Synthesis of 3,6-disubstituted pyridazine derivatives

The synthesis of pyridazine functionalized with dioximes side chains are described. Several 3,6-disubsti-tuted pyridazine derivatives were prepared and their structures determined by spectroscopic methods (nmr, ir and ms).     

Synthesis and reactivities of 10-S-3 trithiadiazapentalene derivatives

1,3-Bis(p-substituted-phenylthiocarbamoyl)-2-imidazolidinethiones 3a-f reacted with bromine to give trithiadiazapentalene derivatives 5a-f , bearing the exocyclic C-N double bonds, in moderate yields. The molecular structure of 5b was elucidated by the X-ray crystallographic analysis. The treatment of 5b-f with hydrochloric acid gave the ring-opening products, 1,3-bis(p-substituted-phenylthiocarbamoyl)-2-imidazo-lidinones 9b-f , accompanied by the production of elemental sulfur. Reduction of 5b , 5d , and 5e with sodium borohydride gave the ring-opening compounds, 1,3-bis(p-substituted-phenylthiocarbamoyl)-2-imidazolidines 13b , 13d , and 13e respectively.     

Porphyrins. 14. Synthesis and properties of 1-substituted derivatives of 5,10,15,20-tetraphenylporphyrin

The Vilsmeier formylatlon of the cobalt complex of 5,10,15,20-tetraphenylporphyrin was realized, and its intermediate salt with the dimethylformamide-POC1₃ complex was isolated; demetallation of the latter gave 1-formyl-5,10,15,20-tetraphenylporphyrin. Formyltetraphenylporphyrin oxime and its 0-acetyl derivative and 1-cyano-5,10,15, 20-tetraphenylporphyrin were synthesized. The Wittig reaction with formylporphyrin and its copper and cobalt complexes with methoxycarbonylmethinyltriphenylphosphorane and diethylamidocarbonylmethinylhexamethyltriamidophosphorane was realized, and conditions that affect the ratios of the Z and E isomers of the acrylic derivatives obtained were studied.See [1] for Communication 13.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 59–64, January, 1982.The authors sincerely thank L. B. Lazukova and A. M. Shul'ge for recording the PMR spectra, V. P. Suboch for recording the mass spectra, and I. I. Mizrakhfor providing us with a sample of phosphorane B.     

Synthesis and transformations of enantiomeric 1,2-disubstituted monoterpene derivatives

Regio- and stereospecific addition of chlorosulfonyl isocyanate to (+)- and (−)-α-pinene 1 resulted in enantiomerically pure β-lactams 2, which were converted to enantiomeric β-amino esters 3 and 1,3-amino alcohols 4 and 6 with ee >99%. The resulting 1,3-difunctional compounds 3, 4 and 6 were transformed to fused saturated 1,3-heterocycles such as tetrahydro-1,3-oxazines 7 and 9, 2,4-pyrimidinedione 11 and 2-thioxopyrimidin-4-one 13 enantiomers.     

Synthesis and antiphospholipase activity of 3,5-disubstituted thiotetronic acid derivatives

The condensation of 3-acetyltetrahydrothiophene-2,4-dione with aromatic aldehydes in the presence of piperidine as a catalyst gave a series of 5-arylmethylidene-3-acetyltetrahydrothiophene-2,4-diones. The reaction with excess aldehyde (2.5 equiv) led to the formation of bis-condensation products, 5-arylmethylidene-3-(3-aryl-1-oxoprop-2-enyl)tetrahydrothiophene-2,4-diones. Analogous 3,5-disubstituted tetrahydrothiophene-2,4-dione derivatives with different aryl groups in the ring and the side chain were synthesized by two-step condensation with the use of differently substituted aromatic aldehydes. Catalytic hydrogenation of both mono-and bis-adducts resulted in the reduction of the side-chain double C=C bond, while ionic hydrogenation with triethylsilane in trifluoroacetic acid in the presence of lithium perchlorate involved both the double C=C bond and carbonyl group in the side chain. The isolated products showed an appreciable effect on the activity of two secretory phospholipases A₂ from various sources.     

Synthesis and properties of furan derivatives. 4. Synthesis of 2,5-disubstituted 1,3,4-oxadiazoles containing furan fragments

The condensation of hydrochloride sats of iminoesters of furan acids with hydrazides of carboxylic acids gives 2,5-disubstituted 1,3,4-oxadiazoles containing furan fragments. Such compounds are also formed in the condensation of hydrazides of 5-R-furan-2-carboxylic acids with hydrocloride salts of carboxylic acid iminoesters. The reaction of furan acids with hydrazine dihydrochloride in polyphosphoric acid gave symmetrically disubstituted 1,3,4-oxadiazoles containing furan fragments.Communication 3, see ref. [1].I. M. Gubkin State Petroleum and Natural Gas Institute, 117917, Moscow. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 238–249, February, 1995. Original article submitted January 24, 1995.     

Synthesis and properties of derivatives ofsym-triazines 14. Cyanoethylation of 4,6-disubstituted 2-amino-sym-triazines

The cyanoethylation of 4,6-disubstituted 2-amino-sym-triazines containing alkyl trichloromethyl, and pyridyl groups was studied, and the corresponding dicyanoethyl derivatives were synthesized. It was shown that the yield of the latter and the duration of the reaction depend on the nature of the substituents in the ring of the initial amino-sym-triazines. A method of obtaining 2-(2-cyanoethyl)amino-sym-triazines is proposed based on the decyanoethylation and disproportionation of the dicyanoethyl derivatives as well as the trans-cyanoethylation.I. M. Gubkin State Petroleum and Gas Academy, Moscow 117917. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 111–129, January, 1995. Original article submitted November 2, 1994.     

Synthesis of dihydro-1,3-thiazine derivatives. III

2-Carbamoylimino- and 2-thiocarbamoylimino-4-oxo-3,4-dihydro-2H-benzo[e]-1,3-thiazine derivatives were obtained by condensation of thiosalicylic acid with 3-alkyl(aryl)-substituted cyanoureas and cyanothioureas. 2-Hydroxy-3-mercaptoquinoline-4-carboxylic acid reacts similarly.See [1] for communication II.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 644–646, May, 1973.     

Synthesis and properties of azoles and their derivatives. 37. Synthesis of 3,5-disubstituted 1,2,4-oxadiazoles containing indole radicals

The 1,3-dipolar cycloaddition of nitrile N-oxides to indole nitriles yields 3,5-di-substituted 1,2,4-oxadiazoles containing an indole radical at the 5 position. Condensation of amidoximes with indole iminoester hydrochlorides yields 1,2,4-oxadiazoles having an indole segment at the 3 and/or 5 position of the oxadiazole ring. Pyrolysis of O-acyl derivatives of indole amidoximes yields 1,2,4-oxadiazoles with an indole residue at the 3 position.For Communication 36, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1609–1615, December, 1984.     

Synthesis of 3,5-disubstituted pyrazole derivatives with a carbamate function

One-pot reaction of 1,3-dipolar cycloaddition of aryldiazamethanes generated in situ from the sodium salts of tosylhydrazones of benzaldehyde, p-nitro-, p-methoxy-, and 3,4-dimethoxybenzaldehyde to propargyl-N-phenyl carbamate under heating led to the formation of 3,5-disubstituted pyrazoles in good yield and high regioselectivity.     

Reactivity of bis-vinylphosphates obtained from imide derivatives. Synthesis of 2,6-disubstituted 1,4-dihydropyridines

The Pd-catalyzed functionalization of lactam-derived vinyl phosphates has become an important tool in the last decade for the synthesis of nitrogen-containing heterocycles. By using this method, we were able to introduce alkenyl, aryl and heteroaryl groups on bis-vinylphosphate derivatives to provide efficient access to 2,6-disubstituted 1,4-dihydropyridines.     

Porphyrins. 23. Synthesis and properties of ethanebisporphyrins

It has been shown that copper complexes of meso-hydroxy(alkoxy)methylporphyrins in trifluoroacetic acid readily dimerize to give copper complexes of ethanebisporphyrins. Selective removal of one copper atom from the dimer molecule has been achieved. The previously unknown conversion of ethanebisporphyrins to ethylenebisporphyrins has been found to take place.For Communication 22, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, Vol. 24, No. 3, pp. 339–344, March, 1988.The authors wish to thank L. I. Krasovskaya for recording the mass spectra.     

Heteroadamantanes and their derivatives. 7. Synthesis and mass-spectrometric study of functional derivatives of 5-mono- and 5,7-disubstituted 1,3-diazaadamantanes

The chemical behavior of the carbonyl group of 5-mono and 5,7-disubstituted 6-oxo-1,3-diazaadamantanes was studied. The structures of the functional derivatives obtained were confirmed by IR and ¹H and ¹³C NMR spectral data. The behavior of the compounds under the influence of electron impact was studied, and the principal pathways of fragmentation of their molecules were ascertained.See [1] for Communication 6.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 647–653, May, 1989.     

Synthesis,Characterization and reactivities of Schiff-base complexes of Ruthenium(III)

Schiff-base complexes of ruthenium (1–5) have been synthesized using Schiff-base ligands derived by condensation of either 1,2-phenylenediamine with aldehydes (salicyldehyde, 2-pyridinecarboxaldehyde) or acetylacetone with amines (2-aminophenol, 2-aminomethylpyridine). All complexes were characterized by analytical, spectroscopic, conductance, magnetic moment and electrochemical studies. At room temperature, complexes 1–5 catalyze the oxidation of both saturated and unsaturated hydrocarbons using tert-butylhydroperoxide (t-BuOOH). A mechanism involving formation of and transfer from a reactive high valency Ru(V)-oxo species as the catalytic intermediate is proposed for the processes.     

Reactions of trichloromethylarenes with hydrazine derivatives. Synthesis of 2,5-disubstituted 1,3,4-oxadiazoles and 1,3,4-thiadiazoles

The effect of the solvent on the course of the reaction between trichloromethylarenes and thioacylhydrazines or acylhydrazines has been considered. In alcohols as solvents, alkyl arenecarboxylates form as a result of alcoholysis, while 2,5-disubstituted 1,3,4-thiadiazoles (1,3,4-oxadiazoles) form as minor products. In pyridine solutions, the major or sole products are those of reductive condensation,i.e., the correspondingN-substituted hydrazones of arenecarbaldehydes. 1,3,4-Thiadiazole or 1,3,4-oxadiazole derivatives are obtained in good yield when the reaction is carried out in a pyridine-alkanol mixture.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1246–1249, May, 1996.     

Dual reactivities of 1,2-disubstituted dihydro-N-heteroaromatic systems. 3. Electrochemical aromatization of substituted N-acyldihydropyridines and imidazoles

The principal pathway in the fragmentation of the cation radicals of N-acyl- ()-substituted 1,4-dihydropyridines and 1,2-dihydroisoquinolines, as well as 1,2-dihydroimidazoles and 1,2-dihydrobenzimidazoles, that are formed in the electrochemical oxidation of the indicated N-acyldihydro-N-heteroaromatic systems is the loss of a proton and the subsequent loss of another electron or detachment of an N-acyl residue in the form of a cation and subsequent detachment of an electron to give the corresponding ()-substituted heteroaromatic cations.See [1] for Communication 2.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 361–366, March, 1982.     

O-Methylephedrine: a versatile and highly efficient ortho-directing group. Synthesis of enantiopure 1,2-disubstituted ferrocene derivatives.

O-Methylephedrine was identified as a very efficient chiral auxiliary for ortho-lithiation reactions of ferrocenes. (1R,2S)-O-Methylephedrine [CH(3)NHCH(CH(3))CH(Ph)OCH(3)] was reacted with N-ferrocenylmethyl-N,N,N-trimethylammonium iodide [FcCH(2)N(CH(3))(3)I; Fc = ferrocenyl] to give (1R,2S)-N-ferrocenylmethyl-O-methylephedrine. Treatment of this compound with t-BuLi in pentane followed by quenching with the electrophiles iodine, dibromotetrafluoroethane, chlorodiphenylphosphine or benzophenone gave 2-substituted ferrocenes in 98% de and with the (R(p))-ferrocene configuration. Subsequently, the chiral auxiliary could be replaced by systems including dimethylamine, acetate, diaryl- or dialkylphosphines to give a number of enantiopure bifunctional 1,2-disubstituted ferrocene derivatives such as (R(p))-N-2-iodo- or (R(p))-N-2-bromoferrocenylmethyldimethylamine or (R(p))-2-acetoxymethyl-1-diphenylphosphinoferrocene. As an application, ferrocenyl diphosphines possessing a planar (R(p))-ferrocene configuration only [1,2-(PPh(2))FcCH(2)PR(2), R = Cy, Ph, [3,5-(CF(3))(2)Ph]] were synthesized in three steps from O-methylephedrine and N-ferrocenylmethyl-N,N,N-trimethylammonium iodide in up to 77% overall yield.     

Synthesis of Octasubstituted Porphyrins

The synthesis of porphyrins having high solubility in organic solvents requires the presence of long chain aliphatic substituents. Such substituted porphyrins are readily prepared in good yields by extension of our general procedure¹ which involves the synthesis of α,β-unsaturated ketones, conversion of these to 3,4-disubstituted pyrroles followed by acid catalyzed condensations of these pyrroles with formaldehyde in the presence of air.