US2468401A - Process of producing substituted 2-amino-thiazoles - Google Patents
Process of producing substituted 2-amino-thiazoles Download PDFInfo
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- US2468401A US2468401A US713391A US71339146A US2468401A US 2468401 A US2468401 A US 2468401A US 713391 A US713391 A US 713391A US 71339146 A US71339146 A US 71339146A US 2468401 A US2468401 A US 2468401A
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- amino
- thiourea
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- sulfur
- oxidizing agent
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/40—Unsubstituted amino or imino radicals
Definitions
- the present invention relates to improvements in the preparation of substituted 2-amino-thiazoles.
- thiazole from a ketone and thiourea can be accomplished by an oxidative process.
- reaction was carried out as follows: Two-tenths mole of acetophenone and 0.4 mole of thiourea were treated with the indicated amount of the oxidizing agent, and the reaction mixture heated overnight on the steambath.
- the Z-amino--phenylthiazole and sulfur were recovered as described by applicants in the Journal of the American Chemical Society, 67, 2242 (1945). lhe thiazole obtained was compared directly with the 2-amino-4-phenylthiazole produced in accordance with the method described in the copending concurrently filed application.
- elementary sulfur Was used as the oxidizing agent the reaction mixture was refluxed in Dowtherm, a commercial mixture of diphenyl ether and biphenyl, B. P. ca. 240.
- oxidizing agents are capable of effecting the desired reaction between a ketone such as acetophenone and thiourea.
- a ketone such as acetophenone and thiourea.
- corresponding Z-amino-thiazoles are formed by the same reaction, and in good yield.
- the products are useful as intermediates in the manufacture of pharmaceutical preparations.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Description
Patented Apr. 26, 1949 UNITED STATES PATENT OFFICE PROCESS OF PRODUCING SUBSTITUTED Z-AMINO-THIAZOLES No Drawing. Application November 30, 1946, Serial No. 713,391
8 Claims.
The present invention relates to improvements in the preparation of substituted 2-amino-thiazoles.
In our copending application Serial No. 713,392, filed concurrently with the present application,
thiazole from a ketone and thiourea can be accomplished by an oxidative process.
In each of the reactions carried out a quantity of sulfur was observed among the by-products. With the exception of reaction 7 (for we have described processes for the production of identification of reactions see the table) in which substituted Z-amino-thiazoles by a reaction benitric acid was used as an oxidizing agent, this tween ketones and thiourea or selenourea in the sulfur could have been formed either from the presence of halogens such as chlorine, bromine reduction of the oxidizing agent or from oxidaand iodine. 10 tion of thiourea. When sulfuryl chloride (reac- It has now been found that it is not necessary tion 1) or when chlorosulfonic acid (reaction 2) to have a halogen present, provided that some was used as the oxidizing agent, very little sulfur other substance be present that will accept two was formed and the yield of thiazole was good. electrons for each molecule of 2-aminothiazole When thionyl chloride (reactions 3a and 3b) or formed. Such a reaction will take the following when sulfur monochloride (reaction 4) was used form: as the oxidizing agent, a large quantity of sulfur was obtained and a good yield of thiazole was also observed. In these cases, most of the sulfur Ewen, SE was probably produced by reduction of the oxidizing agent as follows: 12k (LNH, 211+ 2c mo SOClz 2H+ 28 /2 /2 2HC1 S2012 2H+ 26 2s 2Hc1 When sulfur trioxide (reaction 5), sulfuric acid Accordingly, it is an object of the present in- (reaction 6) or nitric acid (reaction 7) was used vention to prepare substituted Z-aminothiazoles as the oxidizing agent, an appreciable amount of by thus reacting suitable ketones with thiourea sulfur was formed in each reaction, and in each and OXidiZing agentscase the yield of 2-amino-4-phenylthiazole was p s of s ype of reaction involved the lower than that obtained with the first four oxiuse of a considerable variety of oxidizing agents, dizing agents. In these cases, it appears that namely, sulfuryl chloride, chlorosulfom'c acid, 30 two competing reactions are taking place: (1) thionyl chloride, sulfur monochloride, sulfur The reaction of acetophenone with thiourea and trioxide, sulfuric acid, nitric acid, and sulfur. In the oxidizing agent to form the thiazole, and (2) each case a considerable quan ty of 2-amino-4- the direct oxidation of thiourea to form sulfur. phenylthiazole was obtained (see the table, here- This mutual destruction of thiourea and the inbelow). Since some of the above reagents oxidizing agent could account for the lower yields could not possibly produce an intermediary aof 2-amino-4-phenylthiazole obtained in reachaloketone, it is evident that the formation of a tions 5, 6, and 'I.
TABLE Summary of reactions 1 Products Reaction Oxidizoxidiz' 2-Amin0-4- number ingagent gg phenyltlnazole sulfurgl gbggrg e g g. Per cent 0.2 28.5 81 0.5 s02, H 0, H01.
.2 22 63 0.5 Do. .2 2s 63 3.7 Do. .1 15.5 88 2.2 Do. .2 27 76 12 H10, H01. .2 11.5 32 5 SO2,H:O. .2 15 43 7 Do. (excess) 4 11 2 Oxides ofnitrogeu.
1 In each reaction 0.2 mole of acetpphenone and 0.4 mole of thiourea were used. 9 Yield based on ketone or oxidizing agent. I Yield based on oxidizing agent only.
In each case the reaction was carried out as follows: Two-tenths mole of acetophenone and 0.4 mole of thiourea were treated with the indicated amount of the oxidizing agent, and the reaction mixture heated overnight on the steambath. The Z-amino--phenylthiazole and sulfur were recovered as described by applicants in the Journal of the American Chemical Society, 67, 2242 (1945). lhe thiazole obtained was compared directly with the 2-amino-4-phenylthiazole produced in accordance with the method described in the copending concurrently filed application. When elementary sulfur Was used as the oxidizing agent the reaction mixture was refluxed in Dowtherm, a commercial mixture of diphenyl ether and biphenyl, B. P. ca. 240.
From the foregoing, it is evident that oxidizing agents are capable of effecting the desired reaction between a ketone such as acetophenone and thiourea. When using some of the other enumerated ketones, corresponding Z-amino-thiazoles are formed by the same reaction, and in good yield.
The products are useful as intermediates in the manufacture of pharmaceutical preparations.
Applicants claim:
1. Process of producing substituted 2-aminothiazoles which comprises reacting a ketone having the 0 'ioH2- grouping with thiourea in the presence of a substance capable of accepting two electrons per molecule of the substituted 2 amino thiazole formed.
2. Process of producing substituted 2-aminothiazoles which comprises reacting a ketone having the grouping with thiourea in the presence of an oxidizing agent.
3. Process of producing 2-amino-4-phenylthiazole which comprises reacting acetophenone with thiourea in the presence of an oxidizing agent.
l. Process of producing substituted Z-aminothiazoles which comprises reacting one mole of a ketone having the o on2- grouping with at least two moles of thiourea in the presence of a substance capable of accepting two electrons for each molecule of the substituted 2- amino-thiazole formed.
5. Process of producing Z-arninol-phenylthiazole which comprises reacting 1 mole of acetophenone with 2 moles of thiourea in the presence of a sulfur-containing oxidizing agent.
6. Process of producing 2-amino-4-pheny1- thiazole which comprises reacting 1 mole of acetophenone with 2 moles of thiourea in the presence of chlorosulfonic acid.
7. Process of producing 2-amino-4-phenylthiazole which comprises reacting 1 mole of acetophenone with 2 moles of thiourea in the presence of sulfuryl chloride.
REFERENCES CITED The following references are of record in the file of this patent:
FOREIGN PATENTS Country Date Great Britain July 2, 1943 OTHER REFERENCES Annalen, vol. 29, pp. 31-37. Organic synthesis, vol. 19 (1930), pp. 10-11.
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Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US713391A US2468401A (en) | 1946-11-30 | 1946-11-30 | Process of producing substituted 2-amino-thiazoles |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US713391A US2468401A (en) | 1946-11-30 | 1946-11-30 | Process of producing substituted 2-amino-thiazoles |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US2468401A true US2468401A (en) | 1949-04-26 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US713391A Expired - Lifetime US2468401A (en) | 1946-11-30 | 1946-11-30 | Process of producing substituted 2-amino-thiazoles |
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| US (1) | US2468401A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2709172A (en) * | 1951-12-17 | 1955-05-24 | Searle & Co | 2, 4-diaminothiazole derivatives substituted in the 5-position by an aromatic hydrocarbon radical |
| US4225719A (en) * | 1978-12-29 | 1980-09-30 | Eastman Kodak Company | Process for preparing 2-amino-5-formylthiazole and its hydrobromide salt |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB554428A (en) * | 1942-05-08 | 1943-07-02 | Roche Products Ltd | Improvements in the bromination of ketones |
-
1946
- 1946-11-30 US US713391A patent/US2468401A/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB554428A (en) * | 1942-05-08 | 1943-07-02 | Roche Products Ltd | Improvements in the bromination of ketones |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2709172A (en) * | 1951-12-17 | 1955-05-24 | Searle & Co | 2, 4-diaminothiazole derivatives substituted in the 5-position by an aromatic hydrocarbon radical |
| US4225719A (en) * | 1978-12-29 | 1980-09-30 | Eastman Kodak Company | Process for preparing 2-amino-5-formylthiazole and its hydrobromide salt |
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