Electrochemical synthesis of S-arylthiocarbamates

Abstract

Method for the preparation of S-arylthiocarbamates of general formula (I) , wherein R 1 selected is from the group consisting of hydrogen atom, halogen atom, branched or unbranched C1 to C10 alkoxy group, branched or unbranched C1 to C10 alkyl S group, branched or unbranched C1 to C10 alkyl group, branched or unbranched C1 to C10 alkylene group, mono or di(C1 to C10 alkyl)amine group, branched or unbranched C1 to C5 alkyl C(=O) NH group, branched or unbranched C1 to C5 alkyl OC(=O) group, C3 to C10 cycloalkyl group, C3 to C10 heterocycloalkyl group, C6 to C12 aryl group; C6 to C12 aryloxy group, and C5 to C11 heteroaryl group, wherein the C3 to C10 cycloalkyl group, C3 to C10 heterocycloalkyl group, C6 to C12 aryl group, C6 to C12 aryloxy group or C5 to C11 heteroaryl group comprises one or more ring systems which are condensed or separated; R2 , R 3 Each is independently selected from the group consisting of branched or unbranched C1 to C10 alkyl groups; n is an integer in the range of 1 to 5, where for n≥2 the remainders R 1 each independently from the group of R 1 are selected and optionally two or more R 1 together they form a C1 to C8 heterocycloalkyl group; and m 1 is; by electrochemically induced rearrangement of an O-arylthiocarbamate of general formula (II), wherein R 1 , R 2 , R 3 , n and m have the same meaning as in the general formula (I).

Description

[0001] The invention relates to a process for preparing S-arylthiocarbamates of the general formula (I) by electrochemically induced rearrangement of an O-arylthiocarbamate of the general formula (II). Furthermore, the invention relates to the S-arylthiocarbamates prepared or preparable by this process, as well as to S-arylthiocarbamates of the formulas (Ia) to (Id).

[0002] Thiophenol and its derivatives are extremely important building blocks in organic synthesis, play important roles in industrial applications, and are also indispensable in everyday life. Thiophenol derivatives are particularly important in the synthesis of pharmaceutically active substances. Commonly used thiophenol-based medications include thioridazine (neuroleptic), butoconazole (antimycotic), azathioprine (immunosuppressant), albendazole (anthelmintic), and thimerosal (antiseptic). Sulfonamides derived from thiophenol are also of great importance in the pharmaceutical industry due to their biological activity. Other applications of thiophenol derivatives include as masticating agents in the rubber industry and as additives in the manufacture of lubricants.

[0003] US 2009 / 0299074 A1 describes benzo[b]thioprene derivatives and a process for their preparation. Pedersen et al. (Stephan K. Pedersen et al., J. Org. Chem. 2018, 83, 12000-12006) describe a reversal of the selectivity of the Newman-Kwart rearrangement by one-electron oxidation at room temperature.

[0004] The conventional synthesis of thiophenols begins with the corresponding arene and initially proceeds via sulfochlorination with chlorosulfonic acid (see Scheme 1, Route 1).[1] The resulting sulfonyl chloride must then be reduced using zinc dust. A frequently used alternative to Route 1 is the three-step synthesis of thiophenols starting from phenols (see Scheme 1, Route 2).[2] In this process, an O-aryl thiocarbamate is first prepared in a simple upstream reaction, which is then rearranged to the S-aryl thiocarbamate in the subsequent key step. In the final step, the desired thiophenol derivative is released by simple treatment with KOH under the influence of heat. Scheme 1. Conventional synthesis sequences for the preparation of thiophenol derivatives.

[0005] The disadvantages of route 1 lie in the limitations regarding the accessible product range. Due to the directing effects of the substituents, sulfochlorination can only occur in certain positions,[1] which makes the preparation of a wide variety of thiophenol derivatives impossible. A major disadvantage of route 2 lies in the second step (OS rearrangement). Since the conventional variant of the rearrangement proceeds via a nucleophilic ipso attack and thus via an extremely energy-rich spirocyclic intermediate (see Scheme 2), temperatures of 200 - 300 °C are usually required.[2] Since the publications by Newman and Karnes and Kwart and Evans in 1966,[3] this sequence has been widely used for the preparation of thiophenol derivatives despite the harsh conditions,[4] although the elevated temperatures usually favor various side reactions and thus the formation of disturbing by-products.

[0006] Previous attempts to solve the problem described above regarding route 2 are summarized in Scheme 2. Lloyd-Jones et al. took a first major step toward milder conditions with a variant published in 2009.[5] By catalytically using Pd[(tBu3P)2], they succeeded in lowering the required reaction temperature to 100 °C with good yields. Finally, in 2015, Nicewicz et al. were able to show that the rearrangement is, in principle, also possible at room temperature.[6] In their photochemical variant, good to excellent yields of the rearrangement product were obtained by using a pyrylium salt as the photocatalyst and irradiating with blue light. A disadvantage of both improved variants is the need for expensive catalysts, which must be separated in a subsequent step.This makes the process significantly more expensive and time-consuming, while simultaneously increasing waste generation.Scheme 2: Overview of known processes for the rearrangement of O-arylthiocarbamates to S-arylthiocarbamates.

[0007] The object underlying the invention was therefore to provide a process in which the disadvantages described above can be avoided, in particular in which mild conditions can be used and the use of catalysts can be reduced or completely avoided.

[0008] The problem was solved by a process for the preparation of S-arylthiocarbamates of the general formula (I), wherein R 1is selected from the group consisting of hydrogen atom, halogen atom (fluorine, chlorine, bromine, iodine, preferably fluorine or chlorine), branched or unbranched C1- to C10-alkoxy group, branched or unbranched C1- to C10-alkyl-S-group, branched or unbranched C1- to C10-alkyl group, branched or unbranched C1- to C10-alkylene group, mono or di(C1- to C10-alkyl)amine group, branched or unbranched C1- to C5-alkyl-C(=O)-NH-group, branched or unbranched C1- to C5-alkyl-OC(=O)-group, C3- to C10-cycloalkyl group, C3- to C10-heterocycloalkyl group, C6- to C12-aryl group, C6- to C12-aryloxy group, and C5- to C11 heteroaryl group, wherein the C3 to C10 cycloalkyl group, C3 to C10 heterocycloalkyl group, C6 to C12 aryl group, C6 to C12 aryloxy group or C5 to C11 heteroaryl group comprises one or more ring systems which are condensed or separated; R 2 , R 3are each independently selected from the group consisting of branched or unbranched C1 to C10 alkyl group; n is an integer in the range from 1 to 5, where for n≥2 the residues R 1 each independently from the group of R 1 are selected and optionally two or more R 1 together form a C1 to C8 heterocycloalkyl group; and m is 1;by electrochemically induced rearrangement of an O-arylthiocarbamate of the general formula (II),wherein R 1 , R 2 , R 3 , n, and m have the same meaning as in the general formula (I). It is conceivable that several O-arylthiocarbamates of the general formula (II) are used in a mixture. However, with a view to simplified purification, it is preferred that one O-arylthiocarbamate of the general formula (II) be used per process run.

[0009] The process according to the invention is based on the use of electrical energy instead of thermal energy to drive the rearrangement reaction - the rearrangement is induced electrochemically. Carrying out the reaction under electrochemical conditions surprisingly allows a reduction from the otherwise usual reaction temperature of ≥200 °C to room temperature (25 °C). Due to these mild conditions, the otherwise usual side reactions can be avoided with this process and quantitative selectivities can be achieved, which in turn greatly simplifies the purification of the product due to the elimination of by-products. In contrast to the approaches outlined at the beginning, no expensive catalyst is required for the process according to the invention, which significantly simplifies purification. The experimental setup is extremely simple: All that is required is an undivided electrochemical batch cell orA flow cell and a cost-effective power supply are required. The need for the commonly used conductive salt additives is eliminated, at least when operating in flow mode.

[0010] In one embodiment of the process for preparing S-arylthiocarbamates, the electrochemically induced rearrangement of an O-arylthiocarbamate of the general formula (II) to an S-arylthiocarbamate of the general formula (I) takes place in solution, wherein the solution comprises a solvent which is preferably selected from the group of halogenated or perhalogenated alkanols, more preferably from the group of halogenated or perhalogenated C1 to C10 alkanols, more preferably from the group of halogenated or perhalogenated C2 to C5 alkanemonols, where the C1 to C10 alkyl chains or the C2 to C5 alkyl chains are each branched or unbranched and where the halogen atoms are selected from the group consisting of fluorine atom, chlorine atom, bromine atom, iodine atom, more preferably fluorine atom and chlorine atom, more preferably perfluorination is present. The term “perhalogenation” or"Perfluorination" in the context of the present invention means that the attached hydrogen atoms on all C atoms that do not carry a hydroxyl group are replaced by halogen or fluorine atoms; the C atom that carries a hydroxyl group is not halogenated or fluorinated, i.e., no halogen or fluorine atom is in a geminal position to the hydroxyl group. In a preferred embodiment of the process for preparing S-arylthiocarbamates, the solvent is selected from the group of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), 2,2,2-trifluoroethanol (TFE), 2-fluoroethanol, 2,2-difluoroethanol, 1,1,1,3,3,3-hexafluoro-2-(trifluoromethyl)propan-2-ol, 2,2,3,3,3-pentafluoro-1-propanol, 2,2,2-trichloroethanol and 1,1,1,3,3,3-hexafluoro-2-methyl-2-propanol, more preferably the solvent comprises at least HFIP or TFE, more preferably at least HFIP.These halogenated or perhalogenated alkanols are used alone or as a mixture of two or more of these solvents.

[0011] In one embodiment of the process for preparing S-arylthiocarbamates, the O-arylthiocarbamate of the general formula (II) is used in a concentration of 0.001 to 5 mol I -1 , preferably 0.01 to 1 mol I -1 , more preferably 0.01 to 0.5 mol I -1 , more preferably 0.02 to 0.2 mol I -1 , used in the solution.

[0012] According to one embodiment, the solution consists of at least 95% by weight, preferably at least 98% by weight, more preferably 99% by weight, more preferably 99.8% by weight, more preferably 100% by weight, in each case based on the total weight of the solution, of the above-mentioned solvent, in particular the solvent(s) selected from the group of halogenated or perhalogenated alkanols and the O-arylthiocarbamate of the general formula (II) dissolved therein, ie no further substances such as catalysts are contained.

[0013] According to one embodiment of the process for preparing S-arylthiocarbamates, the solution comprises, in addition to the above-mentioned solvent from the group of halogenated or perhalogenated alkanols, at least one further organic solvent, wherein the further organic solvent preferably has a log KOWin the range of -1.5 to +1.5, more preferably from the group consisting of methanol (log KOW -0.82), ethanol (log KOW -0.31), 1-propanol (log KOW 0.25), 2-propanol (log KOW 0.05), acetonitrile (log KOW -0.34), dichloromethane (log KOW +1.25), N,N-dimethylformamide (log KOW -1.01), dimethyl sulfoxide (log KOW - 1.35), ethyl acetate (log KOW 0.73) and tetrahydrofuran (log KOW 0.46) (All log KOW-Data are taken from the following source: https: / / pubchem.ncbi.nlm.nih.gov, as of September 7, 2018). The further organic solvent is used alone or as a mixture of two or more of the further organic solvents. According to one embodiment, the solution consists of at least 95% by weight, preferably at least 98% by weight, more preferably 99% by weight, more preferably 99.8% by weight, more preferably 100% by weight, in each case based on the total weight of the solution, of the above-mentioned solvent, in particular the solvent(s) selected from the group of halogenated or perhalogenated alkanols and the further organic solvent(s) described above, and the dissolved O-arylthiocarbamate of the general formula (II), ie no further substances such as catalysts are present.

[0014] The solution can be anhydrous, but surprisingly, a certain water content is tolerated without affecting the efficiency, etc., of the reaction. In particular, the solution can have a water content of up to 10,000 ppm by weight, preferably up to 1,000 ppm by weight, more preferably up to 500 ppm by weight, more preferably up to 100 ppm by weight, in each case based on the total weight of the solution. According to one embodiment, the solution consists only of the above-mentioned solvent, in particular the solvent(s) selected from the group of halogenated or perhalogenated alkanols and the further organic solvent(s) described above, and the dissolved O-arylthiocarbamate of the general formula (II), i.e. no further substances such as catalysts are present, and the solution optionally has a water content of up to 10,000 ppm by weight, preferably up to 1.000 ppm by weight, more preferably up to 500 ppm by weight, more preferably up to 100 ppm by weight, in each case based on the total weight of the solution.

[0015] The rearrangement from O-arylthiocarbamate to S-arylthiocarbamate is electrochemically induced, wherein in one embodiment the electrochemically induced rearrangement is preferably carried out at a current density in the range of 0.1 to 2000 mA cm -2 , more preferably in the range of 1 to 500 mA cm -2 , more preferably in the range of 5 to 100 mA cm -2 occurs.

[0016] The electrochemically induced rearrangement takes place using an anode, which preferably comprises either a noble metal and / or a carbon-based material, more preferably consists of noble metal and / or a carbon-based material, wherein the anode more preferably comprises a material selected from the group consisting of graphite, glassy carbon, boron-doped diamond, and platinum, more preferably consists of a material selected from the group consisting of graphite, glassy carbon, boron-doped diamond, and platinum. The phrase "the anode comprises a material" means that at least 90% by weight, preferably at least 95% by weight, more preferably at least 98% by weight of the anode consists of this material, in each case based on the total weight of the anode. The anode material is present alone or as a mixture of two or more anode materials.The electrochemically induced rearrangement is further carried out using a cathode, which preferably comprises a metal, which is more preferably selected from the group consisting of platinum, stainless steel, and nickel, more preferably consists of a metal selected from the group consisting of platinum, stainless steel, and nickel. The phrase "the cathode comprises a metal" means that at least 90% by weight, preferably at least 95% by weight, more preferably at least 98% by weight of the cathode consists of this metal, in each case based on the total weight of the cathode. The cathode metal is present alone or as a mixture of two or more metals.

[0017] According to one embodiment of the process for preparing S-arylthiocarbamates, the electrochemically induced rearrangement takes place at an external temperature in the range from 5°C up to and including the boiling point of the solution or solvent, preferably in the range from 15°C up to and including the boiling point of the solution or solvent, more preferably in the range from 5 to 70°C, more preferably in the range from 6 to 60°C, more preferably in the range from 10 to 50°C, more preferably in the range from 15 to 30°C. The term "external temperature" here means the temperature of the space surrounding the apparatus used for the process. The temperature of the solution corresponds to the external temperature ±10°C and is in any case ≤ the boiling point of the solution or solvent.

[0018] According to one embodiment, the process for preparing S-arylthiocarbamates or the electrochemically induced rearrangement is carried out discontinuously, for example in batch mode; in an alternative embodiment, the process is carried out continuously, for example in flow mode. Continuous or flow operation offers the advantage that the use of supporting salt(s) can be dispensed with, i.e. in one embodiment of the process in flow mode, no supporting salt is used. A supporting salt is an additive which is added to the reaction solution and takes over charge transport during electrolysis, greatly reducing the ohmic resistance of the solution and thus closing the electrical circuit. It does not participate in the electrode reactions. In one embodiment, supporting salt is used in batch mode.Conductive salts are known to the person skilled in the art[7] and are, for example, alkylammonium salts or imidazolium salts (for example perchlorates), as well as alkali metal salts of the type AX and alkaline earth metal salts of the type BX2 (A = Li. + , N / a + , K + , Rb + , Cs + ; B = Mg 2+ , Ca 2+ , Sr 2+ , Ba 2+ ; X = Fluoride F - , perchlorate ClO4 , tetrafluoroborate BF4 - , Hexafluorophosphate PF6 - , Methyl sulfate CH3OSO3 - , Ethyl sulfate CH3CH2OSO3 - , trifluoromethanesulfonate CF3SO3 - , bis(trifluoromethane)sulfonimide (CF3SO3)2N - , Tosylate 4-CH3-C6H4SO3 -). Furthermore, Brønsted acids with anodically stable conjugate bases such as sulfuric acid, trifluoromethanesulfonic acid, para-toluenesulfonic acid, and trifluoroacetic acid can be used to ensure ionic conductivity. The respective conducting salt is used alone or as a mixture of two or more conducting salts.

[0019] According to one embodiment of the process, in which the process is carried out in discontinuous or batch operation, the solution consists only of the above-mentioned solvent, in particular the solvent(s) selected from the group of halogenated or perhalogenated alkanols, optionally the further organic solvent(s) described above, the dissolved O-arylthiocarbamate of the general formula (II), and one (or more) conducting salt(s), i.e. no further substances such as catalysts are present, and the solution optionally has a water content of up to 10,000 ppm by weight, preferably up to 1,000 ppm by weight, more preferably up to 500 ppm by weight, more preferably up to 100 ppm by weight, in each case based on the total weight of the solution. According to one embodiment of the process, in which the process is carried out in continuous oris carried out in flow-through operation, the solution consists only of the above-mentioned solvent, in particular the solvent(s) selected from the group of halogenated or perhalogenated alkanols, optionally the further organic solvent(s) described above, and the dissolved O-arylthiocarbamate of the general formula (II), ie no further substances such as, for example, conductive salts or catalysts are present, and the solution optionally has a water content of up to 10,000 ppm by weight, preferably up to 1,000 ppm by weight, more preferably up to 500 ppm by weight, more preferably up to 100 ppm by weight, in each case based on the total weight of the solution.

[0020] In one embodiment of the process for preparing S-arylthiocarbamates, R 2 , R 3of the S-arylthiocarbamate of the general formula (I) or of the O-arylthiocarbamate of the general formula (II) used are each independently selected from the group consisting of branched or unbranched C1 to C10 alkyl groups. In a preferred embodiment of the process for preparing S-arylthiocarbamates, the radicals R 2 and R 3 of the S-arylthiocarbamate of the general formula (I) or of the O-arylthiocarbamate of the general formula (II) used are the same and selected from the group of branched or unbranched C1 to C10 alkyl groups, preferably from the group of unbranched C1 to C5 alkyl groups, further preferably R 2 , R 3 both a methyl or both an ethyl group.

[0021] In a preferred embodiment of the process, n is 1 or 2 and / or m is 1.

[0022] In a preferred embodiment of the process for preparing S-arylthiocarbamates, the radical(s) R 1selected from the group consisting of halogen atom (fluorine, chlorine, bromine, iodine, preferably fluorine or chlorine), branched or unbranched C1 to C10 alkoxy group, branched or unbranched C1 to C10 alkyl-S group, branched or unbranched C1 to C10 alkyl group, branched or unbranched C1 to C10 alkylene group, mono or di(C1 to C10 alkyl)amine group, branched or unbranched C1 to C5 alkyl-C(=O)-NH group, branched or unbranched C1 to C5 alkyl-OC(=O) group, C3 to C10 cycloalkyl group, C3 to C10 heterocycloalkyl group, C6 to C12 aryl group; C6 to C12 aryloxy group, and C5 to C11 heteroaryl group, wherein the C3 to C10 cycloalkyl group, C3 to C10 heterocycloalkyl group, C6 to C12 aryl group, C6 to C12 aryloxy group or C5 to C11 heteroaryl group comprises one or more ring systems which are condensed or separated.

[0023] In a preferred embodiment of the process for preparing S-arylthiocarbamates, the radical(s) R 1 selected from the group consisting of branched or unbranched C1 to C10 alkoxy group, branched or unbranched C1 to C10 alkyl-S group, branched or unbranched C1 to C10 alkyl group, branched or unbranched C1 to C10 alkylene group, mono or di(C1 to C10 alkyl)amine group, branched or unbranched C1 to C5 alkyl-C(=O)-NH group, C3 to C10 cycloalkyl group and C6 to C12 aryloxy group, wherein the C3 to C10 cycloalkyl group, C6 to C12 aryl group, C6 to C12 aryloxy group comprises one or more ring systems which are condensed or separated.

[0024] The process according to the invention for preparing S-arylthiocarbamates makes it possible to obtain the S-arylthiocarbamates of the general formula (I) in a yield of ≥ 80%, preferably ≥ 85%, further preferably ≥ 90%, further preferably ≥ 95%, in each case based on the amount of O-arylthiocarbamate used.

[0025] The following examples serve to illustrate the invention without limiting it thereto. EXAMPLES 1. Variant 1: Execution in batch mode

[0026] A solution of O-arylthiocarbamate (1.0 mmol) and tetrabutylammonium perchlorate (0.34 g, 1.0 mmol) in 10 mL of 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) was electrolyzed in an undivided cell at room temperature under galvanostatic conditions (i = 10 mA, where "i" is the applied current) and with stirring. RVC (porous vitreous carbon; reticulated vitreous carbon, height: 50 mm, width: 10 mm, depth: 5 mm, immersion depth: 10 mm) was used as the anode and a platinum wire (diameter: 0.5 mm) as the cathode. After electrolysis was complete, the RVC electrode was rinsed with a small amount of HFIP, and the reaction solution was combined with the rinse solution. HFIP was then distilled off (reuse), and the solid residue was dissolved in 20 ml of ethyl acetate. The conducting salt was crystallized by adding 10 ml of n-heptane and cooling to -18 °C and recovered by filtration (reuse).The solvents were removed under reduced pressure, and the solid residue was dried in vacuo. If necessary, the products were further purified. Depending on the compound, recrystallization from water / ethanol or from n-heptane / ethyl acetate was suitable.

[0027] Table 1 shows the reactants and products investigated so far with the corresponding isolated product yields, as well as the TON value determined as follows in parentheses: TON = number of molecules converted / number of electrons transferred (“turnover number”).

[0028] Since the reaction proceeds using catalytic amounts of charge, the TON value was defined as a measure of the reaction efficiency. These values ​​were determined from the transferred electrical charge and the isolated yield. Gas chromatography failed to detect any undesired byproducts in any of the reactions investigated, with the exception of the examples with vinyl or dimethylamino substituents. This means that the S-arylthiocarbamates were obtained without byproducts. Table 1 Product spectrum of the electrochemical OS rearrangement (percentages refer to the isolated yields of the respective product in weight %, value in brackets: TON) O-Arylthiocarbamate (starting material) S-Arylthiocarbamate (product) diethylthiocarbamate S-(4-Ethoxyphenyl)-N,N-diethylthiocarbamate *Since in this example the conversion was very slow at room temperature, the reaction was carried out at boiling temperature. 2. Variant 2: Implementation in flow mode

[0029] To carry out the reaction in flow mode, the Fig.The sandwich cell shown was used, in which the anode and cathode were placed on top of each other and separated by a Teflon spacer (spacer thickness: 110 µm). A recess in the spacer (3 x 0.3 cm) served, together with the two electrodes, as a reaction channel, at the ends of which were the inlet and outlet for the reaction solution. The solution was pumped using an HPLC pump at a flow rate of 1 ml min -1 through the reaction vessel (simpler pump models are also suitable in principle). The reaction was carried out at room temperature (25 °C), at a constant current density (j = 19.9 mA cm -2, where "j" is the applied current density), a reactant concentration of 70 mM in HFIP, and without the addition of conducting salt (cathode: platinum sheet, anode: glassy carbon). After the reaction, the solvent was recovered by distillation (reuse). After drying under vacuum, the rearrangement product was obtained in analytical purity without further purification.

[0030] The exemplary implementation resulted in a quantitative yield. 3. Result

[0031] As can be seen from Examples 1 and especially 2, the electrochemical rearrangement was surprisingly possible with sufficient yield even at room temperature (25°C), thus avoiding disruptive thermal side reactions. It was possible to completely dispense with catalysts and, at least in flow mode, completely with the addition of additives such as supporting salts. A series of examples demonstrated that the electrochemical rearrangement of O-arylthiocarbamates can produce the corresponding S-arylthiocarbamates in yields of more than 90 wt. %, based on the starting material used. Because the use of catalysts and additives could be dispensed with and because in most cases no by-products were formed, the workup was extremely simple, as no complex separation was required.In the case of flow-through electrolysis, the separation of the solvent was already sufficient to obtain the product in analytical purity. Description of the illustration Fig. : shows the electrochemical cell used to perform the OS rearrangement in flow mode. (A) Top of the aluminum holder, (B) Teflon block, (C) platinum cathode, (D) Teflon spacer, (E) glassy carbon anode, (F) stainless steel sheet as current collector, (G) Teflon rail, (H) bottom of the aluminum holder. References [1] a) R. Beckert, E. Fanghänel, WD Habicher, P. Metz, D. Pavel, K. Schwetlick, Organikum (22nd edition) 2004, Wiley-VCH, Weinheim. b) T. Wieland, W. Sucrow, The Practice of the Organic Chemist (43rd edition) 1982, DeGruyter, Berlin. [2] G. Lloyd-Jones, J. Moseley, J. Renny, Synthesis 2008, 661. [3] a) H. Quart, ER Evans, J. Org. Chem. 1966, 31, 410; b) MS Newman, HA Karnes, J. Org. Chem. 1966, 31, 3980. [4] a) JS Albert, D. Aharony, D. Andisik, H. Barthlow, PR Bernstein, RA Bialecki, R. Dedinas, BT Dembofsky, D. Hill, K. Kirkland, GM Koether, BJ Kosmider, C. Ohnmacht, W. Palmer, W. Potts, W. Rumsey, L. Shevin, A. Sherwood, Sherwood, BT Dembofsky, D. Hill. PJ Warwick, K. Russel, J. Med. Chem. 2002, 45, 3972; b) J. Ballmann, MGG Fuchs, S. Dechert, M. John, F. Meyer, Inorg. Chem. 2009, 48, 90; c) Y.-H. Cho, A. Kina, T. Shimada, T. Hayashi, J. Org. Chem. 2004, 69, 3811; d) P. Garcia-Garcia, F. Lay, P. Garcia-Garcia, C. Rabalacos, B. List, Angew. Chem. They. Wheat. 2009, 48, 4363; e) V. Novakova, M. Miletin, T. Filandrovä, J. Lenčo, A. Ružička, P. Zimcik, J. Org. Chem. 2014, 79, 2082. [5] JN Harvey, J. Jover, GC Lloyd-Jones, JD Moseley, P. Murray, JS Renny, Angew. Chem. They. Wheat. 2009, 48, 7612. [6] Perkowski AJ, Cross CL, Nicewicz DA, J. Am. Chem. Soc. Rev. 2015, 137, [7] J. Jörissen, B. Speiser, Preparative Electrolysis on the Laboratory Scale, in Organic Electrochemistry-5 th Edition (Editors: B. Speiser, O. Hammerich), CRC Press, Boca Raton, 263 - 330. US 2009 / 0299074 A1 Stephan K. Pedersen et al., J. Org. Chem. 2018, 83, 12000–12006

Claims

[1] Process for the preparation of S-arylthiocarbamates of the general formula (I), wherein R 1 is selected from the group consisting of hydrogen atom, halogen atom, branched or unbranched C1 to C10 alkoxy group, branched or unbranched C1 to C10 alkyl-S group, branched or unbranched C1 to C10 alkyl group, branched or unbranched C1 to C10 alkylene group, mono or di(C1 to C10 alkyl)amine group, branched or unbranched C1 to C5 alkyl-C(=O)-NH group, branched or unbranched C1 to C5 alkyl-OC(=O) group, C3 to C10 cycloalkyl group, C3 to C10 heterocycloalkyl group, C6 to C12 aryl group; C6 to C12 aryloxy group, and C5 to C11 heteroaryl group, wherein the C3 to C10 cycloalkyl group, C3 to C10 heterocycloalkyl group, C6 to C12 aryl group, C6 to C12 aryloxy group or C5 to C11 heteroaryl group comprises one or more ring systems which are condensed or separated; R2 , R 3 are each independently selected from the group consisting of branched or unbranched C1 to C10 alkyl group; n is an integer in the range from 1 to 5, where for n≥2 the residues R 1 each independently from the group of R 1 are selected and optionally two or more R 1 together form a C1 to C8 heterocycloalkyl group; and m is 1; by electrochemically induced rearrangement of an O-arylthiocarbamate of the general formula (II),wherein R 1 , R 2 , R 3 , n and m have the same meaning as in the general formula (I). [2] Process for the preparation of S-arylthiocarbamates according to claim 1, wherein the electrochemically induced rearrangement of an O-arylthiocarbamate of the general formula (II) to an S-arylthiocarbamate of the general formula (I) takes place in solution, wherein the solution comprises a solvent which is selected from the group of halogenated or perhalogenated alkanols, wherein the halogen atoms are selected from the group consisting of fluorine atom, chlorine atom, bromine atom and iodine atom. [3] A process for preparing S-arylthiocarbamates according to claim 2, wherein the solution comprises at least one further organic solvent. [4] A process for the preparation of S-arylthiocarbamates according to any one of claims 1 to 3, wherein the electrochemically induced rearrangement is carried out at a current density in the range of 0.1 to 2000 mA cm -2 occurs. [5] A process for the preparation of S-arylthiocarbamates according to any one of claims 1 to 4, wherein the electrochemically induced rearrangement is carried out using an anode comprising either a noble metal and / or a carbon-based material and / or using a cathode comprising a metal selected from the group consisting of platinum, stainless steel and nickel. [6] A process for the preparation of S-arylthiocarbamates according to any one of claims 2 to 5, wherein the electrochemically induced rearrangement takes place at an external temperature in the range of 5 °C up to and including the boiling temperature of the solution or solvent. [7] A process for the preparation of S-arylthiocarbamates according to any one of claims 2 to 6, wherein the O-arylthiocarbamate of the general formula (II) is used in a concentration of 0.001 to 5 mol I -1 used in the solution. [8] A process for the preparation of S-arylthiocarbamates according to any one of claims 1 to 7, wherein the radicals R 2 and R 3 of the S-arylthiocarbamate of the general formula (I) or of the O-arylthiocarbamate of the general formula (II) used are the same and are selected from the group of branched or unbranched C1 to C10 alkyl groups; and / or wherein n is 1 or 2 and / or m is 1; and / or wherein the radical(s) R 1is / are selected from the group consisting of branched or unbranched C1 to C10 alkoxy group, branched or unbranched C1 to C10 alkyl-S group, branched or unbranched C1 to C10 alkyl group, branched or unbranched C1 to C10 alkylene group, mono or di(C1 to C10 alkyl)amine group, branched or unbranched C1 to C5 alkyl-C(=O)-NH group, C3 to C10 cycloalkyl group and C6 to C12 aryloxy group, wherein the C3 to C10 cycloalkyl group, C6 to C12 aryl group, C6 to C12 aryloxy group comprises one or more ring systems which are condensed or separated.

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