structure of 4,4,6-trimethyl-2-mylamino-5,6-dihydro-4H-1,3-thiazines and -oxazines

It is shown by means of IR, PMR, and UV spectra that 4,4,6-trimethyl-2-arylamino-5, 6-dihydro-4H-1,3-thlazines and 4,4,6-trimethyl-2-arylamino-5,6-dihydro-4H-1,3-oxazines in the crystalline state and in solution exist primarily in the amino form. It was found that ionization to give cations proceeds more readily in the case of 1,3-oxazines than in the case of 1,3-thiazines. In addition, a decrease in the ability to undergo intermolecular association and a decrease in the energy barrier to rotation about the N-heteroring bond are observed for 1,3-oxazines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 346–352, March, 1977.     

Basicities and tautomerism of 4,4,6-trimethyl-2-aryl-amino-4H-1, 3-thiazines

The relative basicities of 4,4,6-trimethyl-2-arylamino-4H-1,3-thiazines, which are capable of amine-imine tautomerism, and of model compounds with fixed amino and imino structures were determined by potentiometric titration in methanol. Good correlation was observed between the pK_a values and the Hammett σ constants in the investigated reaction series. The anomalous pK_a values of the model amines and imines are explained by the different character of the electronic interactions in them, which is due to the change in the three-dimensional orientation of the aromatic ring and the amidine fragment.     

Synthesis of substituted 2-amino-5,6-dihydro-4H-1,3-thiazines and 2-iminotetrahydro-1,3-thiazines

N-Aryl-N′-(2-methyl-4-hydroxy-2-pentyl)thioureas are cyclized in acidic media to 4,4,6-trimethyl-2-arylimino-5,6-dihydro-4H-1,3-thiazines, the methylation of which with methyl iodide gives 4,4,6-trimethyl-2-methylarylamino-5,6-dihydro-4H-1,3-thiazines. 3,4,4,6-Tetramethyl-2-aryliminotetrahydro-1,3-thiazines were synthesized by cyclization of Naryl-N′-methyl-N′-(2-methyl-4-hydroxy-2-pentyl)thioureas.     

Synthesis of substituted 2-amino-5,6-dihydro-4h-1,3-oxazines and 2-iminotetrahydro-1,3-oxazines

3,4,4,6-Tetramethyl-2-aryliminotetrahydro-1,3-oxazines were synthesized by intramolecular cyclization of N-aryl-N′-methyl-N′-(2-methyl-4-hydroxy-2-pentyl)-S-methylisothioureas. 4,4,6-Trimethyl-2-(N-methyl-N-arylamino)-5,6-dihydro-4H-1,3-oxazines were obtained by methylation of 4,4,6-trimethyl-2-arylamino-5,6-dihydro-4H-1,3-oxazines.     

Synthesis of 4,4, 6-trimethyl-2-arylamino-4h-1,3-thiazines

The reaction of 2-isothiocyano-2-methyl-4-pentanone with substituted anilines gave 4,6,6-trimethyl-3-aryl-1,2,3,6-tetrahydropyrimidine-2-thiones, which are converted to the isomeric 4,4,6-trimethyl-2-arylamino-4H-1,3-thiazines by intramolecular rearrangement by heating with hydrochloric acid. In order to study the structure and amino-imino tautomerism of the aminothiazines, their analogs with a fixed amine structure were obtained. The synthesis of model compounds was accomplished by reaction of 2-isothiocyano-2-methyl-4-pentanone with m- and p-substituted N-methylanilines and subsequent cyclization of the resulting N-methyl-N-aryl-N-(2-methyl-4-oxo-2-amyl)thioureas to 4,4,6-trimethyl-2-methylarylamino-4H-1,3-thiazines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 937–940, July, 197     

Synthesis of substituted 2-amino-5,6-dihydro-4h-1, 3-oxazines

4,4,6-Trimethyl-2-alkyl(aryl)amino-5,6-dihydro-4H-1,3-oxazines were synthesized via two methods: amination of 4,4,6-trimetiiyl-2-methylthio-5,6-dihydro-4H-1,3-oxazine and cyclization of N-aryl-N-(2-methyl-4-hydroxy-2-amyl)-S-methylisothiourea.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1037–1040, August, 1972.     

Zur Umsetzung des 3,4,5,6-Tetrahydro-6-hydroxy-4,4,6-trimethyl-1,3-thiazin-2-thions mit primären Aminen

Tetrahydro-6-hydroxy-4,4,6-trimethyl-1,3-thiazine-2-thione (1 a) reacts with methyl-, ethyl- and n-butylamine to the corresponding 1-alkyl-6-alkylaminotetrahydro-2(1H)-pyrimidinethione12 but withi-propylamine to tetrahydro-6-isopropylamino-1,3-thiazine-2-thione (6 d). On treatment withDCC,6 d is rearranged to dihydro-4-isopropylamino-2(1H)-pyridinethione (8 d), and 6-amino-tetrahydro-1,3-thiazinethione (6 a) to dihydro-4,4,6-trimethyl-2(1H)-pyrimidinethione (10 a). The reaction of 6-aminothiazinethiones6 a, d and 6-(4-morpholinyl)-thiazinethione13 resp., with methylamine leads to 1-methyl-6-methylamino-pyridinethione12 b. 1-Alkyl-6-alkylamino-tetrahydro-2(1H)-pyrimidinethiones (12) react at reflux temperature to dihydro-1-alkylpyrimidinethiones10. With methylamine only 6-methylamino-3,4,4,6-tetramethyl-1,3-thiazine-2-thione (6 f) is formed from tetrahydro-6-hydroxy-tetramethyl-1,3-thiazine-2-thione (1 b).     

3-Alkyl- bzw. 3-Aryl-3,4-dihydro-6-methyl-2(1H)-pyrimidinthione durchDimrothumlagerung von 2-Amino-4H-1,3-thiazinen

The 3,4-dihydro-3,4,4,6-tetramethyl- and 4,4,6-trimethyl-3-phenyl-2(1H)-pyrimidinethione (1 c, d), resp. as well as the corresponding trimethyl compound1 e are formed byDimroth rearrangement of 2-methylamino- and 2-amino-4,6,6-trimethyl-6H-1,3-thiazine (2 a, b) and of 3,6-dihydro-4,6,6-trimethyl-2-phenylimino-2H-1,3-thiazine (3 b), resp. The rearrangement takes place under thermal heterolysis of the 1–6 bond of2 a, b and3 b. The reactive behaviour1 c, d is almost equal to1 e, but the pyrimidine ring of1 d is more labile than those of1 c, e.     

New method for the synthesis of the 1,3-thiazine system. 2-phenylamino-5,6-dihydro-4H-1,3-thiazin-5-ones

Treatment of N-phenylthioureidoalkyl--diazo ketones with acids leads to 2-phenyl-amino-5,6-dihydro-4H-1,3-thiazin-5-ones.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1327–1330, October, 1980.     

Synthesis and Structure of Quaternary Salts Derived from 2-Anilino- and 2-Benzylamino-5,6-dihydro-4H-1,3-thiazine

Substituted phenacyl bromides react with 2-anilino-5,6-dihydro-4H-1,3-thiazine at the exocyclic nitrogen atom and with 2-benzylamino-5,6-dihydro-4H-1,3-thiazine at the nitrogen atom in the ring. The structure of the reaction intermediates was elucidated, and their cyclization into 1-benzyl-2-aryl-6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazinium bromides was performed.     

Synthesis and Transformations of 2-R-5-Aryl-5,6-dihydro-7H-[1,2,4]-triazolo[5,1-b][1,3]thiazin-7-ones

A new procedure for preparation of 2-R-5-aryl-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones by condensation of 5-R-1,2,4-triazole-3-thiones with 3-arylacryloyl chlorides was developed. The thiazine ring of the [1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones is easily cleaved by treating with ammonia and hydrazine affording amides and hydrazides of 3-aryl-3-(1H-1,2,4-triazol-5-ylsulfanyl)propanoic acids. The latter react with isothiocyanates furnishing carbamoyl thiohydrazides of 3-aryl-3-(1H-1,2,4-triazol-5-ylsulfanyl)propanoic acids that in alkaline media undergo cyclization into 4-aryl-5-[2-(4H-1,2,4-triazol-5-ylsulfanyl)-2-phenylethyl]-2,4-dihydro-3H-1,2,4-triazole-5-thiones.     

Synthesis of 2-Aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones and 7-Aryl-2,3,6,7-tetrahydro-5H-imidazo[2,1-b]-1,3-thiazin-5-ones

The reaction of 2-mercaptobenzimidazole, 5-ethoxy-2-mercaptobenzimidazole, and 2-mercaptoimidazoline with cinnamoyl chloride, its derivatives, and heteroanalogs was studied. Convenient methods were found for the synthesis of 2-aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones and 7-aryl-2,3,6,7-tetrahydro-5H-imidazo[2,1-b]-1,3-thiazin-5-ones.     

Synthesis of 2-methylthio-4H-1,3-thiazines

2-Methylthio-4H-1,3-thiazines or their mixtures with 5-alkylidene-4H-5,6-dihydro-1,3-thiazines were obtained by cyclization of methyl N-3-oxoalkyldithiocarbamates in sulfuric acid. The regiospecificity of the reaction is determined by the structures of the starting compounds. The structures of the synthesized thiazines were confirmed by spectral methods of analysis (IR and ¹H and ¹³C spectroscopy).Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 991–993, July, 1992.     

Study of exchange processes in 4,4,6-trimethyl-2-phenylamino-4H-1, 3-thiazine derivatives

It is shown that, in contrast to model structures with fixed amine and imine forms, the form and position of some of the signals in the PMR spectra of 4,4,6-trimethyl-2-phenylamino-4H-1, 3-thiazine derivatives depend on the temperature; this is associated with rotational isomerism about the nitrogen-heteroring bond, which is realized at a higher rate in the model derivative with an amine structure and is slowed down in the tautomeric derivatives owing to the formation of hydrogen bonds with solvent molecules (in deuteroacetone) or in dimeric associates (in deuterochloroform). According to data from the low-temperature spectra, the percentages of the syn and anti forms in acetone solutions are comparable. In chloroform solution, the equilibrium between the two rotational forms is shifted markedly to favor the anti isomer as the temperature is lowered because of the formation of cyclic dimeric structures.     

Ab initio molecular orbital calculations of 3,4-dihydro-1,2-dioxin, 3,6-dihydro-1,2-dioxin, 4H-1,3-dioxin (1,3-diox-4-ene), and 2,3-dihydro-1,4-dioxin (1,4-dioxene)

Optimized geometries and total energies for 3,4-dihydro-1,2-dioxin ( 1 ), 3,6-dihydro-1,2-dioxin ( 2 ), 4H-1,3-dioxin (1,3-diox-4-ene, 3 ), and 2,3-dihydro-1,4-dioxin (1,4-dioxene, 4 ) were calculated using ab initio 3-21G, 6-31G*, and MP2/6-31G*//6-31G* methods. The half-chair conformers of 1 (C₁), 2 (C₂), 3 (C₁), and 4 (C₂) are more stable than their respective planar structures [ 1 (C_s), 2 (C_2v), 3 (C_s), and 4 (C_2v)]. Among the four isomers 1 – 4 , the half-chair conformer of 3 is the most stable. It is 53.1, 54.6, and 3.4 kcal mol⁻¹ more stable than 1 , 2 , and 4 , respectively. The largest energy difference (19.0 kcal mol⁻¹) is observed between the half-chair and planar conformers of 2 . The boat conformers of 2 and 4 are less stable than their respective half-chair conformers, but are more stable than their planar structures. Hyperconjugative orbital interactions (anomeric effects) contribute to the greater stability of 3 (n_O(3) →σ*_C(2)—O(1), n_O(3)→σ*,n _O(3)→σ*) and of 4 (n_O(1)→ σ*). The ab initio calculated structural features of the half-chair conformations of the dihydrodioxins 1 – 4 are compared with the half-chair conformations of cyclohexene and the chair conformations of cyclohexane, oxacyclohexane (tetrahydropyran), 1,2-dioxacyclohexane (1,2-dioxane), 1,3-dioxacyclohexane (1,3-dioxane), and 1,4-dioxacyclohexane (1,4-dioxane) © 1997 by John Wiley & Sons, Inc. J Comput Chem 18 : 1392–1406, 1997     

Synthesis of 4-aryl-2,6,6-trimethyl-5-oxo-5,6-dihydro-4H-thieno[3,2-b]pyrroles

The method for the synthesis of 4-aryl-2,6,6-trimethyl-5-oxo-5,6-dihydro-4H-thieno[3,2-b]pyrroles from accessible 4-aminothiophene derivatives was developed.     

Synthesis and crystal structure of 4-acetoxy-5,6-dihydro-5,5-dinitro-2H-1,3-oxazineN-oxide

A novel heterocyclic compound, 4-acetoxy-5,6-dihydro-5,5-dinitro-2H-1,3-oxazineN-oxide, has been synthesized by the reaction of the dipotassium salt of 1,1,5,5-tetranitro-3-oxapentane with aqueous acetic acid. The synthesized compound has been studied by X-ray diffraction analysis.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2207–2210, December, 1994.We would like to thank G. V. Lagodzinskaya (Institute of Chemical Physics in Chernogolovka, Russian Academy of Sciences) for recording and interpreting¹H NMR spectra, A. M. Korolev (Institute of Chemical Physics in Chernogolovka, Russian Academy of Sciences) for helpful discussion, and V. I. Fetisov (Institute of Physiologically Active Compounds, Russian Academy of Sciences) for performing quantum-chemical calculations by the AM1 SCF MO LCAO method.     

Structure of 2-arylamino-5, 6-dihydro-4h-1,3-thiazines

It follows from the data from the PMR, IR, and UV spectra of 2-arylamlno-5,6-dihydro-4H-1,3-thiazines and model derivatives with amine and imine structures that they have amine structures.     

Synthesis and structural determination of 5-arylamino-1,3-dimethylpyrazoles

Treatment of 4-arylamino-4-thioxo-2-butanones with methylhydrazine in acetic acid gives 5-arylamino-1,3-dimethylpyrazoles which are readily halogenated in the 4 position. The thermal decomposition of 3-anilino-1,2,5-trimethyl-1H-pyrazolium chloride gives 1,3-dimethyl-5-phenylaminopyrazole and 1,5-dimethyl-3-phenylaminopyrazole in the approximate ratio of 1:1.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 120–126, January, 2005.