HETEROCYCLES

Paper | Regular issue | Vol. 78, No. 1, 2009, pp. 45-57
Received, 8th May, 2008, Accepted, 5th September, 2008, Published online, 8th September, 2008.
DOI: 10.3987/COM-08-11432

■ Cyclothiomethylation of Functional Substituted Anilines by CH₂O and H₂S

Vnira R. Akhmetova,* Guzel R. Nadyrgulova, Zalifa T. Niatshina, Regina R. Khairullina, Zoya A. Starikova, Alexandra O. Borisova, Michail Yu. Antipin, Raihana V. Kunakova, and Usein M. Dzhemilev

Laboratory of Heteroatomic Compounds, Institute of Petrochemistry and Catalysis, RAS, 450075, Ufa, Prospekt Oktyabrya,141, Russia

Abstract

N-Aryl substituted 1,3,5-dithiazinanes have been synthesized (20-60 °C) in 32-95% yield by cyclocondensation of o-, p-aminobenzoic, 4-, 5-aminosalicylic acids, p-aminobenzoic acid ethyl or (β-diethylamino)ethyl esters and p-aniline sulfamide with CH₂O and H2S (1:3:2 ratio). At ambient temperature p-aminobenzoic acid, 5-aminosalicylic acid and p-aminobenzoic acid ethyl ester together with 1,3,5-dithiazinanes form appropriate N-aryl substituted 1,3-thiazetidines. Cyclothiomethylation of p-aminobenzoic acid ethyl ester (0 °C) results in N,N-diaryl-1,3,5-thiadiazinane. Heterocyclization of p-aniline sulfamide with CH₂O and H₂S at a molar ratio of 1:6:4 (pH 1.3-1.5) was found to afford bis-1,3,5-dithiazinanes involving two amino groups. Condensation of p-aniline sulfacetamide with 37% formalin (CH₂O) and H₂S (pH 2.5) led to the compound, which was built as macroheterocycle from two fragments of p-aniline sulfacetamide molecule bound to each other by sym-dimethyl sulfide chain (CH₂SCH₂).

introduction
In organic chemistry there is an original method for the synthesis of 1,3,5-dithiazinanela-e based on Wohl reaction namely multimolecular cyclocondensation of methyl amine, 37% formalin (CH2O) and H2S. Compounds, which contain dithiazinane ring, are used as insecticides and fungicides2a,b as well as additives modified and intensified product taste,2c-g inhibitors, ferments,2h complexons,3a-g sorbents for gold and silver.4a,b
For the last 5 years we systematically investigated the Wohl reaction using cyclothiomethylation of aliphatic5a and aromatic5b amines, amino acids,5c aminoalcohols5d aminophenols5e as an example to obtain the corresponding N-substituted 1,3,5-dithiazinanes,5a-e 1,3-thiazetidines5a,b,c and 1,3,5-thiadiazinanes.5b The direction of the cyclothiomethylation reaction depends on the structure of initial amines and reaction conditions (ratio and order of reagent mixing,5a,c temperature,5a-e medium pH), under which cyclocondensation is conducted. Thus, it was shown that in the cyclothiomethylation reaction of aliphatic5a and aromatic5b amines with CH2O and H2S (amine:CH2O:H2S = 1:3:2) the decrease in basicity of amines causes the increase in the yield of target 1,3,5-dithiaz inanes. Further more thorough and deep analysis of cyclocondensation of functionally-substituted anilines, namely o-, m- and p-aminophenols, with CH2O and H2S has shown, that the direction of the cyclothiomethylation reaction of aminophenols depends on the position of functional amino group.5e Aminophenols, o- and p-isomers, were established to interact with CH2O and H2S as a reactant mixture (3:2 ratio) to form 1,3,5-dithiazinanes. m-Aminophenol under analogous conditions undergoes intermolecular condensation with CH2O and H2S simultaneously involving OH and NH2 groups to form macroheterocycle, which contains the fragments of m-aminophenol molecules. Different reactivity of isomeric aminophenols under interaction with CH2O and H2S is caused by a change of NH2 group basicity and OH group acidity according to their arrangement in aromatic ring.
Herein we report on the results of our further investigations in the field of cyclothiomethylation of functionally substituted aromatic amines in order to develop novel procedures for a synthesis of new N-aryl substituted 1,3,5-dithiazinanes, 1,3,5-thiadiazinanes and macroheterocycles.
RESULTS AND DISCUSSION
CYCLOTHIOMETHYLATION OF AROMATIC AMINO ACIDS AND p-AMINOBENZOIC ACID ESTERS
In cyclocondensation with CH2O and H2S there have been involved aromatic amino acids and their derivatives namely o- (1a) and p-aminobenzoic 1b acids, 4-(1c) and 5-aminosalicylic 1d acids, and also p-aminobenzoic acid ethyl 1e and (β-diethylamino)ethyl 1f esters. Using o- (1a), p-aminobenzoic 1b and 4- (1c), 5-aminosalicylic 1b acids as an example we have studied the influence of COOH group position in aromatic ring on the activity of NH2 and OH groups in the cyclothiomethylation reaction.
Thus, condensation of aminobenzoic acid 1a with CH2O and H2S (1:3:2 ratio) at 20 °C led exclusively to o-(1,3,5-dithiazinan-5-yl)benzoic acid 2a in 61% yield, whereas p-aminobenzoic acid 1b gave a mixture of p-(1,3,5-dithiazinan-5-yl)- (2b) and p-(1,3-thiazetidin-3-yl)benzoic (3b) acids with good yields (51 and
34%, respectively) (Scheme 1). Dithiazinane 2b has been selectively obtained at 60 °C in 95% yield.

4-Aminosalicylic acid 1c, similar to acid 1a, reacts with CH2O and H2S to form exclusively 4-(1,3,5-dithiazinan-5-yl)-2-hydroxybenzoic acid 2c in 89% yield, and 5-aminosalicylic acid 1d, similar to acid 1b, gave a mixture of 5-(1,3,5-dithiazinan-5-yl)-2-hydrobenzoic acid 2d and 5-(1,3-thiazetidin-3-yl)-2-hydroxybenzoic acid 3d in the yields of 32 and 22%, respectively.
4-Aminosalicylic acid 1c, in which OH and NH2 groups occupy meta- position, in contrast to m- aminophenol, reacts with CH2O and H2S exclusively at the amino group, probably, as a result of the intramolecular hydrogen bonding between OH and COOH groups (OH... O the ortho-effect).6 As is evident, the direction of cyclothiomethylation of isomeric aromatic amino acids with the aid of CH2O and H2S depends on the arrangement of functional groups in aromatic ring and their mutual influence.
Individual compounds 2a-d and 3b,d have been isolated by means of fractional crystallization. The structures of dithiazinanes 2a-d and thiazetidines 3b,d are proven by spectral methods: 1H NMR and 13C NMR, GC/MS, and also by the data of element analysis. Molecular weight was determined by Rast cryoscopic method.7 Heterocycle 2a was obtained earlier4a with 81% yield by cyclocondensation of 1a with NaHS and CH2O, for which any spectral characteristics were absent.
Thus, aromatic amino acids were condensed with CH2O and H2S only at NH2 group with the formation of N,S-containing heterocycles (1,3,5-dithiazinanes and 1,3-thiazetidines). One should notice that para- position of COOH group contributes to an increase of NH2 group activity in the condensation reaction with CH2O and H2S. The greatest yield of target dithiazinanes 2a-d was reached in temperature range from 20 to 60 °C. An increase in reaction temperature up to 80 °C led to a decrease in selectivity with formation of by-product of the reaction – 1,2,4-trithiolane.8
By the reaction of p-aminobenzoic acid ethyl 1e or (β-diethylamino)ethyl 1f esters with CH2O and H2S (1:3:2 ratio) at 20 °C the compounds of dithiazinane row 2e,f has been obtained. Amino ester 1e in this reaction together with ethyl-4-(1,3,5-dithiazinan-5-yl) benzoate 2e gave ethyl-4-(1,3-thiazetidin-3-yl) benzoate 3e and 3,5-di(4-ethylcarboxyphenyl)-1,3,5-thiadiazinane 4e in 56, 18% and 15% yields, respectively (Scheme 2). At 60 and 80 °C the reaction resulted in a mixture of products 2e-4e. The latter compounds were isolated by column chromatography.
The regioselective synthesis of thiadiazinane 4e was carried out at 0 oC by cyclocondensation of p-aminobenzoic acid ethyl ester 1e with CH2O and H2S (2:3:1 ratio) in 93% yield. Heterocyclic 4e in the presence of three-molar excess of a thiomethilation mixture CH2O-H2S at ambient temperature was completely converted into the appropriate dithiazinane 2e.

According to X-ray diffraction analysis the molecule of 4e has local plane of symmetry passing through С(2) and S(1) atoms (Figure 2a). The thiadiazinane ring has a chair conformation with axial cis position of (4-ethoxycarbonyl)phenylic substituent at the nitrogen atoms. In this orientation the lone pairs at the nitrogen atoms occupy cis equatorial position and are antiperiplanar to the lone pairs of the sulfur atom (conformer B).

The orbital repulsion of lone electron-pairs of the nitrogen and sulfur atoms stabilizes an axial cis position of (4-ethoxycarbonyl)phenylic substituent (anomeric effect).9a,b

In crystal structure above there are two types of intermolecular hydrogenous bonds (Figure 2b). The sulfur atom of one thiadiazinane molecule forms hydrogenous bonds with protons on the two aromatic rings at С(4) and with methylene protons of another thiadiazinane molecule at С(2): НC(4)…S(1)…HC(4') и НС(2)...S(1) (where Н.. S distances are equal to 2.83Å (х 2) and 2.78Å, respectively). At the same time, the ester carbonyl groups of the first thiadiazinane molecule are connected with methylene protons of two other thiadiazinane molecules: O(1)…HC(1A) and O(1')…HC(1B) (distances О.. Н 2.54Å (х 2)).
In the 1H NMR spectra of dithiazinane cycles 2a-f one could observe two singlets of methylene protons at δH 3.40-4.22 (SCH2S) and 4.15-5.20 ppm (NCH2S) with integrated intensities ratio of 1:2. The 13C NMR spectra contain signals at δC 30.61-34.80 (SCH2S) and 44.51-56.89 ppm (NCH2S) belonging to the carbon atoms. The 1H NMR spectrum of thiazetidine cycle (compounds 3b,d,e) exhibits singlets of methylene protons (NCH2S) at δH 4.30-5.15 ppm, while the 13C NMR spectra contain peaks at δC 51.97-54.60 ppm. In the 1H NMR spectra of thiadiazinane 4e the signals for CH2SCH2 and NCH2N methylene protons are observed at δH 4.94 and 5.32 ppm (2:1 ratio), while the 13C NMR spectrum contains signals at δС 53.13 and 68.23 ppm assigned to the carbon atoms located between two nitrogen atoms and the sulfur and nitrogen atoms, respectively.

CYCLOMETHYLATION OF p-ANILINE SULFAMIDE AND ITS DERIVATIVES
We investigated cyclothiomethylation of p-aminosulfanyl acid amides, namely, p-aniline sulfamide 1g, p-aminobenzene sulfacetamide 1h, 2-(p-aminobenzenesulfamido)-3-methoxypyrazine and 4-(p-aminobenzenesulfamido)-2,6-dimethoxypirimidine with the aid of CH2O and H2S.
Condensation of p-aniline sulfamide 1g was carried out (1g:CH2O:H2S = 1:3:2) under different temperature conditions (0-80 °C). It was stated that cyclothiomethylation of p-aniline sulfamide 1g within the temperature range from 0 to 40 °C gave rise to the dithiazinane cycle formation exclusively involving the amino group of the aromatic ring to obtain 4-(1,3,5-dithiazinane-5-yl)aniline sulfamide 2g in 35-73% yield (Scheme 3, Table 1). The increase the temperature to 80 °C facilitates the involvement of less reactive SO2NH2 into the cyclocondensation reaction. So, in these experiments together with 2g cyclodimer 4g. The obtained mixture of compounds 2g and 4g (3:1 ratio) was divided by fractional crystallization (Scheme 3).

Cryoscopic determinations7 with a value of 285±10 correspond to the molecular weight (mass) of compound 2g, and a value of 493±10 corresponds to the molecular weight of macroheterocycle 4g. The element analysis of compound 2g confirms the molecular formula С9H12N2O2S3 and the molecular formula С16H20N4O4S4 for compound 4g as well.
To obtain 1,3,5-dithiazinanes simultaneously involving of both amino groups of p-aniline sulfamide 1g into the reaction with CH2O and H2S, we have increased a quantity of a thiomethylation mixture: 1g:CH2O:H2S = 1:6:4 (0, 20, 40, and 80 °C). As a result, cyclocondensation proceeded via both NH2 groups to give the four-component mixture, GC/MS spectrum of which contains peaks of molecular ions of the characteristic residual fragments with m/z 318 (7g), 334 (6g), 364 (8g) and 380 (5g), apparently corresponding to compounds with the (oxy)thiazethidine 6g,7g and (oxy)dithiazinane 5g,8g cycles.

Сyclocondensation of 1g by a mixture of CH2O and H2S (1g:CH2O:H2S = 1:6:4) in acid medium (pH 1.3-1.5) at 40 °C led to the formation of 5-[4-(1,3,5-dithiazinane-5-sulfonyl)phenyl]-1,3,5-dithiazinane 5g in 93% yield and with 100% selectivity (Scheme 3, Table).

The 1H NMR spectrum of heterocycle 2g exhibits proton signals of aromatic ring at δH 6.80-7.67 ppm. Singlet signals at δH 3.82 and 4.32 ppm correspond to methylene protons located between the sulfur atoms and atoms of N and S, respectively, with integrated intensity of 1:2. The 13C NMR spectrum for 2g contains signals of the carbon atoms in aromatic rings at δC 116.48, 127.12, 133.99, and 147.86 ppm. The signals at δC 32.96 and 53.30 ppm evidences the presence of the dithiazinane ring methylene groups in compound 2g.
The 1H NMR spectrum of heterocycle 4g exhibits proton signals of aromatic ring at δH 6.73-7.11 ppm. The singlet signals, which correspond to the methylene protons between the nitrogen and sulfur atoms, appeared at 3.98 and 4.52 ppm at a ratio of 1:1. The proton signals at δH 7.54 and 7.63 ppm belong to NH group. The 13C NMR spectrum of compound 4g contains the carbon atom signals of aromatic rings at δC 112.73, 127.35, 131.91, and 149.39 ppm. The presence of signals at δC 44.74 and 63.49 ppm for 4g characterizes the presence of CH2 groups between N and S atoms.
In 1H NMR spectrum of compound 5g the protons of aromatic ring are observed at δH 6.73-8.02, the methylene protons of SCH2S and SCH2N groups of the dithiazinane ring, linked with aromatic ring, are observed at δH 3.93 and 4.72 ppm (1:2 ratio), and of sulfo group at δH 4.26 and 5.14 ppm, respectively. The 13C NMR spectrum of compound 5g exhibits the signals of dithiazinane cycle carbon atoms, bound with aromatic ring, at δC 31.48 and 56.05 ppm, and with sulfo group at δC 33.10 and 63.40 ppm.
Cyclothiomethylation of p-aniline sulfacetamide 1h was found to proceed simultaneously via NH2 and SO2(Ac)NH groups in acid medium (pH 2,5). Under these conditions cyclodimer 4h has been obtained in 50% yield as a result of intermolecular condensation of two molecules of 1h with a thiomethylation reagent CH2O-H2S (Scheme 5) with 70% conversion. In neutral and alkaline medium, p-aniline sulfacetamide 1h did not react with CH2O and H2S and 1,2,4-trithiolane was predominantly formed.8

The molecular weight of 543.53±10 (calc. Mcr 544) determined by Rast cryoscopy method7 and the data of element analysis correspond to molecular formula C20H24N4O6S4 that proved the formation of macroheterocycle 4h. The 1H NMR spectrum shows signals of methylene sulfide protons connected with amino group at δH 4.50 ppm, and connected with the sulfo acetamide group at δH 5.11 ppm. The 13C NMR spectrum contains signals at δC 43.61 and 44.28 ppm assigned to carbon atoms of CH2NH and CH2NSO groups, respectively.
Cyclocondensation of [(p-aniline)sulfamido]-3-methoxypyrazine and [4-(p-aniline)sulfamido]-2,6- dimethoxypyrimidine containing pyrimidine rings under conditions described above does not proceed with CH2O h H2S. The low activity of NH2 group in compounds 1i and 1k is, apparently, connected with the formation of the intermolecular hydrogenous bonds between NH2 group and the nitrogen atoms of pyrimidine ring.
In conclusion, cyclocondensation of o- (1a), p- (1b) aminobenzoic, 4- (1c), 5- (1d) aminosalicylic acids, ethyl- (1e), (β-diethylamino)ethyl esters- (1f) of p- (1b) and p-aniline sulfamide 1g with CH2O and H2S under optimized conditions leads to the formation of the corresponding ditiazinanes 2a-g, whereas p-aminobenzoic 1b, 5-aminosalicylic acid 1d and p-aminobenzoic acid ethyl ester 1e together with dithiazinanes give rise to thiazetidines. Cyclothiomethylation of p-aminobenzoic acid ethyl ester by the CH2O-H2S reagent at 0 °C was found to afford N,N-diaryl-1,3,5-thiadiazinane 4e in quantitative yield (93%). The reaction for obtaining bis-1,3,5-dithiazinanes 5g (93%) from p-aniline sulfamide 1g are more effective in acid medium (pH 1.3-1.5) at 40 oC. It was shown that in the cyclothiomethylation at 80 oC together with the formation of dithiazinane (56%) p-aniline sulfamide 1g undergoes intermolecular condensation to give cyclodimer 4g (14%). The analogous intermolecular cyclocondensation of p-aniline sulfacetamide in acid medium (pH 2,5) leads to cyclodimer 4h (50%) built from two fragments of p-aniline sulfacetamide linked by sym dimethyl sulfide chain (CH2SCH2).
EXPERIMENTAL
All solvents were freshly distilled. The 1H NMR spectra of compounds 2a-g, 3b,d,e and 4g, 5g were measured on spectrometer “Tesla BS-487”, 13C NMR - on spectrometer Jeol FX 90Q (22.50 MHz), internal standard - Me4Si. NMR experiments of compounds 4e and 4h were recorded on a Bruker AVANCE-400 spectrometer. The GLC-mass spectrometry was carried out on Finigan 4021 instrument. The IR-spectra were recorded on Specord 75 IR in spectrophotometer in Nujol mulls. Elemental analysis of C, H, N, S samples was determined on element analysator of Karlo Erba, model 1106. The pH values of solutions were determined on a pH meter (pH – 340). Melting points were determined on Kofler unit. Column chromatography was performed with the use of silica gel.
Single-crystal X-ray diffraction experiments were carried out with a Bruker SMART 1000 CCD area detector, using graphite monochromated Mo-Kα radiation at 100 K. All calculations were performed on an IBM PC/AT using the SHELXTL software [G. M. Sheldrick, SHELXTL-97, Version 5.10, Bruker AXS Inc., Madison, WI-53719, USA]. Atomic coordinates, bond lengths, bond angles and termal parameters have been deposited at the Cambrigdge Crystallographic Data Centre (CCDC), deposition numbers 679451 (4e).
Cyclothiomethylation of functional substituted anilines (1a-1h). The calculated amount of 37% formalin (1.1 mL, 0.015 mol) or (2.2 mL, 0.030 mol) were charged to a three-neck flask equipped with a stirrer and barbotager thermostated at the chosen temperature. Hydrogen sulfide (prepared in excess amount from Na2S and HCI) was barbotaged to give CH2O–H2S mixture at a ratio of 3:2 or 6:4. Then calculated amount of anylines (la, 1b, 1c, 1d, le, 1f, 1g or 1h; 0.005 mol) was added to the reaction mixture. The mixture was stirred for 2-3 h at a chosen temperature. Compounds 2e, 3e, 4e were isolated by column chromatography with C6H6/EtOAc (10:1) as the eluent. The products 2a–d, 3b, 3d, 2g, 4g were selected by fractional crystallization from CHCl3. Compounds 5g and 4h were filtered.
7-(1,3,5- Dithiazinane-5-yl)-2-benzoic acid (2a). White powder (61%). mp 159-160 °С. m/z (%): 241 (5) [М]+, 197 (47), 163 (5), 150 (30), 120 (53), 105 (5), 92 (44), 77 (12), 61 (100). 1H NMR (80 MHz, DMSO-d6): δ (ppm) 3.75 (s, 2H, 2H-2), 4.66 (s, 4H, 2Н-4, 2H-6), 6.64-7.00 (m, 2Н, H-10, H-12), 7.28-7.53 (m, 2Н, Н-9, H-11), 8.00 (s, Н, Н-15). 13C NMR (22.5 MHz, DMSO-d6): δ (ppm) 32.2 (C-2), 44.5 (C-6, C-4), 109.9 (C-8), 114.9 (C-10), 116.6 (C-12), 131.5 (C-9), 134.0 (C-11), 151.7 (C-7), 169.9 (C-13). IR (KBr): 750, 1230, 1600, 1660, 2900, 3320 cm-1. Anal. Calcd for C10H11O2NS2: C 49.79, H 4. 56, N 5.80, S 26.55. Found: C 50.11, H 4.60, N 5.79, S 26.46.
7-(1,3,5-Dithiazinane-5-yl)-4-benzoic acid (2b). White powder (95%). mp 227-229 °С. m/z (%): 241 (9) [М]+, 207 (12), 91 (15); 44 (100). 1H NMR (80 MHz, DMSO-d6): δ (ppm) 4.00 (d, J=8.0 Hz, 2H, 2H-2), 4.64 (br. s, 4Н, 2Н-4, 2H-6), 6.72 (d, J=8.0 Hz, 2Н, Н-8, H-12), 7.17 (d, J=8.0 Hz, 2Н, Н-9, H-11), 7.83 (s, Н, Н-13). 13C NMR (22.5 MHz, DMSO-d6): δ (ppm) 33.7 (C-2), 56.3 (C-6, C-4), 113.8 (C-8, C-12), 121.0 (C-10), 131.0 (С-9, C-11), 149.1 (C-7), 167.7 (С-13). IR (KBr): 780, 1200, 1600, 1680, 2900, 3300 cm-1. Anal. Calcd for C10H11O2NS2: C 49.79, H 4. 56, N 5.80, S 26.55. Found: C 49.79, H 4.56, N 5.80, S 26.63.
5-(1,3-Thiazetidine-3-yl)-4-benzoic acid (3b). White powder (51%). mp 209-210 °С. m/z (%): 195 (52) [М]+, 150 (33); 120 (57); 92 (48); 61 (100). 1H NMR (80 MHz, DMSO-d6): δ (ppm) 4.36 (br. s, 4 Н, 2H-2, 2H-4), 6.72 (d, J=8.0 Hz, 2 Н, Н-6, H-10), 7.17 (d, J=8.0 Hz, 2 Н, Н-7, H-9), 7.75 (s, Н, Н-11). 13C NMR (22.5 MHz, DMSO-d6): δ (ppm) 53.3 (C-2, C-4), 116.4 (C-6, C-10), 120.0 (C-8), 131.0 (С-7, C-9), 147.2 (C-5), 167.7 (С-11). IR (KBr): 780, 1200, 1600, 3300 cm-1. Anal. Calcd for С9H9O2NS: C 55.38, Н 4.61, N 7.17, S 16.41. Found: C 55.53, Н 4.59, N 7.29, S 16.92.
4-(1,3,5-Dithiazinane-5-yl)-2-hydroxybenzoic acid (2c). White powder (89%). mp 258-260 °С. 1H NMR (80 MHz, DMSO-d6): δ (ppm) 4.06 (s, 2 H, 2H-2), 5.20 (s, 4 Н, 2H-4 and 2H-6), 6.23 (s, Н, Н-12), 6.70 (s, Н, Н-8), 7.85 (s, Н, Н-11), 8.50 (br. s, 2 Н, H-13, Н-14). 13C NMR (22.5 MHz, DMSO-d6): δ (ppm) 33.6 (С-2), 53.2 (C-4, C-6), 103.7 (C-10), 106.4 (C-8), 108.4 (С-12), 131.4 (С-11), 151.5 (C-7), 163.1 (С-9), 172.3 (С-13). IR (KBr): 720, 1170, 1450, 1600, 2900, 3360 cm-1. Anal. Calcd for С10H11O3NS2: C 46.69, Н 4.28, N 5.44, S 24.90. Found: C 47.21, Н 4.33, N 5.48, S 25.16.
5-(1,3,5-Dithiazinane-5-yl)-2-hydroxybenzoic acid (2d). White powder (32%). mp 194-196 °С. 1H NMR (80 MHz, DMSO-d6): δ (ppm) 4.00 (s, 2 H, 2H-2), 5.20 (s, 4 Н, 2H-4 and 2H-6), 6.80-7.50 (m, 3 Н, Н-8, H-11 and H-12), 8.45 (br. s, 2 Н, H-13, Н-14). 13C NMR (22.5 MHz, DMSO-d6): δ (ppm) 33. 5 (С-2), 56.9 (C-4, C-6), 113.0 (C-9), 114.7 (С-11), 117.9 (C-8), 123.0 (С-12), 137.7 (С-7), 155.0 (С-10), 171.8 (C-14). IR (KBr): 800, 1190, 1440, 1600, 1660, 2900 cm-1. Anal. Calcd for С10H11O3NS2: C 46.69, Н 4.28, N 5.44, S 24.90. Found: C 46. 73, Н 4.27, N 5.54, S 25.00.
5-(1,3-Thiazetidine-3-yl)-2-hydroxybenzoic acid (3d). White powder (22%). mp 164-166 °С. 1H NMR (80 MHz, DMSO-d6): δ (ppm) 4.35 (s, 4 Н, 2Н-2, 2H-4), 6.80-7.50 (m, 3 Н, Н-6, H-9, H-10) 8.47 (br. s, 2 Н, Н-11, H-12). 13C NMR (22.5 MHz, DMSO-d6): δ (ppm) 54.5 (C-2, C-4), 113.0 (C-7), 115.1 (С-9), 119.2 (C-6), 126.3 (С-10), 138.1 (С-5), 158.8 (С-8), 172.2 (C-12). IR (KBr): 800, 1190, 1440, 1600, 1660, 2900 cm-1. Anal. Calcd for C9H9O3NS: C 51.17, H 4.29, N 6.63, S 15.18. Found: C 51.53, H 4.36, N 6.42, S 15.03.
Ethyl-4-(l,3,5-dithiazinan-5-yl)benzoate (2e). White powder (56%). mp 136-138 °С. m/z (%) = 269 (40) [М]+, 191 (21), 177 (70), 163 (24), 149 (33), 132 (100), 77 (36) 45 (52). 1H NMR (80 MHz, CDCl3): δ (ppm) 1.38 (t, J=7.2 Hz, 3 Н, Н3С-16), 3.92 (s, 2 Н, 2Н-2), 4.30 (s, 4 H, 2H-4, 2H-6), 5.10 (br. s, 2 Н, 2Н-15), 7.05 (d, J=9.0 Hz, 2 Н, Н-8, H-12), 8.05 (d, J=9.0 Hz, 2 H, H-9, H-11). 13C NMR (22.5 MHz, CDCl3): δ (ppm) 14.3 (C-16), 34.8 (С-2), 54.5 (С-4, C-6), 60.4 (C-15), 116.2 (С-8, C-12), 121.9 (С-10), 131.0 (С-9, C-11), 148.5 (С-7), 164.6 (С-13). IR (KBr): 750, 1230, 1450, 1660, 3320 cm-1. Anal. Calcd for С12H15O2NS2: C 53.53, Н 5.58, N 5.20, S 23.79. Found: C 54.19, Н 5.48, N 5.11, S 23.77.
Ethyl-4-(l,3-thiazetidin-3-yl)benzoate (3e). White powder (18%). mp 175-177 °С. m/z (%) = 225 (0.4) 223 (9) [М]+, 177 (9), 150 (15), 149 (100), 132 (15), 44 (42), 46 (1.7). 1H NMR (80 MHz, CDCl3): δ (ppm) 1.34 (t, J=7.2 Hz, 3Н, Н3С-14), 4.25 (k, J= 9.0 Hz, 2 H, Н2С-13), 5.10 (br. s, 4Н, 2Н-2, 2H-4), 6.98 (d, J=6.3 Hz, 2 Н, Н-6, H-10), 7.68 (d, J=6.3 Hz, 2 H, H-7, H-9). 13C NMR (22.5 MHz, CDCl3): δ (ppm) 14.4 (C-14), 53.2 (С-2, C-4)), 60.6 (C-13), 116.4 (С-10, C-6), 125.5 (С-8), 131.2 (С-7, C-9), 155.0 (С-5), 165.6 (С-11). IR (KBr): 750, 1230, 1450, 1660, 3320. Anal. Calcd for С11H13O2NS: C 59.19, Н 5.83, N 6.28, S 14.35. Found: C 57.20, Н 5.42, N 6.11, S 15.77.
3,5-Di-(4-ethylcarboxyphenyl)-l,3,5-thiadiazinane (4е). Compound 4e was isolated by column chromatography (yield 15%). And also the compound 4e has selectively been received at 0 °С, the starting reagents were taken in the ratio 1e:CH2O:H2S = 2:3:1 (yield 93%). White powder, mp 184-186 °С. 1H NMR (400 MHz, CDCl3): δ (ppm) 1.32 (t, J=6.5 Нz, 6 H, Н3С-22, Н3С-26), 4.24 (d, J= 6.8 Hz, 4 Н, 2H-21, 2Н-25), 4.94 (s, 4 Н, 2Н-2, 2Н-6), 5.32 (s, 2 Н, 2Н-4), 6.91 (d, J=8.1 Hz, 4 Н, Н-8, H-12, H-14, H-18), 7.79 (d, J=8.1 Hz, 4 H, Н-9, H-11, H-15, H-17). 13C NMR (100 MHz, CDCl3): δ (ppm) 14.4 (C-22, C-26), 53.1 (С-2, C-6), 60.57 (C-25, C-21), 68.2 (C-4), 116.3 (С-12, C-8, C-18, C14), 122.1 (С-16, C-10), 131.2 (С-11, C-9, C-17, C-15), 150.5 (С-7, C-13), 166.4 (С-23, C-19). IR (KBr): 750, 1230, 1450, 1660, 3320. Anal. Calcd for С11H13O2NS: C 62.98, Н 5.04, N 6.99, S 8.01. Found: C 63.25, Н 5.32, N 7.11, S 8.65.
4-(1,3,5-Dithiazinane-5-yl)-2-(diethylamino)ethylbenzoate (2f). White powder (79%). mp 51-52 °С. 1H NMR (80 MHz, CDCl3): δ (ppm) 0.45 (t, J=6.3 Hz, 6 H, Н3С-19, Н3С-22), 1.30 (t, J=9.0Hz, 2 H, 2H-16), 3.12 (k, J=10.1 Hz, 4 Н, 2H-18, 2H-21), 3.80 (t, J=9.0 Hz, 2 H, 2H-15), 4.22 (s, 2 H, 2H-2), 4.68 (s, 4 Н, 2Н-4, 2H-6), 7.3 (br. s, 2Н, Н-8, H-12), 7.87 (s, 2 Н, H-9, Н-11). 13C NMR (22.5 MHz, CDCl3): δ (ppm) 8.5 (C-19, C-22), 32.4 (С-2), 47.1 (C-18, C-21), 49.5 (С-4, С-6), 53.8 (C-16), 58.2 (C-15), 116.9 (С-8, C-12), 131.1 (С-9, C-11), 150.5 (С-7), 164.5 (С-13). IR (KBr): 770, 1100, 1380-1450, 1600, 1680, 2900 cm-1. Anal. Calcd for С16H24O2N2S2: C 56.47, Н 8.24, N 8.24, S 18.82. Found: C 51.97, Н 7.46, N 7.70, S 19.50.
4-(1,3,5-Dithiazinane-5-yl)benzenesulfonamid (2g). White powder (73%). mp 135-137 ºС. 1H NMR (80 MHz, DMSO-d6): δ (ppm) 3.90 (s, 2 H, 2H-2), 4.56 (s, 4 Н, 2Н-4, 2H-6), 5.16 (s, 2 Н, 2H-14), 6.80 (d, J=8.3 Hz, 2Н, Н-8, H-12), 7.67 (d, J=8.3 Hz, 2 Н, Н-9, H-11). 13C NMR (22.5 MHz, DMSO-d6): δ (ppm) 33.0 (С-2), 53.3 (С-4, C-6), 116.5 (С-8, C-12), 127.1 (С-9, C-11), 134.0 (С-7), 147.9 (С-10). IR (KBr): 685, 820, 1090, 1140, 1305, 1450, 1600, 2905, 3365 cm-1. Anal. Calcd for С9H12N2S3O2: С 39.11, Н 4.38, N 10.14, S 34.80. Found: С 39.47, Н 4.84, N 11.84, S 35.67.
2,2,12,12-Tetraon-2λ6,5,12λ6,15-tetrathia-3,7,13,17-tetraazatricyclo[16.2.2.28,11]-tetracosa-1(20),8,10,18,21,23-hexaene (4g). White powder (14%). mp 146-148 ºС. 1H NMR (80 MHz, DMSO-d6): δ (ppm) 3.98 (s, 4 Н, 2H-6, 2H-16), 4.52 (s, 4 Н, 2Н-4, 2H-14), 6.73 (d, J = 8.44 Hz, 4 Н, Н-9, H-22, H-19, H-23), 7.11 (d, J = 8,44 Hz, 4 Н, Н-10, H-20, H-22, H-24), 7.54 (m, 2 Н, NН-7, NH-17), 7.63 (s, 2 Н, NН-3, NH-13). 13C NMR (22.5 MHz, DMSO-d6): δ (ppm) 44.7 (С-6, C-16), 63.5 (С-4, 14), 112.7 (С-9, C-19, C-21, C-24), 127.4 (С-10, C-20, C-22, C-23), 131.9 (С-8, C-18), 149.4 (С-1, C-11). IR (KBr): 560, 815, 1095, 1150, 1305, 1460, 1600, 2910, 3370 cm-1. Anal. Calcd for С16H20N4S4O4: С 41.72, Н 4.38, N 12.16, S 27.85. Found: С 39.35, Н 4.54, N 11.82, S 33.73.
5-[4-(1,3,5-Dithiazinan-5-ylsulfonyl)phenyl]-1,3,5-dithiazinane (5g). Analogously to the above-described procedure compound (5g) was prepared with accompaniment of the 0.01 mol HCl. After 2 h the reaction mixture was neutralized with an aqueous KOH solution. White powder (93%). mp 154-156 ºС. 1H NMR (80 MHz, DMSO-d6): δ (ppm) 3.93 (s, 2 H, 2H-2), 4,26 (s, 2 H, 2H-17), 4.72 (s, 4 Н, 2Н-4, 2H-6), 5.14 (s, 4 Н, 2Н-15, 2H-19), 6.73 (d, J=7.98, 2 Н, Н-8, H-12), 8.02 (d, J=7.98, 2 Н, Н-9, H-11). 13C NMR (22.5 MHz, DMSO-d6): δ (ppm) 31.5 (C-2), 33.1 (С-17), 56.1 (C-4, C-6), 63.4 (С-15, C-19), 114.0 (С-8, C-12), 127.0 (С-9, C-11), 128.0 (С-10), 146.6 (С-7). IR (KBr): 645-695, 1005, 1090, 1140, 1300, 1445, 1595, 2900 cm-1. Anal. Calcd for С12H16N2S5O2: С 37.87, Н 4.24, N 7.36, S 42.13. Found: С 37.71, Н 4.53, N 8.18, S 43.91.
5-[4-(1,3-Thiazetan-3-ylsulfonyl)phenyl]-1,3,5-dithiazinane (6g). White powder (20%). m/z (%): 334 (5) [М]+, 156 (15), 108 (35), 43 (50). IR (KBr): 550, 1005, 1090, 1140, 1300, 1445, 1595, 2900 cm-1.
5-[4-(1,3-Oxazetan-3-ylsulfonyl)phenyl]-1,3,5-dithiazinane (7g). White powder (20%). m/z (%): 318 (5) [М]+, 156 (12), 108 (40), 76 (24), 43 (95). IR (KBr): 550, 1005, 1140, 1300, 1445, 1595, 2900 cm-1.
5-[4-(1,3,5-Oxathiazinan-5-ylsulfonyl)phenyl]-1,3,5-dithiazinane (8g). White powder (20%). m/z (%): 364 (2) [М]+, 200 (20), 136 (60), 78 (30), 43 (100). IR (KBr): 550, 810, 1090, 1300, 1445, 2900 cm-1.
2,2,12,12-Tetraon-2λ6,5,12λ6,15-tetrathia-(3,13-diacyl)-3,7,13,17-tetraasatricyclo[16.2.2.28,11]-
tetracosa-1(20),8,10,18,21,23-hexaene (4h). Analogously to the above-described procedure compound (4h) was prepared with accompaniment of the 0.01 mol HCl. After 3h the reaction mixture was neutralized with an aqueous KOH solution. White powder (51%). mp 126-127 °С. 1H NMR (400 MHz, DMSO-d6): δ (ppm) 1.88 (s, 6 Н, Н3С-26, Н3С-28), 4.5 (s, 4 Н, 2H-6, 2H-16)); 5.11 (s, 4 Н, 2Н-4, 2H-14); 6.73 (d, J = 6.85, 4 Н, Н-9, H-23, H-19, H-22); 7.63 (d, J = 6,85, 4 Н, Н-10, H-24, H-20, H-21); 21 (m, 2 Н, NН-7, NH-17). 13C NMR (100 MHz, DMSO-d6): δ (ppm) 23.4 (C-26, C-28), 43.6 (С-6, C-16); 44.3 (С-4, C-14); 116.3 (С-9, C-19, C-22, C-24); 129.6 (C-20, C-21, C-10, C-24), 147.4 (С-1, C-11), 153.8 (С-8, C-18), 169.0 (С-25, C-27). IR (KBr): 770, 1100, 1400-1450, 1570, 1620, 2900 cm-1. Anal. Calcd for С20H24N4S4O6: C 44.10, Н 4.48, N 10.09, S 23.55. Found: C 42.78, Н 5.07, N 9.88, S 23.65.

References

1. a) A. Wohl, Bericht, 1886, 19, 2344; b) E. R. Braithwaite and J. Graymore, J. Chem. Soc., 1953, 1, 143; CrossRef c) D. Collins and J. Graymore, J. Chem. Soc., 1953, 4089; CrossRef d) D. Collins and J. Graymore, J. Chem. Soc., 1958, 2893; e) E. R. Braithwaite and J. Graymore, J. Chem. Soc., 1950, 2, 208. CrossRef
2. a) Brit. Patent, 943.273, 1963 (Chem. Abstr., 1964, 60, 5528a); b) N. Nohyaku, Chem. Abstr., 1985, 102, 149292d; c) T. Shibamoto, J. Agr. Food Chem., 1980, 28, 237; CrossRef d) H. W. Brinkman, H. Copier, Joop J. M. de Leuw and S. B. Tjan, J. Agr. Food Chem., 1972, 20, 177; CrossRef e) M. Boelens, L. M. van der Linde, P. J. de Valois, H. M. van Dort and H. J. Takken, J. Agr. Food Chem., 1974, 22, 1071; CrossRef f) T. Shibamoto and G. F. Russell, J. Agr. Food Chem., 1976, 24, 4, 843; CrossRef g) G. MacLeod and B. M. Coppock, J. Agr. Food Chem., 1977, 25, 113; CrossRef h) H. Paulsen and F. R. Heiker, Liebigs. Ann. Chem. 1981, 2180. CrossRef
3. a) J. C. Galves-Ruiz, H. Nöth and A. Flores-Parra, Inorg. Chem., 2003, 42, 7569; CrossRef b) C. J. Galvez-Ruiz, C. Guadarrama-Perez, H. Nöth and A. Flores-Parra, Eur. J. Inorg., Chem., 2004, 601; CrossRef c) A. Flores-Parra, S. A.Sanchez-Ruiz, C. Guadarrama, H. Nöth and R. Contreras, Eur. J. Inorg. Chem., 1999, 2069; CrossRef d) C. Guadarrama-Perez, G. Cadenas-Pliego and A. Flores-Parra, Chem. Ber., 1997, 130, 813; CrossRef e) L. M. Martinez-Aguilera, G. Cadenas-Pliego, R. Contreras and A. Flores-Parra, Tetrahedron: Asymmetry, 1995, 6, 1585; CrossRef f) A. Flores-Parra, G. Cadenas-Pliego, L. M. Martinez-Aguilera, M. L. Garcia-Nares and R. Contreras, Chem. Ber., 1993, 126, 863; CrossRef g) A. Flores-Parra, N. Farfan, A. I. Hernandez-Bautista, L. Fernandez-Sanchez and R. Contreras, Tetrahedron, 1991, 47, 6903. CrossRef
4. French Patent, 1.341.792, 1963 (Chem. Abstr., 1964, 60, 5528d).
5. a) S. R. Khafizova, V. R. Akhmetova, L. F. Korzhova, T. V. Tyumkina, G. R. Nadyrgulova, R. V. Kunakova, E. A. Kruglov and U. M. Dzhemilev, Russ. Chem. Bull., 2005, 2, 432; CrossRef b) S. R. Khafizova, V. R. Akhmetova, R. V. Kunakova and U. M. Dzhemilev, Russ. Chem. Bull., 2003, 8, 1817; CrossRef c) S. R. Khafizova, V. R. Akhmetova, G. R. Nadyrgulova, I. V. Rusakov, R. V. Kunakova, and U. M. Dzhemilev, Petrochemistry, 2005, 5, 345; d) V. R. Akhmetova, G. R. Nadyrgulova, T. V. Tyumkina, Z. A. Starikova, M. Yu. Antipin, R.V. Kunakova and U. M. Dzhemilev, Russ. J. Org. Chem., 2007, 41, 151; e) V. R. Akhmetova, G. R. Nadyrgulova, S. R. Khafizova, T. V. Tyumkina, A. A. Yakovenko, M. Yu. Antipin, L. M. Khalilov, R. V. Kunakova and U. M. Dzhemilev, Russ. Chem. Bull., 2006, 2, 312. CrossRef
6. R. D. Lindsay in Comprehensive Org. Chem., Moscow, Chemistry, 1982, 3, 168 ; [S. D. Barton and W. D. Ollis, Comprehensive Org. Chem., Pergamon Press, Oxford-N. Y.-Toront, 1979].
7. C. E. Bennett, Am. Laboratory, 1971, 3, 67.
8. R. S. Aleev, Yu. S. Dalnova, Yu. N. Popov, R. M. Masagutov and S. R. Rafikov, Dokl. Acad. Nauk SSSR, 1988, 303, 873.
9. a) L. Angiolini, R. P. Duke, R. A. Y. Jones and A. R. Katritzky, J. Chem. Soc., Perkin 2, 1972, 674; CrossRef b) Yu. Yu. Samitov, Chem. Heter. Comp., 1980, 11, 1443