KR800001129B1 - Process for 2-(thienyl-3'-amino)-1,3-diaza-cycloalkene - Google Patents

Abstract

Title compds. (I; R1, R2 = H, lower alkyl, halogen, cyano or phenyl; R2, R3 = may be trimethylene or tetramethylene;Z=C2-4 straight chain or side chain alkylene) were prepd. by reaction of aminothiophene with 2-alkylmercapto-1, 3-diazacycloalkene in presence of solvent(MeOH, cyclohexane, benzene). Thus, 4-methyl-3-aminothiophene HCl salts 1.8g was reacted with 4-methyl-mercapto-1,3-diazacyclopentene 1.4g for 20 hr at 60-70≰C. The precipitation base was extd. with CH2Cl2 and this soln. was filtered in oxidized aluminium column to give I.

Description

Method for preparing 2- (thienyl-3'-amino) -1,3-diaza-cycloalkene

The present invention relates to a method for producing a novel 2- (thienyl-3'-amino) -1,3-diazacycloalkene represented by the following general structural formula (I).

In the above formula

R ₁ , R ₂ is hydrogen, lower alkyl, halogen, cyano, or phenyl group and R ₂ and R ₃ together may be trimethylene or tetramethylene group.

Z is straight or branched alkylene containing 2 to 4 carbon atoms, of which 2 to 3 carbon atoms form a ring.

The compound of formula (I) according to the present invention reacts the amino thiophene of formula (II) with 2-alkylmercapto-1,3-diazacycloalkene of formula (III) at 70 ° to 200 ° C. To make it.

The above-mentioned preparation reacts 3-amino-thiophene of formula (II) with alkylmercapto-1,3-diazacycloalkene of formula (III) in the presence of a solvent. Sufficient high temperatures of 70 to 200 ° C. should be used to remove alkyl mercaptans from the reaction mixture.

Examples of the solvent include methanol, ethanol, propanol, saturated cyclic hydrocarbons such as cyclohexane, methylcyclohexane, and aromatic hydrocarbons such as benzene, toluene, xylene, and chlorobenzene and dichlorobenzene in chlorinated hydrocarbons.

Alkylmercapto-1,3-diazacycloalkenes represented by the formula (III) are used in the form of salts such as hydroiodide, which are prepared by alkylating the corresponding alkylene-thio-ureas by the methods in the literature.

(See Organic Synthesis III, page 394).

Example 1

Preparation of 2- (4'-methylthienyl-3'-amino) -1,3-diazacyclopentene- (2)

1.8 g of 4-methyl-3-aminothiophene hydrochloride are heated with 1.4 g of 4-methyl-mercapto-1,3-diazacyclopentene- (2) at 60 to 70 ° C. for 20 hours. The reaction mixture is dissolved in dilute hydrochloric acid, mixed with activated charcoal and filtered.

The filtrate is alkalined with 5N sodium hydroxide solution. The precipitated base is extracted with methylene chloride and the solution is filtered over an aluminum oxide column. The filtrate is evaporated to afford 2- (4'-methylthienyl-3'-amino) -1,3-diazacyclopentene- (2), which has a melting point of 156 to 158 ° C. when recrystallized from isopropanol.

The melting point of the hydrochloride is 200 to 202 캜.

Example 2

a) 2- (2 ', 5'-dibromo-4'-methylthienyl-3'-amino) -1,3-diazacyclopentene- (2)

1.8 g of 2- (4'-methylthienyl-3'-amino) -1,3-diazacyclophenene- (2) was dissolved in 15 ml of glacial acetic acid, and 1.02 ml of bromine solution dissolved in 15 ml of glacial acetic acid was added thereto. It is added dropwise while stirring at room temperature. The whole is stirred for 20 minutes and the suspension is placed in 50 ml of ice water and made alkaline with ice cooling.

The precipitated base is removed by suction filtration, washed with ice water, dried and converted to hydrochloric acid with etheric hydrochloric acid. 2- (2 ', 5'-dibromo-4'-methylthienyl-3'-amino) -1,3-diazacyclopentene- (2, recrystallized with isopropanol and ether and has a melting point of 224 to 225 ° C. Get)

The following compounds can be prepared by the methods described in Example 2.

b) 2- (2 ′, 5′-dibromo-thienyl-3′-amino) -1,3-diazacyclopentene- (2)

c) 2- (2 ', 5'-dibromo-4'-chlorothienyl-3'-amino) -1,3-diazacyclopentene- (2)

d) 2- (2'-bromo-4 ', 5'-dimethylthienyl-3'-amino) -2,3-diazacyclopentene- (2)

e) 2- (2'-bromo-4'-ethyl-5'-methylthienyl-3'-amino) -1,3-diazacyclopentene- (2)

f) 2- (2 ′, 5′-dibromothienyl-3′-amino) -1,3-diazacyclohexene- (2)

Example 3

a) 2- (2'-chloro-4'-methyl-thienyl-3'-amino) -1,3-diaza cyclopentene- (2)

10 g of 2 (4'-methyl-thienyl-3'-amino) -1,3-diazacyclopentene- (2) was dissolved in 125 ml of chloroform, and a solution of 7.5 ml of sulfuryl chloride dissolved in 15 ml of chloroform was added thereto. Add dropwise at 0 ° C. and boil for 2 hours. After cooling, chloroform and excess sulfuryl chloride are distilled off under reduced pressure. After cooling, the chloroform and excess of sulfyl chloride are distilled off under reduced pressure. The residue is dissolved in dilute hydrochloric acid, the hydrochloric acid layer is shaken with methylene chloride, extracted from you and filtered over activated carbon. The acid solution is alkaline with 6N-sodium hydroxide solution on ice cooling and the base is immediately extracted with methylene chloride. The methylene chloride layer is dried, the solvent is distilled off under reduced pressure and the residue is dissolved in a large amount of ether. Hydrochloride is precipitated using etheric hydrochloric acid and recrystallized from a mixture of isopropanol and petroleum ether. This material had a melting point of 228-229 ° C. Recrystallization from methyl-cyclohexane benzene affords the desired product with a melting point of 152 ° C.

As a compound which can be manufactured by such a method, it is as follows.

b) Decomposition point of 2- (2 ′, 4′-dichlorothienyl-3′-amino) -1,3-diazacyclopentene- (2) hydrochloride: 295 ° C.

c) 2- (2'-chloro-5'-methylthienyl-3'-amino) -1,3-diaza cyclopentene- (2)

(d) 2- (2'-chloro-4 ', 5'-dimethylthienyl-3'-amino) -1,3-diazacyclopentene- (2)

e) 2- (2'-chloro-4'-ethyl-5'-methylthienyl-3'-amino) -1,3-diazacyclopentene- (2)

f) 2- (2'-chloro-4'-methylthienyl-3'-amino) -1,3-diazacyclohexene- (2)

g) 2- (2'-chloro-4 ', 5'-tetramethylenethienyl-3'-amino) -1,3-diazacyclopentene- (2)

h) 2- (2'-chloro-4'-methylthienyl-3'-amino) -1,3-diaza-4-cyclopentene- (2)

Hydroclyde (melting point 168-169 ° C),

i) 2- (2′-chlorothienyl-3′-amino) -1.3-diazacyclopentene- (2)

Hydrochloride (melting point 181-182 ° C.).

k) 2- (2'-chloro-4'-ethylthienyl-3'-amino) -1.3-diaza cyclopentene- (2)

Example 4

a) 2- (2′-iodine-4′-methylthienyl-1,3-aminodiazacyclopentene- (2)

1.8 ml of 2- (4'-methylthienyl-3'-amino) -1,3-diazacyclopentene- (2) was dissolved in 30 ml of glacial acetic acid and 17 ml of iodine-monochloride solution in 17 ml of glacial acetic acid at room temperature. Drop by Then 75 ml of water is added and heated to 80 ° C. within 20 minutes and left until iodine coloration disappears.

After cooling it is filtered over activated charcoal and alkaline with sodium hydroxide solution while cooling. The solid residue is dissolved in ether, acidified with etheric hydrochloric acid and the solvent is removed.

The residue is boiled with acetone and then suction filtered.

2- (2'-iodine-4'-methylthienyl-3'-amino) -1,3-diazacyclopentene- (2 having a melting point of 215 to 216 DEG C, recrystallized from a mixture of ethanol and diisopropyl ether Get)

The compound obtained by such a method is as follows.

b) 2- (2′-iodothienyl-3′-amino) -1,3-diazacyclopentene- (2)

c) 2- (2'-iodo-4'-methylthienyl-3'-amino) -1,3-diaza-4-cyclopentene- (2)

d) 2- (2'-iodine-4'-chlorothienyl-3'-amino) -1,3-diazacyclopentene- (2)

e) 2- (2'-iodo-4'-methylthienyl-3'-amino) -1,3-diazacyclohexene- (2)

f) 2- (2'-iodo-5'-methylthienyl) -3'-amino) -1,3-diazacyclopentene- (2)

g) 2- (2'-iodo-4 ', 5'-dimethylthienyl-3'-amino) -1,3-diazacyclopentene- (2)

h) 2- (2′-iodo-4 ′, 5′-tetramethylenethienyl-3′-amino) -1,3-diazacyclopentene- (2)

i) 2- (2′-iodo-4 ′, 5′-tetramethylenethienyl-3′-amino) -1,3-diazacyclo-hexene- (2)

k) 2- (2 ', 5'-diiodo-4'-methylthienyl-3'-amino) -1,3-diazacyclo when using 3,25 g of iodo monochloride in Example 4a Pentene- (2) is obtained.

(Melting point of hydrochloride: 204-205 ° C.).

The compound obtained by such a method is as follows.

l) 2- (2 ', 5'-dioodothienyl-3'-amino) -1,3-diazacyclopentene- (2)

m) 2- (2 ′, 5′-dioodo-4′-methylthienyl-3′-amino) -1,3-diaza-4-cyclopentene- (2)

n) 2- (2 ', 5'-diiodo-4'-methylthienyl-3'-amino) -1,3-diazacyclohexene- (2)

o) 2- (2 ', 5'-diiodo-4'-chlorothienyl-3'-amino) -1,3-diazacyclopentene- (2)

p) 2- (2 ', 5'-diiodo-4'-chlorothienyl-3'-amino) -1,3-diazacyclohexene- (2)

q) 2- (2 ', 5'-dioodo-4'-chlorothienyl-3'-amino) -1,3-diaza-4-methyl-cyclopentene- (2)

Example 5

a) 2- (2 ', 5'-dichloro-4'-methylthienyl-3'-amino) -1,3-diazacyclopentene- (2)

5 g of hydrochloride of 2- (4'-methylthienyl-3'-amino) -1,3-diazacyclopentene- (2) are suspended in 10 ml of benzene, then 5 ml of sulfuryl chloride is added dropwise for 2 hours. After heating to the boiling point, benzene is distilled off and the residue is suction filtered with acetone.

2- (2 ', 5'-dichloro-4-methylthienyl-3'-amino) -1,3-diazacyclopentane- (2, recrystallized from ethanol and diisopropyl ether, having a melting point of 167 to 168 캜. Get) Compounds that can be prepared in this manner are as follows.

b) 2- (2 ', 5'-dichlorothienyl-3'-amino) -1,3-diazacyclopentene- (2)

c) 2- (2 ', 4', 5'-trichlorothienyl-3'-amino) -1,3-diazacyclopentene- (2)

d) 2- (2 ', 5'-dichlorothienyl-3'-amino) -1,3-diaza-4-cyclopentene- (2)

e) 2- (2 ', 5'-dichloro-4'-methylthienyl-3'-amino) -1,3-diazacyclohexene- (2)

f) 2- (2 ', 5'-dichloro-4'-methylthienyl-3'-amino) -1,3-diaza-4-cyclopentene- (2)

g) 2- (2 ', 5'-dichlorothienyl-3'-amino) -1,3-diazacyclohexane- (2)

h) 2- (2 ', 4', 5'-trichlorothienyl-3'-amino) -1,3-diaza-4-methylcyclopentene- (2)

i) 2- (2 ′, 4 ′, 5′-trichlorothienyl-3′-amino) -1,3-diazacyclohexene- (2)

Claims (1)

Aminothiophene of the following formula (II) is reacted in a high boiling point organic solvent with 2-alkylmercapto-1,3-diazacyclo alken of the following formula (III) at 70 ° to 200 ° C. A process for preparing 2- (thienyl-3′-amino) -1,3-diazacyclo alken of formula (I).

Wherein R ₁ , R ₂ , R ₃ are hydrogen, lower alkyl, halogen, cyano or phenyl group. R ₂ and R ₃ may together be trimethylene or tetramethylene. Z is a straight or branched chain alkylene group containing 2 to 4 carbon atoms of which 2 to 3 carbon atoms form a ring. R ₅ means lower alkyl.