and Rb-containing catalysts

Tetrahedron 73 (2017) 7079e7084

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Tetrahedron journal homepage: www.elsevier.com/locate/tet

Synthesis of a new class of heterocycles 1,7-dithia-3,5diazacycloalkan(e)-4-(thi)ones using Cs- and Rb-containing catalysts Regina R. Khairullina*, Alfiya R. Geniyatova, Tatyana V. Tyumkina, Diana S. Karamzina, Askhat G. Ibragimov, Usein M. Dzhemilev Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, 141 Prospekt Oktyabrya, 450075, Ufa, Russian Federation

a r t i c l e i n f o

a b s t r a c t

Article history: Received 25 August 2017 Received in revised form 19 October 2017 Accepted 26 October 2017 Available online 29 October 2017

An efficient method for the synthesis of 1,7-dithia-3,5-diazacycloalkan-4-ones and 1,7-dithia-3,5diazacycloalkane-4-thiones has been developed via the cyclothiomethylation reaction of (thio)urea with bis(N,N-dimethylamino)methane and a,u-alkanedithiols such as 1,2-ethanedithiol, 1,3propanedithiol, 1,4-butanedithiol, 1,5-pentanedithiol, and 1,6-hexanedithiol under the action of catalysts based on Rb and Cs salts. A theoretical conformational analysis has been carried out on the example of 1,7-dithia-3,5-diazacycloethane-4-thione, being a representative of new heteromacrocycles with flattened -HN(CO)NH- fragment. © 2017 Elsevier Ltd. All rights reserved.

Keywords: 1,7-Dithia-3,5-diazacycloalkan-4-ones 1,7-Dithia-3,5-diazacycloalkane-4-thiones Cs- and Rb-containing catalysts Сonformational analysis

1. Introduction According to,1,2 one of the best known methods for the synthesis of 1,3,5-thiadiazinan-4-ones and 1,3,5-thiadiazinane-4-thiones is the cyclothiomethylation reaction of urea or thiourea using CH2O and H2S under conditions of acid catalysis. Аcid-catalyzed double nucleophilic addition of bisthiols to heterocyclic bisacetals gives sulfur-containing benzimidazolone-сontaining [2.2]сyclophanes.3 At the beginning of our research there were no data in the literature on selective methods for the synthesis of 1,7-dithia-3,5diazacycloalkan-4-ones and 1,7-dithia-3,5-diazacycloalkane-4thiones. Interest in the class of N,S-containing heterocycles is conditioned by a manifestation in the latter of potential antibacterial,4,5 antioxidant6,7 and diuretic8 activity. In continuation of ongoing research in the field of chemistry of S,N-containing heterocycles,9 we have investigated into the multicomponent reaction of (thio)urea with a,u-alkanedithiols and bis(N,N-dimethylamino)methane under the action of catalysts based on Rb and Cs salts. The reaction of N,N0 -bis[(dimethylamino) methyl](thio)urea with a,u-alkanedithiols, and the reaction between a,u-bis-1,3-aminosulfide and (thio)urea have been also successfully implemented under the same reaction conditions.

* Corresponding author. E-mail address: [email protected] (R.R. Khairullina). https://doi.org/10.1016/j.tet.2017.10.068 0040-4020/© 2017 Elsevier Ltd. All rights reserved.

In this paper, we report the results from our studies of a new class of heterocycles, namely, 1,7-dithia-3,5-diazacycloalkan-4ones and 1,7-dithia-3,5-diazacycloalkane-4-thiones, their preparation and physicochemical properties.

2. Results and discussion On the example of the reaction between urea, bis(N,N-dimethylamino)methane, and 1,2-ethanedithiol we have shown that, among the catalysts based on alkali (Na, K, Rb, Cs) metals tested under the selected reaction conditions (urea - bis(N,N-dimethylamino)methane - 1,2-ethanedithiol - [catalyst] ¼ 1:2:1:0.1, 60 C, 8 h, EtOH), Cs2CO3 and RbNO3 were the most efficient in producing 1,7-dithia-3,5-diazonan-4-one (2a) in 38e65% yield (Scheme 1, Table 1). In the absence of the catalyst, the cyclothiomethylation reaction of urea does not occur. To expand the application of the accomplished reaction we have studied cyclothiomethylation of (thio)urea with bis(N,N-dimethylamino)methane and a,u-alkanedithiols such as 1,2-ethane-, 1,3propane-, 1,4-butane-, 1,5-pentane- and 1,6-hexanedithiols under the selected reaction conditions. These reactions proceed via the selective formation of 1,7-dithia-3,5-diazacycloalkan-4-ones 2a-e and 1,7-dithia-3,5-diazacycloalkane-4-thiones 3а-е employing Cs2CO3 as the catalyst. Structural identification of the synthesized compounds was

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R.R. Khairullina et al. / Tetrahedron 73 (2017) 7079e7084

Scheme 1. Cyclothiomethylation of (thio)urea with bis(N,N-dimethylamino)methane and a,u-alkanedithiols.

performed using 1D and 2D (COSY, HSQC, HMBC) experiments of 1H and 13C NMR spectroscopy. A characteristic feature of 1,7-dithia3,5-diazacycloalkan-4-ones(thions) is the observation of signals of C¼O and C¼S groups at ~157 ppm and ~183 ppm, respectively, as well as of the signals of a methylene fragment between heteroatoms in the region dС ~44.08 ppm. Long-range heteronuclear interactions from the HMBC spectrum provide evidence for the interactions between the carbon and hydrogen atoms of the molecular fragments (-C ¼ X) - (-NHCH2S) and (-H2S- (-NHCH2S-) that also support the formation of the target heterocycles 2a-e and 3a-e. It should be noted that, unlike 1,3,5-thiadiazinane-4-thione9 and 1,7-dithia-3,5-diazacycloalkan-4-one 2a, in 1H and 13C NMR spectra of 3a-e the signals corresponding to C¼S and -NHCH2Sfragments are significantly broadened. For example, for the methylene fragment, the half-width of the 13 C NMR signal is W1/ 2 ¼ 60 Hz. Apparently, this is due to slow conformational inter conversion on the NMR time scale for these compounds. To determine the behavior in the solution of new of N,S heterocycles containing a flattened carbamide fragment we carried out a theoretical conformational analysis for 3a as an example. Its results are represented in SI. Thus, conformational dynamics of the heterocycle is connected with the inversion of hydrogen atoms at nitrogen atoms and the inversion of a nine-membered cycle. It is found that both hydrogen atoms of the carbamide fragment in the cycle may be situated in one plane with each other and C¼O group forming B conformation (Fig. 1). Conformer А with a different configuration of hydrogen atoms exists as well, moreover, it corresponds to the global minimum on the PES molecule (Fig. 1). Transformation А/В is realized in the inversion process of one of the nitrogen atoms. Its calculated barrier for this system is high and equals ~10 kkal/mol (Fig. 2). Fig. 2 demonstrates conformational passes connected with different organization of the cyclic core as well. As a result, in spite of the huge size of the cycle a limited number of stable conformers was found, eight for each of the two isomer

structures with a different configuration of the flattened carbamide fragment (SI, Table S1). The activation parameters analysis shows that not all conformational passes can be carried out at room temperature (SI, Table S2). Positive ion mode MALDI-TOF mass spectra exhibit molecular ion peaks of the form [MþK]þ for 1,7-dithia-3,5-diazacycloalkan-4ones 2a-e and [MþNa]þ for 1,7- dithia-3,5-diazacycloalkane-4thiones 3a-e. It can be assumed10e13 that the cyclothiomethylation reaction of (thio)urea with bis(N,N-dimethylamino)methane and a,u-alkanedithiols proceeds in two probable directions I and II to produce the target heterocycles 2а-е and 3а-е (Scheme 2). Pathway I implies the initial aminomethylation of (thio)urea with bis-(N,N-dimethylamino)methane to form N,N0 -bis[(dimethylamino)methyl](thio)urea 4 or 5 as intermediates, the interaction of which with a,u-alkanedithiol in situ leads to the desired 1,7-dithia3,5-diazacycloalkan-4-ones 2a-e and 1,7-dithia-3,5diazacycloalkane-4-thions 3a-e. To check this assumption, we have pre-synthesized N,N0 -bis [(dimethylamino)methyl](thio)urea 4 and 5,10,11 which were involved in the cyclothiomethylation reaction with a,u-alkanedithiols catalyzed by 10 mol% Cs2CO3. The reaction between N,N0 bis[(dimethylamino)methyl]urea 4 and 1,2-ethanedithiol was found to efficiently proceed under selected conditions (4: 1,2ethanedithiol: [Cs2CO3] ¼ 1:1:0.1, 60 C, 8 h, EtOH) to afford the target product 2а in 82% yield. Without the catalyst, the reaction does not take place (Scheme 3). Cyclothiomethylation of N,N0 -bis[(dimethylamino)methyl](thio) urea 4 and 5 with a,u-alkanedithiols such as 1,2-ethane-, 1,3propane-, 1,4-butane, 1,5-pentane - and 1,6-hexanedithiols selectively afforded 1,7-dithia-3,5-diazacycloalkan-4-ones 2a-e and 1,7dithia-3,5-diazacycloalkane-4-thiones 3aee in 54e84% yield. Pathway II implies initial aminomethylation of the original a,ualkanedithiols with bis(N,N-dimethylamino)methane to form intermediate bis-1,3-aminosulfides 6aec,12 whose interaction with (thio)urea leads to the corresponding 1,7-dithia-3,5diazacycloalkan-4-ones 2aec and 1,7-dithia-3,5-diazacycloalkane4-thiones 3aec. In order to check this possibility, N1,N1,N6,N6-tetramethyl-2,5-dithiohexane-1,6-diamine 6а13 was pre-synthesized and involved in the reaction with urea. Our experiments showed that under reaction conditions (urea: N1,N1,N6,N6-tetramethyl-2,5-dithiohexane-1,6-diamine: [Cs2CO3] ¼ 1:1:0.2, 60 C, 8 h, EtOH) the above reaction provides the formation of 2а with low yields (10%). The increase in the duration of the reaction up to 96 h enlarged the yield of 2а up to 38%. In the absence of the catalyst, the reaction did not take place (Scheme 4). In an analogous fashion, cyclothiomethylation of (thio)urea with N1,N1,N7,N7-tetramethyl-2,6-dithioheptane-1,7-diamine 6b and N1,N1,N8,N8-tetramethyl-2,7-dithiooctane-1,8-diamine 6c led to

Table 1 The effect of the nature of a catalyst, promoter and solvent on the yield of 1,7-dithia-3,5-diazonan-4-one 2аa. Entry

Catalyst or promoter [M] /mol %

Solvent

Yield of 2а, %

Entry

Catalyst or promoter [M] /mol %

Solvent

Yield of 2а, %

1 2 3 4 5 6 7 8

Cs2CO3/10 CsCl/10 RbNO3/10 Rb2CO3/10 RbCl/10 Cs2CO3/100 e//e RbNO3/100

EtOH EtOH EtOH EtOH EtOH EtOH n-BuOH EtOH

65 48 38 35 25 95 80 58

9 10 11 12 13 14 15 16

t-BuOK/100 t-BuONa/100 n-BuOK/100 n-BuONa/100 n-BuONa/100 n-BuONa/100 n-BuONa/100 K2CO3/100

EtOH EtOH EtOH n-BuOH EtOH i-PrOH CHCl3 þ EtOH n-BuOH

50 48 44 46 30 30 20 5

a Reaction conditions: bis-(N,N-dimethylamino)methane (2 mmol) in solvent (5 mL); 1,2-ethanedithiol (1 mmol); urea (1 mmol) and catalyst (0.1 mmol) or promoter (1 mmol) were premixed for 15 min in solvent (5 mL); 60 C; 8 h.


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Fig. 1. Optimized structures of some stable conformers of compound 3a.

Fig. 2. Energy plot of the ring inversion and the inversion at nitrogen atom in compound 3a.

1,7-dithia-3,5-diazacycloalkan-4-ones 2а-с and 1,7-dithia-3,5diazacycloalkane-4-thiones 3аeс with low (5e10%) and moderate (18e38%) yields in 8 and 96 h respectively. The results obtained allow us to conclude that under cyclothiomethylation conditions ((thio)urea e bis-(N,N-dimethylamino) methane - a,u-alkanedithiol e [catalyst] ¼ 1:2:1:0.2, 60 C, 8 h, EtOH) the formation of 2а-е and 3a-e according to pathway I is the most preferable. Concerning the probable mechanism of cyclothiomethylation of (thio)urea, it can be assumed that the nitrogen atom of N,N0 -bis [(dimethylamino)methyl](thio)urea 4 or 510,11 coordinates with the central atom of the catalyst.10,14,15 The subsequent nucleophilic

addition of a,u-alkanedithiol to carbocation formed under the reaction conditions leads to the formation of the corresponding 1,7dithia-3,5-diazacycloalkan-4-ones 2a-e and 1,7-dithia-3,5diazacycloalkane-4-thiones 3a-e (Scheme 5). 3. Conclusion In conclusion, we have developed an efficient catalytic method for the synthesis of novel 1,7-dithia-3,5-diazacycloalkan-4-ones and 1,7-dithia-3,5-diazocycloalkane-4-thiones through cyclothiomethylation of (thio)urea with bis(N,N-dimethylamino) methane and a,u-alkanedithiols using the Cs- and Rb-based

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Scheme 2. Two possible pathways for the synthesis of 2a-e and 3а-е.

Scheme 3. Reaction of N,N0 -bis[(dimethylamino)methyl](thio)urea 4 (5) with a,ualkanedithiols (1,2-ethane-, 1,3-propane-, 1,4-butane-, 1,5-pentane- and 1,6hexanedithiols) (pathway A).

Scheme 4. Synthesis of 2a-c and 3a-c by the reaction of (thio)urea with N1,N1,N6,N6tetramethyl-2,5-dithiohexane-1,6- (a), N1,N1,N7,N7-tetramethyl-2,6-dithioheptane-1,7(b) and N1,N1,N8,N8-tetramethyl-2,7-dithioctane-1,8-diamines (c) (pathway B).

catalysts. A theoretical conformational analysis of 1,7-dithia-3,5diazacycloethene-4-thione showed the presence of high barriers of conformational passes during the ring inversion and the nitrogen atom inversion in a carbamide fragment, which leads to signals broadening in 1H and 13C NMR spectra. 4. Experimental 4.1. General The 1H and 13C NMR spectra were recorded on a Bruker Avance400 spectrometer (400 and 100 MHz, respectively) in DMSO-d6, internal standard was TMS. Two-dimensional homonuclear (COSY, NOESY) and heteronuclear (HSQC, HMBC) experiments were

carried out under Bruker standard procedures at the same operating frequencies. The mixing time for the NOESY experiments was 0.3 s. Infrared spectra (IR) were recorded using FT-IR spectrometer Bruker Vertex 70 v (Vaseline oil). Mass spectra were recorded on a Bruker Autoflex III MALDI TOF/TOF instrument with a-cyano-4hydroxycinnamic, 2,5-dihydroxybenzoic and sinapic acids as a matrix Samples of the compounds were prepared by the ‘dried droplet method’. Elemental analysis was carried out on a Carlo Erba 1106 analyzer. Melting points were determined on a PHMK 80/2617 apparatus. Monitoring of the progress of reactions was effected by TLC on Sorbfil (PTSKh-AF-A) plates, eluent was acetone/ethyl acetate, 2:1, visualization with I2 vapor. Quantum chemical calculations were carried out using the Gaussian 09W program.16 The geometry optimization for the complexes, vibrational frequency analysis, TS search by QST2 approach, and calculation of entropy and thermodynamic corrections to the total energy of the compounds were carried out on the DFT level with the B3LYP functional in combination with a 631G(d,p) basis set. No constraints were imposed on changes in the geometric parameters of the subsystems studied. Thermodynamic parameters and activation energies were determined at 298.15 K. Both the minima and the TSs (first-order saddle point) were confirmed through the calculation of the force constant (Hessian) matrix and the analysis of the resulting frequencies, with the presence of only one negative frequency in the TS cases. Visualization of quantumchemical data was carried out with ChemCraft17 programs. 4.2. Cyclothiomethylation of (thio)urea with bis-(N,Ndimethylamino)methane and a,u-alkanedithiols. Method A In a glass reactor placed on a magnetic stirrer bis-(N,N-dimethylamino)methane (2 mmol), a,u-alkanedithiol (1 mmol) and EtOH (5 mL) are charged and stirred for 5 min at room temperature (~20 C), and then, (thio)urea (1 mmol) and Cs2CO3 (0.1 mmol) in EtOH (5 mL) are added. The reaction mixture is stirred for 8 h at 60 C. The separated powder of compounds 1,7-dithia-3,5diazacycloalkan-4-ones 2а-е or 1,7-dithia-3,5-diazocycloalkane-4thiones 3а-е are filtered off, washed with water, and dried. 4.3. Condensation of N,N0 -bis[(dimethylamino)methyl](thio)urea with a,u-alkanedithiols. Method B In a glass reactor placed on a magnetic stirrer N,N0 -bis


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Scheme 5. Proposed mechanism of the cyclothiomethylation reaction between (thio)urea, bis(N,N-dimethylamino)methane, and a,u-alkanedithiols catalyzed by Cs and Rb compounds.

[dimethylaminomethyl](thio)urea (1 mmol) and Cs2CO3 (0.1 mmol) in EtOH (5 mL) are loaded and stirred for 10 min at room temperature (~20 C). Then, a,u-alkanedithiol (1 mmol) is added and the reaction mixture is stirred for 6 h at 60 C. The separated powder of compounds 1,7-dithia-3,5-diazacycloalkan-4-ones 2а-е or 1,7dithia-3,5-diazocycloalkane-4-thiones 3а-е are filtered off, washed with water, and dried. 4.4. Condensation of (thio)urea with N1,N1,N6,N6-tetramethyl-2,5dithiohexane-1,6-, N1,N1,N7,N7-tetramethyl-2,6-dithioheptane-1,7 and N1,N1,N8,N8-tetramethyl-2,7-dithioctane-1,8-diamines. Method C In a glass reactor placed on a magnetic stirrer of N1,N1,N6,N6tetramethyl-2,5-dithiohexane-1,6-diamine, (or [N1,N1,N7,N7-tetramethyl-2,6- dithioheptane-1,7-diamine or N1,N1,N8,N8-tetramethyl2,7-dithioctane-1,8-diamine]) (1 mmol), Cs2CO3 (0.2 mmol) in EtOH (5 mL) and (thio)urea (1 mmol) in EtOH (5 mL). The reaction mixture was stirred for 96 h. Then, from the reaction mixture 1,7dithia-3,5-diazacycloalkan-4-ones 2а-с or 1,7-dithia-3,5diazacycloalkane-4-thiones 3а-с are isolated as described above. 1,7-Dithia-3,5-diazonan-4-one (2a). Yield 0.143 g (80%, method A), 0.150 g (84%, method B), 0.067 g (38%, method C); white powder, mp 179e181 С. [Found: C, 33.86; Н, 5.53; N, 15.72; S, 36.02. C5H10N2OS2 requires С, 33.69; Н, 5.65; N, 15.71; S, 35.98%]; Rf (acetone/ethyl acetate, 2:1) 0.46. IR v cm1: 3329, 2924e2954, 1631, 1573, 1461, 1415, 1377, 1271, 1133, 1040, 723, 670. 1Н NMR (400.13 MHz, DMSOed6): 2.76 (4Н, s, СH2-S), 4.29 (4Н, d, 3J 6.0 Hz, НN-СH2-S), 6.79 (2Н, br s, NH-CH2-S). 13C NMR (100.62 MHz, DMSOed6): 30.91 (СH2-S), 42.15 (НN-СH2-S), 157.28 (C¼O). MALDI TOF, m/z: 217.170 [МþK]þ (217.376 calculated for C5H10N2KOS2). 1,7-Dithia-3,5-diazecan-4-one (2b). Yield 0.145 g (75%, method A), 0.157 g (82%, method B), 0.054 g (29%, method C); white powder, m.p. 135e137 С. [Found: С, 37.45; Н, 6.31; N, 15.00; S, 33.29. C6H12N2OS2 requires С, 37.47; Н, 6.29; N, 14.57; S, 33.35%]; Rf (acetone/ethyl acetate, 2:1) 0.36. IR v cm1: 3331, 2924e2854, 1633, 1573, 1460, 1410, 1244, 1042, 775, 679. 1Н NMR (400.13 MHz, DMSOed6): 1.79e1.84 (2Н, m, СH2-СH2-СH2), 2.58 (4Н, t, 3J 7.0 Hz, СH2-S), 4.25 (4Н, d, 3J 6.4 Hz, НN-СH2-S), 6.66 (2Н, br s, NH-CH2-S). 13 C NMR (100.62 MHz, DMSOed6): 29.43 (СH2-S), 30.09 (СH2-СH2СH2), 42.18 (НN-СH2-S), 157.23 (C¼O). MALDI TOF, m/z: 231.214 [МþK]þ (231.403 calculated for C6H12N2KOS2). 1,7-Dithia-3,5-diazacycloundecan-4-one (2c). Yield 0.152 g (74%, method A), 0.145 g (70%, method B), 0.040 g (20%, method C); white powder, m.p. 260e263 С. [Found: С, 40.70; Н, 6.82; N, 13.61; S, 31.07. C7H14N2OS2 requires С, 40.75; Н, 6.84; N, 13.58; S, 31.08%]; Rf

(acetone/ethyl acetate, 2:1) 0.48. IR v cm1: 3333, 2924e2854, 1641, 1570, 1460, 1303, 1153, 1076, 722. 1Н NMR (400.13 MHz, DMSOed6): 1.60 (4Н, br s, СH2-(СH2)2-СH2), 2.52 (4Н, br s, СH2-S), 4.24 (4Н, br s, W1/2 45 Hz, НN-СH2-S), 6.79 (2Н, br s, NH-CH2-S). 13C NMR (100.62 MHz, DMSOed6): 29.92 (СH2-(СH2)2-СH2), 29.02 (СH2-S), 42.13 (НN-СH2-S), 157.74 (C¼O). MALDI TOF, m/z: 245.185 [МþK]þ (245.429 calculated for C7H14N2KOS2). 1,7-Dithia-3,5-diazacyclododecan-4-one (2d). Yield 0.155 g (70%, method A), 0.152 g (69%, method B); white powder, m.p. 80e85 С. [Found: С, 43.63; Н, 7.35; N, 12.81; S, 29.24. C8H16N2OS2 requires С, 43.60; Н, 7.32; N, 12.71; S, 29.11%]; Rf (acetone/ethyl acetate, 2:1) 0.58. IR v cm1: 3320, 2923e2854, 1632, 1567, 1460, 1377, 1294, 1236, 1073, 722. 1Н NMR (400.13 MHz, DMSOed6): 1.31e1.39 (2Н, m, (СH2)2-СH2-(СH2)2), 1.51e1.53 (4Н, m, СH2-(СH2)2-СH2), 2.52e2.54 (4Н, m, СH2-S), 4.24 (4Н, d, 3J ¼ 4.0 Hz, НN-СH2-S), 6.94 (2Н, br s, NH-CH2-S). 13C NMR (100.62 MHz, DMSOed6): 28.14, 29.48, 30.33 (S-(СH2)5-S), 42.14 (НN-СH2-S), 157.60 (C¼O). MALDI TOF, m/z: 259.180 [МþK]þ (259.456 calculated for C8H16N2KOS2). 1,7-Dithia-3,5-diazacyclotridecan-4-one (2е). Yield 0.160 g (68%, method A), 0.125 g (54%, method B); white powder, m.p. 134e136 С. [Found: С, 46.11; Н, 7.78; N, 11.92; S, 27.35. C9H18N2OS2 requires С, 46.12; Н, 7.74; N, 11.95; S, 27.36%]; Rf (acetone/ethyl acetate, 2:1) 0.66. IR v cm1: 3337, 2924e2854, 1630, 1576, 1460, 1377, 1240, 1188, 1043, 723, 647. 1Н NMR (400.13 MHz, DMSOed6): 1.32 (4Н, br s, (СH2)2-(СH2)2-(СH2)2), 1.52 (4Н, br s, СH2-(СH2)2СH2), 2.52 (4Н, br s, СH2-(СH2)4-СH2), 4.23 (4Н, br s, W1/2 40 Hz, НN-СH2-S), 6.59 (2Н, br s, NH-CH2-S). 13C NMR (100.62 MHz, DMSOed6): 28.40, 29.85, 30.35 (S-(СH2)6-S), 42.17 (НN-СH2-S), 157.32 (C¼O). MALDI TOF, m/z: 273.192 [МþK]þ (273.482 calculated for C9H18N2KOS2). 1,7-Dithia-3,5-diazonane-4-thione (3a). Yield 0.165 g (85%, method A), 0.142 g (73%, method B), 0.067 g (36%, method C); white powder, m.p. 112e114 С. [Found: С, 30.92; Н, 5.20; N, 14.35; S, 50.47. C5H10N2S3 requires С, 30.90; Н, 5.19; N, 14.41; S, 49.50%]; Rf (acetone/ethyl acetate, 2:1) 0.39. IR v cm1: 3441, 2924e2854, 1619, 1537, 1461, 1377, 1254, 1197, 1026, 733, 677. 1Н NMR (400.13 MHz, DMSOed6): 2.83 (4Н, br s, СH2-S), 4.73 (4Н, br s, W1/2 45 Hz, НNСH2-S), 8.29 (2H, br s, NH-CH2-S). 13C NMR (100.62 MHz, DMSOed6): 31.57 (СH2-S), 46.05 (W1/2 60 Hz, НN-СH2-S), 183.14 (W1/2 60 Hz, С¼S). MALDI TOF, m/z: 217.208 [МþNa]þ (217.334 calculated for C5H10N2NaS3). 1,7-Dithia-3,5-diazecane-4-thione (3b). Yield 0.170 g (82%, method A), 0.165 g (80%, method B), 0.052 g (25%, method C); white powder, m.p. 118e122 С. [Found: С, 34.63; Н, 5.77; N, 13.50; S, 46.10. C6H12N2S3 requires С, 34.58; Н, 5.80; N, 13.45; S, 46.17%]; Rf (acetone/ethyl acetate, 2:1) 0.79. IR v cm1: 3400, 2924e2854,

7084


1610, 1540, 1461, 1377, 1235, 1171, 1002, 753, 636. 1Н NMR (400.13 MHz, DMSOed6): 1.72 (2Н, s, СH2-СH2-СH2), 2.50 (4Н, s, СH2-S), 4.54 (4Н, br s, W1/2 40 Hz, НN-СH2-S), 8.12 (2Н, br s, NHCH2-S). 13C NMR (100.62 MHz, DMSOed6): 29.70 (СH2-S), 30.49 (СH2-СH2-СH2), 46.12 (W1/2 60 Hz, НN-СH2-S), 183.01 (W1/2 60 Hz, С¼S). MALDI TOF, m/z: 231.177 [МþNa]þ (231.361 calculated for C6H12N2NaS3). 1,7-Dithia-3,5-diazacycloundecane-4-thione (3c). Yield 0.170 g (76%, method A), 0.150 g (68%, method B), 0.004 g (18%, method C); white powder, m.p. 92e95 С. [Found: С, 37.86; Н, 6.32; N, 12.72; S, 43.10. C7H14N2S3 requires С, 37.80; Н, 6.35; N, 12.60; S, 43.25%]; Rf (acetone/ethyl acetate, 2:1) 0.89. IR v cm1: 3293, 2924e2854, 1607, 1553, 1462, 1365, 1266, 1194, 1021, 720, 667. 1Н NMR (400.13 MHz, DMSOed6): 1.62 (4Н, s, СH2-(СH2)2-СH2), 2.58 (4Н, s, СH2-S), 4.67 (4Н, br s, W1/2 52 Hz, НN-СH2-S), 8.07 (2Н, br s, NHCH2-S). 13C NMR (100.62 MHz, DMSOed6): 29.22 (СH2-(СH2)2СH2), 30.20 (СH2-S), 45.80 (W1/2 50 Hz, НN-СH2-S), 183.08 br (С¼S). MALDI TOF, m/z: 245.188 [МþNa]þ (245.387 calculated for C7H14N2NaS3). 1,7-Dithia-3,5-diazacyclododecane-4-thione (3d). Yield 0.142 g (60%, method A), 0.130 g (55%, method B); white powder, m.p. 169e172 С. [Found: С, 40.62; Н, 6.83; N, 11.85; S, 40.70. C8H16N2S3 requires С, 40.64; Н, 6.82; N, 11.85; S, 40.69%]; Rf (acetone/ethyl acetate, 2:1) 0.66. IR v cm1: 3438, 2924e2856, 1682, 1555, 1433, 1380, 1180, 1070, 730, 630. 1Н NMR (400.13 MHz, DMSOed6): 1.37 (2Н, s, (СH2)2-СH2-(СH2)2), 1.54 (4Н, s, СH2-(СH2)2-СH2), 2.55 (4Н, s, СH2-S), 4.65 (4Н, br s, W1/2 50 Hz, НN-СH2-S), 7.99 (2Н, br s, NHCH2-S). 13C NMR (100.62 MHz, DMSOed6): 28.07, 29.67, 30.60 (S(СH2)5-S), 45.98 (W1/2 60 Hz, НN-СH2-S), 182.94 (W1/2 60 Hz, С¼S). MALDI TOF, m/z: 259.181 [МþNa]þ (259.414 calculated for C8H16N2NaS3). 1,7-Dithia-3,5-diazacyclotridecane-4-thione (3е). Yield 0.163 g (65%, method A), 0.145 g (58%, method B); white powder, m.p. 85e87 С. [Found: С, 43.11; Н, 7.25; N, 11.21; S, 38.43. C9H18N2S3 requires С, 43.16; Н, 7.24; N, 11.19; S, 38.41%]; Rf (acetone/ethyl acetate, 2:1) 0.94. IR v cm1: 3282, 2923e2853, 1633, 1530, 1461, 1377, 1261, 1169, 974, 722, 645. 1Н NMR (400.13 MHz, DMSOed6): 1.31 (4Н, br s, (СH2)2-(СH2)2-(СH2)2), 1.52 (4Н, br s, СH2-(СH2)2СH2), 2.55 (4Н, br s, СH2-(СH2)4-СH2), 4.64 (4Н, br s, W1/2 45 Hz, НN-СH2-S), 7.14 (2Н, br s, NH-CH2-S). 13C NMR (100.62 MHz, DMSOed6): 28.91, 30.00, 30.62 (S-(СH2)6-S), 45.98 (W1/2 60 Hz, НN-СH2-S), 184.00 br (С¼S). MALDI TOF, m/z: 273.038 [МþNa]þ

(273.440 calculated for C9H18N2NaS3). Acknowledgements This study was financially supported by the RF President (Grant NSh-6651.2016.3). The structural studies of the compounds were performed with unique equipment in “Agidel” collective usage centre. Appendix A. Supplementary data Supplementary data related to this article can be found at https://doi.org/10.1016/j.tet.2017.10.068. References 1. 2. 3. 4. 5. 6.

7. 8. 9. 10. 11.

12.

13.

14. 15. 16. 17.

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