DE1493728A1 - Process for the preparation of aminophenylthioethers - Google Patents

Description

U93728 FARBENFABRIKEN BAYER AG

'LlVlItEUSlN'

Fy / IB U - · ~ - * "~ ^ lm ^ .AI« il «f July 16, 1965 PROCEDURE FOR THE PREPARATION OF AMINOFHENYLTHIOATHERS

It has been found that if necessary, substi in the core tuierte o- or p-aminophenylthioether is obtained if one Nitrohalogenobenzenes of the general formula which are optionally substituted in the nucleus

respectively.

in which

Zi, Z ₃ , Y ₁ and Y ₂ ^! stand for identical -od -.r different, optionally substituted radicals such as hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl ·, alkoxy, alkenyloxy, aryloxy, alkylthio, arylthio or a heterocyclic radical, |

Y ₁ and Y _{2 can} also be halogen and X is halogen,

are reacted in a molar ratio from about 1 to about 2.5 with sodium sulfide in aqueous suspension at temperatures of about 0 to about 2QO ⁰ C and without isolation of the aminothiophenols the aqueous alkaline solution of the Aminothiophenolates formed, optionally with the addition of a water miscible organic solvent, at temperatures alkylated from about 0 to about 100 ⁰ C at the sulfur atom or arylated and the resulting Aminophenylthioäther isolated. ι / Le A 9563 - 1 -

The optionally substituted aminophenylthioethers obtainable by the process and partly new and correspond to the general formula

respectively.

in which

% x , Z _t , T ₁ and Y _{1 have} the meaning given above and

A for «an optionally substituted alkyl (with 1 to 20 carbon atoms), alkenyl (with 1 to 10 carbon atoms), cycloalkenyl (with 5 to 8 Ring carbon atoms) or aryl radical and

η is 1 or 2, where in the case of η = 2

A represents an optionally substituted saturated or unsaturated bifunctional alkylene radical (having 1 to 10 carbon atoms), an optionally substituted arylene radical or A _r alkylenr, est.

The following are preferably mentioned as radicals Z ₁ , Z _a , Y ₁ , Y ₂ and X: alkyl radicals with 1 to 20 carbon atoms, alkenyl radicals with 2 to 20 carbon atoms, alkynyl radicals with 2 to 20 carbon atoms} cycloalkenyl radicals with 3 to β carbon atoms in the ring system; Aryl radicals such as phenyl, Napkfchyl,

Le A9563

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BATH ORIGINAL

Anthracenyl or phenanthrenyl radical and all halogens fluorine, Chlorine, bromine and iodine *

Examples of these radicals are: alkyl radicals such as methyl, ethyl, propyl, isopropyl, isobutyl, eexyl, dodecyl, octadeoylj alkenyl radicals such as vinyl, allyl, methallyl, isobutenyl, pentenyl, octenyl, butadienyl, methylbutadienyl, cyclohexanyl, cyclohexanyl, cyclohexanyl, cyclohexanyl, cyclopropanyl ; Cycloallcenylreete such as cyclopentenyl _t cyclohexenyl, Cyoloheptenyl or Cyclooctenylj alkynyl ä radicals as acetylenyl, Methylacetylenyl, pentynyl, or hexynyl} aryl radicals such as phenyl, tolyl, dimethylphenyl, Ifaphthyl, Phenanthrenylreet, an optionally ether (having 1 to 10 carbon atoms), thioether (with 1 to 10 carbon atoms, sulfoxide, sulfon, sulfinic acid, sulfonic acid, sulfonic acid ester (with 1 to 20 carbon atoms), sulfonic acid amide, N-mono- and Ν, Ν-dialkylsulfonic acid amide (alkyl radical with 1 to 10 carbon atoms), N-alkyl-N-phenylsulfonic acid amide (Alkyl with 1 to 10 carbon atoms), N, N-diphenyl- 'sulfonic acid amide, carboxylic acid, carboxylic acid ester (with 1 to 20 carbon atoms ^, carboxamide, N-mono- and N, N-dialkylcarboxamide (alkyl radical with 1 to 10 carbon atoms) N-alkyl ~ N-phenyloarboxamide (alkyl with 1 to 10 carbon atoms), N, N-diphenyloarboxamide, nitrile, hydroxyl, carbonyl, amino, alkylamino (with 1 to 20 carbon atoms), dialkyl mino (alkyl with 1 to 20 carbon atoms), arylamino- Le A 9563 - 3 -

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groups (preferably phenylamino) eubstituted radical such as methoxyphenyl, ethoxyphenyl, methoxynaphthyl, methyi-thiophenyl, diphenyl ether, diphenyl sulfide, diethyl sulfoxyd, piphenyl sulfoxyd, dimethyl sulfonic acid, methyl sulfonic acid, phenyl sulfone, , Phenylsulphonic acid, naphthylsulphonic acid, methyleulphonamide, phenyleulphonamide, toluenesulphonamide, ethyleulphonic acid ethyl ester, toluenesulphonic acid methyleter, acetic acid, propionic acid, β-chloroic acid, phthalic acid or jteromopropionic acid, acrylic acid, malonic acid, Terephthalic acid, n-butyric acid, isobutyric acid ^ ienyleseige acid, ri-heptyl acid, vinyl acetic acid, oleic acid, linolenic acid, methylol, ethanol, isopropanol, allyl alcohol, amyl alcohol, cyclohexanol, ootyl alcohol , Stearyl alcohol, benzyl alcohol, acetyl, propionyl, benzophenonyl radical, methylamine, dimethylamino, ethylamino, diethylamino, hexylamino, laurylamino, ethylenediamino, Xthanolami.no- , Allylamino, aniline, toluidine, anisidine, phenetidine, bromaniline, diphenylamine, benzidine, phenylenediamine, trichloroaniline or methylaniline radical, an alkoxy radical such as methoxy, xthoxy, propoxy, iso- ₄ propoxy , Allyloxy radical, an aroxy radical such as phenoxy, aminophehoxy, naphthyloxy, aminonaphthyloxy radical} a thioether radical such as methyl mercapto, ethyl mercapto, phenyl mercapto radical, the heterocyclic radicals e.g. of pyridine, picoline,

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Ohinolins, isoquinolines, 1,2,3,4-tetrahydroquinolines, indoles, Carbazoles, pyridazines, pyrimidines, pyrazines, quinoxalines, Acridines, indazoles, furans, tetrahydrofurans, thiophenes, Benzofurans, dibenzofurans, dioxanes, morpholines.

All monofunctional radicals A may be mentioned, for example: alkyl radicals such as methyl, ethyl, ieopropyl, hexyl, dodecyl, alkenyl radicals such as allyl, methallyl, pentenyl, cycloalkenyl radicals such as cyclopentenyl or oyelohexenyl, optionally with ether (with 1 to 10 carbon atoms), carbon atoms with 1 to 10 carbon atoms ), Sulfoxide, sulfon, sulfinic acid, sulfonic acid, sulfonic acid ester (with 1 to 20 carbon atoms), sulfonic acid amides N-Moho- and N, IT-dialkyl sulfonic acid amide (with 1 to 5 carbon atoms), N-alkyl-N-phenyl sulfonic acid amide (with 1 to 5 Carbon atoms), carbonic acid, carbonic acid ester (with 1 to 20 carbon atoms), carbonic acid amide, T-mono- and Ν, Η-dialkyl carbonic acid amide (with 1 to 5 carbon atoms), N-alkyl-N-phenyl carbonic acid amide ^ (with 1 to 5 carbon atoms) Nitrile, hydroxyl, carbonyl, I amino, F-alkylamino (with 1 to 20 carbon atoms), N, N-dialkylamino groups (with a total of 2 to 20 carbon atoms) eubstituted reed, which is connected via a carbon atom Let the sulfur atom bond, such as methoxymethyl, ethoxymethyl, Ieopropoxymethyl, methylthiomethyl, ethylthiomethyl, methyleulfinylmethyl and Äthylaulfonylmethylreetf also the sea of a methane sulfonic acid, ethane sulfire. acid, ÄthaneulfonsHure, vinylsulfonic acid, an Äthaneulfoneäuremethyleeter, Äthansulfoneäureamide, the reed of . ' ; _ - »-« 9g3S / 1515

German

Acetic acid, propionic acid, ethyl acetate, acetamides, Acetonitrile and a ß-hydroxyethyl, oC-phenoxymethyl-ßhydroxyäthyl, oC-methyl-ß-hydroxyethyl, oC-chloromethyl-ß-hydroxy-

tthyl, oL-phenyl-ß-hydroxyethyl, acetonyl, aeeto-

phenonyl, ß-aminoethyl, ß-mercaptoethyl radical or an aryl

rest (preferably phenyl and naphthyl), in o- and / or p-position to the sulfur atom with substituents of the 2nd order such as

J ³ ß P

i-NOg, -CN, -COOH, -CF ₈ , -f , -C, -C -SO ₂ H, azide-, ^V H CH ₈ ° 6 ^H 5- »

Dlazonium groups, trialkylammonium groups, sulfonium groups, Carboxylic acid ester groups (with 1 to 10 carbon atoms), Carboxamide groups, N-mono- and Ν, Ν-dialkylcarboxamide (Alkyl radical with 1 to 10 carbon atoms), N-alkyl-N-phenylcarboxamide (Alkyl with 1 to 10 carbon atoms), Ν, Ν-diphenyloarboxamide, sulfonamide groups, N-mono- and N, I-dialkyl sulfonic acid amide (alkyl radical with 1 to 10 carbon atoms) , N-alkyl-N-phenylsulfonic acid amide (alkyl with 1 up to 10 carbon atoms), N, N-Diphenylsulfonsäureamid occupied is, means.

As bifunctional radicals A selenium mentioned for example: -CHg-CH ₁ -J- (CHg) ₈ -, - (CHg) ₄ -, - (CHg) ₈ -, -CH ₂ -CH = CH-CHg-, -CHg- CSC-CHg-, arylene radicals such as 2,5-dinitrophenylene-t aralkylene radicals such as the p-xylylene radical or an ether (with 1 to 10 carbon atoms), thioether (with 1 to 10 carbon atoms), sulfoxide, sulfonic acid, sulfinic acid , SuIfon-

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': - ■■ SAD

U9372.8

acid esters (with 1 to 20 carbon atoms), carbonamide, Nitrile, hydroxyl, carbonyl, amino, alkylamino (with 1 bie 20 carbon atoms), arylamino groups substituted alkylene radical (with 1 to 20 carbon atoms) such as;

-OH - CH- -OH-OH, -OH, -CH- -CH, -CH-CH, -0-CH ₈ -CH-CH ₈ HO-H, C CH, -OH OH OH OH OH

■ '· ■ ·

-0-0H ₈ -OH-CH, - -CH ₁ -CH-CH, _{-N-CH 8} -CH-CHr OH OH ^ OH

O.

NH, -OH, -CH-OH-CH, -NH, -CH-CH, -CH, -OH- -OH, -0-OH, ό CN CN

-CH ₁ -C-OH ₁ -

-CH ₈ -S-CH ₈ - -CH ₈ -N-CH, - -CH CH-

CH ₈ CH ₈ OH ₈

SO ₈ H SO ₈ H

-CH ■ CH- Qg . , Qjj ■■

° ^{Om έθΟΗ} COHH, COSH,

Examples of alkylating and arylation agents used for the process are: dimethyl sulfate, diethyl sulfate, dipropyl sulfate, 2-chloropropane, allyl chloride, methallyl chloride, l-chloropentene-2.3 _t 1-chlorocyclopentene-2,3, l-chlorocyclohexene 2,3, 1,4-dichlorobutene-2,3,

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U93728

1,2-dichloro-3-butene-4, chlorodimethyl ether, chloromethyl ether, chlorinethylopropyl ether, chlorodimethyl sulfide, Chloromethylethyl sulfide, chlorodimethyl sulfoxide, chloromethyl ethyl sulfone, chloromethane sulfonic acid, ß-chloroethanesulfinic acid, Vinyl sulfenic acid ester, ß-chloroethane sulfonic acid, ß-chloroethane-BUlfonamide, chloroacetic acid, ethyl bromoacetate, chloroetamide, chloroacetonitrile, ol-chloropropionic acid, chloroacetone, Chloroetophenone, zti-bihydroxy-ohloracetophenone, 1,3-dichloro

• acetone, l, 4 ~ Diohlor-adipinsauredinitril, bis-dichloromethylether, 1,3-dichloropropane-2-sulfonic acid, 1,2-dichloro-succinic acid, ethylene oxide, propylene oxide, epichlorohydrin, phen-.oxypropylene oxide, butylene oxide, butadiene dioxide, Styrene oxide, 1,2-epoxy-1-ethyl-1-phenylethane, 1,2-dimethylethylene oxide, anethole oxide, bit - ^ ?, 3-epoxypropySZäther, 1 ^ -Bie-ZJ ^ -epoxypropyloxj ^ -benzene, ethyleneimine, cyolohexenimine, Styrenesulfide, p-chloronitrobenaol, o-chloronitrobtneol, 3i4-diohlomitrol> enzol 2,4-dinitrochlorbenaol, 3-chloro-4-nitroacetanilide _t ·% Ϋ́ <* ·. 2-nitro-5-chloroacetanilide, 2,5-dichloro-4-nitroacetanilide, 4-chloro-3-nitro-benzoetrifluoride, 6-chloro-3-nitro-benaonitrile, 3,4,5-trichloronitrobenzene, 2,3 »4-trichloronitrobenzol, o-chlorobenzoic acid, p-chlorobenzoic acid, p-chlorobenzenesulfonic acid, p-chlorophenyldiazonium chloride, p-chlorophenyltrimethylammonium chloride, p-bromoacetophenone, o-chlorobenzophenone.

The process is explained using the example of the reaction of 3,4-dichloro-nitrobenaol with allyl chloride:

Le A 9563 - 8 -

S0Ö83S / 1S1S

NO ₃ - (/ ^ -Cl + 2.5 Ka ₈ S +1.75 H ₈ O

'Cl

0.75 Na ₈ S ₈ O ₈ +1.5 NaOH + NaCl

Cl

H ₈ N- ^ A-SNa + "Cl. - CH ₈ -CH = CH ₈ NH ₈ - / ~ AS-CH ₈ -CH = CH ₂ +

NaCl

The reaction of the optionally substituted ο- and p-Nitrohalogenbenzoie with sodium sulfide is carried out at about 0 to about 200 ⁰ C, preferably at 50 to 150 ⁰ C is performed. The optionally substituted nitrohalogenobenzene is suspended in water and the suspension is heated ¹ to 100 ⁰ C, for example. One, preferably about 20, is added dropwise to this suspension

warmth
up to about 50 ° C / solution of sodium sulfide so quickly that the reaction temperature remains at about 105 ° C without external heat supply. After completion of the addition for about 15 hours under reflux is heated at about 105 ⁰ C in general. The reaction can be accelerated by increasing the pressure and the temperature. The yields of amino-thiophenolates are over 90% of theory. The mole ratio of nitrohalobenzene to sodium sulfide is about 1 to about 2.5.

The aminothiophenolate solution thus obtained is added

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- after filtration has taken place at about 5 ⁰ C - at about 0 to about 100 ⁰ C, preferably at 20 to 40 ⁰ C, slowly the alkyl

lating or arylation agents - preferably in the molar - *

holdings of about 1: 1-, if necessary using Jj

formation of an organic water-miscible solvent, GO

such as methanol, ethanol, isopropanol, fetrahydrofuran or ^

Dioxane. .oo

When using alkylating or arylating agents with particularly reactive halogen atoms, it can be useful to work in the presence of a buffer system, e.g. an alkali or alkaline earth phosphate or hydrogen carbonate. However, it is preferred to provide the buffer system in the reaction mixture by adding organic carboxylic acids such as formic acid, Acetic acid, propionic acid or benzoic acid.

The reaction time is about 1 to 10 hours, preferably 2 to 4 hours.

The batches are worked up and the aeinophenylthioethers formed are isolated in the customary manner. The method according to the invention for the preparation of 2- and 4-aminoarylthioethers has a number of considerable advantages. It starts from easily accessible starting materials, uses only simple auxiliary materials, is used under mild reaction conditions carried out and supplies aminoarylthioether in a simple way Catfish in excellent yields and high purity. In addition, the process is also easy to carry out continuously.

Although it is already known, some of the compounds accessible by the process by reduction of corresponding compounds To produce haloaryl thioether. This known method

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ΛΑ

(Journal of the American Chemical Society jS6, pp. 874-825 (1944)) has several disadvantages. In most cases, the required nitrothiophenols are difficult accessible and their implementation to the nitrothioethers also causes difficulties. Also, the reduction must to the amine can be carried out as a separate step after isolation.

It is also already known that some of the abovementioned meroaptoanilines can be obtained by alkylating the isolated aminothiophenols on sulfur in a non-aqueous medium (months booklet 88, pp. 822-829 (1957)). This procedure too does not come into imprint for an implementation on an industrial scale, because the isolation of the aminothiophenols after their per se, simple representation from the corresponding nitrohalobenzenes is accompanied by a very strong auto-oxidation to dieulfide, which can only be excluded with difficulty and the yield is considerably reduced. For example, the o-amino-thiophenol is not, as it would be obvious, from the f o-nitro-chlorobenzene by reaction with sodium sulfide, but rather represented by alkaline hydrolysis of behzothiazole E.P. 558 887 Monsanto Chemicals Limited "U.S.A. .P. 2,791,612 American (jyanamid Company).

Some other known special processes for the preparation of aminoarylthioether are multi-stage and complicated (Journal of the American Chemical Society 80, p. 4939 toie 4940J BeIg. Patent 645 615). Le A 9563 -U - ORIGINAL BATHROOM

The method according to the invention, on the other hand, provides the desired ones o- or p-Aminophenylthloether in technically simple catfish in high purity and good yields in one operation.

The odor nuisance and the dangers when handling the thiophenols, some of which are toxicologically unacceptable turned off in the process according to the invention. In addition, there are reductions in yield due to the formation of bisulfides -I-, as occurs in the isolation of the free autoxidizable thiophenols are inevitable - prevented. Bs is pronounced as Surprisingly to denote that the selective alkylation or Arylation of Amlnothlophenolate on sulfur in an aqueous reaction medium trots the additionally present reactive Hebenet off β such as thioeulfate anions, hydroxyl anions and of the residues of sulfide anion and the amino phenyl thioethers in yields above 80 ° C of theory (based on Nitrohalogenbenzene used) and obtained high purity

* .will.

I ■ ■. '·

The products obtainable by the process are only partially known and can be used, for example, as intermediates for the production of pharmaceuticals and dyes are used. Above all, however, they can be used directly as aoarioids. They show low toxicity to warm-blooded animals and phytotoxicity have a stronger acaricidal effect than Parathion. The effects set in quickly and last a long time. The active ingredients were used against Tetranychus urticae (common

300 835 / $ 151 Le A 9565 - 12 -

BAD ORJGHNAL

H93728

Spider mites) on bean plants that are strong with all stages of development the common spider mite were used.

After the specified times, the effectiveness of the active ingredient preparation was determined by counting the dead animals. The degree of destruction obtained in this way is given in i » : ,,

Active ingredient:

Concentration degree of destruction after 8 days

NO ₈ - (/ VO-P (OC ₈ H ₆ ) ₂

It

(Parathion)

0.2

20th

C, CH ₈ -S-

Cl

0.2

0.02

0.002

100

100

20th

Cl C ₈ H ₆ -S-

-NH ₈

Cl

0.2 100 0.02 98 0.002 70

Cl

C ₅ H ₇ -S-

-NH ₂

0.2

0.02

100 70

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Active ingredient:

Concentration ^

Degree of kill in after 8 days

Eq

Cl

Cl

(CH ₈ ) _t CH-S-A -NH ₂

Cl

0.2

0.2 0.02

70

100 70

Cl

GH, = CH-CHj -S-

Cl

Br
CH ₈ -S- ^ A-NH ₂

Br

0.2 0.02

0.2

100 70

The method according to the invention is carried out by the following Examples explained:

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example 1

a) 158 g (1 mol) of p-nitrochlorobenzene and 500 ml of water are placed in a four-neck flask with a volume of 4 liters, equipped with a stirrer, dropping funnel, internal thermometer and reflux condenser. The mixture is then heated to 100 ^° C. and a warm solution of 340 g (about more than 2.5 mol) of Na ₈ S ^ Ag in 670 ml of water is added dropwise with stirring. The dropping speed is measured in such a way that the temperature remains ^{at around 100 ° C. without external heat input.} Upon complete addition, the Ka triumsulfidlösung maintaining the reaction solution ϊ a further 15 hours at 105 ⁰ C (reflux). The mixture is then cooled to +5 ⁰ O with stirring, the small amount of crystalline by-products which have precipitated is filtered off with suction and the clear solution is processed further.

a)
b) 1 mol (158 g) of p-nitro-chlorobenzene is added at room temperature to the solution of p-amino-thiophenolate obtained after / and the mixture is stirred for two hours. It is then slowly heated to 90 ^° C., held at this temperature for 4 hours and allowed to cool while stirring. The precipitated crystals are filtered off with suction and dried in a drying cabinet. Yield of p-amino-p '^ diphenyl sulfide 86 to 88 * of theory * F .: 139 to 141 ⁰ C.

Analysis i C * ₄ H ₁₀ O ₈ N ₂ S (molar weight 246, 22)

0 H 0 N S-Ber.i 58.53 * 4.09 * 12.95 * 11.38 * 12.95 j 58.47 * 4.10 * 13.02 * 11.42 * 12.70 *

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U93728

in an analogous way one obtains:

When using 2,5-dichloro-4-nitro-acetanilide at room temperature the thioether of the formula

NH.CO.CH ₈

NH ₁ -

F. 230 to 231.5 C.

Analysis: C ₁₄ H _1x O ₈ N,

C.
49.98 *

lSCI

Ber .:
Found:

49.59 *

(Molecular weight 337.69)

O N

14.22 * 12.46 *

3.58 * 14.16 * 12.73 *

H
3.56 *

S Cl

9.5 * 10.39 * 9.27 * 10.35 *

Using 2,5-dichloro-4-nitroacetanilide at 90 C the thioftther of the formula

-Cl

NH, -

F .: 215-216 ° C

Analysis: C _1X H ₁ QO _x N ₁ SCl (molar weight 295.65)

C H ON

Ber .: 48.8 * 3.38 * 10.84 * 14.25 *

Found: 48.73 * 3.38 * 10.95 * 14.38 *

S Cl 10.84 * 12.02 *

10.55 * 11.75 *

When using 3-chloro-4-nitroacetanilide at 90 C the thioether of the formula

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BATH

U 93 728

F .: 193 to 194 ⁰ C.

Analysis: C ₁₁ E _xt O ₈ N ₈ S (molar weight 261, 23)

C H 0 N S

Bex .: 55.17Ji 4.24 * 12.25 * 16.09 * 12.25 *

Found: 55.89 * 4.49 * 12.27 * 15.78 * 11.30

When using 2-nitro-5-chloroacetanilide at room temperature, the thioether of the formula,

NH-CO.CH ₈

-NO,

P.! 167 to 169 ⁰ C

Analysis: C ₁₄ H ₁₈ O ₈ N ₈ S (molar weight 303.27)

C H 0 N S

Ber .: 55.44 * '4.32 *, 15.80 * 13.80 * 10.44 *

Found: 54.78 * 4.38 * 16.00 * 13.86 * 10.57 *

In an analogous way one obtains: With 2-Sitro-5-ehloracetanilid at 90 ⁰ C the thioether the

formula

NH ₈ 'J

HH ₈ - / ~ \ -S- / ~ ^ -N0 _s

P .: 162 to 163 ⁰ C

Analysis: C ₁₂ H ₁₁ O ₃ N ₈ S (molar weight 261 »23)

Ber .: 55 C.
.17 * H
4th 24 * 12th 0
.25 * 16 N
.09 * 12th S.
25 * Found j 55 .18 * 4th 33 * 12th .47 * 16 .20 * 12th 15 * 1
Le A - 17th

With 4-chloro-3-nitrobenzotrifluoride at room temperature the thioether of the formula

-S- ß \ -CF ₈ HO,

f.ι 84 to 85 ⁰ G

Analysis: C ₁₈ H ₉ O ₁ KjSF ₈ (molar weight 314.21)

18.15%

Ber .: C.
49. 6% 2 H
.87% 8th N
.9% 10. S.
20% Found: 49. 54% 3 .13% 8th .86% 10. 20% example 2

a) The solution of o-chloro-p-aminothiophenolate is made from 192 g

(1 mol) 3,4-dichloro-1-nitrobenzQl obtained analogously to Example 1 a).

b) 1 mol (192 g) of 3,4-Liohlor-1-nitroeenaol is added to the solution of o-chloro-p-amino-thiophenolate at room temperature and the mixture is stirred for two hours. Danaoh is slowly warmed to 10O ⁰ C, Holds 5 hours at this temperature and lets cool while stirring. The precipitated crystals of p-amino-p ¹ -

nitro-o, 0'-dichlorodipheny! sulfide of the formula

Cl

egg

are suctioned off and dried in a drying cabinet. Yield 83 to 85% of the Sheoriej fi 133 to 135 ⁰ C L e A 9563 - 18 -

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Analysis:

(Molecular weight 315.16)

Ber .: 45 C.
.6 Ji H
2. 52ji 10 0
.15Ji K
8th. Λ 9 Ji S.
10.15Ji 22nd Cl
.46Ji Found: 45 .76 * 2. 91Ji 10 .16Jl Θ. 86jt February 10th 22nd .40Ji example 3

158 g (1 mol) of p-nitrochlorobenzene are added to the solution of o-chloro-p-ftminothiophenolate according to Example 2a) at room temperature and the mixture is stirred for two hours. The mixture is then slowly heated to 100 ^° C., kept at this temperature for 5 hours and then allowed to cool while stirring. The precipitated crystals of p-aminoo-chloro-p'-nitrodiphenyleulfida are filtered off with suction and dried in a drying cabinet. Yield 81Ji of theory | l, t 148 to 150 ⁰ C.

NH ₈ -

Analysis: C ₁₂ H ₉ O ₂ NjSCl (molar weight 280.67)

Ber. : 51 C.
.4 Ji H
3. 21Ji 19th 11 0
.40Ji H
lO.OOji • S
¹ Il .40Ji Cl
12.62 Found ι 51 .24Ji 3. 40Ji 11 .47Ji lO.Oljt 11 .60Ji 12.6C Le A α.? ⁶ ?

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SLO

Example 4

To the solution of p-amino-thiophenolate according to Example 1 a) 60 g of glacial acetic acid and then a solution of 172 g (1 mol) of p-nitrobenzyl chloride in 400 ml of ethanol are added dropwise at room temperature. To complete the reaction, the reaction

misohung at 60 ⁰ C and maintained for 3 hours at this temperature.

After cooling, the resulting crystals become / p-aminophenyl

-p-nitrobenzylthioether filtered off with suction and dried. Yield: 75 * of theory; F. 99 to 10O ⁰ C.
j Analysis: C ₁₈ H ₁₈ O ₈ N ₈ S (molar weight 260.24)

ΒθΓ.Σ C.
59 .99 * 4th H
.65 * 12th 0
.29 * H
10.77 * S.
12th 29 * Gef ,: 58 .84 * 4th ♦ 60 * 12th .56 * 10.81 * 12th 00 * example 5

60 g of glacial acetic acid and then a warm solution of 202 g (1 mol) of 2,4-dinitrochlorobenzene in 800 ml of ethanol are added dropwise at room temperature with stirring to the solution of p-aminothiophenolate according to Example 1 a). When the addition is complete, the reaction mixture is left to react at room temperature for 5 hours. After cooling, the crystals of p-amino-p ¹ , o'-dinitrodiphenyl sulfide formed are sucked off, boiled with methanol and dried in a drying cabinet. Yield: 79% of theory; P. 154 to 156 ^° C. Analysis: C ₁₈ H ₉ O ₄ H ₅ S (molar weight 291.22)

Ber .: 49 C.
.47 * H
3.12 * 21 0
.98 * 14th H
.43 * 10 3
.95 * Found: 48 .95 * 3.34 * 21 .91 * 14th .39 * 10 .90 * Le A 95 - 20 - 809 * J35 / 1 51S

^BATH

U93728

In an analogous manner, one obtains with allyl chloride »auoh without Eieessigeueat *

H, 1 - / "A-S-CH, -GH = CH, from bp 113 to 114 ° C / 0.15 Torr,

When using τοη ChloreeaigBäure obtained asm ation without ice • MigSttMts dia fhioäther der? Ornel

HH, - / "" ^ - 5.CH, .COOH '

from f «i 197 to 198.5 ° C (decomposition) yy

If the amino group © is in the o-position to the sulfur, then form However, 1,4-thiaines.

Example 6

a) For the preparation of the o-aminothiophenolata one starts from o-Nitroohlorbensol and carries out the reaction analogously to Example 1 a) the end. Since the byproducts here are oily, they'll get through Removed steam distillation after the reaction. The cooled solution is filtered anaohllesssnd and added to further Conversions used,, "

b) To the solution of the o-amino-thiophenolete from a) is added at room temperature .158 g (1 Hol) of o-nitrochlorobenzene and stirred 2 hours. Thereafter, the mixture is heated slowly to 100 ⁰ C ₁ has four hours at this temperature and then allowed to cool with stirring. The o-amino-o'-nitrodiphenyl sulphide crystals which have fallen out of powder are filtered off with suction and dried. Yield 81 to 83 with the theory F. 82 to 84 ⁰ C

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_{B. r} ., 58.5, *

, 58.50 *

I »« »lied« way receives .an the formula .it, -nitro- ^ chlortolucl den

F. 104

r. 274.27)

Btr. Ι *> Α: .ί 61.2716 xo.il *

5.17 * U.WH 10.17 *

S 11.6 (

11.84 *

I "di. lift

"Ton pA.ino-m., H.nolat after Bipi.l 1.)" rt 10 W. H ⁰ O (1 MD Xthylenoxyd a. The P

IB ₁ - / ~ \ -S-OH, -OH, -OH

82 * 4 «r Tneori ·.

909835/151 5

bad o _RIGINAL

/ Zö

In an analogous way one obtains:

With ethylene oxide the thioether of the formula

NH ₂

-S-OH ₈ -GBa -OH

01
as an oil that is difficult to dilute. The urea of the formula obtained from reaction with phenyl isocyanate

HH-CO-NH- ß ~ \

I?

-S-OH ₂ -CH ₈ -0-C-8H- / ~ A,

melts at 194 to 195 C.

Analysis: Gj ₂ H ₈₀ O ₈ N ₈ SCl (molar weight 441.85)

C H Q H

Ber .: 59.7 * 4.559t 10.889t 9.51 *

Found 59-42 * 4.90 * 10.95 * 9.63

7 .; 6.16 *

Cl 8.02

7.80

In a corresponding manner, the thioether of the formula is obtained from 2-amino-4-ehlorthiophenolate and ethylene oxide:

NH ₈
r ^^ t- S-CH ₈ -CH ₂ -OH

Cl
obtained as an oil that is difficult to distill. The urea of the formula formed by reaction with phenyl isocyanate

HH-CO-NH

ä / .O INs-CH ₂ -CH ₈ -O-BH- / "

Le A9563

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BATH

U93728

melts at 186 to 188 ° C.

Analysis: C ₁₈ H ₂₀ O ₈ N ₈ SCl (Holgew. 441 * 85

Ber .: 59 C.
.7 96 4th H
5596 10. O
8896 9 N
.5196 7th S.
.2496 8th Cl
.0296 Found: 59 .1596 4th 9196 10. 9696 9 .5096 7th .2596 7th .7096 BeisDiel 8th

94.5 g (1 mol) of chloroacetic acid are added to the solution of o-chloro-p-aminothiophenolate according to Example 2 a) at room temperature. The temperature rises to 15 to 20 ⁰ C. Thereafter, the solution is kept for 5 hours at 8O ⁰ C, cooled to 10 ⁰ C, dropwise Izsäure to pH 4 to lO ^ S-owned and sucks the precipitated crystals of the formula

-S-CH, -COOH

away. Yield: 8996 of theory? F. 149 to 151 ⁰ C

Analysis: 44 ^C 8 ^H 8 ° ₂ NS01 ( . Follow w.217.6 6th 1) S.
14th .896 16 Cl
.3696 Ber .: 43 C.
.296 H
3.6896 0
14th 896 6th N
.4596 15th .2996 16 .3496 Found: .5196 3.8O96 15th 3396 .4896 example

A solution of 76.5 g (1 mol) of allyl chloride in 200 ml of tetrahydrofuran is added dropwise to the solution of o-chloro-p-aminothiophenolate according to Example 2 a) at room temperature with stirring. After complete addition, heat the contents of the flask at 60 ⁰ C, holding Le A 9563-24 -

909835/151 5

U93728

4 hours »at this temperature and let it cool down. The reaction product is deposited oily on the surface and can be separated. Purification is carried out by distillation in vacuo. The ^ p-amino-o-chlorphβnyl7-allyl sulfide solidifies in crystalline form in the template. F .: 36 to 38 ⁰ G; Yield: 839 * of theory.
Analyae: C ₉ H ₁₀ KSCl (molar weight 199.53)

CH N S Cl Ber.s 54.25Ji 5.02 * 7.043ί 16.1 * 17.8 *

Found: 54.425t 5.05 * 7.28 * 16.11 * 17.70 *

In an analogous way one obtains:.

From 2-amino-4-chlorothiophenolate and allyl chloride the thioether

the formula '

Cl- / \ -S. CH ₈ . CH «CH, bp 123 ° C / 0.09 torr ^; 'n | ° 1.6175 analysis »C ₉ H ₁₀ HSCl (molar weight 199 , 53)

C H Ii S Cl Ber.i 54.25 * 5.02 * 7 »04 * 16.1 * 17.8 *

Found J 54.45 * 5.08 * 7.16 * 16.30 * · 17.65 * "

From 2-amino-6-chlorothiophenolate and allyl chloride the thioether the formula /

J r-B.CH, .CH-CH ₈

01 '' ■■ '

Bp .: 107 ^ö C / 0.06 Torrr n | ° s 1.6206 Analyeej C ₉ H ₁₀ NSCl (molar weight 199.53)

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Ber.i C.
54.2536 5. H
0296 Found: 54.2136 5. 0336 example 10

AC U937.28

N S Cl

16,196 17,896

7.4996 15.736 17.5036

A solution of 62.5 g (1/2 mol) of 1,4-dichlorobutene in 200 ml of tetrahydrofuran is added dropwise to the solution of p-aminothiophenolate according to Example 1 a) at room temperature with stirring, heated to 60 ^° C. and held for 5 hours at this temperature. After cooling, the reaction product is deposited partly in crystalline and partly in an oily form on the surface. The aqueous layer is separated off and the 1,4-di- / p-aminophenylsulfide-7-butene-2,3 of the formula is crystallized

NH, - / \ -S-CH ₁ -C ^ CH-CH ₁ -S- rf \ -NH,

from aqueous methanol. 9 ": 115 to 13O ⁰ C (Cis-trana-Iao mere-Gemisoh); Yield! 79 pounds of theory. Analysis j CißH ^ NgSg (molecular weight 302.32)

Ber. s C.
63 .56? 6 6th H
.OO36 S.
21st 1736 9 N
.2796 Gef.j 63 .4636 6th .5436 22nd 0036 9 .3156 example U

a) The solution of the 2-amino-6-chlorothiophenolate is analogous to the example 1 a) when using 192 g (1 mol) of "2,3-dichloro-1-nitrobenzene obtain. Purification of by-products by steam distillation as in Example 6a).

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U93728

b) A solution of 154 g (1 mol) of diethyl sulfate in 300 ml of tetrahydrofuran is added dropwise to the solution of 2-amino-6-chlorothiophenolate according to a) at room temperature with stirring. After complete addition, heat the contents of the flask at 60 ⁰ G, kept for 4 hours at this temperature and allowed to cool. Of the

(2-Amino-6-chlorophettyl) -äthylthiöether of the formula

, Cl

-SC, H ₆

NH ₈

deposits oily on the surface and can be separated. The purification is carried out by distillation in vacuo. Bp. 109 to Ul ⁰ C / 0.05 Torr} nj " ⁰ = 1.6138; yield 79 * of theory.
Analysis: CqH ₁₀ NSCI (molar weight 187.53)

C H N S Cl Ber.:. 51.2 * 5.34 * 7.45 * 17.08 * 18.9 *

Found: 50.7 * 5.29 * 7.75 * 17.15 * 18.70 *

Example 12

To a solution of 2-methoxy-4-aminothiophenolate, which is prepared analogously to Example 1 a) from 1 mol of 6-chloro-3-nitroanieol, a solution of 126 g (1 mol) of dimethyl sulfate is added dropwise at room temperature with stirring 300 ml of tetrahydrofuran. After complete addition, heat the contents of the flask at 60 ⁰ C, holding for 5 hours at this temperature and allowed to cool. The reaction product is taken up in methylene chloride and purified by distillation in vacuo. The (2-methoxy-4-aminophenyl) ~ Le A 9563 - 27 -

909835/1516

methyl sulfide of the formula

-SOH,

eretarrt tn the original crystalline. Fs 91 to 93 ⁰ Cj yield 73 # of theory.

Example 13

In a procedure corresponding to the preceding examples, the following table can be seen Get connections:

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ORIGINAL

labe lie

O CO OO

constitution

Kp. Or P ⁰ C

N in% S in % O in # Cl in j

ber. - gef. ber. - gef. ber. - gef. ber. - eref,

HH ₈ - / A- SCH, (au p-Ajninothiophenolat and

HH ₁ - / Sy-SC, H,

(from p-aminothiophenolate and Diethyl sulfate)

HH ₈ - / \\ - S.CH ₈

HH, -

-SC ₈ H ₆

Cl- ß \ -SC ₈ H. BH ₈

101-101.5 ⁰ C / 07-10 03-10 23-00 22.55 0.0.6 torr

104-105 ⁰ C /
0.06 Torr

48-49.5

100-105 ⁰ C /
0.05 torr

100-105 ⁰ C /
0.05 torr

9, H 9.05 20.89 20.55

8.15 8.18 18.65 18.65

7.45 7.46 17.08 17.02

7.45 7.69 17.08 16.95

8.15 8.21 18.65 18.80

18.9 18.7 '

20.4 20.3 (

Le A9565

constitution

Table (Forte.) Kp. Bsv. F ⁰ CH In. * S in ber. - ff ^gf - ber. - gef

! 09 ⁰ C / 8.15 8.07 18.65 18.60

0.01 Torr 0 in * Cl in% b er. - found ber. - gef.

20.4 20.35

OCH ₈

ua »

91 -

.28 8.49 18.86 19.05 9.43 9.54

44 "46 8.28 8.24 18.86 18.80 9.43 9.57

^{80-82 0} C / 8.28 8.33 18.86 17.9 9.43 10.04 0.04 torr

OCH,

SCH ₈

HH,

93-95 ⁰ C / 0.05 torr

.28 8.25 18.86 18.85 9.43 9.32

CD GO.

Le A9563

-3V

Claims (1)

Claim ^l Process for the preparation of O- or »p-aminophenylthioethers, optionally substituted in the core, by means of implementation of nitrohalobenzenes with sodium sulfide and alkylation or arylation of the optionally substituted aminothiophenolates formed, characterized in that nitrohalobenzenes of the general formula which are optionally substituted in the nucleus are used rr-r \ respectively. Y ₁ in which Z ₁ , Z _s , Y ₁ and Y _{2 represent} identical or different, optionally substituted radicals such as hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, alkoxy, alkenyloxy, aryloxy, alkylthio, arylthio or a heterocyclic component, Y ₁ and Y _{8 can} also be halogen and X is halogen, are reacted in a molar ratio from about 1 to about 2.5 with Katriumsulfid in aqueous suspension at temperatures of about 0 to about 200 ⁰ C and without isolation of the aminothiophenols ^wässrl-: ge alkaline solution of Aminothiophenolates formed, optionally with the addition of a water miscible organic solvent alkylated at temperatures of about 0 to about 100 ⁰ C at the sulfur atom or arylated and the resulting Aminophenylthioäther isolated. Le A 9563 - 31 - 909835/1515 ÖAD ORIGINAL