Tetrahydro 2-thione

Similarly, the reaction of carbethoxyisothiocyanate (EtO CNCSl with 2-aminoselenazo ine leads to 2.3,6.7-tetrahydro-4H-selenazoio[3.2-fl]-s-triazin-2-one-4-thione Scheme 62 (66). 

E. V. Karaseva, S. N. Dedyukhina, and A. A. Dedyukhin. Treatment of water-based drilling solution to prevent microbial attack— by addition of dimethyl-tetrahydro-thiadiazine-thione bactericide. Patent RU 2036216-C, 1995. 

Mellors JW, Im G-J, Tramontano E, Winkler SR, Medina DJ, Dutschman GE, Bazmi HZ, Piras G, Gonzalez CJ, Cheng Y-C. A single conservative amino acid substitution in the reverse transcriptase of human immunodeficiency virus-1 confers resistance to ( + )- (5S)-4,5,6,7-tetrahydro-5-methyl-6-(3-methyl-2-butenyl)imidazo[4,5,l-y ][l,4]benzodiazepin-2(lH)-thione (TIBO R82150). Mol Pharmacol 1993 43 11-16. 

Reaction of 2-pyridineacetamides 197 with Me2NCH(OMe)2 afforded 3//-pyrido[l,2-f]pyrimidin-3-ones 198 (Equation 42) <1998WO98/027098, 2000USP6147080>. Reaction of l-(2-aminocthyl)-l, 2,3,4-tetrahydroisoquino-lincs with CS2, C(OEt>4, and nitroguanidine gave 1,2,3,6,7,1 1 h-hexahydro-4//-pyrimido[6,l -<2 isoquinoline-4-thiones, 4-ethoxy-1,6,7,1 lb-tetrahydro-2//-pyrimido[6,l -zz isoquinolines, and 4-(nitroimino)-l,2,3,6,7,l lb-hexahydro-... 

The treatment of 1,4-di hydro-2 7/-pyrido[ 2,3-< [ 1,2,4]triazine-3-thione 82 with dimethyl acetylenedicarboxylate (DMAD) in methanol at room temperature leads to the formation of 5-oxo-8,8a,9,10-tetrahydro-5//-4,4b,9,10-tetra-azaphenanthrene-7-carboxylic acid methyl ester 83 <1998IJH303> (Equation 5). 

The synthesis of 6-oxo-2,3,4,6-tetrahydro[l,2,4]triazino[5,6-c]isoquino-line-3-thione 178 was achieved by the reaction of the keto acid 174 with thiosemicarbazide to give azauracil 175. Its esterification gave 176, which was converted to the amide 177 and cyclized (84PHA186 92CCC123) in presence of acetic acid to give 178. 

With ketones. The 17/-imidazole-2(377)-thione 378 and 2-mercaptobenzoimidazole 380 reacted separately with cycloheptanone to form the tetrahydro-imidazo[2,l- ]thiazole 379 and the dihydro-thiazolo[3,2-tf]benzimidazole 381, respectively (Equations 170 and 171) <2000JHC943, 2001RJ0564>. 

Lewis acid SnCLj-assisted reaction between the l,3-thiazole-5-thione 434 and /ra r-2,3-dimethyloxirane led to the m 4,5-dimethyl-l,3-oxathiolane 435 The same Lewis acid enabled a second addition of /ra/ -2,3-dimcthyloxirane onto the C—N bond of the 1,3-thiazole ting of 434, leading to the formation of the tetrahydro-2//-thiazolo[2,3- ]-oxazole adduct 436 (Equation 200) <2000HCA3163>. Condensation of 2,4-dinitroimidazole, 8-bromotheophylline, and 8-bromoadenine with substituted methyloxiranes involved sequential A -alkylation-r/wo-substitution and furnished a series of 2,3-dihydro-imidazo[2,l- ]oxazole derivatives 437, 438, and 439 (Equations 201-203) <2000CCC1126, 2000EJ03489, 2005TL3561, 2004JHC51>. 

The synthesis of imidazo[2,Tc][l,2,4]triazolo-3-thiones has been investigated. For instance, the reaction of 1,2,4-triazoline-3-thione 361 <1995JHC275> with methyl trifluoromethanesulfonate affords the stable 3-methylmercapto-1,2,4-triazolium trifluoromethanesulfonate 362 in quantitative yield, which after treatment with sodium bicarbonate and bromine provides 6-bromomethyl-2,6-dimethyl-7-ethoxycarbonyl-2,3,5,6-tetrahydro-7//-imidazo[2,T4-[l,2,4]triazolo-3-thione 10 in 47% yield, via intermediate 363 (Scheme 36) <1996T791>. 

Synthetic approaches to representatives of this ring system have been discussed in CHEC-II(1996) <1996CHEC-II(8)496>. Research activity in this area has been considerably extended during the past years. Thus, the basic starting material is a 6,6-disubstituted tetrahydro[l,2,4,5]tetrazin-3-thione 52, which has been converted in three different ways reaction with phenacyl bromides led to 3,3-disubstituted 3,4-dihydro-6-phenyl-2//-thiazolo[3,2-4]-[l,2,4,5]tetrazines 53, reaction of 52 with 1,2-dibromoethane gave 3,4,6,7-tetrahydro-2//-thiazolo[3,2-7][l,2,4,5]tetra-zines 54, whereas transformation of 52 with chloroacetic acid in the presence of sodium acetate yields substituted 3,4-di hydro-1-2//-thiazolo[3,2- 1 [ 1,2,4,5]tctrazin-6(7//)-oncs 55 <2001IJB584> (Scheme 17). Details are shown in Table 2. 

The reaction of tetrahydro-l,3-thiazine-2-thione and diethyl 2-chloro-malonate in the presence of triethylamine in boiling methylene chloride for 1.5 hr gave tetrahydro-1,3-thiazin-2-ylidenemalonate (508) in 33% yield via 507 through Eschenmoser sulfur elimination, together with traces of the mesoionic derivative (509) [77JCS(P 1) 1107]. In a similar reaction, diethyl 2-bromomalonate afforded the mesoionic compound (509) in 80% yield. Tetrahydro-l,3-thiazin-2-ylidenemalonate (508) was also obtained in 42% yield from 509 by irradiation in the presence of tributylphosphine in ethanol for 15 hr under argon [77JCS(P1)1107]. 

Triazine-3-ones and triazine-3-thiones can also be reduced in two consecutive steps leading to the corresponding dihydro and tetrahydro derivatives. However, according to the experimental conditions, a ring contraction can occur at the second step [250]. 

To increase the yields of the ring closure reactions, a new method was developed that was successfully applied for the synthesis of alicyclic fused systems of both the parent oxazolidine-2-thione and tetrahydro-1,3-oxazine-2-thione (85S1149). As an example, the synthesis of 2-thioxoperhydro-l,3-benzoxazine 103 is described. The dithiocarbamate 101, prepared from the amino alcohol 100, carbon disulfide and triethylamine, was treated with ethyl chloroformate in the presence of triethylamine, to give the thioxo derivative 103 via the transition state 102 (85S1149). In this way, the fused-skeleton thioxooxazines (91, X = S, 92) can be prepared with considerably higher yields (50-70%) than by the earlier methods (85S1149). 

In accordance with the H and NMR parameters, the heterocyclic moiety of the -substituted (R = Me, Et, Ph, p-MeQH4, P-CIC6H4) diendo- and diexo-fused 4-oxo-4a,5,6,7,8,8a-hexahydro-lH- and -4a,5,8,8a-tetrahydro-lH-5,8-methanoquinazoline-2-thiones 353 assumes a distorted sofa conformation in which the N(l) —C(=S) —N(3) grouping forms the tip of the sofa [85JCS(P1)2483]. 

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