K. A. Volkova

Thiocyanation of 4,5,6,7-Tetrahydroindole

One procedure for the introduction of sulfur atom into the pyrrole ring is based on the reaction of pyrroles with thiocyanogen, which leads to 2-thiocyanatopyrroles [1]; the latter can be converted into 2-alkylsulfanylpyrroles by reaction with alkyl halides in the presence of bases [1]. The thiocyanation of pyrrole with thiocyanogen occurs at the 2-position of the pyrrole ring, whereas indole reacts with thiocyanogen to give 3-thiocyanatoindole [2]. 4,5,6,7-Tetrahydroindole (I) is an important heterocyclic compound which is used to prepare many difficultly accessible substances [3], including indole derivatives. Some difficultly accessible indole derivatives functionalized at the 2-position were synthesized by reaction of I with electrophiles and subsequent dehydrogenation [4]. The reaction of thiocyanogen with tetrahydroindole (I) was not reported. The site of electrophilic substitution in molecule I cannot be always predicted a priori. For example, formylation of 1-vinyl-4,5,6,7-tetrahydroindole involves the 2-position [5], whereas the reaction of I with 6-chloropyrimidine-4-carbonyl chloride resulted in electrophilic substitution at C [6]. We were the first to react tetrahydroindole (I) with thiocyanogen with formation of previously unknown 2-thiocyanato-4,5,6,7-tetrahydroindole (II) in 80% yield. Thiocyanogen was prepared in situ by addition of bromine to a suspension of potassium thiocyanate in methanol at –65 to –78°C. A solution of I in methanol was cooled to –78oC and added in one portion to a solution of thiocyanogen, and the mixture was stirred for 3 h at –65 to –78°C and allowed to warm up to room temperature. The structure of II was proved by H and C NMR spectroscopy with the aid of HMBC (C–H) and HSQC (C–H) two-dimensional correlation techniques. Thus, the thiocyanation of tetrahydroindole (I) with thiocyanogen occurs at the 2-position with formation of 2-thiocyanato-4,5,6,7-tetrahydroindole (II) which is promising as intermediate product for the synthesis of sulfanyl derivatives of tetrahydroindole. Compound I was prepared by the Trofimov reaction from cyclohexanone oxime and acetylene [3]. 2-Thiocyanato-4,5,6,7-tetrahydro-1H-indole (II). Dark yellow oily substance. H NMR spectrum (CDCl3), δ, ppm: 1.67–1.74 m (2H, 5-H), 1.74–1.81 m (2H, 6-H), 2.44 t (2H, 4-H, J = 5.5 Hz), 2.54 t (2H, 7-H, J = 5.9 Hz), 6.34 s (1H, 3-H), 8.26 s (NH). C NMR spectrum (CDCl3), δC ppm: 22.56 (C), 22.77 (C), 22.83 (C), 23.29 (C), 99.57 (SCN), 111.23 (C), 119.36 (C), 120.40 (C), 134.41 (C). Found, %: C 60.32; H 5.52; N 15.98; S 18.21. C9H10N2S. Calculated, %: C 60.64; H 5.65; N 15.72; S 17.99. The H and C NMR spectra were recorded on a Bruker DPX-400 spectrometer at 400.13 and 100.61 MHz, respectively, using CDCl3 as solvent and hexamethyldisiloxane as internal reference. ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 4, pp. 619–620.

Regioselective reaction of selenium dichloride and dibromide with diallyl sulfide

Selenium-centered electrophilic reagents play an important role in modern organic synthesis; their cyclization reactions lead to both carbocyclic compounds via formation of new carbon–carbon bond and heterocycles [1]. Our studies on reactions of selenium dichloride and dibromide with unsaturated chalcogenides [2–4] showed that selenium dihalides are efficient reagents for the synthesis of heterocyclic compounds [2, 3]. Reactions of selenium dichloride and dibromide with divinyl sulfide [2] gave the corresponding Markovnikov adducts, six-membered 1,4-thiaselenanes which readily underwent rearrangement into five-membered 1,3-thiaselenolanes. Diallyl sulfide is homologous to divinyl sulfide; due to the presence of two double C=C bonds in its molecule it can also give rise to heterocycles. Reaction of selenium dichloride or dibromide with diallyl sulfide was not reported. We have found that selenium dichloride and dibromide react with diallyl sulfide in acetonitrile, chloroform, and carbon tetrachloride in regioselective fashion, yielding six-membered heterocyclic compounds, 3,5-bis(chloromethyl)-1,4-thiaselenane (I) and 3,5-bis(bromomethyl)-1,4-thiaselenane (II), as a result of anti-Markovnikov addition of selenium dihalide at the allyl group. The best yields (91–93%) of compounds I and II were obtained in acetonitrile at 0°C; when the reactions were carried out in carbon tetrachloride or chloroform, the yield decreased to 70–80%. The structure of compounds I and II was determined on the basis of their H and C NMR spectra and elemental analyses. The coupling constant between the selenium nucleus and CH carbon nuclei (67 Hz) is typical of direct C–Se coupling (JCSe) [2, 3], indicating anti-Markovnikov addition of SeX2 at both allyl groups in diallyl sulfide. Migalina et al. [5] previously reported on the synthesis of compound II by addition of selenium tetrabromide to diallyl sulfide, followed by reduction of selenium(IV) derivative with sodium sulfide; the IR and H NMR spectra of the product were given in [5], and the H NMR data differed from those obtained by us. 3,5-Bis(chloromethyl)-1,4-thiaselenane (I). A solution of 1.5 g (10 mmol) of SeCl2 in 20 ml of anhydrous acetonitrile was added dropwise under stirring to a solution of 1.14 g (10 mmol) of diallyl sulfide in 45 ml of anhydrous acetonitrile, cooled to 0°C. The mixture was stirred for 2 h at 0°C, the solvent was distilled off under reduced pressure, and the residue was recrystallized from chloroform. Yield 2.46 g (93%). H NMR spectrum, δ, ppm: 2.95 m (2H, SCH2), 3.08 m (2H, SeCH), 3.32 m (2H, SCH2), 3.93 m (2H, ClCH2), 4.23 m (2H, ClCH2). C NMR spectrum, δC, ppm: 31.74 (SCH2), 33.37 (SeCH, JCSe = 67 Hz), 47.02 (ClCH2). Found, %: C 26.92; H 3.64; Cl 26.51; Se 30.19. C6H10Cl2SSe. Calculated, %: C 27.29; H 3.82; Cl 26.85; Se 29.90. 3,5-Bis(bromomethyl)-1,4-thiaselenane (II) was synthesized in a similar way. Yield 3.21 g (91%). H NMR spectrum, δ, ppm: 2.98 m (2H, SCH2), I, X = Cl; II, X = Br. ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 12, pp. 1580–1581.

Reaction of divinyl selenide with selenourea

Reaction of divinyl sulfide with thiourea proceeds in the presence of hydrochloric acid (EtOH/H2O/HCl) and leads to the formation of a cyclization product, 2H,6H-2,6-dimethyl-4-amino-1,3,5-dithiazinium hydrochloride [1, 2]. No data on the reaction of divinyl selenide with selenourea was published before, but it was presumable that under the same conditions it would be analogous to the above-mentioned process. Formation of the corresponding cyclic compound, diselenoazinium hydrochloride, could be expected. We have found that contrary to this suggestion the reaction of divinyl selenide with selenourea (EtOH/ H2O/HCl, 50–56oC) resulted in the formation of a previously unknown bis[1-carbamimidoylselanyl) ethyl] selenide dihydrochloride I, the product of selenourea addition to the double bonds of divinylselenide. At the double molar excess of selenourea in respect to the divinyl selenide the yield of compound I was quantitative.

α-Haloacetylene and diacetylene alcohols

Results of investigations of α-haloacetylene and diacetylene alcohols in reactions with various reagents are discussed. Frequently the reactions do not stop at monoadduct formation but are followed by intramolecular cyclization or by rearrangement providing polyfunctional compounds.

Reactions of aliphatic, aromatic, and heterocyclic aminothiols with diacetylene

Reactions of aliphatic, aromatic, and heterocyclic aminothiols with diacetylene in liquid ammonia or methanol furnished the corresponding aminoorganylsulfanylbutenynes of predominantly Z-configuration.

Reaction of thiosemicarbazide with 1,3-dibromopropyne

Thiosemicarbazide reacted with an equimolar amount of 1,3-dibromopropyne in aqueous ethanol (1:1) to give (4-bromomethylidenethiazolidin-2-ylidene)hydrazine hydrobromide. The reaction of thiosemicarbazide with 2 equiv of 1,3-dibromopropyne in ethanol on heating resulted in the formation of 3,6-bis-(bromomethylidene)-3,4,6,7-tetrahydro-2H-thiazolo[2,3-c][1,2,4]triazine hydrobromide. The corresponding free base was obtained when the reaction performed in the presence of triethylamine.

Reaction of dithiomalonic acid dianilide with methyl propiolate

Dithiomalonic acid dianilide reacted with methyl propiolate in acetic acid in the presence of excess perchloric acid to give 4-anilino-2-methoxycarbonylmethyl-1,3-dithiine-6-phenyliminium perchlorate.

1H and 13C NMR study of the structure of alkylthio enyne alcohols and glycols

Steric structure of some alkylthio enyne alcohols and glycols was determined by 1H and 13C NMR spectroscopy. Analysis of cross peaks in the 2M NOESY spectra showed that the double bond in these compounds has Z configuration. Criteria were found which indicate the position of the hydroxy-containing substituent with respect to the triple or double bond.

Reaction of azolethiones with diacetylene

Reactions of 2,3-dihydro-1H-benzimidazole-2-thione, 2,3-dihydro-1H-1,2,4-triazole-3-thione, 4-amino-5-phenyl-3,4-dihydro-2H-1,2,4-triazole, and 6-aminopurine-2-thiol with diacetylene in DMSO gave the corresponding 1-(azolylsulfanyl)but-1-en-3-ynes having Z configuration of the double bond.