DE965233C - Process for the preparation of N-substituted thiocarbamates and N, N'-disubstituted bis-thiocarbamates - Google Patents

Description

ISSUED JUNE 6, 1957

F 13555 IVb.11? ό

The invention relates to the production of N-substituted thiocarbamic acid S-esters (thiocarbamates) and N, N'-disubstituted bis-thiocarbamic acid S-esters (bis-thiocarbamates).

It has been found that N-substituted thiocarbamates or N, N'-disubstituted bis-thiocarbamates can be prepared by adding rhodanides of the formula R ₁ SCN or R ₁ (SCN) ₂ , in which R _{1 is} an aliphatic, aromatic or alicyclic radical means with secondary or tertiary aliphatic or cycloaliphatic acid-resistant alcohols or their corresponding olefins in the presence of acids, preferably sulfuric acid, at about ο to 20 ° and the reaction product is then hydrolyzed.

For the reaction found, acid-resistant aliphatic or cycloaliphatic secondary or tertiary alcohols or the corresponding olefins are used, e.g. isopropyl alcohol, tertiary butyl alcohol, isobutylene, cyclohexanol, cyclohexene, camphene and others. The implementation is carried out in acids, preferably in sulfuric acid.

The concentration of sulfuric acid can be between 50 and 8 ° / ₀ . For example, glacial acetic acid and formic acid are suitable for dilution. If the sulfur

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Acid concentrations do not produce the desired substances or only in a very low yield. The speed of response is largely influenced by the acid concentration. The for a maximum yield required sulfuric acid concentration varies with the individual components. In the implementation Tertiary alcohols usually have a lower acid strength than when converting secondary ones. the The reaction temperature is given by the behavior of the components towards sulfuric acid. the Decomposition reactions of rhodanides recede at temperatures below 10 °. Regarding side reactions it can be said that the thiocarbamate formation to be expected from the action of sulfuric acid on rhodanide can be suppressed by an excess of alcohol or olefin; in addition, the formation of the N-substituted thiocarbamates faster than the formation of unsubstituted thiocarbamates from rhodanides alone.

Compared to the known method (S. Rivier, Bull. Soc. Seances France, 4, 1, 733 [1912]) for the production of N-substituted thiocarbamates, the present process offers because of its one-step nature and the better yield advantages.

The starting materials of the known process for the production of N-substituted thiocarbamates are the mercaptans, which first have to be reacted with COCl ₂ to form monothiocarbonic acid chlorides:

R ₁ -SH + COCl ₂ - -R ₁ -S-CO-Cl-I-HCl

The monothiocarbonic acid chlorides then only provide the N-substituted thiocarbamates in the second stage:

R ₁ -S-CO-CH-ZRNH ₂ R ₁ -S-CO -NH-R + HCl-RNH ₂

(2)

The production of monothiocarbonic acid chlorides, which are very moisture-sensitive and which have to be distilled before further processing, usually has a very poor yield. When the radical R _{1 is} e.g. B. C ₃ , C ₇ and the like, then according to (1) the desired monothiocarbonic acid chlorides are formed only in very small amounts (less than 20 ° / ₀ ); The main products are the corresponding dithiocarbonic acid - S, S '- di - R ₁ -ester, R ₁ -SCOS-R ₁ . According to (2), 2 moles of amine are required to carry out the reaction. According to the new process, the radical R can be introduced by using 1 mol of alcohol or olefin.

In the following tables are some N-substituted thiocarbamates and N, N'-disubstituted bisthiocarbamates compiled, which have been produced by the one-step process described above are, in Table 1, N-Cyclohexylmonothiocarbamic acid S-R-ester from cyclohexanol and R-SCN (or NCS-R-SCN). In Table 2, N-Isopropylmonothiocarbamic acid S-R ester from isopropyl alcohol and R · SCN (or NCS-R-SCN). In table 3 N-tert-butyl-monothiocarbamic acid-S-R-ester from tert-butanol or. Isobutylene and R-S C N. In Table 4 N - isobornyl - monothiocarbamic acid - S - R - ester from camphene and R · SCN (or NCS · R · SCN).

Table 1
N-Cyclohexyl-monothiocarbamic acid-SR-ester from cyclohexanol and R · SCN or NCS · R · SCN

the end
booty ¹ ) F. ⁰ C ² ) Gross formula Mole
weight N analyzes in ° / o found Solution
medium ³ ) 7o calculated 7.7 CH ₃ - 45 112 C ₈ H ₁₅ ONS *) 173.2 8.1 7.6 H C ₂ H ₅ - 60 67 C ₉ H ₁₇ ONS *) I87.3 7.5 7.2 H nC ₃ H ₇ - 67 44 C ₁₀ H ₁₉ ONS *) 201.3 7.0 6.7 H nC ₄ H ₉ - 66 68 C ₁₁ H ₂₁ ONS *) 215.3 6.5 6.6 H HC ₅ H ₁₁ - 80 39 C ₁₂ H ₂₃ ONS *) 229.3 6.2 5.0 H n- C ₆ H ₁₃ - 41 35 C ₁₃ H ₂₅ ONS ⁵ ) 243.4 5.8 5.7 H nC ₇ H ₁₅ - 88 56 C ₁₄ H ₂₇ ONS *) 257.4 5.5 5.8 H nC ₈ H ₁₇ - 87 43 C ₁₅ H ₂₉ ONS *) 271.4 5.2 5.2 H nC ₉ H ₁₉ - 88 65 C ₁₆ H ₃₁ ONS *) 285.4 4.9 4.3 H nC ₁₀ H _ai 90 58 C ₁₇ H ₃₃ ONS *) 299.5 4.7 7, o H - (CEy ₄ - 87 173 C ₁₈ H ₃₂ O ₂ N ₂ S ₂ *) 372.5 7.5 7, i A. - (CH ₂ ), - 88 138 C ₁₉ H ₃₄ O ₂ N ₂ S ₂ *) 386.6 7.3 6.0 A. CeH ₅ 80 114 C ₁₃ H ₁₇ ONS ⁶ ) 235.3 6.0 6.4 H: B = i: i PH ₃ C- C ₆ H ₄ - 90 124 C ₁₄ H ₁₉ ONS ⁶ ) 249.3 5.7 5.3 H: B = i: 2 p-Cl —C ₆ H ₄ - 98- 136 C ₁₃ H ₁₆ ONSCl ⁶ ) 269.7 5.2 H: B = i: 2

¹ J The yield data refer to the crude product.

² ) All melting points are not corrected.

³ ) H = hexane; A = ethyl alcohol; B = benzene.

⁴ ) The reaction was carried out in a solvent mixture which consisted of 4 parts by volume of concentrated sulfuric acid and ϊ part by volume of glacial acetic acid. The reaction time was 20 to 24 hours.

⁵ ) Same solvent mixture. Reaction time 5 hours. ¹² 5 ⁶ J The reaction was carried out in concentrated sulfuric acid. The reaction time was 6 hours.

Table 2
N-isopropyl-monothiocarbamic acid-SR-ester from isopropyl alcohol and R-SCN or NCS-R-SCN

R = the end
booty ¹ ) Solution
medium ³ ) F. ⁰ C ² ) Gross formula Mole
weight N analyzes in ° / " found % calculated 10.4 CH ₃ - i8 H 75 C ₅ H ₁₁ ONS *) 133.2 10.5 9.5 25th H 60 C ₆ H ₁₃ ONS *) 147.2 9.5 9.3 - (CH ₂ I ₄ - 48 A. 166 C ₁₂ H ₂₄ O ₂ N ₂ S ₂ *) 292.4 9-6 6.5 PH ₃ CC ₆ H ₄ - 49 H: B = i: i 96 to 97 C ₁₁ H ₁₅ ONS *) 209.3 6.7 8.8 PC ₆ H ₄ - 90 A. 203 to 204 C ₁₄ H ₈₀ O ₂ N ₂ S ₂ *) 312.4 9.0

^x ) to ³ ) as in table 1.

⁴ ) The reaction was carried out in concentrated sulfuric acid. The reaction time was 4 to 6 hours.

Table 3
N-tert-butyl-monothiocarbamic acid-SR-ester from tert-butanol or isobutylene and R-SCN

R =

Yield ¹ )

Solvent ³ )

Gross formula

Molecular weight

N-analyzes calculated in% found ° 5

CH ₃ -C ₂ H ₅
C ₆ H ₅ -PH ₃ CC ₀ H ₄

25 13 40

H H H H

C ₆ H ₁₃ ONS *)
C ₇ H ₁₅ ONS *)
C ₁₁ H ₁₅ ONS *)
C ₁₂ H ₁₇ ONSS)

147.2
161.2
209.3
223.3

9.5 8.7 6.7 6.3

9.3 8.8

6.5 6.3

i) to ³ ) as in table 1.

⁴ ) The reaction was carried out in concentrated sulfuric acid with tert-butanol. The reaction time was 5 hours.

⁶ ) The reaction was carried out in sulfuric acid-glacial acetic acid (i: 6) with isobutylene. The reaction time was 24 hours.

Table 4
N-isobornyl-monothiocarbamic acid RS-ester from camphene and R-SCN or NCS-R-SCN

R = CH ₃ - the end
booty ¹ ) Solvent ³ ) F. ° C ² ) Gross formula Mole
weight N analyzes in ° / ₀ found C ₂ H ₅ - % calculated 6.9 HC ₄ H ₉ - 34 H 80 C ₁₂ H ₂₁ ONS ⁶ ) 227.3 6.2 6.3 nC ₅ H _u - * 9 H 9 ¹ C ₁₃ H ₂₃ ONS ⁵ ) 241.3 5.8 5.7 C ₅ H ₉ - *) 66 H 36 C ₁₅ H ₂₇ ONS ⁵ ) 269.4 5.2 5.3 - (CH ₂ J ₄ - 54 H 36 to 37 C ₁₈ H ₂₉ ONS ⁵ ) 283.4 4.9 5.3 C ₆ H ₅ - 76 H III C ₁₆ H ₂₇ ONS ⁵ ) 281.4 5.0 5.4 PH ₃ CC ₆ H ₄ - 60 H 64 C ₂₆ H ₄₄ O ₂ N ₂ S ₂ ⁵ ) 48o, 7 5.8 4.7 P-Cl-C ₆ H ₄ - 85 H 90 C ₁₇ H ₂₃ ONS ⁵ ) 289.4 .4.9 5.2 PC ₆ H ₄ - 48 H 75 C ₁₈ H ₂₅ ONS ⁵ ) 303.4 4.7 51 H 103 C ₁₇ H ₂₂ ONSCl ⁵ ) 323.8 4.3 6.1 64 H: B = i: 2 173 C ₂₈ H ₄₀ O ₂ N ₂ S ₂ ⁵ ) 500.7 5.6

^l ) to ³ ) as in table 1.

⁴ ) cyclopentyl -

⁵ ) The reaction was carried out in a sulfuric acid-glacial acetic acid mixture composed of equal parts by volume. The reaction time was 24 hours.

55 The experimental finding that only secondary and tertiary alcohols or olefins react with rhodanides is due to the fact that in secondary and tertiary alcohols the C - OH bond is looser than with primary alcohols. The basicity

60 of the alcohols takes in the order primary <secondary < tertiary too.

The same applies to olefins.

The reaction of the rhodanides with alcohols or olefins is reversible. When adding p-chloro- iao rhodanbenzene to a solution of N-cyclohexylmonothiocarbamic acid-S-phenyl-ester The following reaction was observed in sulfuric acid-glacial acetic acid :

C ₆ H ₅ -S-CO-NH-C ₆ H ₁₁ -I-Cl-C ₆ H ₄ -SCN ===== Cl-C ₆ H ₄ -S-CO-NH-C ₆ H ₁₁ -IC ₆ H ₅ -SCN

Example ι N-cyclohexyl-monothiocarbamic acid-S-methyl ester

3 g (0.03 mol) of cyclohexanol are dissolved in a mixture of 20 ecm of 25% strength sulfuric acid and 5 ecm of glacial acetic acid, which is cooled with an ice-common salt mixture. There is no noticeable increase in temperature and no coloration of the solution. 2.2 g (0.03 mol) of methyl rhodanide are then added dropwise to this mixture with stirring. Since the reaction mixture heats up when the rhodanide is added, the dropping in must be regulated so that the temperature in the solution does not exceed 0 °. After 24 hours storage in sealed vessel at about 3 to 5 ⁰ now become yellow solution is stirred into 200 cc of ice feinzerstoßenes.

Colorless crystals separate out and are filtered off with suction and dried on a clay plate.

The crude product is recrystallized several times from hexane. Yield of crude product: 2.35 g = 45% of theory. Colorless little needles made from hexane. F .: ii2 ° _;

Analysis:

Calculated: C = 55.4%; H = 8.7%; N = 8.1%; found: C = 56.1%; H = 8.5%; N = 7.7%.

Example 2 N-Cyclohexyl-monothiocarbamic acid-S-n-butyl ester

a) From cyclohexanol: The preparation takes place analogously to Example 1. 2.9 g (0.025 mol) of n-butyl rhodanide are obtained reacted with 2.5 g (0.025 mol) of cyclohexanol in 20 ecm of concentrated sulfuric acid and 5 ecm of glacial acetic acid. Yield of crude product: 4 g = 74% of theory. Colorless sticks made of hexane. F .: 68 °.

Analysis:

Calculated: C = 61.4%; H = 9.8%; N = 6.5%; found: C = 60.4%; H = 9.4%; N = 7.2%.

b) From cyclohexanol using 98% strength Formic acid instead of glacial acetic acid.

It is worked under the same test conditions and with the same amounts as in a), only that instead of glacial acetic acid the same volume of 98% Formic acid is used. By the action of the sulfuric acid on the formic acid occurs first low carbon oxide development, which does not interfere with the course of the reaction. Yield of crude product : 2.1g = 39% of theory. F .: 68 °.

A mixed melting point with the product shown in a) does not result in a depression.

c) From cyclohexene. 2.05 g (0.025 mol) of cyclohexene are dissolved in a mixture of 20 ecm of concentrated sulfuric acid and 10 ecm of glacial acetic acid, which is cooled with an ice-common salt mixture, and the solution turns brown. After 2.8 g (0.025 mol) of n-butylrhodanide have been added dropwise, the closed reaction vessel is kept in the refrigerator for 24 hours, the solution taking on a deep brown color. When stirred into ice, a yellow oil separates out, which solidifies to yellow-brown crystals after a few minutes. After suctioning off and drying, the crude product is recrystallized several times from hexane to which a little activated charcoal has been added. Yield of crude product: 3.15 g = 58 ° / ₀ of theory. Q .: 66 to 67 ⁰ .

A mixed melting point with the product shown in a) does not result in a depression.

d) From cyclohexanol. The preparation is carried out as in Example 1. 2.9 g (0.025 mol) of n-butyl rhodanide are obtained reacted with 2.5 g (0.025 mol) of cyclohexanol in 20 ecm of superchloric acid and 2 ecm of glacial acetic acid. In the Working up, colorless rods were obtained from hexane. F. = 68 °. A mixed melting point with that according to a) available preparation does not result in depression. The yield is 41%.

Example 3

i, 4-B1S-N, N'-cyclohexyl-monothiocarbamic acid

S, S'-n-butyl ester s ₀

To an on - 5 ⁰ cooled mixture in 20 cc of concentrated sulfuric acid and 5 cc of glacial acetic acid 2.5 g (0.025 mol) of cyclohexanol are added quickly. 1.75 g (0.01 mol) of i, 4-dirhodane butane are then slowly added dropwise with stirring, so that the temperature does not rise above 0 °. The sealed reaction vessel is held for 20 hours in the refrigerator at about 3 ⁰ and then stirred into ice feinzerstoßenes. A pale yellow colored, extremely viscous mass separates out, which only becomes uniformly crystalline after several hours of storage. After the crystals have been filtered off with suction and dried, they are recrystallized several times from alcohol. Yield of crude product: 3.2 g = 87% of theory. Alcohol needles. F .: 173 °. Analysis: N calculated 7.5%; found 7%.

Example 4

N-Cyclohexyl-monothiocarbamic acid-S-phenyl ester

From cyclohexanol and phenylrhodanide: 2.5 g (0.025 mol) of cyclohexanol are dissolved in 20 ecm of concentrated sulfuric acid with shaking. The solution is then in an ice-mix saline on ⁰ · -5 cooled and slowly 3.5 g (0.025 mol) Phenylrhodanid added dropwise, so that a temperature rise is avoided above 0 °. If the temperature rises slightly, the solution turns red. The closed reaction vessel is kept for 6 hours at 0 ° and then stirred into 250 ecm of ice water. Yellow crystals separate out instantly, which are sucked off and dried on a clay plate. The crude product is recrystallized several times from a mixture of hexane and benzene consisting of equal parts by volume, some activated carbon being added. Yield of crude product: 4.7 g = 80% of theory. Colorless small crystals. Q .: 114 ⁰ . Analysis: N calculated 6%; found 6%.

Example 5

N-Isopropyl-monothiocarbamic acid-S-methyl ester 1.8 g (0.03 mol) of isopropyl alcohol are dissolved in 25 ml of concentrated sulfuric acid. This solution is cooled in a freezing mixture to -5 ⁰ and slowly comparable with 2.4 g (0.033 mol) Methylrhodanid; ow. When the temperature is increased slightly, the solution turns faintly yellow. That locked

This reaction vessel is kept for 6 hours and then slowly stirred into 300 ecm of finely crushed ice. At the moment, colorless crystals separate out, which are sucked off and dried on a clay plate. The crude product is recrystallized several times from hexane. Yield of crude product: 0.7 g = 18% of theory. Colorless little sticks made of hexane. Q .: 75 ⁰

Example 6

i, 4-bis-N, N'-isopropylmonothiocarbamic acid-S, S'-methyl ester

Production takes place as in Example 5. 1.5 g (0.01 mol) of 1,4-dirhodanobenzene and 2 g (0.02 mol) of isopropyl alcohol are reacted in 20 ecm of concentrated sulfuric acid. The crude product is recrystallized from alcohol. Yield of crude product: 2.8 g = 90% of theory. Colorless little needles made from alcohol. F .: 203 to 204 ⁰ (Z.)

Example 7 N-tert-butyl-monothiocarbamic acid

S-methyl ester

20 ecm of concentrated sulfuric acid, which are cooled in an ice-table salt mixture, are added with 2.2 g (0.03 mol) of tert-butanol. Since the alcohol is hardly soluble in sulfuric acid, it must be done mechanically be stirred. 2.4 g (0.033 mol) of methyl rhodanide are slowly added dropwise to this mixture, with a slight increase in temperature occurs. Stirring is continued for 5 hours; after that time is the reaction mixture is completely homogeneous and pale yellow in color. When stirring into 250 ecm ice Colorless crystals separate immediately after vacuuming and drying on a clay plate be recrystallized several times from hexane. Yield of crude product: i, ig = 25% of theory. Small crystals of hexane. F .: 88 °.

Example 8 N-tert-butyl-monothiocarbamic acid-S-phenyl ester

a) From phenylrhodanide and tert-butanol: The preparation is carried out analogously to Example 7. 3.5 g (0.025 mol) of phenylrhodanide and 1.85 g (0.025 mol) of tert-butanol are reacted in 25 ecm of concentrated sulfuric acid. The yellow colored crude product is recrystallized from hexane with the addition of some activated charcoal. Yield of crude product: 2.1 g = 40% of theory. Colorless long hexane needles. Q .: 115 ⁰ . Analysis:

Calculated: C = 63.1%; H = 7.2%; N = 6.7 ° / ₀ found: C = 63.5%; H = 7.5%; N = 6A ⁰ Io-

b) Made of isobutylene and phenylrhodanide: In a 100 ecm three-necked round-bottomed flask equipped with a gas inlet tube, Thermometer and potassium chloride tube is provided, you add 30 ecm of glacial acetic acid and 5 ecm of 95% strength Sulfuric acid. The mixed solvent is cooled in an ice bath and added dropwise with 7 g (0.05 mol) phenylrhodanide added. Care is taken that the temperature does not rise above 10 °. At the same time, a weak stream of isobutylene is introduced. After 40 minutes, the gas inlet

stopped after 6 g (0.107 mol) of isobutylene are dissolved in the reaction mixture. The now yellow solution is stored in the closed reaction vessel at 10 ° for 24 hours. During the subsequent stirring into 250 ecm of ice water, a yellow oil separates out, which after several hours of storage in the refrigerator cannot be made to crystallize. It is therefore extracted with ether, the ether is dried over calcium chloride and then distilled off. The residue is subjected to vacuum distillation. 5.5 g of unchanged Phenylrhodanid distilled off at 71 to 73 ⁰ (1.5 mm).

A brownish yellow mass remains as a residue, which is recrystallized from hexane. Yield of crystalline residue: 0.7 g = 7% of theory. Colorless hexane needles. Q .: 115 ⁰ .

A mixed melting point with the product shown in Table 3 does not result in a depression.

Example 9
N-Isobornyl-monothiocarbamic acid-S-methyl ester

In a mixture of 10 ecm more concentrated Sulfuric acid and 10 ecm of glacial acetic acid, which is cooled in a weak cold mixture, are dissolved 3.5 g (0.025 mol) of camphene with swirling. The solution turns yellow. While stirring one then adds 1.85 g (0.025 mol) of methyl rhodanide dropwise, whereby a slight Temperature increase occurs. The dropping is regulated so that the temperature does not rise above 0 °. The closed reaction vessel is kept between 3 and 5 ° for 24 hours and then stirred into 200 ecm of ice water. A gray-white smear separates out after several hours Store solidified in crystalline form. After the crude product has been filtered off with suction and dried, it is crystallized several times from hexane. Yield of crude product: 1.9 g = 34% of theory. Colorless panels off Hexane. F .: 8o °.

Analysis:

Calculated: C = 63.4 ° / ₀ ; H = 9.3%; N = 6.2%; found: C = 63.0 ° / ₀ ; H = 8.9 "/"; N = 7.0 "/".

Example 10 N-Isobornyl-monothiocarbaric acid S-4-tolyl ester

Production takes place as in Example 9. 3.7 g (0.025 mol) of p-tolylrhodanide are reacted with 3.5 g (0.025 mol) of camphene in 10 ecm of concentrated sulfuric acid and 10 ecm of glacial acetic acid. When the reaction mixture is stirred into ice water, a brown smear separates out, which remains unchanged after storage in the refrigerator for 24 hours. It is therefore extracted with ether and the ethereal solution dried over sodium sulfate. After the ether has been distilled off, the viscous residue is subjected to vacuum distillation. Between 85 and 90 ⁰ (1.5 mm) some unreacted p-Tolylrhodanid distilled off. After the distillation has ended, the residue becomes crystalline on cooling.

The yellow-brown crude product is recrystallized several times from hexane with the addition of some activated charcoal. Yield of crude product: 3.6 g = 48%

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the theory. Colorless small crystals of hexane. F .: 75 °. Analysis: N calculated 4.7%; found 5.2%.

Claims (1)

PATENT CLAIM: Process for the preparation of N-substituted thiocarbamates or N, N'-disubstituted bisthiocarbamates, characterized in that rhodanides of the form ₁ SCN or R ₁ (SCN) ₂ , in which R _{1 is} an aliphatic, aromatic or alicyclic radical, with secondary or tertiary aliphatic or cycloaliphatic acid-resistant alcohols or the corresponding olefins in the presence of acids, preferably sulfuric acid, at about ο to 20 ⁰ and the reaction product is then hydrolyzed. Considered publications:
Ber. German former Ges. '81, 417 to 422 [1948]; 82, [1949]. © 609 738/371 12.56 (709 532/268 5. 57)