- Email: [email protected]
A new method for the synthesis of N-substituted 1,3,5-dithiazinanes via the catalytic recyclization of 1,3,5-trithiane with aryl(benzyl) hydrazines and aryl amines
Tetrahedron Letters 52 (2011) 4090–4092
Contents lists available at ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
A new method for the synthesis of N-substituted 1,3,5-dithiazinanes via the catalytic recyclization of 1,3,5-trithiane with aryl(benzyl) hydrazines and aryl amines Nataliya N. Murzakova ⇑, Elena B. Rakhimova, Inna V. Vasil’yeva, Kirill I. Prokof’yev, Askhat G. Ibragimov, Usein M. Dzhemilev Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, 141 Prospekt Oktyabrya, Ufa 450075, Russian Federation
a r t i c l e
i n f o
Article history: Received 14 March 2011 Revised 12 May 2011 Accepted 20 May 2011 Available online 13 June 2011
a b s t r a c t An efficient method for the synthesis of N-substituted 1,3,5-dithiazinanes based on the amination reaction of 1,3,5-trithiane with aryl(benzyl) hydrazines and N-aryl amines in the presence of Ti and Fe catalysts has been developed. Ó 2011 Elsevier Ltd. All rights reserved.
Keywords: N-Substituted 1,3,5-dithiazinanes N-Aryl(benzyl) hydrazines Aryl amines 1,3,5-Trithiane Catalysis Recyclization
1,3,5-Dithiazinane compounds are widely used as food additives,1–3 and as adsorbents for noble metals.4 They also exhibit fungicidal activity.5 According to previous experimental data,6 cyclothiomethylation of N-aryl(benzyl) hydrazines with CH2O–H2S leads to a mixture of S,N-containing heterocycles. In this case, the yield of the target N-phenyl(benzyl)-(1,3,5-dithiazinan-5-yl)amines does not exceed 30%. Nitrophenyl-substituted hydrazines, under these conditions, do not enter into the above reaction giving rise instead to a mixture of hydrazone, trithiolane, and tetrathiepane.6 Our recent work7 reported low selectivity for the cyclothiomethylation reaction of primary aryl amines with CH2O and H2S providing appropriate 1,3,5-dithiazinanes. No reports have appeared in the literature which describe the selective synthesis of N-aryl-1,3,5-dithiazinanes, and N-phenyl- and N-benzyl-(1,3,5-dithiazinan-5-yl)amines. In order to develop an efficient method for synthesizing Nphenyl(benzyl)-(1,3,5-dithiazinan-5-yl)amines and N-aryl-1,3,5dithiazinanes in high yields and selectivity, we have studied the reaction of aryl(benzyl) hydrazines and aryl amines with commercially available 1,3,5-trithiane, which contains reactive sulfur atoms in the ring,8 in the presence of transition metal based catalysts.
We assume that 1,3,5-trithiane (1), which contains nucleophilic centres in the ring, under the influence of substituted hydrazines and aryl amines, may undergo recyclization9–11 to give the corresponding N-substituted 1,3,5-dithiazinanes (Scheme 1). Our preliminary experiments revealed that the non-catalytic reaction between phenyl hydrazine or benzyl hydrazine and an equimolar amount of 1,3,5-trithiane (1) in MeCN for 3 h ( 10 to 60 °C) gave N-phenyl-(1,3,5-dithiazinan-5-yl)amine (2) in yields not exceeding 10%. To optimize the yield of the product 2, we investigated the reaction of 1,3,5-trithiane with phenyl hydrazine in the presence of salts and transition metal based (Cu, Co, Mn, Ti, Hf, V, Fe, Sm) catalysts, which favor changes in the reactivity of the initial reagents to form coordination compounds.12 Among the catalysts tested, the activity of Cp2TiCl2 (7 mol %) in the reaction of hydrazine with 1,3,5-trithiane proved to be the highest. In this case (MeCN, 20 °C, 3 h), N-phenyl(benzyl)-(1,3,5-dithiazinan-5-yl)amines 2 and 3 were obtained in 63% and 60% yields, respectively.13 An excess of phenyl (or benzyl) hydrazine with re-
S RNH2 + S
catalyst
S ⇑ Corresponding author. E-mail addresses: [email protected], [email protected] (N.N. Murzakova). 0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2011.05.097
S R N S
1 Scheme 1.
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N. N. Murzakova et al. / Tetrahedron Letters 52 (2011) 4090–4092
R'
S R' N N H
S
N NH2 H
O2N
N NH2 H
S S
[M], 20 oC, MeCN − H2S
S
S
R
[M], 20 oC, MeCN − H2S
O2N
S R
Catalyst = [M] = Cp2TiCl2
R' = Ph (2), Bn (3)
NH N
R = H (4), NO2 (5)
Scheme 2.
OH
OH S
NH2
N
S
NH2
S
S
[Fe], −H2S
S
R
R
N
[Fe], −H2S
S
S R = OH (7), NH2 (8), SH (9)
6 Scheme 3.
+
S
S
S
RNH2
S
+
..
S
S
S
S
S
S
..
+
S
S
Met
Met
R
NH
S Met
NH
N
R
R
Scheme 4.
spect to 1,3,5-trithiane did not influence the reactivity of the second S atom, which in this reaction remained inert. In each run, N-substituted 1,3,5-dithiazinanes were formed exclusively (Scheme 2). These positive results on the catalytic recyclization of 1,3,5-trithiane with phenyl (or benzyl) hydrazines into N-substituted 1,3,5dithiazinanes 2 and 3 inspired us to implement this reaction with nitrophenyl hydrazines, which under normal conditions do not undergo the cyclomethylation reaction with CH2O–H2S as the cyclothiomethylation agent.6 1,3,5-Trithiane reacted with both 4nitrophenyl hydrazine and 2,4-dinitrophenyl hydrazine in the presence of Cp2TiCl2 as the catalyst under optimized conditions (7 mol %, 20 °C, 3 h, MeCN) to give N-(4-nitrophenyl)-(1,3,5dithiazinan-5-yl)amine14 (4) and N-(2,4-dinitrophenyl)-(1,3,5dithiazinan-5-yl)amine15 (5) in 69% and 65% yields, respectively. Aryl amines, like aryl hydrazines, also underwent reaction with an equimolar amount of 1,3,5-trithiane giving rise to N-aryl-1,3,5dithiazinanes16 (Scheme 3). In this reaction, iron(III) chloride hexahydrate (FeCl36H2O) showed the highest catalytic activity. Recyclization of 1,3,5-trithiane with 2-aminophenol, 4-aminophenol, 4-phenylenediamine, and 4-aminothiophenol (5 mol % FeCl36H2O, 60 °C, 6 h, MeCN) allowed the selective synthesis of 2-(1,3,5-dithiazinan-5-yl)phenol17 (6), 4-(1,3,5-dithiazinan-5yl)phenol (7), 4-(1,3,5-dithiazinan-5-yl)phenyl amine18 (8), and 4-(1,3,5-dithiazinan-5-yl)phenyl hydrosulfide19 (9) in 60–75% yield. A potential mechanism for this trithiane recyclization is shown in Scheme 4. It can be assumed that 1,3,5-trithiane, under selected conditions, is activated by the positively charged metal ion. The subsequent recyclization20,21 of the 1,3,5-trithiane, under the influence of the catalyst, affords the corresponding N-substituted 1,3,5dithiazinanes. In conclusion, we have developed a catalytic recyclization reaction of 1,3,5-trithiane with aryl hydrazines, benzyl hydrazines, and
primary aryl amines mediated by Ti- and Fe-based catalysts. This novel procedure provides an effective route for the selective synthesis of previously inaccessible N-substituted 1,3,5-dithiazinanes. Acknowledgments This work was supported by the Russian Foundation for Basic Research (Grant 08-03-00789-a) and the President of the Russian Federation (Sci. School 2349.2008.3). References and notes 1. Hirai, C.; Herz, K. O.; Pokorny, J.; Chang, S. S. J. Food Sci. 1973, 38, 393. 2. Farka, P.; Sadecka, J.; Kova, M.; Siegmund, B.; Pfannhauserb, W. Food Chem. 1997, 60, 617. 3. Kawai, T.; Ishida, Y. J. Agric. Food Chem. 1989, 37, 1026. 4. Dzhemilev, U. M.; Aleev, R. S.; Dal’nova, Yu. S.; Kunakova, R. V.; Khafizova, S. R. Pat. 2206726 RF; Byull. Izobret. [Bulletin of Inventions] 2003, 17 (in Russian). 5. Saraç, S.; Ertan, M.; Balkan, A.; Yulug, N. Archiv. Pharm. 1990, 7, 449. 6. Akhmetova, V. R.; Nadyrgulova, G. R.; Tyumkina, T. V.; Starikova, Z. A.; Golovanov, D. G.; Antipin, M. Yu.; Kunakova, R. V.; Dzhemilev, U. M. Izv. Akad. Nauk Ser. Khim. 2006, 1758; Russ. Chem. Bull. Int. Ed. 2006, 55, 1824 (Engl. Transl.). 7. Akhmetova, V. R.; Nadyrgulova, G. R.; Niatschina, Z. T.; Dzhemilev, U. M. Chem. Heterocycl. Compd. 2009, 45, 1155. 8. Voronkov, M. G.; Deryagina, E. N. Uspekhi Khim. 2000, 69, 90; Russ. Chem. Rev. 2000, 69, 81 (Engl. Transl.). 9. Shvaika, O. P.; Artemov, V. N. Uspekhi Khim. 1972, 41, 1788; Russ. Chem. Rev. 1972, 41, 833 (Engl. Transl.). 10. Aksenov, A. V.; Aksenova, I. V. Chem. Heterocycl. Compd. 2009, 45, 167. 11. Wellmar, U. J. Heterocycl. Chem. 1998, 35, 1531. 12. Kukushkin, Yu. N. The Reactivity of Coordination Compounds [in Russian]; Khimiya: Leningrad, 1987. p 228. 13. Synthesis of N-phenyl- and N-benzyl-(1,3,5-dithiazinan-5-yl)amines via the reaction of 1,3,5-trithiane with aryl or benzyl hydrazines (general procedure). A calcined and argon-filled Schlenk vessel equipped with a magnetic stir bar was charged with MeCN (5 mL), Cp2TiCl2 (0.7 mmol) and 1,3,5-trithiane (11 mmol). The mixture was stirred at 20 °C for 1 h. Next, the corresponding aryl(benzyl) hydrazine (10 mmol) was added dropwise to the mixture which was stirred for 3 h at 20 °C under a dry argon atmosphere. The product mixture was separated by column chromatography on silica gel (SiO2) with CHCl3:benzene:EtOAc
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N. N. Murzakova et al. / Tetrahedron Letters 52 (2011) 4090–4092
(1:5:1) as eluent. The final products 2–5 were identified by means of spectral methods. Compounds 2 and 3 were further identified by comparison with known samples.6 14. N-(4-Nitrophenyl)-1,3,5-dithiazinan-5-yl amine (4). Mp 140–141 °C. Rf 0.7 (CHCl3:benzene:EtOAc, 1:5:1). Anal. Calcd for C9H11N3O2S2: C, 42.01; H, 4.31; N, 16.33; S, 24.92. Found: C, 41.95; H, 4.29; N, 16.25; S, 24.88. 1H NMR (400 MHz, CDCl3): d 3.6 (s, 1H, NH (7)); 3.55 (s, 2H, C(2)H2); 4.28 (s, 4H, C(4,6)H2); 7.27 (s, 2H, C(10,12)H); 8.19 (s, 2H, C(9,13)H). 13C NMR (100 MHz, CDCl3): d 29.75 (C(2)), 58.23 (C(6,4)), 112.48 (C(13,9)), 128.68 (C(12,10)), 138.42 (C(11)), 145.93 (C(8)). 15. N-(2,4-Dinitrophenyl)-1,3,5-dithiazinan-5-yl amine (5). Mp 153–154 °C. Rf 0.6 (CHCl3:benzene:EtOAc, 1:5:1). Anal. Calcd for C9H10N4O4S2: C, 35.75; H, 3.33; N, 18.53; S, 21.22. Found: C, 35.63; H, 3.27; N, 18.36; S, 21.09. 1H NMR (400 MHz, CDCl3): d 3.39 (s, 1H, N(7)H); 4.09 (s, 2H, C(2)H2); 4.43 (s, 4H, C(4,6)H2); 7.98 (d, J = 8.1 Hz, 1H, C(13)H); 8.34 (d, J = 8.1 Hz, 1H, C(12)H); 9.14 (s, 1H, C(10)H). 13C NMR (100 MHz, CDCl3): d 34.27 (C(2)), 58.23 (C(6,4)), 114.56 (C(13)), 121.91 (C(12)), 127.67 (C(9)), 130.18 (C(12)), 139.42 (C(11)), 153.93 (C(8)). 16. Recyclization of 1,3,5-trithiane with aryl amines (general procedure). A calcined and argon-filled Schlenk vessel equipped with a magnetic stir bar was charged with MeCN (5 mL), FeCl36H2O (0.5 mmol) and 1,3,5-trithiane (11 mmol). The mixture was stirred at 20 °C for 1 h. Next, the corresponding aryl amine (10 mmol) in MeCN (5 mL) was added dropwise to the mixture which was stirred for 6 h at 60 °C under a dry argon atmosphere. The product mixture was separated by column chromatography on silica gel (SiO2). The final products 6–
17.
18.
19.
20.
21.
9 were identified by means of spectral methods. Compounds 6 and 7 were further identified by comparison with known samples.17 Akhmetova, V. R.; Nadyrgulova, G. R.; Khafizova, S. R.; Tyumkina, T. V.; Yakovenko, M. Yu.; Antipin, M. Yu.; Khalilov, L. M.; Kunakova, R. V.; Dzhemilev, U. M. Izv. Akad. Nauk Ser. Khim. 2006, 305; Russ. Chem. Bull. Int. Ed. 2006, 55, 312 (Engl. Transl.). (1,3,5-Dithiazinan-5-yl)phenyl amine (8). Mp 240–242 °C. Rf 0.6 (benzene:EtOH, 9:1). IR (m, cm 1): 720, 1100, 1600, 1650, 2900, 3300. HRMS (RP) C9H12N2S2 [M++H] calcd: 213.345, found: 213.379. 1H NMR (400 MHz, CDCl3): d 4.25 (br s, 2H, C(2)H2); 4.97 (br s, 4H, C(4,6)H2); 6.70 (d, J = 8.8 Hz, 2H, C(8,12)H); 7.70 (d, J = 8.8 Hz, 2H, C(9,11)H). 13C NMR (100 MHz, CDCl3): d 36.5 (C(2)), 52.7 (C(4,6)), 114.7 (C(8,12)), 124.3 (C(9,11)), 145.8 (C(10)), 148.5 (C(7)). 4-(1,3,5-Dithiazinan-5-yl)phenyl hydrosulfide (9). Mp 185–187 °C. Rf 0.5 (CHCl3:benzene:EtOAc, 1:5:1). IR (m, cm 1): 720, 1100, 1600, 2600, 2900, 3300. Anal. Calcd for C9H11NS3: C, 47.12; H, 4.83; N, 6.11; S, 41.94. Found: C, 47.10; H, 4.75; N, 6.07; S, 41.93. GC–MS (m/z): 197 [M+ S] (35), 136 [M+ CH3SCH2S] (100), 109 [M+ SPh] (35). 1H NMR (400 MHz, CDCl3): d 4.25 (br s, 2H, C(2)H2); 4.93 (br s, 4H, C(4,6)H2); 6.66–7.49 (m, 4H, C(8,9,11,12)H). 13 C NMR (100 MHz, CDCl3): d 33.23 (C(2)), 55.02 (C(4,6)), 114.70 (C(8,12)), 118.03 (C(9,11)), 131.96 (C(10)), 137.72 (C(7)). Mokrov, G. V.; Likhosherstov, A. M.; Lezina, V. P.; Gudasheva, T. A.; Bushmarinov, I. S.; Antipin, M. Yu. Izv. Akad. Nauk Ser. Khim. 2010, 1228; Russ. Chem. Bull. Int. Ed. 2010, 59 (Engl. Transl.). Krohn, K.; Cludius-Brandt, S. Synthesis 2010, 1344.
Contents lists available at ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
A new method for the synthesis of N-substituted 1,3,5-dithiazinanes via the catalytic recyclization of 1,3,5-trithiane with aryl(benzyl) hydrazines and aryl amines Nataliya N. Murzakova ⇑, Elena B. Rakhimova, Inna V. Vasil’yeva, Kirill I. Prokof’yev, Askhat G. Ibragimov, Usein M. Dzhemilev Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, 141 Prospekt Oktyabrya, Ufa 450075, Russian Federation
a r t i c l e
i n f o
Article history: Received 14 March 2011 Revised 12 May 2011 Accepted 20 May 2011 Available online 13 June 2011
a b s t r a c t An efficient method for the synthesis of N-substituted 1,3,5-dithiazinanes based on the amination reaction of 1,3,5-trithiane with aryl(benzyl) hydrazines and N-aryl amines in the presence of Ti and Fe catalysts has been developed. Ó 2011 Elsevier Ltd. All rights reserved.
Keywords: N-Substituted 1,3,5-dithiazinanes N-Aryl(benzyl) hydrazines Aryl amines 1,3,5-Trithiane Catalysis Recyclization
1,3,5-Dithiazinane compounds are widely used as food additives,1–3 and as adsorbents for noble metals.4 They also exhibit fungicidal activity.5 According to previous experimental data,6 cyclothiomethylation of N-aryl(benzyl) hydrazines with CH2O–H2S leads to a mixture of S,N-containing heterocycles. In this case, the yield of the target N-phenyl(benzyl)-(1,3,5-dithiazinan-5-yl)amines does not exceed 30%. Nitrophenyl-substituted hydrazines, under these conditions, do not enter into the above reaction giving rise instead to a mixture of hydrazone, trithiolane, and tetrathiepane.6 Our recent work7 reported low selectivity for the cyclothiomethylation reaction of primary aryl amines with CH2O and H2S providing appropriate 1,3,5-dithiazinanes. No reports have appeared in the literature which describe the selective synthesis of N-aryl-1,3,5-dithiazinanes, and N-phenyl- and N-benzyl-(1,3,5-dithiazinan-5-yl)amines. In order to develop an efficient method for synthesizing Nphenyl(benzyl)-(1,3,5-dithiazinan-5-yl)amines and N-aryl-1,3,5dithiazinanes in high yields and selectivity, we have studied the reaction of aryl(benzyl) hydrazines and aryl amines with commercially available 1,3,5-trithiane, which contains reactive sulfur atoms in the ring,8 in the presence of transition metal based catalysts.
We assume that 1,3,5-trithiane (1), which contains nucleophilic centres in the ring, under the influence of substituted hydrazines and aryl amines, may undergo recyclization9–11 to give the corresponding N-substituted 1,3,5-dithiazinanes (Scheme 1). Our preliminary experiments revealed that the non-catalytic reaction between phenyl hydrazine or benzyl hydrazine and an equimolar amount of 1,3,5-trithiane (1) in MeCN for 3 h ( 10 to 60 °C) gave N-phenyl-(1,3,5-dithiazinan-5-yl)amine (2) in yields not exceeding 10%. To optimize the yield of the product 2, we investigated the reaction of 1,3,5-trithiane with phenyl hydrazine in the presence of salts and transition metal based (Cu, Co, Mn, Ti, Hf, V, Fe, Sm) catalysts, which favor changes in the reactivity of the initial reagents to form coordination compounds.12 Among the catalysts tested, the activity of Cp2TiCl2 (7 mol %) in the reaction of hydrazine with 1,3,5-trithiane proved to be the highest. In this case (MeCN, 20 °C, 3 h), N-phenyl(benzyl)-(1,3,5-dithiazinan-5-yl)amines 2 and 3 were obtained in 63% and 60% yields, respectively.13 An excess of phenyl (or benzyl) hydrazine with re-
S RNH2 + S
catalyst
S ⇑ Corresponding author. E-mail addresses: [email protected], [email protected] (N.N. Murzakova). 0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2011.05.097
S R N S
1 Scheme 1.
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R'
S R' N N H
S
N NH2 H
O2N
N NH2 H
S S
[M], 20 oC, MeCN − H2S
S
S
R
[M], 20 oC, MeCN − H2S
O2N
S R
Catalyst = [M] = Cp2TiCl2
R' = Ph (2), Bn (3)
NH N
R = H (4), NO2 (5)
Scheme 2.
OH
OH S
NH2
N
S
NH2
S
S
[Fe], −H2S
S
R
R
N
[Fe], −H2S
S
S R = OH (7), NH2 (8), SH (9)
6 Scheme 3.
+
S
S
S
RNH2
S
+
..
S
S
S
S
S
S
..
+
S
S
Met
Met
R
NH
S Met
NH
N
R
R
Scheme 4.
spect to 1,3,5-trithiane did not influence the reactivity of the second S atom, which in this reaction remained inert. In each run, N-substituted 1,3,5-dithiazinanes were formed exclusively (Scheme 2). These positive results on the catalytic recyclization of 1,3,5-trithiane with phenyl (or benzyl) hydrazines into N-substituted 1,3,5dithiazinanes 2 and 3 inspired us to implement this reaction with nitrophenyl hydrazines, which under normal conditions do not undergo the cyclomethylation reaction with CH2O–H2S as the cyclothiomethylation agent.6 1,3,5-Trithiane reacted with both 4nitrophenyl hydrazine and 2,4-dinitrophenyl hydrazine in the presence of Cp2TiCl2 as the catalyst under optimized conditions (7 mol %, 20 °C, 3 h, MeCN) to give N-(4-nitrophenyl)-(1,3,5dithiazinan-5-yl)amine14 (4) and N-(2,4-dinitrophenyl)-(1,3,5dithiazinan-5-yl)amine15 (5) in 69% and 65% yields, respectively. Aryl amines, like aryl hydrazines, also underwent reaction with an equimolar amount of 1,3,5-trithiane giving rise to N-aryl-1,3,5dithiazinanes16 (Scheme 3). In this reaction, iron(III) chloride hexahydrate (FeCl36H2O) showed the highest catalytic activity. Recyclization of 1,3,5-trithiane with 2-aminophenol, 4-aminophenol, 4-phenylenediamine, and 4-aminothiophenol (5 mol % FeCl36H2O, 60 °C, 6 h, MeCN) allowed the selective synthesis of 2-(1,3,5-dithiazinan-5-yl)phenol17 (6), 4-(1,3,5-dithiazinan-5yl)phenol (7), 4-(1,3,5-dithiazinan-5-yl)phenyl amine18 (8), and 4-(1,3,5-dithiazinan-5-yl)phenyl hydrosulfide19 (9) in 60–75% yield. A potential mechanism for this trithiane recyclization is shown in Scheme 4. It can be assumed that 1,3,5-trithiane, under selected conditions, is activated by the positively charged metal ion. The subsequent recyclization20,21 of the 1,3,5-trithiane, under the influence of the catalyst, affords the corresponding N-substituted 1,3,5dithiazinanes. In conclusion, we have developed a catalytic recyclization reaction of 1,3,5-trithiane with aryl hydrazines, benzyl hydrazines, and
primary aryl amines mediated by Ti- and Fe-based catalysts. This novel procedure provides an effective route for the selective synthesis of previously inaccessible N-substituted 1,3,5-dithiazinanes. Acknowledgments This work was supported by the Russian Foundation for Basic Research (Grant 08-03-00789-a) and the President of the Russian Federation (Sci. School 2349.2008.3). References and notes 1. Hirai, C.; Herz, K. O.; Pokorny, J.; Chang, S. S. J. Food Sci. 1973, 38, 393. 2. Farka, P.; Sadecka, J.; Kova, M.; Siegmund, B.; Pfannhauserb, W. Food Chem. 1997, 60, 617. 3. Kawai, T.; Ishida, Y. J. Agric. Food Chem. 1989, 37, 1026. 4. Dzhemilev, U. M.; Aleev, R. S.; Dal’nova, Yu. S.; Kunakova, R. V.; Khafizova, S. R. Pat. 2206726 RF; Byull. Izobret. [Bulletin of Inventions] 2003, 17 (in Russian). 5. Saraç, S.; Ertan, M.; Balkan, A.; Yulug, N. Archiv. Pharm. 1990, 7, 449. 6. Akhmetova, V. R.; Nadyrgulova, G. R.; Tyumkina, T. V.; Starikova, Z. A.; Golovanov, D. G.; Antipin, M. Yu.; Kunakova, R. V.; Dzhemilev, U. M. Izv. Akad. Nauk Ser. Khim. 2006, 1758; Russ. Chem. Bull. Int. Ed. 2006, 55, 1824 (Engl. Transl.). 7. Akhmetova, V. R.; Nadyrgulova, G. R.; Niatschina, Z. T.; Dzhemilev, U. M. Chem. Heterocycl. Compd. 2009, 45, 1155. 8. Voronkov, M. G.; Deryagina, E. N. Uspekhi Khim. 2000, 69, 90; Russ. Chem. Rev. 2000, 69, 81 (Engl. Transl.). 9. Shvaika, O. P.; Artemov, V. N. Uspekhi Khim. 1972, 41, 1788; Russ. Chem. Rev. 1972, 41, 833 (Engl. Transl.). 10. Aksenov, A. V.; Aksenova, I. V. Chem. Heterocycl. Compd. 2009, 45, 167. 11. Wellmar, U. J. Heterocycl. Chem. 1998, 35, 1531. 12. Kukushkin, Yu. N. The Reactivity of Coordination Compounds [in Russian]; Khimiya: Leningrad, 1987. p 228. 13. Synthesis of N-phenyl- and N-benzyl-(1,3,5-dithiazinan-5-yl)amines via the reaction of 1,3,5-trithiane with aryl or benzyl hydrazines (general procedure). A calcined and argon-filled Schlenk vessel equipped with a magnetic stir bar was charged with MeCN (5 mL), Cp2TiCl2 (0.7 mmol) and 1,3,5-trithiane (11 mmol). The mixture was stirred at 20 °C for 1 h. Next, the corresponding aryl(benzyl) hydrazine (10 mmol) was added dropwise to the mixture which was stirred for 3 h at 20 °C under a dry argon atmosphere. The product mixture was separated by column chromatography on silica gel (SiO2) with CHCl3:benzene:EtOAc
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(1:5:1) as eluent. The final products 2–5 were identified by means of spectral methods. Compounds 2 and 3 were further identified by comparison with known samples.6 14. N-(4-Nitrophenyl)-1,3,5-dithiazinan-5-yl amine (4). Mp 140–141 °C. Rf 0.7 (CHCl3:benzene:EtOAc, 1:5:1). Anal. Calcd for C9H11N3O2S2: C, 42.01; H, 4.31; N, 16.33; S, 24.92. Found: C, 41.95; H, 4.29; N, 16.25; S, 24.88. 1H NMR (400 MHz, CDCl3): d 3.6 (s, 1H, NH (7)); 3.55 (s, 2H, C(2)H2); 4.28 (s, 4H, C(4,6)H2); 7.27 (s, 2H, C(10,12)H); 8.19 (s, 2H, C(9,13)H). 13C NMR (100 MHz, CDCl3): d 29.75 (C(2)), 58.23 (C(6,4)), 112.48 (C(13,9)), 128.68 (C(12,10)), 138.42 (C(11)), 145.93 (C(8)). 15. N-(2,4-Dinitrophenyl)-1,3,5-dithiazinan-5-yl amine (5). Mp 153–154 °C. Rf 0.6 (CHCl3:benzene:EtOAc, 1:5:1). Anal. Calcd for C9H10N4O4S2: C, 35.75; H, 3.33; N, 18.53; S, 21.22. Found: C, 35.63; H, 3.27; N, 18.36; S, 21.09. 1H NMR (400 MHz, CDCl3): d 3.39 (s, 1H, N(7)H); 4.09 (s, 2H, C(2)H2); 4.43 (s, 4H, C(4,6)H2); 7.98 (d, J = 8.1 Hz, 1H, C(13)H); 8.34 (d, J = 8.1 Hz, 1H, C(12)H); 9.14 (s, 1H, C(10)H). 13C NMR (100 MHz, CDCl3): d 34.27 (C(2)), 58.23 (C(6,4)), 114.56 (C(13)), 121.91 (C(12)), 127.67 (C(9)), 130.18 (C(12)), 139.42 (C(11)), 153.93 (C(8)). 16. Recyclization of 1,3,5-trithiane with aryl amines (general procedure). A calcined and argon-filled Schlenk vessel equipped with a magnetic stir bar was charged with MeCN (5 mL), FeCl36H2O (0.5 mmol) and 1,3,5-trithiane (11 mmol). The mixture was stirred at 20 °C for 1 h. Next, the corresponding aryl amine (10 mmol) in MeCN (5 mL) was added dropwise to the mixture which was stirred for 6 h at 60 °C under a dry argon atmosphere. The product mixture was separated by column chromatography on silica gel (SiO2). The final products 6–
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9 were identified by means of spectral methods. Compounds 6 and 7 were further identified by comparison with known samples.17 Akhmetova, V. R.; Nadyrgulova, G. R.; Khafizova, S. R.; Tyumkina, T. V.; Yakovenko, M. Yu.; Antipin, M. Yu.; Khalilov, L. M.; Kunakova, R. V.; Dzhemilev, U. M. Izv. Akad. Nauk Ser. Khim. 2006, 305; Russ. Chem. Bull. Int. Ed. 2006, 55, 312 (Engl. Transl.). (1,3,5-Dithiazinan-5-yl)phenyl amine (8). Mp 240–242 °C. Rf 0.6 (benzene:EtOH, 9:1). IR (m, cm 1): 720, 1100, 1600, 1650, 2900, 3300. HRMS (RP) C9H12N2S2 [M++H] calcd: 213.345, found: 213.379. 1H NMR (400 MHz, CDCl3): d 4.25 (br s, 2H, C(2)H2); 4.97 (br s, 4H, C(4,6)H2); 6.70 (d, J = 8.8 Hz, 2H, C(8,12)H); 7.70 (d, J = 8.8 Hz, 2H, C(9,11)H). 13C NMR (100 MHz, CDCl3): d 36.5 (C(2)), 52.7 (C(4,6)), 114.7 (C(8,12)), 124.3 (C(9,11)), 145.8 (C(10)), 148.5 (C(7)). 4-(1,3,5-Dithiazinan-5-yl)phenyl hydrosulfide (9). Mp 185–187 °C. Rf 0.5 (CHCl3:benzene:EtOAc, 1:5:1). IR (m, cm 1): 720, 1100, 1600, 2600, 2900, 3300. Anal. Calcd for C9H11NS3: C, 47.12; H, 4.83; N, 6.11; S, 41.94. Found: C, 47.10; H, 4.75; N, 6.07; S, 41.93. GC–MS (m/z): 197 [M+ S] (35), 136 [M+ CH3SCH2S] (100), 109 [M+ SPh] (35). 1H NMR (400 MHz, CDCl3): d 4.25 (br s, 2H, C(2)H2); 4.93 (br s, 4H, C(4,6)H2); 6.66–7.49 (m, 4H, C(8,9,11,12)H). 13 C NMR (100 MHz, CDCl3): d 33.23 (C(2)), 55.02 (C(4,6)), 114.70 (C(8,12)), 118.03 (C(9,11)), 131.96 (C(10)), 137.72 (C(7)). Mokrov, G. V.; Likhosherstov, A. M.; Lezina, V. P.; Gudasheva, T. A.; Bushmarinov, I. S.; Antipin, M. Yu. Izv. Akad. Nauk Ser. Khim. 2010, 1228; Russ. Chem. Bull. Int. Ed. 2010, 59 (Engl. Transl.). Krohn, K.; Cludius-Brandt, S. Synthesis 2010, 1344.