Iminium carbonic acid derivative salts. VIII. Electrophilic reactions of 2-methylthio-5,6-dihydro-1,3-thiazinium iodides, 2-methylthio-5,6-dihydrothiazolium iodides and 5-methyl-2-methylthiothiazolium iodides. Part II. With active methylene compounds

The title compounds 1a-c and 2 werre reacted with several doubly activated methylene components to yield the cyclic ketene S,N-acetals 3-10 .     

Iminium carbonic acid derivative salts. IX. Synthesis of N,S-containing heterobicycles from N-protected 2-methylthio-1,3-thiazinium and 2-methylthiothiazolium salts part 1. Preparation of N-protected 2-methylthio-1,3-thiazinium and 2-methylthiothiazolium salts and their reaction with CH-acidic compounds

N-Boc-protected 1,3-thiazine-2-thiones and thiazolidin-2-thiones were transformed into the corresponding 2-methylthio-1,3-thiazinium and 2-methylthiothiazolium salts by methyl iodide or trimethyloxonium tetrafluoroborate. This activated species were reacted with CH-acidic compounds forming ketene-N,S-acetals. The protection group was removed with trifluoracetic acid to yield the N-unsubstituted ketene-N,S-acetals.     

Pyridinethiones. XV. 3-Methylthio-2-pentene-1,5-diones as synthons for 4-methylthio-2(1H)-pyridinethiones,and synthesis of 4-methylene-1,4-dihydropyridines

Starting from α-oxoketene dithioacetals the 3-methyithio-1,5-pentenedione enolates 4 obtained from ketones 3 give 4-methylthio-2(1H)-pyridinethiones with isothiocyanates. Enolates 4 can be alkylated with methyl iodide at C-2, giving 5-methyl-4-methylthio-2-(1H)-pyridmethiones with isothiocyanates. The S-alkylated pyridinethiones react with the anion of malodinitrile, giving 4-(1,1-dicyanomethylene)-1,4-dihydropyridines.     

Quantum-chemical study of possible structural transformations in 3-methylthio-3-phenyl-2-propenethial

The plausible formation of 3-methylthio-1-phenyl-2-propene-1-thione and 3-methylthio-3-phenyl-2-propenethial in the reaction of 3-methylthio-3-phenyl-2-propene-1-N,N-dimethyliminium iodide with hydrogen sulfide was shown in the framework of semiempirical AM1 and PM3 methods. In polar media, these products can be trimerized into four types of structures. The kind of trimer depends on the shift of the equilibrium in the 3-methylthio-3-phenyl-2-propenethial ⇄ 3-methylthio-1-phenyl-2-propene-1-thione mixture. Each of the four types of trimers is characterized by the presence of three nearly planar sixmembered pseudo-chelate rings. The possibility of obtaining derivatives of 1,2-dithiolane (the basic fragment of lipoic acid) from the reaction products in nonpolar solvents was considered. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1273–1277, July, 1997.     

Synthesis and herbicidal activity of (Z)-ethoxyethyl 2-cyano-3-(2-methylthio-5-pyridylmethylamino)acrylates

2-Methylthio-5-pyridinemethylene amine was prepared from 2-chloro-5-methylpyridine. Ethoxyethyl 2-cyano-3,3-dimethylthioacrylate was prepared from ethoxyethyl cyanoacetate, carbon disulfide, and dimethyl sulfate in 86.2% yield. Its reaction with 2-methylthio-5-pyridinemethylene amine yielded (Z)-ethoxyethyl 2-cyano-3-methylthio-3-(2-methylthio-5-pyridylmethylamino)acrylate. Ethoxyethyl (Z+E)-2-cyano-3-ethoxyacrylate was synthesized from ethoxyethyl 2-cyanoacetate and triethyl or- thoacetate in 90.7% yield, and its reaction with 2- methylthio-5-pyridinemethylene amine yielded (Z)-ethoxyethyl 2-cyano-3-methyl-3-(2-methylthio-5-pyri-dylmethylamino)acrylate. The structures of all of the products were confirmed by ¹H NMR, elemental analysis, IR, and mass spectroscopy. The herbicidal activities of the products were evaluated, and the results of bioassay showed that (Z)-ethoxyethyl 2-cyano-3-methyl-3-(2-methylthio-5-pyridylmethylamino)acrylate exhibits good herbicidal activity on rape (Brassica napus) at a dose of 1.5 kg/ha. © 2003 Wiley Periodicals, Inc. 15:67–70, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/.hc10214     

Alkylation of 2-methylthio-4-hydroxypyrimidines by methyl bromoacetate

2-Methylthio-4-hydroxypyrimidines react with methylbromoacetate in methanol-sodium methoxide solution to give O- and N₍₃₎-alkylated products, namely, 2-methylthio-4-(methoxycarbonyl)methoxypyrimidines and 2-methylthio-3-(methoxy-carbonyl)methylpyrimid-4-ones.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1520–1522, November, 1987.     

Synthesis and structure of 2-amino-1-benzyl-4-methylthio-6-oxo-<Emphasis Type="Italic">N</Emphasis>-phenyl-5-cyano-1,6-dihydropyridin-3-ylcarboxamide

Reaction of 3,3-bis(methylthio)-2-cyano-N-phenylacrylamide with N-benzyl-2-cyanoacetamide proceeds regiospecifically to give 2-amino-1-benzyl-4-methylthio-6-oxo-N-phenyl-5-cyano-1,6-dihydropyridin-3-ylcarboxamide. The structure of the latter was studied by means of XRD analysis.     

Substituted N-cyanomethyl-2-halo-N-methylarenecarboxamides as precursors of 1,4-benzothiazepines

2-Halogeno substituted N-cyanomethyl-N-methylbenzamides 1a-1i were investigated in a correlation analysis by ir spectroscopy to determine the conformational behavior. Compound 1h gives 4-methyl-2-methylthio-8-nitro-5-oxo-4,5-dihydro-1,4-benzothiazepine-3-carbonitrile 3 by dithiocarboxylation procedure whereas 1b was not able to react to heterocyclic seven-membered ring system.     

Synthesis of 4-methylthio-2(1H)-pyridone derivatives using ketene dithioacetals

Reaction of various active methylene compounds with ketene dithioacetals, bis(methylthio)methylenemalononitrile (1a) and bis(methylthio)methylenecyanoacetamide (1b) gave the corresponding 3-cyano-4-methylthio-2(1H)-pyridone derivatives. The transformation of 4-methylthio-2-oxo-2H-pyran-3-carbonitrile in-to 4-methylthio-2(1H)-pyridone derivatives was also described.     

Acyl iodides in organic synthesis: XIII. Reaction of acyl iodides with nitrogen-containing heteroaromatic compounds

Reactions of acetyl iodide with pyridine at room temperature and with quinoline both at 20–25°C and on cooling to −50°C involve dehydrohalogenation of acetyl iodide with formation of ketene and pyridinium or quinolinium iodides. The reaction of acetyl iodide with pyridine at −5 to −50°C led to the formation of N-acetylpyridinium iodide. Benzoyl iodide reacted with both pyridine and quinoline at both −50°C and at 20–25°C to form stable N-benzoylpyridinium and N-benzoylquinolinium iodides. The reaction of pyrrole with acetyl iodide under analogous conditions was accompanied by polymerization.     

Crystal solvates and polymorphs of N-(3-methylthio-1,2,4-thiadiazol-5-yl-aminocarbonylmethyl)cytisine

A polymorphs, crystallohydrate and crystallosolvates of N-(3-methylthio-1,2,4-thiadiazol-5-yl-aminocarbonylmethyl)cytisine, C₁₆H₁₉N₅O₂S₂, with chloroform, methanol, benzene have been obtained and crystal structures have been determined by the method of single crystal X-ray diffraction. In the investigated crystals N-(3-methylthio-1,2,4-thiadiazol-5-yl-aminocarbonylmethyl)cytisine have taken four types of conformation due to intra-molecular rotations around N–C and C–C bonds. So free rotations in the molecule assisted in formation a different crystallosolvates and polymorphs depending on nature of solvents. The thermal decomposition of the hydrate and methanol solvated crystals was studied by means of a TG-DSC.     

Synthese von 1-Ary1-4-methylthio-2-azetidinonen

TheN-arylthioformimidates4 a-e, which may be obtained byS-alkylation of the thioformanilides3 a-e, react with chloroacetylchloride/triethylamine to yield the (3R,4S/3S,4R)-1-aryl-3-chloro-4-methylthio-2-azetidinones5 a-e and the formanilides6 a-e. Dehalogenation of5 b-e with tri-n-butyltinhydride yield the title compounds7 b-e. Hydrogenolysis of7 b and7 c yields7 f and7 g.

     

Synthesis and reaction of 6-substituted 3-methoxycarbonyl-4-methylthio-2H-pyran-2-one derivatives

Reaction of aryl and styryl methyl ketones 1a-m with dimethyl bis(methylthio)methylenemalonate ( 2 ) in the presence of potassium hydroxide in dimethyl sulfoxide gave the corresponding methyl 6-aryl- and 6-styryl-4-methylthio-2-oxo-2H-pyran-3-carboxylates 3a-m . 6-Aryl derivatives 3a-d,g were treated with sodium methoxide in methanol to give the corresponding 6-aryl-4-methoxy-2H-pyran-2-ones 8a-d and 9. Phenylcoumalin ( 7a ) and paracotoin ( 7b ) were synthesized by the desulfurization of 6-aryl-4-methylthio-2H-pyran-2-ones 4a,b. Similarly, anibine ( 8e ) was also synthesized from 3g . Treatment of 3 with hydrogen peroxide or 3-chloroperoxybenzoic acid gave the corresponding 4-methylsulfiny-2H-pyran-2-ones 10a-f in good yields. Displacement reactions of 10a-f with nucleophilic reagents are also described.     

Heterocyclization of 3-(R-amino)-3-methylthio-1-phenylpropenones and 5-benzoyl-6-methylthio-1,2-dihydropyridin-2-ones with 1,2- and 1,3-dinucleophilic reagents

The interaction of 3-(R-amino)-3-methylthio-1-phenylpropenones and 1-alkyl-5-benzoyl-3-ethoxy-carbonyl-6-methylthio-1,2-dihydropyridin-2-ones with N,N- and N,C-1,2- and 1,3-dinucleophiles proceeded regioselectively by [3 + 2] and [3 + 3] cyclocondensation with the formation of derivatives of pyrazole, benzimidazo[1,2-a]-pyridine, benzimidazo[1,2-a]pyrimidine, imidazo[1,2-a]pyrimidine, [1,2,4]triazolo[4,3-b]pyridazine, and 6,7-dihydro-2H-pyrazolo[3,4-b]pyridine. The regioselectivity of the reactions carried out was analyzed.     

Electron-impact induced skeletal re-arrangement of 2-methoxy-3-methylpyrazine and 2-methylthio-3-methylpyrazine

The mass spectra of 2-methoxy-3-methylpyrazine (I), 2-methoxy-6-methylpyrazine (II), 2-methylthio-3-methylpyrazine (III) and 2-methylthio-6-methylpyrazine (IV), are given and the major fragmentation pathways discussed. The novel loss of H₂O from the molecular ion of I and the corresponding loss of H₂S from the molecular ion of III indicate that a skeletal rearrangement takes place in the molecular ion preceding the expulsion of H₂O and H₂S. Proposed mechanisms for this behavior are discussed with evidence being drawn from accurate mass measurement, metastable ions, and deuterium and carbon-13 labeling of the methoxy group. The absence of ions in the spectra of II and IV corresponding to the loss of H₂O and H₂S from these molecular ions clearly indicates that the position of the methyl group with respect to the methoxy group, or the methylthio group is in-timately involved in this mechanism.     

Synthesis and herbicidal activity of novel 6-arylthio-3-methylthio-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones

A series of pyrazolo[3,4-d]pyrimidine-4-one derivatives was conveniently synthesized via tandem aza-Wittig and annulation reactions of the corresponding iminophosphoranes, arylisocyanate, and substituted thiophenols. The structures of the target compounds were confirmed by IR, ¹H NMR, ¹³C NMR, LC-MS, and elemental analysis. The preliminary bioassay demonstrated that some title compounds such as 6-(3-chlorophenylthio)-1-phenyl-3-methylthio-5-(4-chlorophenyl)-1H-pyrazolo[3,4-d]-pyrimidin-4(5H)-one and 6-(4-fluorophenylthio)-1-phenyl-3-methylthio-5-(3-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one showed good inhibition activities against the root of Brassica napus (rape) and Echinochloa crusgalli (barnyard grass) at a dosage of 100 mg/L.     

Thiosulfonium ions. Methylthiolation of 3-methylthio-1-butene and cis- and trans-1-methylthio-2-butene

Whereas sulfenyl reagents commonly add to carbon double bonds, addition to sulfur of 3-methylthio-1-butene precedes attack at carbon to give allylic thiosulfonium ions that form reversibly and which rearrange rapidly to $\text{trans}$-2-butenyl analogs. Likewise, rearrangement of $\text{cis}$- to $\text{trans}$-1-methylthio-2-butene occurs by way of thiosulfonium ions.     

Synthesis and spectral properties of 2-methylthio-3H-4-(para-substituted-phenyl)-7-[(o-, and p-substituted)-phenylthio]-1,5-benzodiazepines

A series of twelve new 2-methylthio-3H-4-(p-substituted phenyl)-7-[(o-, and p-substituted)phenylthio]-1,5-benzodiazepines, which have potentially useful pharmacological properties, has been synthesized by condensing the 3,3-dimercapto-1-(para-substituted-phenyl)-2-propen-1-one with 3,4-diamino phenyl-R-phenylthio ethers, and subsequently the 1H-1,5-benzodiazepine-2-thiones obtained were treated with sodium hydride and methyl iodide. The structure of all products was corroborated by ir, ¹H-nmr, ¹³C-nmr and ms.     

Synthesis of 1-aryl-3-trifluoromethyl-5-methylthio-1,2,4-triazoles from 2-arylmethylisothiosemicarbazides and 1,1,1-trichloro-3,3,3-trifluoroacetone

The reaction of 1,1,1-trichloro-3,3,3-trifluoroacetone with S-methyl-2-arylisothiosemicarbazides affords an unusual synthesis of 1-aryl-3-trifluoromethyl-5-methylthio-1,2,4-triazoles from which 1-aryl-3-trifluoromethyl-1,2,4(4H)-triazole-5-ones are obtained on treatment with base.     

Synthesis and mass spectral fragmentation of 2-methylthio-7-(p-R-phenyl)-8-phenoxy-4,5-benzo-3-aza-2-nonem. III

A series of new 2-methylthio-7-(p-R-phenyl)-8-phenoxy-4,5-benzo-3-aza-2-nonem, IIIa, have been synthesized by regiospecific cycloaddition of phenoxyacetyl on to 2-methylthio-4-(p- R -phenyl)-3H-1,5-benzodiazepines IV. The structure was established by ir, ¹H-nmr and ms spectral data together with ¹³C-nmr spectral data of desulfurization products, VIa. Likewise, a study has been made of the fragmentation upon electron impact of IIIa and IV. All the spectra analyzed contain molecular ions and the principal fragmentation routes takes place either from the molecular ion or from m/e (M⁺ — 134) ion. This ion is the base peak for all the compounds analyzed.