| Burton | Antibiotics from penicillia | |
| PL95766B1 (en) | METHOD OF MANUFACTURING NEW PHARMACOLOGICALLY ACTIVE DERIVATIVES OF BENZYHYDROL SUBSTITUTED IN THE-ALPHA POSITION | |
| US4153710A (en) | N-(4-[2-(pyrazole-1-carbonamide)-ethyl]-benzenesulphonyl)-urea | |
| DE2721987C2 (en) | p-Acetamidophenyl diethylaminoacetate, its pharmacologically acceptable addition salts, process for their production and pharmaceuticals with these compounds as active ingredients | |
| US3903285A (en) | Method for treating parkinsonism | |
| US3271398A (en) | Orotic acid salt of 4-amino-5-imidazolecarboxamide | |
| DE2518986A1 (en) | 8-AMINOMETHYLISOFLAVONE DERIVATIVES SUBSTITUTED IN 7 POSITION AND METHOD FOR THEIR PRODUCTION | |
| US2419230A (en) | Therapeutic compositions and method of preparing same | |
| US3825590A (en) | Hydroxy-hydroxymethyl-substituted phenylalanine derivatives | |
| KR870010036A (en) | Process for preparing organozinc complex and pharmaceutical composition containing same as active ingredient | |
| DE2541932A1 (en) | PIPERIDINE DERIVATIVES, THE PROCESS FOR THEIR MANUFACTURING AND THE PHARMACEUTICAL PRODUCTS CONTAINING THEM | |
| US4182775A (en) | Benzoic acids and process for their preparation | |
| US2645638A (en) | Penicillin salts of nu-methyl-(2-hydroxy-1, 2-diphenylethyl)-amine | |
| DE1543764A1 (en) | Phenoxy-substituted alkanoic acids and processes for their preparation | |
| DE1934551B2 (en) | 5- [2- (Pheny! Amino) 3-pyridyl] tetrazoles, process for their preparation and pharmaceuticals containing them |