Thermal Decomposition of Aromatic Thioureas [1]

Cyril Párkányi* and Mohammed A. Al-Salamah [2] Department of Chemistry, The University of Texas at El Paso, El Paso, Texas 79968-0513, U.S.A. Z. Naturforsch. 41b, 101 — 104 (1986); received August 14, 1985 Thioureas, Isothiocyanates, Thermal Decomposition, Side-Chain Elimination, Kinetics Thermal decomposition of aromatic and heteroaromatic thioureas in boiling chlorobenzene is a first-order reaction. The reaction involves intramolecular hydrogen transfer followed by a cleav­ age of the C -N bond which is the rate-limiting step. The rate constants of decomposition have been determined and correlated with quantum-chemical reactivity indices.

Aromatic and heteroaromatic thioureas are inter­ On the basis of the experimental evidence, Shaw esting both from the theoretical and the practical and Walker [7] concluded that the most acceptable points of view as some of them are used as pesticides, mechanism of the thermal decomposition of thiourea preservatives, and pharmaceuticals. Also, thioureas and of its mono-, di-, and trimethyl derivatives can have found applications in photography, dye indus­ be depicted as follows, with thiourea as an example try, and textile industry [3]. Furthermore, thioureas (cf. also [9]): can be conveniently employed as starting materials in H,N-C-NH, HN C=S HN=C= S the synthesis of various heterocyclic compounds 1 II 1 I V S A [3, 4], H'HNH H H H One of the reactions of substituted thioureas whose mechanism has received only limited attention ■NH, HNCS : ( 2 ) so far is their thermal decomposition leading to the formation of the corresponding isothiocyanate and In the decomposition of the methylthioureas, the ammonia as the products (eq. ( 1 )), although the methyl group does not migrate and the hydrogen reaction is used in synthetic organic chemistry for the transfer is not a rate-determining step because, in an preparation of isothiocyanates [5, 6]. Shaw and aqueous medium, the isomerization of thiourea and Walker [7] studied the thermal decomposition of N,N-dimethylthiourea is pH-dependent over a wide thiourea and its derivatives in an aqueous medium range of pH values. Thus, they concluded that the and suggested two possible decomposition mecha­ rate-determining step involves a cleavage of the nisms: a mechanism involving intramolecular hydro­ C—N bond with the activated complex as shown gen transfer and another one, with an intermolecular above and composed of two parts: an ammonia-like hydrogen transfer and an activated complex with sol­ (or amine-like) fragment, and an isothiocyanate-like vent participation. In the first case, the reaction is fragment. expected to be first order, whereas the mechanism In their study, Ledovskikh and Shapovalova [10] involving solvent participation should be second or­ investigated the decomposition of several aryl- der. The experimental results obtained by Shaw and thioureas in boiling chlorobenzene and determined Walker [7] and by Kappanna [ 8] indicate that the that the reaction was first order with respect to the reaction is first order with respect to thiourea. substrate and that hydrogen chloride did not affect the rate of the reaction but that it increased the yield A r—NH —C—NH2^> A r—N=C=S + NH3 (1) of the corresponding isothiocyanate by suppressing the various side reactions. Also, they studied [11] the S effect of intramolecular hydrogen bonding upon the A ability of arylthioureas to undergo conversion to Ar = aryl or heteroaryl arylisothiocyanates. The goal of the present work was to investigate the * Reprint requests to Prof. Dr. Cyril Pärkänyi. kinetics of thermal decomposition of several aro­ Verlag der Zeitschrift für Naturforschung. D-7400 Tübingen matic and heteroaromatic thioureas to determine 0340-5087/86/0100-0101/$ 01.00/0 whether their decomposition follows the same 102 C. Pärkänyi —M. A. Al-Salamah • Thermal Decomposition of Aromatic Thioureas mechanism as that formerly suggested for thiourea The kinetics of thermal decomposition of the and N-alkylthioureas [7, 8]. thioureas was studied at 132 °C in boiling chloroben- The thioureas used in this study were N-phenyl- zene. The reaction was followed spectrophotometri- thiourea (1), N-2-naphthylthiourea (2), N-2- cally in the infrared region by measuring the intensity biphenylylthiourea (3), N-2-pyridylthiourea (4), N-3- of the NCS band of the product (see Experimental). quinolylthiourea (5), and N- 8-quinolylthiourea ( 6), The results indicate that the thermal decomposition with a general formula A (see above). of N-aryl- and N-heteroarylthioureas is a first-order Among the various methods available for the reaction and that it takes place via intramolecular synthesis of aromatic and heteroaromatic thioureas, hydrogen transfer followed by a cleavage of the C—N two methods were employed. In the first method bond which is the rate-limiting step (see eq. ( 2)). (method A), ammonium or sodium thiocyanate was Among other factors (steric hindrance, hydrogen heated with an aromatic amine hydrochloride. The bonding), the reaction rate depends on the elec- obtained salt of the amine with thiocyanic acid was trophilicity of the aryl group. The specific rate con­ converted into the corresponding thiourea by heating stants for the compounds under study are shown in [12]. The second method (method B) involved the Table II. use of benzoyl isothiocyanate (obtained from ben­ We have attempted to use quantum-chemical reac­ zoyl chloride and ammonium or potassium thio­ tivity indices to correlate the kinetic data. In the case cyanate in acetone) which upon heating with an aro­ of the arylthioureas, PMO localization energies for matic amine in acetone gave the intermediate N-ben- electrophilic substitution, Lr+, were used as the zoyl-N'-arylthiourea. The latter was then decom­ theoretical reactivity index (the lower the Lr+, the posed into the corresponding N-arylthiourea by heat­ more reactive the position; Lr+ reflects the elec- ing with diluted aqueous solution of sodium hydrox­ trophilicity of a particular position) [16]. It can be ide [13, 14]. We have found that heating with con­ seen (Table II) that there is a good qualitative agree­ centrated aqueous sodium hydroxide leads to the for­ ment between the experimental reaction rates and mation of hydrogen sulfide and decreases the yield of the atom localization energies for the respective posi­ the final product. tion in the aromatic hydrocarbons, Lr+, with N-2- The synthesized N-aryl- and N-heteroarylthio- biphenylylthiourea (3) as the fastest and N-phenyl- ureas 1—6 are summarized in Table I, along with the thiourea (1) as the slowest reacting compound. In the method of preparation, yield, and the melting point. case of the heteroaromatic thioureas, 4—6, because

Table I. Synthesized thioureas. No. Compound M ethod Yield Melting Lit. melting of synthesis3 [%] point [°C] point [°C] (ref.)

1 N-Phenylthiourea A 75 154 156(12) 2 N-2-Naphthylthiourea B 47 185 185(12) 3 N-2-Biphenylylthiourea A 38 200 198(13) 4 N-2-Pyridylthiourea B 60 145 144(13) 151(15) 5 N-3-Quinolylthiourea B 77 168 169-169.5(14) 6 N-8-Quinolylthiourea B 33 160 - a Method A: ref. [12]; method B: refs. [13, 14],

Table II. Thermal decomposition No. Compound k. sec~la *-TL +b qrc of the thioureas. 1 N-Phenylthiourea 0.725 x 10“4 2.310 - 2 N-2-Naphthylthiourea 2.372 x 10~4 2.120 - 3 N-2-Biphenylylthiourea 2.695 x 10“4 2.067 - First-order rate constant; 4 N-2-Pyridylthiourea 1.746 x 10~4 - 0.923 PMO localization energy, ref. 5 N-3-Quinolylthiourea 2.245 x 1 0 '4 - 1.009 [16]; 6 N-8-Quinolylthiourea 2.503 x 10~4 - 1.013 HMO jr-electron density, ref. [17]. C. Pärkänyi —M. A. Al-Salamah • Thermal Decomposition of Aromatic Thioureas 103 of the complications connected with the use of locali­ Spectral measurements. The IR spectra were zation energies, HMO jr-electron densities, qr, were recorded on Perkin-Elmer 710 B and Beckman used as the appropriate reactivity index [17]. The AccuLab spectrophotometers. higher the 7r-electron density in a position, the more Kinetic studies. A 250 ml three-necked flask con­ reactive it is in this type of reaction. In the hetero­ taining a known volume of chlorobenzene and fitted cyclic group of thioureas studied, N-2-pyridyl- with a reflux condenser and a thermometer was heated on an oil bath to 132 °C (boiling point of thiourea (4) is the slowest, N- 8-quinolylthiourea (6) chlorobenzene). The temperature was kept constant the fastest reacting compound, in full agreement with at 132 ± 1 °C by placing the oil bath in a heating the prediction based on ^-electron densities. The mantle connected to a powerstat used to control the first-order specific rate constants for the compounds temperature. Then the reactant was added quickly, under study vary in the range from 0.73xlCT 4 sec-1 and the time was recorded. The concentrations of the (N-phenylthiourea) to 2.70x 1(T 4 sec-1 (N-2-bi- different thiourea substrates in the experiments were phenylylthiourea). in the range between 0.8xl0-2 and 1.4xl0_1 M. At The two indices used in this work, Lr+ and qr, can various stages of the reaction a 2 ml sample was re­ be considered as good criteria of electrophilicity of moved quickly by using a syringe rinsed out with 1 ml of the solution. The sample was placed in the various positions in benzenoid hydrocarbons and crushed ice to slow the reaction down and, after it pyridine-like heterocycles, respectively. It is worth was chilled (3 — 5 min), 1 ml of it was used to clean mentioning that the order of reactivity of the three the IR cells. Then one cell was filled with the remain­ N-arylthioureas parallels the order of reactivity of ing sample, and the other cell was filled with the respective aryl radicals (phenyl < 2-naphthyl < chlorobenzene as a reference. The IR spectrum of 2-biphenylyl) in the free-radical arylation of thio- each sample was obtained and the absorbance of the phene [18]. Also, the order of reactivity of the three isothiocyanate band, i>NCs (~2000 cm-1), due to N-heteroarylthioureas is the same as the reactivity of Fermi resonance, was determined [ 6]. the heteroaryl radicals in the free-radical hetero- The absorbance was obtained by using eq. (3), arylation of thiophene (2-pyridyl < 3-quinolyl < 8-qui- A = log = —log T (3) nolyl) [18]. Our conclusions and the results obtained in this were A is the absorbance, and T is the transmittance. work are in agreement with those obtained by Shaw By plotting A 1: vs. time (order 1/2), log A vs. time and W alker [7], (order 1), and A -1 vs. time (order 2), the order of the reaction can be obtained as well as the reaction rate constant [19]. It has been determined that the reaction is first order with respect to the substrate Experimental (linear plots of log A against time). The first-order rate constants, k, were obtained from these linear Materials. Two methods described in the literature plots as were used to synthesize the thioureas under study, method A [12] and method B [13, 14]. They are dis­ k = -2.303 slope (4) cussed in the above text and the synthesized They are summarized in Table II. thioureas, the yields, and the melting points are given in Table I. The starting amines were commer­ Financial support from the Welch Foundation, cially available compounds. Houston, Texas (Grant AH-461) is gratefully Instruments. Melting points were determined on a acknowledged. The authors wish to express their sin­ Thomas-Hoover capillary melting point apparatus cere thanks to Dr. Magdalena E. Wojciechowska for and are uncorrected. valuable discussions and her interest in this work.

[1] Presented, in part, at the 37th Southwest Regional [3] F. Duus, in D. Neville Jones (ed.): Comprehensive Meeting of the American Chemical Society, San An­ Organic Chemistry. The Synthesis and Reactions of tonio, Texas, December 9—11, 1981. Organic Compounds (D. Barton and W. D. Ollis), [2] Present address: Department of Chemistry, University Vol. 3, p. 373, Pergamon Press, Oxford 1979. of Arizona, Tucson, Arizona 85721, U.S.A. [4] A. Vogel (revised by B. S. Furniss, A. J. Hannaford, 104 C. Pärkänyi—M. A. Al-Salamah • Thermal Decomposition of Aromatic Thioureas

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