GB2198436A

GB2198436A - Isomerisation of 1.2.4-triazoles

Info

Publication number: GB2198436A
Application number: GB08726876A
Authority: GB
Inventors: Michael Gordon Hutchings; Andrew Small; Keith Smith
Original assignee: Imperial Chemical Industries Ltd
Current assignee: Imperial Chemical Industries Ltd
Priority date: 1986-12-04
Filing date: 1987-11-17
Publication date: 1988-06-15
Also published as: GB8726876D0

Abstract

Heating a 4H-substituted-1,2-4-triazole of the formula: <IMAGE> wherein R is a monovalent organic radical, at a temperature above 100 DEG C, in the presence of a compound R-X, wherein X is a leaving group, causes the compound of Formula I to be transformed into the isomeric 1H-substituted-1,2,4-triazole.

Description

Isomerisation Process This specification describes an invention relating to an isomerisation process and more particularly one for converting a 4H-substituted-1,2,4-triazole into the isomeric 1H-substituted1,2,4-triazole.

According to the present invention there is provided a process which comprises heating a 4H-substituted-1,2,4-triazole of the formula:

wherein R is a monovalent organic radical, at a temperature above 1000C, in the presence of a compound R-X, wherein X is a leaving group, whereby the compound of Formula I is transformed into the isomeric 1H-substituted-1 , 2, 4-triazole.

The monovalent organic radical, R, may be any organic radical which is stable under the conditions of the isomerisation reaction. Classes of suitable organic radical are: (a) Aliphatic groups, such as alkyl, cycloalkyl and cycloalkylalkyl, preferably C120-alkyl, and more especially C alkyl; C3 8-cycloalkyl and C3 8-cycloalkyl-Cl~4-alkyl e.g. methyl, ethyl, pentyl, 2-ethylhexyl, octadecyl, cyclohexyl, 1-(cyclo propyl)ethyl, cyclohexylethyl and cyclohexylmethyl.

(b) Arylaliphatic groups, such as arylalkyl, especially phenyl- and substituted-phenyl-Cl 4-alkyl, e.g. benzyl, 2-phenylethyl, 2-(4-chlorophenyl)ethyl.

(c) Aryl groups, especially optionally substituted phenyl or naphthyl, e.g. phenyl, 4-chlorophenyl, 4-nitrophenyl, 4-hydroxyphenyl, l-napthyl and 2-naphthyl.

(d) Hydrocarbylcarbonylalkyl groups of the formula:

R1 and R2 in which R and R are each independently optionally sub stituted hydrocarbyl (where hydrocarbyl includes cycloalkyl, alkyl, cycloalkylalkyl, aralkyl, aryl, preferably of the type defined in (a), (b) and (c) above, and optional substituents include halogen, alkyl, haloalkyl and alkoxy, especially those in which the alkyl contains up to 4 carbon atoms); R1 is optionally substituted hydrocarbyl as hereinbefore defined and R is H; or R1 and R2 are linked to form an aliphatic ring, especially a cycloalkanone containing from 4 to 8 carbon atoms, which groups and combinations of groups are described in GB 1,464,224 and GB 1,595,696.Specific examples of alkyl- and aryl-carbonylalkyl groups are: acetylmethyl, (t-butyryl)-methyl, 1-(t-butyryl)-ethyl, 1-(t-butyryl)-2-(4-chlorophenyl)-ethyl, I-(t-butyryl)-2-(2,4-dichlorophenyl)-ethyl, and arylcarbonylmethyl groups, such as 4-fluorophenacyl, 4-chlorophenacyl, 4-cyano-2-fluorophenacyl, 4-bromophenacyl, 2,4-dichlorophenacyl, 2,4-difluorophenacyl and phenacyl.

(e) Secondary alcohols derived by reduction of the hydrocarbyl carbonylalkyl groups described in (d) above, such as 1- (4-chlorobenzyl)-2-hydroxy-2-t-butyl-ethyl and 1-(2,4-dichlorobenzyl)-2-*lydroxy-2-t-butyl-ethyl (f) Heterocyclic groups, both aromatic and alicyclic, especially 5 and 6 membered mono- and bi-heterocyclic groups, e.g. pyridyl, piperidino, morpholino, piperazino, furyl, thienyl.

The monovalent radical R may be substituted by groups which are inert under the isomerisation reaction conditions. Suitable substitutents include halogen, especially fluorine, chlorine and bromine; alkyl, haloalkyl, alkenyl and alkoxy, especially those containing up to 4 carbon atoms; nitro; cyano; phenyl; hydroxy; amino; acyl, such as alkyl- and aryl-carbonyl and sulphonyl, carbamoyl, such as unsubstituted and mono- and di- alkyl- & BR< aryl-aminocarbonyl; acylamino, such as alkyl- and aryl-carbonylamino; and acyloxy such as aryl- and alkyl-carbonyloxy.

Preferred radicals represented by R are benzyl, phenacyl, 4-chlorophenacyl, 4-fluorophenacyl, 4-bromophenacyl, 2,4-dichlorophenacyl, 2,4-difluorophenacyl, 4-cyano-2-fluorophenacyl, 3-(4-chlorophenyl)-acetonyl, l-(t-butyryl)-2-(4-chlorophenyl)-ethyl, 1-(t-butyryl) -2-(2,4-dichlorophenyl) -ethyl.

The identity of the leaving group, X, is not critical but preferred leaving groups include halogen, especially chlorine or bromine; aryl- and alkyl-sulphonates and carboxylates and derivatives thereof, such as tosylate, mesylate, acetate, trifluoroacetate.

Only catalytic quantities of the compound R-X are required to effect the isomerisation though larger quantities are not generally detrimental. However, for technical and economic reasons it is preferred to use from about 1 - 15 %mole and more especially from 2 - 7 %mole, of R-X.

The isomerisation is preferably performed at a temperature above 1200C especially above 150 C. Preferred temperature ranges are from 1200C to 2000C, and especially from 1500C to 1800C. The precise temperature employed will, however, depend upon the stability of the radical, R, the nature of X, the presence or absence of a reaction medium, the period on temperature and the energy barrier to be overcome in the isomerisation.

The compound of Formula I and the catalyst may be heated alone or suspended or dissolved in a suitable reaction medium, such as an organic liquid. Suitable organic liquids are preferably those with a boiling point in the range 1200C to 2000C or above and more especially at or above 1500C. Examples of suitable solvents are N-methylpyrrolidone, dimethylformamide, formamide, dimethylaniline, ureas, dimethylsulphoxide, nitrobenzene, halobenzenes, 1,3-dimethyl2-imidazolinone, glycols, polyglycols, glycol ethers and esters.

The isomerisation may be performed in the presence of the isomeric 1H-substituted-1,2,4-triazole, which generally being more thermodynamically stable than the 4H-substituted-1,2,4-triazole remains unchanged in the reaction mixture. Thus, the process is of especial value in converting the relatively minor proportion, generally around 15% or below, of the less desirable 4H-substituted1,2,4-triazole (which is formed during the preparation of a 1H-substituted-1,2,4-triazole by reaction between a 1,2,4-triazole and the compound R-X or the epoxide derivative thereof) into the more desirable 1H-substituted-1,2,4-triazole.

A specific example of the present invention is the conversion of 4H-benzyl-1,2,4-triazole into 1H-benzyl-1,2,4-triazole by heating the former at 1800C for 21 < hours in the presence of 3% mole of benzyl chloride. Another example is the conversion of 4H-(phenacyl)-1,2,4-triazole into 1H-(phenacyl)-1,2,4-triazole by heating the former at 160-180"C for 6 hours in the absence of solvent, or at 1500C for 36 hours in N-methylpyrrolidone, in the presence of 13 or 10% mole, respectively, of alpha-chloroacetophenone.

The invention is further illustrated by the following Examples in which all percentages are by weight unless otherwise indicated.

Example 1 Conversion of 4H-benzyl-1,2,4-triazole into lH-benzyl-1 ,2,4-triazole 4H-Benzyl-1,2,4-triazole (0.2g, 1.26mmol) was placed in a 5 ml round bottomed flask fitted with a reflux condenser and drying tube. Benzyl bromide (7.2mg, 4.2x10 5mole, 3.3 mole%) was added and the mixture heated to 1800C for 21 < hours before being analysed by 'H nmr spectroscopy. More than 90% of the starting material had been converted to lH-benzyl-1,2,4-triazole.

Example 2 4H-Phenacyl-1,2,4-triazole (0.1359g, 0.73mmoles) and alphachloroacetophenone (0.0154g, 0.096 mmoles, 13.6 %mole) were placed in a 5 ml round bottomed flask. Methanol (5 ml) was added to dissolve both compounds and then removed in vacuo to produce a white solid evenly covered in alpha-chloroacetophenone. The solid was heated at 1600C for 1 hour and then at 1800C until complete conversion had taken place. The relative proportions of lH-phenacyl-1,2,4-triazole (1,2,4-isomer) and 4H-phenacyl-1,2,4-triazole (1,3,4-isomer) were determined by HPLC at regular intervals and the results are shown in the following table.

Temperature & Isomer Ratio Period on Temperature 1,2,4-isomer: 1,3,4-isomer 1600C 1 hour + 1800C 1 hour 44 : 56 1600C 1 hour + 1800C 2 hours 61 : 39 1600C 1 hour + 1800C 4 hours 92 : 8 1600C 1 hour + 1800C 6 hours 100 : 0

Claims

CLAIM A process which comprises heating a 4H-substituted1,2-4-triazole of the formula:

wherein R is a monovalent organic radical, at a temperature above 100"C, in the presence of a compound R-X, wherein X is a leaving group, whereby the compound of Formula I is transformed into the isomeric 1H-substituted-1,2,4-triazole.