JPH0873445A - Production of 1,2,3-triazole - Google Patents

Abstract

PURPOSE: To easily and safely obtain the subject compound useful as an intermediate for antibiotics, by reaction between a vinyl compound and an azide compound. CONSTITUTION: This compound, 1,2,3-triazole, of formula II is obtained by the reaction between a vinyl compound of formula I ((n) is 1-2; R<1> is a lower alkyl, lower alkenyl or aryl) and an azide compound of formula R<2> -N3 (R<2> is a lower alkyl-substituted silyl or alkali metal) in a solvent (e.g. DMF) in the presence, if needed, of a base (e.g. diisopropylethylamine) at 20 deg.C to the boiling point of the solvent for 10min to 72h. Compared with the conventional method using an explosive, flammable acetylene gas, there is no need of any special equipment or particular safety operation, also obviating the necessity of such a process as to eliminate the substituent(s) from a substituted 1,2,3-triazole derivative, therefore being industrially advantageous.

Description

Detailed Description of the Invention

[0001]

The present invention relates to an intermediate raw material of an antibiotic useful as a medicine, which is represented by the chemical formula [III]
The present invention relates to a novel method for producing 2,3-triazole.

[0002]

[Prior Art and Problems to be Solved by the Invention]
As a method for synthesizing a substituted 1,2,3-triazole derivative, there is known a method in which a hydrazoic acid or an azide compound is reacted with acetylene or an acetylene compound (complementary heterocyclic chemistry, 5 , 708-710 (1984)) or a method of reacting polyvinylbenzyl azide with phenylvinyl sulfoxide (Journal of Polymer Science: Polymer Chemistry Edition, 2).
2 , 2293-2294 (1984)) and the like are known.

Further, as a method for synthesizing 1,2,3-triazole itself, a method for reductively debenzylating 1-benzyl-1,2,3-triazole obtained by the above method (JP-A-1 -143861 publication), 1,
2,3-triazole-4-carboxylic acid, 1,2,3-
Method of decarboxylation by heating triazole-4,5-dicarboxylic acid (Chemical Abstracts, 83 (11), 9
7148), a method for desulfurizing and reducing 5-mercapto-1,2,3-triazole (JP-A-63-230675), a method for dehydrating and ring-closing glyoxal monooxime hydrazone (JP-A-6-41092), or A method of deaminating 2-amino-1,2,3-triazole (Berichte., 42 , 659 (1909)) and the like are known.

However, in these production methods, acetylene which is an explosive and flammable gas is used when synthesizing the triazole ring, and special equipment, safe operation, etc. are required for industrial handling. There is a problem as an industrial manufacturing method. On the other hand, the method of synthesizing 1,2,3-triazole by removing the substituent from the substituted 1,2,3-triazole derivative requires a long number of steps, and violent conditions such as high temperature and high pressure may be required. It is necessary and there is a problem in economy.

[0005]

Therefore, the inventors of the present invention have conducted intensive studies on a method for producing a compound of the formula [III], and as a result, completed the present invention. That is, the general formula [I]

[Chemical 3] [In the formula, n indicates 1 to 2, R ¹ represents a lower alkyl group, lower alkenyl group or an aryl group. And a vinyl compound represented by the general formula [II] R ² —N ₃ [II] [In the formula, R ² represents a silyl group substituted with the same or different lower alkyl group or an alkali metal. ] The chemical formula [III] characterized by reacting with an azide compound represented by

[Chemical 4] The present invention provides a method for producing 1,2,3-triazole represented by

Then, this is represented by the following general reaction process formula.

[Chemical 5]

In the present invention, the lower alkyl group represented by R ¹ is, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group. Examples thereof include linear or branched alkyl groups having 1 to 6 carbon atoms such as a group, a pentyl group, a neopentyl group, and a hexyl group. Also,
Examples of the lower alkenyl group include carbon numbers such as vinyl group, 1-propenyl group, isopropenyl group, allyl group, 2-butenyl group, 2-methyl-2-butenyl group, 3-pentenyl group and 4-hexenyl group. Examples thereof include 2 to 6 linear or branched alkenyl groups. Furthermore, as the aryl group, for example, a phenyl group, a p-tolyl group,
Examples thereof include a benzthiazoyl group.

In the present invention, the silyl group substituted by the same or different lower alkyl group represented by R ² includes, for example, trimethylsilyl group, ethyldimethylsilyl group, t-butyldimethylsilyl group and the like. 1
Examples thereof include silyl groups substituted with linear or branched alkyl groups of 4 to 4. Examples of the alkali metal include metals such as lithium, sodium and potassium.

The vinyl compound represented by the general formula [I] is
It is a known and readily available compound, and is also available in Journal of American Chemistry Society, 75 , 2073.
It can also be produced by a conventionally known synthesis method described in (1952) and the like. The azide compound represented by the general formula [II] is a known and easily available compound.

The above reaction is carried out in a suitable solvent at room temperature or by heating. The solvent used in the reaction is not particularly limited as long as it does not affect the reaction, for example, alcohols such as methanol, ethanol, isopropanol, butanol, ethers such as tetrahydrofuran, dioxane, diphenyl ether, methylene chloride. , Halogenated hydrocarbons such as chloroform and 1,1,2,2-tetrachloroethane, aromatic hydrocarbons such as benzene, toluene and xylene, alkyl ketones such as acetone and methyl ethyl ketone, N, N
-Aprotic polar solvents such as dimethylformamide, dimethylsulfoxide and acetonitrile, water and the like can be used alone or in combination. Further, for the purpose of supplementing sulfinic acid or sulfenic acid generated during the reaction,
Organic amines such as triethylamine, diisopropylethylamine and viridine, basic compounds such as sodium hydroxide and potassium hydroxide may be added, and organic amines may be used as a substitute for the solvent.

As for the reaction rate, the azide compound of the general formula [II] is added to 1 mol of the compound of the general formula [I].
It is preferable to use 1 to 20 molar equivalents, preferably 0.5 to 5 molar equivalents. The reaction temperature is about 20 ° C to the boiling point of the solvent, preferably 80 ° C to the boiling point of the solvent. The reaction time is about 10 minutes to 72 hours, preferably 1 to 15
It's time. The compound obtained by the production method of the present invention can be easily purified by ordinary purification methods such as recrystallization, chromatography and distillation.

[0012]

EXAMPLES The present invention will be described in more detail with reference to experimental examples. Example 1 1.3 g of sodium azide was suspended in 50 ml of dimethylformamide, 2.1 g of vinylmethyl sulfone was further added, and the mixture was heated and stirred at a bath temperature of 130 ° C. for 12 hours. The solvent was distilled off under reduced pressure, and the residue was distilled under reduced pressure to give the desired compound 1,2,3-triazole at 0.9%.
7 g (yield 71%) was obtained. The measurement results and the boiling points by the NMR analyzer are as follows. ¹ H-NMR (CDCl ₃ ): 15.15 (1 H, brs),
7.86 (2H, s) Boiling point: 97 ° C / 25mmHg

[Example 2] Trimethylsilyl azide 1.
15 g was dissolved in 30 ml of toluene, 1.06 g of vinylmethyl sulfone was further added, and the mixture was heated with stirring at a bath temperature of 130 ° C. for 6 hours. The solvent was distilled off under reduced pressure, and the residue was distilled under reduced pressure to obtain 0.38 g (yield 55%) of the target compound 1,2,3-triazole. The measurement results and the boiling points by the NMR analyzer are as follows. ¹ H-NMR (CDCl ₃ ): 15.15 (1 H, brs),
7.86 (2H, s) Boiling point: 97 ° C / 25mmHg

[Example 3] Trimethylsilyl azide 1.
2 g was dissolved in 30 ml of toluene, 1.1 g of vinylmethyl sulfone and 1.3 g of diisopropierethylamine were added, and the mixture was heated and stirred at a bath temperature of 130 ° C. for 8 hours. The solvent was distilled off under reduced pressure, and the residue was distilled under reduced pressure to obtain 0.36 g of the target compound 1,2,3-triazole.
(Yield 50%) was obtained. The measurement results and the boiling points by the NMR analyzer are as follows. ¹ H-NMR (CDCl ₃ ): 15.15 (1 H, brs),
7.86 (2H, s) Boiling point: 97 ° C / 25mmHg

[Example 4] 1.3 g of sodium azide was suspended in 30 ml of dimethylformamide, 1.2 g of divinyl sulfone was further added, and the mixture was heated and stirred at a bath temperature of 130 ° C for 12 hours. The solvent was distilled off under reduced pressure, and the residue was distilled under reduced pressure to obtain the target compound 1,2,3-triazole (0.48 g, yield 68%). The measurement results and the boiling points by the NMR analyzer are as follows. ¹ H-NMR (CDCl ₃ ): 15.15 (1 H, brs),
7.86 (2H, s) Boiling point: 97 ° C / 25mmHg

Example 5 1.3 g of sodium azide was suspended in 30 ml of dimethylformamide, 1.8 g of vinylmethyl sulfoxide was further added, and the mixture was heated and stirred at a bath temperature of 130 ° C. for 10 hours. The solvent was distilled off under reduced pressure, and the residue was distilled under reduced pressure to obtain 0.88 g (yield 64%) of the target compound 1,2,3-triazole. The measurement results and the boiling points by the NMR analyzer are as follows. ¹ H-NMR (CDCl ₃ ): 15.15 (1 H, brs),
7,86 (2H, s) Boiling point: 97 ° C / 25mmHg

[0017]

EFFECT OF THE INVENTION 1, 2, 3 represented by the chemical formula [III]
-Triazole is useful as a raw material for antibiotics,
Compared with the conventional manufacturing method that uses explosive and flammable acetylene gas, it does not require special equipment, special safe operation, etc., and also removes the substituents from the substituted 1,2,3-triazole derivative. The process is not necessary, and the effect is great as an industrial manufacturing method.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Shozo Yamada 25-7 Nakamachi, Hanno-shi, Saitama 25-7 Oyama No. 2 Mansion 101 (72) Inventor Tetsuji Asao Yamaguchi 5063-1, Tokorozawa, Saitama Prefecture 48-2-504

Claims (1)

[Claims] 1. A compound represented by the general formula [I]: [In the formula, n indicates 1 to 2, R ¹ represents a lower alkyl group, lower alkenyl group or an aryl group. And a vinyl compound represented by the general formula [II] R ² —N ₃ [II] [In the formula, R ² represents a silyl group substituted with the same or different lower alkyl group or an alkali metal. ] Reaction with an azide compound represented by the formula [III] A method for producing 1,2,3-triazole represented by: