DD289527A5 - PROCESS FOR PREPARING NEW 4-SUBSTITUTED 5-ACYLIMINO-3,3-PENTAMETHYLENE-1,2,4-THIADIAZOLIDINES - Google Patents

Abstract

The invention relates to a process for the preparation of novel 4-substituted * by reacting N-acyl-N-substituted thioureas with 3,3-pentamethyleneoxaziridine, which can be realized with simple technological steps (reaction at room temperature, isolation of the products by crystallization) , The invention can be used for the production of biologically active compounds having fungicidal properties. The new thiadiazolidines are also useful as aids to the rubber industry, e.g. As a regulator of vulcanization rate, suitable. {3,3-Pentamethylenoxaziridin; acylthiourea; * Fungicide; vulcanization accelerators}

Description

R-CO-NH-CS-NHR 'II

in the

R and R 'have the meanings given for the general formula I, which may also be present in a tautomeric form, in powdered or dissolved form with a solution of 0.8 to 3.0mol3,3-pentamethyleneoxaziridine at temperatures of -70 ⁰ C. to + 11O ⁰ C reacted and the reaction product I by crystallization, optionally after concentration of the reaction solution and addition of further solvents, is isolated.

2. The method according to claim 1, characterized in that the acylthiourea derivative Il is an N- (ethoxycarbonyl) -N'-arylthiourea, an N-alkanoyl (eg an acetyl), N-benzoyl or N- (substituted benzoyl) -N'-arylthiourea is used.

3. The method according to claim 1 or 2, characterized in that 1 mol of acylthiourea derivative II is reacted with 1.0 to 1.7mol3,3-Pentamethylenoxaziridin.

4. The method according to any one of claims 1 to 3, characterized in that the 3,3-Pentamethylenoxaziridin is used in Toluenischer solution.

5. The method according to any one of claims 1 to 4, characterized in that the reaction takes place at temperatures between 0 and + 6O ⁰ C.

6. The method according to any one of claims 1 to 4, characterized in that the reaction is started at room temperature.

7. The method according to any one of claims 1 to 4, characterized in that the reaction is carried out under cooling, so that a temperature of 40 to 60 ⁰ C is not exceeded.

Field of application of the invention

The invention relates to a process for the preparation of novel 4-substituted S-acylimino-S ^ -pentamethylene-i ^ / lthiadiazolidinen, as intermediates or components of biologically active formulations due to their fungicidal activity or as an aid to the rubber industry, for. B. can be used as a regulator of Vulkanisationsgeschwindigkeit.

Characteristic of the known state of the art

Technical solutions that meet the objective of the present invention have not yet become known. All compounds described here, prepared by the process according to the invention are new.

From our own, sometimes unpublished studies is known that of simple N-acylthioureas only the benzoyl derivative in good yield and the N-acetyl derivative in low yield with 3,3-Pentamethylenoxaziridin to cyclic 5-imino-3,3-pentamethylene-1 2,4-thiadiazolidines (S.ANDREAE, E.SCHMITZ: J. prakt. Chem. 329 [19871, 1008]. Thiourea itself and simple arylthioureas gave, as stated in that publication, consuming oxaziridines complex reaction mixtures which could not be characterized. Thus, it was not promising, in a combination of two recognized as "unfavorable" structural features (acylated thiourea or N-arylthiourea) the 'preparation of corresponding 5-acylimino-3,3-p8ntamethylen-1,2,4-thiadiazolidine to try.

Object of the invention

It is an object of the invention to develop a rational process for the preparation of novel 4-substituted S-acylimino-S.S-pentamethylene-1,2,4-thiadiazolidines.

Explanation of the essence of the invention

The object of the invention is to produce, starting from acyliorton thiourea derivatives, new 4-substituted 5-acylimino-3,3-pentamethylene-1,2,4-thiadiazolidines.

The object of the invention is achieved by a process for the preparation of novel 4-substituted 5-acylimino-3,3-pentamethylene-1,2,4-thiadiazolidinen of the general formula I,

O / ~ N = S-NH / C \ \ N \ / \ \ / W \ / / C ~ / \ / \

I

R-

in the

R may be alkyl, aryl, alkoxy, aryloxy or aralkoxy, optionally with substituents, and R 'may be alkyl, alkenyl, aryl, aralkyl or hetaryl radicals, optionally with substituents, by adding 1 mol of an acylthiourea derivative according to the invention the general formula II,

R-CO-NH-CS-NHR'II,

in which R and R 'have the meanings given for the general formula I, which may also be present in a tautomeric form, in pulverized or dissolved form with a solution of 0.8 to 3.0 mol, preferably 1.0 to 1, 7 mol, 3,3-Pentamethylenoxaziridin at temperatures from -7O ⁰ C to +110 ⁰ C, preferably reacted at ^{0 0} C to +60 ⁰ C and the reaction product I by crystallization, optionally after concentration of the reaction solution and addition of further solvents isolated becomes.

As the acylthiourea derivative II, for example, N- (ethoxycarbonyl) -, N-alkanoyl (eg 6-N-acetyl), N-benzoyl or N- (substituted benzoyl) -N'-arylthioureas can be used.

The 3,3-pentamethyleneoxaziridine is advantageously used in toluene solution.

It is possible to start the reaction at room temperature. Also, the reaction can also be cooled, so that a temperature of 4O ⁰ C to 6O ⁰ C is not exceeded, are performed.

The reaction is after a few minutes to a maximum of 6 hours b jendet, which can be easily monitored by thin layer chromatography. Depending on the batch size, a more or less siarc warming occurs, which may need to be limited by cooling.

The products are isolated by suction if they are immediately crystalline or after concentration of the reaction solutions, optionally after addition of gasoline, ether, an alcohol-water mixture or another suitable solvent combination.

The products I are stable, colorless to yellow substances that do not oxidize iodide in the cold.

In some cases, by-products are sulfenamides of structure III,

O S-NHi

W /

C ~~ N = C III

R NHR

where R and R 'have the meanings given for the general formula I, which may optionally also be present in a tautomeric form. However, owing to their low solubility, the sulfenamides III are usually readily separable from the target products I during the work-up.

The following examples are given to illustrate the invention and are not intended to limit its applicability. All compounds described therein have been characterized by elemental analysis, ¹ H, ⁶ C NMR, and mass spectra.

embodiments

example 1

B-Ethoxycarbonylimino-SS-pentamethyl-phenyl-, 2,4-thiadiazolidine I (R = EtO, R '= Ph) 1.55 g (6.9 mmol) of N-ethoxycarbon, i-N'-phenylthiourea are stirred in a solution of 10.3 mmol of 3,3-pentamethyleneoxaziridine in toluene (about 0.3 mmol / l) until virtually complete conversion of the starting material by thin-layer chromatography

(Silufol®, toluene / EtOH 10: 3, phosphomolybdic acid in EtOH), which is the case after about 1 h. After filtering off small amounts of amorphous portions and concentration under reduced pressure, 1.5 g (68% of theory) of the title compound precipitate out as almost colorless crystals. Recrystallization from petrol gives an analytically pure sample of mp. 147 ⁰ C.

Example 2

5-Ethoxycarbonylimino-4- (2-methoxyphenyl) -3,3-pentamethylene-1,2,4-thiadiazolidine I (R = EtO ₁ R '= 2-MeO-C ₆ H ₄ ) 1.7g (6.68mmol ) N-ethoxycarbonyl-N '- (2-methoxyphenyl) thiourea give analogously to Example 1 with 11 mmol of 3,3-Pentamethylenoxaziridin after addition of the concentrated mixture with ether, 1.5 g (64% of theory) of the title compound, after recrystallization from toluene between 165 ⁰ C and 166 ⁰ C melts.

Example 3

δ-ethoxycarbonyl-imino-O-methoxyphenyl-SS-pentamethylene-Ⓒ - thiadiazolidine I (R = EtO, R '= 3-0-C ₆ H ₄ ) 12g (47 mmol) N-ethoxycarbonyl-N' - (3 methoxyphenyl) thiourea give analogously to Example 1 with 60 mmol of 3,3-Pentamethylenoxaziridin after addition of the concentrated mixture with a mixture of petroleum ether / ether 9.8 g (59% of theory) of the title compound, which after recrystallization from i-propanol at 118 ⁰ C. melts.

Example 4

5-ethoxycarbonylimino-4- (4-methoxyphenyl) -3,3-pentameihylen-1,2,4-thiadiazolidin I (R = Et, R '= 4-MeO-C ₆ H ₄₎ 2.9 g (11,4mmol ) N-Ethoxycarbonyl-N '- (4-methoxyphenyl) thiourea give analogous to Example 1 with 16 mmol of 3,3-Pentamethylenoxaziridin after addition of the concentrated mixture with ether 1.6 g (40% of theory) of the title compound, which after recrystallization from i-propanol between 148 ⁰ C and 15O ⁰ C melts.

Example 5

S -ethoxycarbonylimino ^ -fS-methylphenyl-SS-pentamethylene-1H-indiadiazolidine I (R = EtO, R '= 3-Me-CeH ₄ ) 1,12g (4,7mmol) N -ethoxycarbonyl-N' - (3 Methylphenyl) thiourea obtained analogously to Example 1 with 6.1 mmol of 3,3-Pentamethylenoxaziridin after addition of the concentrated mixture with a mixture of petroleum ether / ether 0.8 g (51% of theory) of the title compound, which after recrystallization from i-propanol melts at 148 ⁰ C.

Example 6

S-ethoxycarbonylimino-methylphenyO ^ -M-SS-pentamethylene-i ^ -thiadiazolidin 1 (R = Et, R '= 4-Me-C ₆ H ₄₎ 1.45 g (6,08mmol) of N-ethoxycarbonyl-N'- (4-Methylphenyl) thiourea give analogously to Example 1 with 10 mmol of 3,3-Pentamethylenoxaziridin after addition of the concentrated mixture with a mixture of petroleum ether / ether 1.0 g (49% of theory) of the title compound, which after recrystallization from i-propanol melts between 141 ⁰ C and 142 ⁰ C.

Example 7

5-ethoxycarbonylimino-4- (2,6-dimethylphenyl) -3,3-pentamethylene-1,2,4-thiadiazolidine I (R = EtO, R '= 2,6-Me ₂ -C ₆ H ₃ ) 7, 9g (31.3 mmol) of N-ethoxycarbonyl-N '- (2,6-dimethylphenyl) thiourea give analogous to Example 1 with 46mmol 3,3-Pentamethylenoxaziridin after 30min reaction time, a precipitate of 1.3 to 2.0g (16 to 24% d .Th.) Sulfenamide III (R = EtO ₁ R '= 2,6-Me ₂ -C ₆ H ₃ ) of mp. 13O ⁰ C to 1322 ° C (from ethanol). After admixing the concentrated mixture with petroleum ether, 2.4 to 6.4 g (22 to 59% of theory) of the title compound are obtained, which, after recrystallization from ethanol, melts between 12O ⁰ C and 123 ° C.

Example 8

5-ethoxycarbonylimino-4- (2,4-dimethylphenyl) -3,3-pentamethylene-1,2,4-thiadiazolidine I (R = EtO, R '= 2,4-Me ₂ -C ₆ H ₃ ) 3, 0g (12 mmol) of N-ethoxycarbonyl-N '- (2,4-dimethylphenyl) thiourea give analogously to Example 1 with 19 mmol of 3,3-Pentamethylenoxaziridin after addition of the concentrated mixture with petroleum ether or ether 2.1 g of the title compound, with further 1 , 2g (total yield 80% of theory) are obtainable by an equal treatment of the mother liquor. The melting point after recrystallization from ethanol 155 ⁰ C to 156 ⁰ C.

Example 9

5-ethoxycarbonylimino-4- (2,3-dichlorophenyl) -3,3-peniamethylene-1,2,4-thiadiazolidine I (R = EtO, R '= 2,3-CI ₂ -C ₆ H ₃ ) 7, 5 g (23.1 mmol) of N-ethoxycarbonyl-N '- (2,3-dichlorophenyl) thiourea give, analogously to Example 7, 33 mmol of 3,3-pentamethylene-oxaziridine, a precipitate of 3.4 g (4% by wt.) Of sulfenamide III (R = EtO, R '= 2,3-CI ₂ -C ₆ H ₃ ) of mp. 127 ° C to 13O ⁰ C (from ethanol). After addition of the concentrated filtrate with petroleum ether or ether 4.65 g (52% of theory) of the title compound are obtained, which melts after recrystallization from ethanol between 134 ⁰ C and 135 ⁰ C.

Example 10

4-Allyi-5-ethoxycarbonylimino-3,3-pentamethylene-1,2,4-thiadiazolidine I (R = EtO, R '= allyl) 1.4 g (7.4 mmol) of N'-allyl-N-ethoxycarbonylthiourea give analogously Example 1 with 11 mmol.3,3-Pentamethylenoxaziridin after addition of the concentrated mixture with petroleum ether 1.1 g (52% of theory) of the title compound, which melts after recrystallization from gasoline between 122 ° C and 123 ⁰ C.

Example 11

5-Benzoylimino-4- (2-methoxyphenyl) -3,3-pentamethylene-1,2,4-thiadiazolidine I (R = Ph, R '= 2-MeO-C ₆ H ₄ ) 2.5g (8.7 mmol ) N-Benzoyl-N '- (2-methoxyphenyl) thiourea obtained analogously to Example 1 with 12 mmol of 3,3-Pentamethylenoxaziridin after addition of the concentrated mixture with a mixture of petroleum ether / ether 1.4 g (42% of theory) of Title compound, which melts after recrystallization from ethanol between 144 ° C and 145 ° C.

Example 12

5-Benzoylimino-3,3-pentamethylene-4-phenyl-1,2,4-thiadiazolidine I (R = Ph, R '= Ph) 2.4 g (9.4 mmol) N-benzoyl-N'-phenylthiourea analogously to Example 1 with 14mmol3,3-Pentamethylenoxaziridin 1.45 g (44% of theory) of the title compound, which can be filtered off with suction immediately after the exothermic reaction and after recrystallization from ethanol between 145 ⁰ C and 147 ⁰ C melts.

Example 13

5-Ethoxycarbonylimino-4- (2-methoxycarbonylphenyl) -3,3-pentamethylene-1,2,4-thiadiazolidine I (R = EtO, R '= 2-MeOCO-C ₆ HJ 6.0g (21.3mmol) N -Ethoxycarbonyl-N '- (2-methoxycarbonylphenyl) thiourea give analogous to Example 7 with 30mmol 3,3-Pentamethylenoxaziridin a precipitate of 3.5 g (55% of theory) of sulfenamide III (R = EtO, R' = 2-MeOCO -CeH ₄ ) of the mp 138 ⁰ C (from ethanol) as the main product, the title compound of mp 106 ° C (from ethanol) is formed only in small quantities.

Example 14

4-n-butyl-5-ethoxycarbonylimino-3,3-pentamethylene-1,2,4-thiadiazolidine KR = EtO ₁ R '= n-Bu) 3.4 g (1 mmol) N-ethoxycarbonyl-N'-n-butylthiourea obtained analogously to Example 1 m ^: t 24mmol 3,3-Pentamethylenoxaziridin after addition of the concentrated mixture with petroleum ether 2.6 g (52% of theory) of the title compound, which melts after recrystallization from gasoline at 13O ⁰ C.

Example 15

4-Benzyl-5-ethoxycar'jonylimino-3,3-pentamethylene-1,2,4-thiadiazolidine I (R = EtO, R '= CH ₂ Ph) 14g (58.7mmoi) N -ethoxycarbonyl-N'-benzylthiourea obtained analogously to Example 1 with 80mmol3,3-Pentamethylenoxaziridin after addition of the concentrated mixture with a mixture of ether / petroleum ether 12.5 g (64% of theory) of the title compound, the crude product (mp 155 ⁰ C to 16O ⁰ C) still contains small amounts of the corresponding sulfenamide III, but after recrystallization from gasoline and from i-propanol in pure form (mp 163 ° C to 164 "C) is obtained.

Claims (1)

1. A process for the preparation of novel 4-substituted-5-acylimino-3,3-pentamethylene-1,2,4-thiadiazolidinen of the general formula I, O S-NH K H R can be alkyl, aryl, alkoxy, aryloxy or aralkoxy radicals, if appropriate with substituents, and R 'can be alkyl, alkenyl, aryl, aralkyl or hetaryl radicals, optionally with substituents, characterized in that a Acylthiourea derivative of general formula II,