PL191568B1 - Novel thiamides, intermediate product for obtaining them and method of obtaining them - Google Patents

Abstract

1. New thioamides of formula 1 in which R1 is at least phenyl substituted one hydroxyl group, R2 is phenyl, unsubstituted or substituted one or more the same or different substituents selected from the group consisting of: halogen atoms, (C1-C2) alkyl substituted with halogens, -OH, -COOH, -O- (C1-C2) alkyl, (C1-C4) alkyl, -CO- (C1-C2) alkyl and CO-O- (C1-C2) alkyl; and R3 is hydrogen. 14. Bis (2,4-dihydroxybenzothiocarbonyl) sulfoxide formula 32. 15. A process for the preparation of thioamides of formula 1, wherein: R1 is at least substituted phenyl one hydroxyl group, R2 is phenyl, unsubstituted or substituted one or more, same or different substituents selected from the group consisting of: halogen atoms, (C1-C2) alkyl substituted with halogens, ..

Description

The subject of the invention is new thioamides, an intermediate product for the preparation of new thioamides and a method for the preparation of new thioamides.

A number of methods for the preparation of thioamides are known. Currently, the most recommended method is the method that uses the classic syntheses of variously substituted carboxyanilides, most often from acid chlorides and appropriate arylamines, which are further converted to sulfur analogues by the action of P2S5. This reaction takes about three days and presents a great deal of difficulty in separating the mixture. The transition from> C = O to> C = S excludes the presence of many groups which give the new compounds specific and desired properties. Such groups include, for example, -CO2H, R-C / = O / - or NHC / = O / -.

So far, there are no known compounds with a thioamide system containing hydroxyl groups.

The essence of the invention are the new thioamides of formula I, in which:

R1 is a phenyl group substituted with at least one hydroxyl group,

R2 is a phenyl group, unsubstituted or substituted by one or more, same or different substituents selected from the group consisting of: halogen, (C1-C2) alkyl substituted with halogen,

-OH,

-COOH,

-O- (C1-C2) alkyl, (C1-C4) alkyl,

-CO- (C1-C2) alkyl and

CO-O- (C1-C2) -alkyl; and

R3 is hydrogen.

A preferred R 1 group is a phenyl group substituted with two hydroxyl groups meta-position to each other.

Preferred compounds of the invention are:

2,4-dihydroxybenzocarbothioamide of formula 31, N- (3-methylphenyl) -2,4-dihydroxybenzocarbothioamide, N- (4-sec-butylphenyl) -2,4-dihydroxybenzocarbothioamide, N- (3-fluorophenyl) -2,4-dihydroxybenzocarbothioamide, N- (2,3-dichlorophenyl) -2,4-dihydroxybenzocarbothioamide, N- (2-methyl-3-chlorophenyl) -2,4-dihydroxybenzcarbothioamide, N- (3-trifluoromethylphenyl) ) -2,4-dihydroxybenzocarbothioamide, N- (2-methoxyphenyl) -2,4-dihydroxybenzocarbothioamide, N- (4-hydroxyphenyl) -2,4-dihydroxybenzocarbothioamide, N- (3-carboxyphenyl) -2,4 -dihydroxybenzocarbothioamide, N- (4-propionylphenyl) -2,4-dihydroxybenzocarbothioamide.

The invention also relates to a new compound - bis (2,4-dihydroxybenzothiocarbonyl sulfoxide), hereinafter referred to as SBKT, of formula 32, which is an intermediate for the preparation of new thioamides.

The essence of obtaining new thioamides of formula 1, in which:

R1 is a phenyl group substituted with at least one hydroxyl group,

R2 is a phenyl group, unsubstituted or substituted with one or more, same or different substituents selected from the group consisting of:

halogen atoms, (C1-C2) alkyl substituted with halogen atoms,

-OH,

-COOH,

-O- (C1-C2) alkyl, (C1-C4) alkyl,

-CO- (C1-C2) alkyl and

CO-O- (C1-C2) -alkyl; and

R3 is hydrogen, the starting 1,3-dihydroxybenzene is subjected to electrophilic substitution reaction with CS2, then the obtained 2,4-dihydroxybenzocarbodithioic acid is converted

By treatment with thionyl chloride to give bis (2,4-dihydroxybenzothiocarbonyl) sulfoxide, which is then reacted with an amine derivative of formula R3NHR2, where R2 is as in formula 1 and is hydrogen.

A portion of SBKT and the corresponding amine, preferably in excess, are introduced into benzene or methanol, depending on the type of substitution in the N-aromatic system of the amine in the R2 group. Then it is heated and the mixture is kept at reflux.

In most cases, the reaction mixture is filtered hot and the filtrate is allowed to cool. The separated compounds are crystallized from benzene, methanol or methanol-water systems of various volume proportions.

The reaction of 1,3-dihydroxybenzene with CS2 is carried out in the presence of potassium hydroxide and C2H5OH.

The reaction of the bis (2,4-dihydroxybenzothiocarbonyl) sulfoxide with the aniline derivative is preferably carried out in the presence of pyridine.

In turn, SBKT, i.e. bis (2,4-dihydroxybenzothiocarbonyl sulfoxide) of formula 32 is preferably obtained by reacting 2,4-dihydroxybenzocarbodithioic acid of formula 33 with thionyl chloride in the presence of anhydrous diethyl ether according to equation 2.

2,4-dihydroxybenzocarbodithioic acid of formula 33 is preferably obtained by reacting resorcinol with carbon disulfide in the presence of potassium hydroxide and C2H5OH according to Equation 3.

Preferred amine derivatives of formula R3NHR2 are, respectively, aniline, 3-toluidine, 4-sec-butylaniline, 3-fluoroaniline, 2,3-dichloroaniline, 3-chloro-2-methylaniline, 3-trifluoromethylaniline, 2-methoxyaniline, 4- aminophenol, 3-aminobenzoic acid chloride, or 4-aminopropiophenone.

Example I: N-phenyl-2,4-dihydroxybenzocarbothioamide of the formula 31.

0.025 mole of aniline and 0.01 mole of SBKT are introduced into 100 ml of benzene, and then 5 ml of pyridine are added. It is heated in a water bath and kept under reflux for a total of two hours. The resulting mixture was filtered hot and the filtrate was allowed to cool overnight. The isolated compound is then crystallized from benzene.

The thioamide was obtained in the form of yellow needles with a melting point of 181-183 ° C. The process yield was 86%.

Elemental analysis for the formula: C13H11NO2S, M = 245.30: Calculated: 63.65% C Found: 63.48% C;

4.51% H 4.57% H;

5.71% 5.85% N

Parameters of the EI-MS spectrum.

Molecular peak M * ®, [C13H11NO2S ·] ® (245 m / e), B = 44.64, isotope lines found: M + 1 (246 m / e), B = 7.74%

M + 2 (274 m / e), B = 2.97%

M-1 (244 m / e), B = 27.98%

Major fragmentations from the analysis of [MS] N-phenyl-dihydroxybenzocarbothioamide.

Fragment (R ^® ) B% m / e [M-SH *] ® (HO) 2C6H3 (C = N) C6H ₅ 100 212 [M-C6H5NH ^· ] ^® ® (HO) 2C6H3C = S 15.77 153 (S =) CNHC6H4, (HO) C6H3 (O) C = O 2.67 136 (HO) 2C6H3 2.38 109 C6H5 14.28 77 C5H5 12.36 65

In addition, there are ion peaks: 97, 93, 78, 63, 53 and 51 m / e.

Peaks 136 and 109 m / e may correspond to cationic fragmentation associated with haemolytic cleavage of the bonds in the molecular ion M ^{· ®} (decay between carbon atoms a and b to heteroatom).

^[1 H] NMR, DMSO-d6 (TMS), d (ppm): 11.56 (HOC-4, singlet); 11.25 (NH, singlet); 10.06 (HOC-2 singlet); 7.88-7.79 (HC-3.2 ', 6', 3H, integrated quartet with roof effect on low lows); 7.67-7.23 (HC-3 ', 4', 5 '; multiplet, 3H); 6.41-6.29 (HC-5.6; sextet, 2H).

UV (lmax, nm) C2H5OH: 216, 242, 295, 326

IR (cm ^-1 , KBr): 3587, 3319 ns, as OH, NH (polymers), 3052, 2603 n CH, 1625, 1588, 1514 n C = C (skeletal in ring plane, conjugated) 1500 n NHC / = S / (characteristic for the second order acyclic, solid amide), 1468, 1442 n C = C, 1418 n N "C / S / (under con4

PL 191 568 B1 formation of cis-imidothiol structures) 1348 n C = C (n _as , _s CO), 1289 n CN (band intensity and bond strength constant increased, presumably as a result of ring resonance) 1240 nas, s CO (d OH) , 1168, 1128 d CH, d 1072 d C-OH, 1029 n C = S, 988, 910, 848, 794, 759, 740 d CH, 650 d NH (dimers).

Selected analytical data of N-phenyl-2,4-dihydroxybenzocarbothioamide and further compounds described in Examples II-XI are shown in Table I.

It should be noted that over 80 new thioamides have already been obtained.

Example II: N- (3-methylphenyl) -2,4-dihydroxybenzocarbothioamide

0.03 mole of 3-toluidine and 0.01 mole of SBKT in 70 ml of benzene was heated to reflux and heated further, for a total of one hour. The reaction mixture was allowed to crystallize. The separated compound was filtered off and crystallized from benzene.

The compound was obtained in the form of yellow fine needles. M = 259.32; mp 155 ° C.

Example III: N- (4-sec-butylphenyl) -2,4-dihydroxybenzocarbothioamide

0.025 mole of 4-sec-butyaniline and 0.01 mole of SBKT in 80 ml of methanol was heated to reflux for one hour. The reaction mixture was filtered hot and the filtrate was allowed to stand at room temperature overnight. The isolated compound was crystallized from dilute methanol (3: 1) 40 ml.

Yellow needles were obtained with M = 301.41, mp = 139-140 ° C.

Example IV: N- (3-fluorophenyl) -2,4-dihydrobenzocarbothioamide

0.025 mole of 3-fluoroaniline and 0.01 mole of SBKT were heated in benzene under reflux for one hour. The reaction mixture was filtered and allowed to cool. The isolated compound was crystallized from benzene (50 ml).

The compound was obtained in the form of yellow needles. M = 263.29, mp. = 163-164 ° C.

Example V: N- (2,3-dichlorophenyl) -2,4-dihydroxybenzocarbothioamide

0.025 mol of dichloroaniline and 0.012 of SBKT in 50 ml of methanol was heated to reflux and further heated for two hours. The reaction mixture was filtered hot and the filtrate was concentrated to 10 ml. The isolated compound was then crystallized from dilute methanol (3: 2).

Long yellow needles were obtained. M = 314.19; mp 175-176 ° C (R).

Example VI: N- (2-methyl-3-chlorophenyl) -2,4-dihydroxybenzocarbothioamide

0.03 mol of 3-chloro-2-methylalanine and 0.01 of my SBKT in 60 ml of methanol was heated to reflux for 2 hours. The reaction mixture was filtered hot and the filtrate was concentrated to a low volume. The isolated compound was crystallized from dilute (2: 1) methanol - 75 ml.

Yellow plates were obtained; M = 293.78; mp = 193-194 ° C.

Example VII: N- (3-trifluoromethylphenyl) -2,4-dihydroxybenzcarbothioamide

0.025 mole of 3-trifluoromethylaniline and 0.01 mole of SBKT in 80 ml of benzene was heated to reflux and further heated for one hour. The reaction mixture was filtered hot, and the filtrate was allowed to cool. Then the isolated compound was crystallized in 35 ml of benzene.

Long light yellow needles were obtained. M = 313.3; mp 164 ° C.

Example d VIII: N- (2-methoxyphenyl-2,4-dihydroxybenzocarbothioamide

0.025 mole of 2-methoxyaniline and 0.01 mole of SBKT in 80 ml of methanol was heated to reflux and heated further for a total of 1.5 hours. The reaction mixture was filtered hot and the filtrate was allowed to cool. The isolated compound was crystallized from methanol diluted with water 1: 1. Yellow plaques with M = 275.33 were obtained; mp Mp 169-170 ° C.

Example IX: N- (4-hydroxyphenyl-2,4-dihydroxybenzocarbothioamide

0.03 mole of aminophenol and 0.01 mole of SBKT in 80 ml of methanol was refluxed and further heated for one hour. The reaction mixture was filtered hot and the filtrate was allowed to cool. The isolated compound was crystallized from diluted with water (2: 1) methanol (30ml).

Yellow needles of M-261.30 were obtained, mp. = 206-207 ° C.

Example X: N- (3-carboxyphenyl) -2,4-dihydroxybenzocarbothioamide

0.025 mole of 3-aminobenzoic acid and 0.01 mole of SBKT were refluxed in 80 ml of methanol and further heated for one hour. The reaction mixture was filtered hot and the filtrate was allowed to cool to room temperature for 12 hours. The isolated compound was crystallized from diluted with water (1: 1) to 60 ml of methanol.

Yellow needles with M = 289.31 were obtained, mp. = 192-193 ° C (R).

Example XI: N- (4-propionylphenyl-2,4-dihydroxybenzocarbothioamide

0.03 of 4-aminopropiophenone and 0.01 mole of SBKT were boiled in 80 ml of methanol and further heated for two hours. The reaction mixture was filtered hot and the filtrate was allowed to cool to room temperature for 12 hours. The isolated compound was crystallized from diluted with water (3: 1) to 40 ml of methanol.

Yellow plates were obtained with M = 30.37 and mp. - 171-172 ° C (R)

EXAMPLE XII: Methyl bis (2,4dihydroksybenzotiokarbonylu) SBK formula 32 ₃

0.35 mol of 2,4-dihydroksybenzenokarboditiowego of formula 33 was dissolved in 250 cm ^{3 of} anhydrous diethyl ether. At 20 ° C the solution was saturated with dry CO 2 and 0.7 mol of thionyl chloride (SOCl 2) was slowly added dropwise, followed by heating in a water bath for four hours. The solvent and SOCl2 residues were separated by distillation under reduced pressure. The obtained product was washed several times with DMSO.

A red amorphous powder is obtained, mp 259-260 ° (R), yield 88.5%.

Elemental analysis for the formula: C14H10O5S3 with M = 354.32 Calculated: 47.45% C Found: 47.57% C

2.84% H 2.75% H 27.11% S 27.34% S

Parameters of the EI-MS spectrum. No molecular ion line was found in the SBKT mass spectrum.

It is related to the instability of the M · ion under the assay conditions (electron ionization, 70 eV). Using the high-resolution field, fragmentation peaks were assigned a computer formula selection, interpreted based on the mass and elemental analysis of the ion:

Major fragmentations from the EI-MS analysis of the SBKT compound Fragment (R ^® ) Ion mass (u) Assumed structure ^C 7 ^H 5 ^S 2 ^O 3 199.940 (HO) 2C6H3C / = S / S = O ^C 7 ^H 4 ^S 2 ^O 2 183,960 (HO) C6H3 (O) CS2 ^C 7 ^H 6 ^O 4 154.026 (HO) 2C6H3CO2H C7H5SO2 153.002 (HO) 2C6H3C (= S) C7H5O3 137.022 (HO) 2C6H3C (= O) C6H4SO 123.997 In addition, ion peaks were found: 110, 108, 97, 69, 65 (C5 ° H5), 51, 48 (S ° O), 45 C ° OOH and 34m / e

(B = 100%, major peak in the spectrum).

^[1 H] NMR, CD3COCD3 (TMS), d (ppm): 8,1886-7,5369 (HC-3,3 ', multiplet, 2H), 6,9218-6,2725 (HC-5, 6, 5 ', 6' multiplet, 4H) (in the area of proton absorption of -OH groups there are indecipherable blurred bands).

UV (lmax, nm) (C2H5OH): 210, 238, 315, 345, 390

IR (cm ^-1 KBr): 3392 µm, s OH; 2960,2728,2602n CH; 1614, 1542, 1507, 1457 n C = C, 1396 n C = C (n S = O; conjugate), 1372 n CO, 1237 n CO (v C-OH, conjugate), 1135 n CO (d OH), 1048 n S = 0.1019 n C = S, 976, 948, 902, 876 dC-H.

The SBKT polarogram contains sharp peaks of reduction transformations at the potential values of -0.02 V and -0.009 V. These results indirectly determine the magnitude of the positive charge on the thiocarbonyl carbon atoms and the susceptibility of the compound to the nucleophilic attack of the first and second order amines.

Using EI-MS spectrometry, differential pulsed polarography (DPP) and electrocapillary measurements (EK), the conditions for the preparation of SBKT for the synthesis of substituted 2,4-dihydroxybenzocarbothioamides were developed.

The method presented in the following example allows the preparation of many groups of compounds not described in the literature with virtually any constitutionally and sterically arbitrary N-aryl substitution system.

P r x l a d XIII

A three-step synthesis was carried out to prepare the new thioamide. The general course of subsequent reactions is shown by equations 3, 2 and 1. In the first stage, according to equation 3, 1,3-dihydroxybenzene was used for the synthesis, from which 2,4-dihydroxybenzcarbodithic acid of formula 33 was obtained in the electrophilic substitution of CS2. The transition from this compound and thionyl chloride-SOCl2 gave the SO ^2- (sulfinyl) activated bridge structures of the 2,4-dihydroxybenzcarbothia of the formula 32, transformed to the final compounds by the aminolysis process, according to equation 1.

The use of the 1,3-dihydroxybenzene system in the process according to the invention is justified by:

- specific biological properties of resorcinol: bacteriostatic, antifungal, keratolytic and astringent action;

- potential - oxidation / reduction;

PL 191 568 B1

- influence on the reduction properties of the -C / = S / SH groups of the starting acid in the synthesis of the acid and the stability of the thioamide bond (it determines the susceptibility of compounds to the action of membrane amidases and the ability to release toxic amines blocking succinate dehydrogenase systems).

Due to the fact that the course of the reaction according to equations 1 and 2, according to the SN1 mechanism, is definitely limited by spatial conditions, the elimination-addition mechanism was considered the most probable. The disruption as a result of solvolysis and the formation of bonds is asynchronous, and subsequent reactions, presumably, proceed without changing the hybridization of thiocarbonyl carbon atoms (in the released - reaction 2 and bonded -reaction 3 2,4-dihydroxybenzcarbonothioic cations):

The MS spectra and the results of polarographic studies indicate that, as assumed, the carbocations released in successive passages are characterized by different electrophilicity, which determines their ability to bind nucleophilic arylamine residues and stabilize by charge scattering.

The starting acid of formula 33 was obtained by the modified Kolbe-Schmidt reaction, equation 3. Crystallized from ethanol and water, C ₇ H ₆ O ₂ S ₂ · H ₂ O mp = 132-133 ° C.

EI-MS spectrum parameters:

M'® molecular peak; [C ₇ H ₆ O ₂ S ₂ ·] ® (186 m / e), B = 36.12% (line intensity in relation to the main run). Isotope lines were found: M + 1 (187 m / e) and M + 2 (188 m / e).

Major fragmentations from the MS analysis

Fragment (R ^® ) B% m / e [M-SH ^· ] ^® ® (HO) 2C6H3C ^® = S 100 153 12.35 141 8.72 124 11.59 97 5.16 69 ^C 5 ^H 5 13.77 65

In the study of the acid of formula 33 by mass spectrometry (MS), it was found that the preferred direction of fragmentation of the compound M'® molecular ions is the elimination of energy-poor SH ^· radicals. This direction of ion decay is consistent with the product stability theory, and the intensity of the R® line is indicative of the stability of secondary [M-SH ·] ® cations stabilized by charge transfer resonance. Thus, the course of the spectrum determines the bond stability of the -OH groups in the system and, in a way, the resistance of polyhydroxy residues to oxidative processes. This is confirmed by the polarogram of the acid of formula 33, in which only the peaks associated with constitutional changes in the carbodithium moiety (-C / = S / SH) are recorded.

This is confirmed in EK studies by strong changes in mercury surface tension. These changes indicate that the acid of formula 33 has changed from molecular to anionic form, and then to radical and agglomerated form (formula 34). The nature of the reversible reactions of the formation and reduction of surface active dimers:

and further forms:

PL 191 568 B1

confirms the course of the surface tension curves and differential curves with the minimum and, respectively, the maximum at the potential of -0.3 V.

The course of the EK curves shows at the same time the blocking of the electrode due to the chemisorption of elemental sulfur released in the reaction of forming forms of the formula 35, which is confirmed by the characteristic refractions at the potentials of -0.55 V; -0.65 V and -0.89 V and faults at potentials from -0.16 V and -0.24 V.

The highly reductive properties of the acid of formula 33 and the proven desulfhydration capacity thereof explain the specific course of the selective SOCl2 reduction (equation 2) with the formation of the SBKT compound. In this reaction, the SH groups cleaved from the acid reduce the chlorine from thionyl chloride to HCl. In this process elemental sulfur is formed and thionyl residues are bound by 2,4-dihydroxybenzcarbonothioic cations.

The presented method enables the synthesis to be carried out with the use of reagents with hydroxyl groups (this applies to both the benzthiacyl system and the N-aryl part). This ensures that the new thioamides maintain constitutional hydrophilic-hydrophobic equilibria, which determine the ability of compounds to penetrate the cell walls and membranes of microorganisms.

The new thioamides are distinguished by their antimicrobial properties. So far it has been found that the effects include phytopathogenic fungi, dermatophytes, molds and yeasts as well as gram-positive bacteria.

Doses of 10-20 ppm (in vitro) significantly reduce the development of colonies of pathogens in agricultural crops.

The most active compounds completely inhibit the development of Fusarium culmorum. Phytopthora cactorum, Rhizoctonia solani and Botrytis cinerea are more resistant. In a dose of 20 ppm, the degree of growth inhibition is in the range of 60-90%.

Among the pathogenic fungi, the development of dermatophytes is the most effective. In relation to Trichophyton mentagrophytes, Trichpphyton rubrum, Trichophyton gallinae, Trichophyton interdigitale, Epidermophyton flucossum (I and II), the activity expressed in MIC is in the range of 0.98 - 7.8 μg / ml.

The molds of Aspergillus niger, Aspergillusfiimigatus, Penicillinum sp., Scopulariopsis brevicalis and yeasts Candida albicans, Cryptococus neoformans, Geotrichum candidum, Trichosporon sp. Show MIC sensitivity in the range of 3.9-62.5 μg / ml.

The bacteriostatic activity of the compounds in relation to the appropriate groups and types of bacteria is similar to the activity of commonly used synthetic quinalone derivatives and some natural antibiotics (MIC = 3.9-31.2 μg / ml).

Due to the identified properties, it can be successfully predicted that the new thioamides and their derivatives will find wide application as pharmaceutical preparations or their components, especially for the treatment of aspergillosis, cryptococcosis, dermatomycoses, or other mycoses caused by yeast (Candida spp.).

PL 191 568 B1

Table a 1

Selected analytical data for the compounds of Examples III-XI

Example no R® (m / e) ¹ H-NMR (d, ppm) IR n, (cm ′ ¹ ) UV-VIS l max (nm) 1 2 3 4 5 II 226 11.51 1490 218 153 11.26 1398 235 107 10.08 1040 327 91 2.51 714 65 III 268 11.51 1515 210 153 11.28 1225 295 149 10.07 1181 302 91 3.38 1017 329 77 1.63-1.42 710 1.23-1.16 0.85-0.70 IV 230 11.73 1494 220 153 11.05 1194 238 137 10.09 1072 296 111 325 95 75 V 280 11.75 1505 215 278 11.71 1410 240 243 10.28 1300 295 153 1048 336 109 VI 278 11.49 1496 211 260 11.41 1403 236 257 10.15 1379 284 225 2.23 1270 233 153 1076 106 1019 VII 280 11.65 1489 220 244 11.07 1397 237 212 10.07 1302 300 161 1141 330 153 1076 136 69

PL 191 568 B1 continued from Table 1

1 2 3 4 5 VIII 260 11.76 1491 217 244 10.65 1458 235 212 9.10 1406 300 227 3.86 1242 334 153 1046 92 1020 IX 228 11.48-11.37 1512 220 153 10.05 1441 238 136 9.53 1015 292 65 325 53 X 273 11.67 1694 217 256 1505 239 244 1441 295 153 1015 327 136 121 45 39 XI 268 11.76 1662 207 244 11.01 1510 235 239 10.07 1407 296 153 2.93-2.79 1377 334 121 1.16-1.02 1016 109 65 57

Patent claims

Claims (28)

Patent claims 1. New thioamides of formula 1 in which R1 is a phenylic group substituted with at least one hydroxyl group, R2 is a phenyl group, unsubstituted or substituted by one or more, same or different substituents selected from the group consisting of: halogen, (C1-C2) alkyl substituted with halogen, -OH, -COOH, -O- (C1-C2) alkyl, (C1-C4) alkyl, -CO- (C1-C2) alkyl and CO-O- (C1-C2) -alkyl; and R3 is hydrogen. PL 191 568 B1 2. The thioamides according to claim 1 2. The compounds of claim 1, wherein R1 is a phenyl group substituted with two hydroxyl groups meta to each other. 3. The thioamide according to claim 1 1 which is N-phenyl-2,4-dihydroxybenzocarbothioamide. 4. The thioamide according to claim 1 1 which is N- (3-methylphenyl) -2,4-dihydroxybenzocarbothioamide. 5. The thioamide according to claim 1 1 which is N- (4-sec-butylphenyl) -2,4-dihydroxybenzocarbothioamide. 6. The thioamide according to claim 1 1 which is N- (3-fluorophenyl) -2,4-dihydroxybenzocarbothioamide. 7. The thioamide according to claim 1 1 which is N- (2,3-dichlorophenyl) -2,4-dihydroxybenzocarbothioamide. 8. The thioamide according to claim 1 1 which is N- (2-methyl-3-chlorophenyl) -2,4-dihydroxybenzocarbothioamide. 9. The thioamide according to claim 1 1 which is N- (3-trifluoromethylphenyl) -2,4-dihydroxybenzocarbothioamide. 10. The thioamide according to claim 1 1 which is N- (2-methoxyphenyl) -2,4-dihydroxybenzocarbothioamide. 11. The thioamide according to claim 1 1 which is N- (4-hydroxyphenyl) -2,4-dihydroxybenzocarbothioamide. 12. The thioamide according to claim 1 1 which is N- (3-carboxyphenyl) -2,4-dihydroxybenzocarbothioamide. 13. The thioamide according to claim 1 1 which is N- (4-propionylphenyl) -2,4-dihydroxybenzocarbothioamide. 14. Bis (2,4-dihydroxybenzothiocarbonyl) sulfoxide of formula 32. 15. A process for the preparation of thioamides of formula 1, wherein: R1 is a phenyl group substituted with at least one hydroxyl group, R2 is a phenyl group, unsubstituted or substituted with one or more, same or different substituents selected from the group consisting of: halogen atoms, (C1-C2) alkyl substituted with halogen atoms, -OH, -COOH, -O- (C1-C2) alkyl, (C1-C4) alkyl, -CO- (C1-C2) alkyl and CO-O- (C1-C2) -alkyl; and R3 is a hydrogen atom, characterized in that 1,3-dihydroxybenzene is subjected to electrophilic substitution with CS2, then the obtained 2,4-dihydroxybenzocarbodithioic acid is converted by treatment with thionyl chloride into bis (2,4-dihydroxybenzothiocarbonyl) sulfoxide, which is then reacted with the amine derivative of formula R3NHR2 wherein R2 is as in formula 1 and R3 is hydrogen. 16. The method according to p. 15, characterized in that the reaction of 1,3-dihydroxybenzene with CS2 is carried out in the presence of potassium hydroxide and C2H5OH 17. The method according to p. A process as claimed in claim 15 or 16, characterized in that the reaction of the bis (2,4-dihydroxybenzothiocarbonyl) sulfoxide with an aniline derivative is carried out in the presence of pyridine. 18. The method according to p. The process of claim 15, wherein aniline is used as the derivative of the amine of formula R3NHR2. 19. The method according to p. The process of claim 15, characterized in that 3-toluidine is used as the derivative of the amine of formula R3NHR2. 20. The method according to p. The process of claim 15, characterized in that 4-sec-butylaniline is used as the derivative of the amine of formula R3NHR2. 21. The method according to p. The process of claim 15, characterized in that 3-fluoroaniline is used as the derivative of the amine of formula R3NHR2. 22. The method according to p. The process of claim 15, characterized in that 2,3-dichloroaniline is used as the derivative of the amine of formula R3NHR2. 23. The method according to p. The process of claim 16, wherein the amine derivative of formula R3NHR2 is 3-chloro-2-methylaniline. 24. The method according to p. The process of claim 15, wherein the amine derivative of formula R3NHR2 is 3-trifluoromethylaniline. 25. The method according to p. The process of claim 15, wherein the amine derivative of the formula R3NHR2 is 2-methoxyaniline. PL 191 568 B1 26. The method according to p. A process as claimed in claim 15, characterized in that 4-aminophenol is used as the amine derivative of formula R3NHR2. 27. The method according to p. The process of claim 15, wherein the amine derivative of formula R3NHR2 is 3-aminobenzoic acid. 28. The method according to p. The process of claim 15, characterized in that 4-aminopropiophenone is used as the amine derivative of formula R3NHR2.