Synthesis and reduction of <Emphasis Type="Italic">N</Emphasis>-substituted 5-nitrosoquinolin-8-amines

N-Substituted 5-nitrosoquinolin-8-amines were synthesized for the first time by amination of 5-nitrosoquinolin-8-ol with primary aliphatic amines. The amination of 5-nitrosoquinolin-8-ol with hexamethylenediamine afforded N¹,N⁶-bis(5-nitrosoquinolin-8-yl)hexane-1,6-diamine. The resulting nitrosoquinolinamines were reduced with hydrazine hydrate over Pd/C to N⁸-alkylquinoline-5,8-diamines and N¹,N⁶-bis-(5-aminoquinolin-8-yl)hexane-1,6-diamine.     

Synthesis of 8,16-diarylacridino[4,3-<Emphasis Type="Italic">c</Emphasis>]acridine-1,9-dione derivatives

A number of new acridino[4,3-c]acridinedione derivatives have been synthesized for the first time by condensation of N¹,N⁵-bis(arylmethylidene)naphthalene-1,5-diamines with cyclic 1,3-diketones (cyclohexane-1,3-dione and dimedone). The product structure has been determined by two-dimensional NMR spectroscopy, and a probable reaction mechanism has been proposed.     

Synthesis of <Emphasis Type="Italic">N</Emphasis>-and <Emphasis Type="Italic">C</Emphasis>-trimethylsilyl-substituded anililes

N-Metallation of bromoanilines with ethylmagnesium bromide followed by a reaction with trimethylchlorosilane provided N-mono and N-bis(trimethylsilyl)bromoanilines depending on the structure of substrate. The metallation of bissilylated bromoanilines with butyllithium permitted the introduction of a trimethylsilyl substituent in the aromatic ring. Previously unknown 2-bromo-N,N-bis(trimethylsilyl)aniline, 2,6-dibromo-N-trimethylsilylaniline, 2,6-dibromo-N,N-bis(trimethylsilyl)aniline, 2-bromo-6-trimethylsilylaniline, 2-bromo-6-trimethylsilyl-N,N-bis(trimethylsilyl)aniline, 2-bromo-6-trimethylsilyl-N-trimethylsilylaniline, 2,4,6-tribromo-N-trimethylsilylaniline, and 2,4,6-tribromo-N,N-bis(trimethylsilyl)aniline were prepared. The structures of the compounds obtained were established by the chromato-mass spectrometry and ¹H, ¹³C, and ²⁹Si NMR spectroscopy.     

1,3-Bis[2-(ethynyldimethylsilyl)vinyl]tetramethyldisiloxane and Macrocyclic Polyunsaturated Siloxanes on Its Basis

Hydrosilylation of diethynyldimethylsilane with tetramethyldisiloxane in the presence of chloroplatinic acid give rise to a mixture of three stereoisomers of 1,3-bis[2-(ethynyldimethylsilyl)vinyl]tetramethyldisiloxane: trans-trans, gem-trans, and gem-gem. Hydrolysis of chloro[2-(ethynyldimethylsilyl)vinyl]dimethylsilane provides the trans-trans isomer of 1,3-bis[2-(ethynyldimethylsilyl)vinyl]tetramethyldisiloxane exclusively. Reactions of an organomagnesium derivative of the disiloxane with dichlorodiorganylsilanes allowed synthesis of novel polyunsaturated macrocyclic siloxanes. The ¹H, ¹³C, and ²⁹Si NMR spectra of the products were studied.     

Synthesis and conformational analysis of 6-[N,N-bis(dihydroxyphosphorylmethyl)amino]methyl-2-hydroxy-2-oxido-1,4,2-oxazaphosphorinane-4-methylphosphonic acid by NMR spectroscopy

The Kabachnik—Fields methylphosphorylation of 1,3-diaminopropan-2-ol affords a mixture of 1,3-diamino-2-hydroxypropane-N,N,N′,N′-tetrakismethylphosphonic acid and its intramolecular cyclic ester. Subsequent heating of this mixture led to the thermal dehydration of the acid with the 1,4,2-oxazaphosphorinane ring closure and the formation of 6-[N,N-bis(dihydroxyphosphorylmethyl)amino]methyl-2-hydroxy-2-oxido-1,4,2-oxazaphosphorinane4-methylphosphonic acid. A predominant chair conformation of the formed six-membered heterocycle was inferred from the data of 2D homonuclear (¹H, ¹H; J-resolved) and heteronuclear (¹H, ¹³C; HSQC, HMBC) NMR correlation spectra.     

Cycloaminomethylation of dihydric phenols catalyzed by <Emphasis Type="Italic">d</Emphasis>- and <Emphasis Type="Italic">f</Emphasis>-metal compounds

An efficient method has been developed for the synthesis of 7,16,25-triaryl-7,8,16,17,25,26-hexahydro-6H,15H,24H-tribenzo[f,m,t][1,5,8,12,15,19,3,10,17]hexaoxatriazacyclohenicosines, 3,8-diaryl-2,3,4,7,8,9-hexahydrobenzo[1,2-e:4,3-e′]bis[1,3]oxazines, 3,9-bis(chlorophenyl)-3,4,9,10-tetrahydro-2H,8H-benzo[1,2-e:3,4-e′]bis[1,3]oxazines, and 2,9-bis(chlorophenyl)-1,2,3,8,9,10-hexahydrobenzo[1,2-e:6,5-e′]bis-[1,3]oxazines via cycloaminomethylation of pyrocatechol, resorcinol, and hydroquinone with N,N-bis(methoxymethyl) anilines in the presence of samarium catalysts.     

Hetero-diels–alder reaction of 5-ylidene-4-sulfanylidene-1,3-thiazolidin-2-ones with <Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>′-bis(methoxycarbonyl)-1,4-benzoquinone diimine

Hetero-Diels–Alder reaction of 5-(propan-2-ylidene)-4-sulfanylidene-1,3-thiazolidin-2-one with N,N′-bis(methoxycarbonyl)-1,4-benzoquinone diimine in boiling toluene afforded 87% of dimethyl 9,9-dimethyl-2-oxo-8a,9-dihydro-2H-thiochromeno[2,3-d][1,3]thiazole-5,8(3H,4aH)-diylidenedicarbamate. Analogous reactions of 5-benzylidene-, 5-{[4-(dimethylamino)phenyl]methylidene}-, and 5-[(2-hydroxyphenyl)-methylidene]-4-sulfanylidene-1,3-thiazolidin-2-ones led to the formation of the corresponding dimethyl 9-aryl-2-oxo-3,9-dihydro-2H-thiochromeno[2,3-d][1,3]thiazole-5,8-diyldicarbamates in 64–82% yield.     

<Emphasis Type="Italic">N</Emphasis>-(4-methoxy-3-nitrobenzyl) derivatives of some nitrogen-containing heterocycles

A number of nitrogen heterocycles reacted with 4-methoxy-3-nitrobenzyl chloride in dimethyl-formamide in the presence of potassium carbonate to give the corresponding N-(4-methoxy-3-nitrobenzyl) derivatives. The reaction of 5-fluoro-1,3-bis(4-methoxy-3-nitrobenzyl)pyrimidine-2,4(1H,3H)-dione with aqueous methylamine afforded N,N′-bis(4-methylamino-3-nitrobenzyl)urea, whereas analogous reaction with 1-(4-methoxy-3-nitrobenzyl)-2-(methylsulfanyl)-1H-benzimidazole resulted in substitution of the methoxy group by methylamino.     

Regioselective addition of primary amines to 2-halopyridine-3,4-dicarbonitriles. Synthesis of pyrrolo[3,4-<Emphasis Type="Italic">c</Emphasis>]pyridines

Reaction of 2-chloropyridine-3,4-dicarbonitriles with primary amines in the presence of potassium carbonate in ethanol results in the fusion of pyrrole cycle and the formation of N ¹-substituted 4-halo-1H-pyrrolo-[3,4-c]pyridine-1,3(2H)-diimines.     

Synthesis of benzimidazolone derivatives based on 2-acylcyclohexane-1,3-diones alkoximes

2-(1-Alkoxyiminoalkyl)cyclohexane-1,3-diones undergo at heating Beckmann rearrangement to give 6,7-dihydro-1,3-benzoxazol-4(5H)-one derivatives that under treatment with amines in acid medium are converted into 1,5,6,7-tetrahydro-4H-benzimidazol-4-ones. In reaction of 6,7-dihydro-1,3-benzoxazol-4(5H)-ones with O-ethylhydroxylamine 4-ethoxyimino derivatives were obtained that treated with hydrochloric acid formed the corresponding N-ethoxybenzimidazolones.     

Peculiarities of the reaction of alkali metal bis(trimethylsilyl)amides with halobenzenes

Lithium and sodium bis(trimethylsilyl)amides react with fluoro-, bromo-, and chlorobenzenes in THF or toluene to give a mixture of N,N-bis(trimethylsilyl)aniline and N,2-bis(trimethylsilyl)aniline. The latter compound is resulted from 1,3-shift of the trimethylsilyl group from nitrogen to ortho-carbon atom of the benzene ring. Effects of the solvent, halogen, and alkali metal nature as well as the reaction conditions on the ratio of isomers were examined. Reaction of iodobenzene with sodium bis(trimethylsilyl)amide in THF produces N,N-bis(trimethylsilyl)aniline and 2-iodo-N,N-bis(trimethylsilyl)aniline, while in toluene a mixture of three products, two indicated above and N,N-bis(trimethylsilyl)benzylamine, was obtained.     

Reaction of thiourea with formaldehyde and simplest aliphatic diamines

N,N′-Bis(hydroxymethyl)thiourea reacted with propane-1,3-diamine at a molar ratio of 2 : 1 to give 5,5′-propane-1,3-diylbis(1,3,5-triazinane-2-thione), whereas 1,3,5,7,11,13,15,17-octaazatricyclo[15.3.1.1^7,11]-docosane-4,14-dithione was obtained in the reaction with equimolar amounts of the reactants. Tricyclic product was also formed in the three-component condensation of thiourea with formaldehyde and propane-1,3-diamine at a ratio of 1 : 3 : 1. The reactions of N,N′-bis(hydroxymethyl)thiourea with ethane-1,2-diamine (2 : 1) and of thiourea with formaldehyde and butane-1,4-diamine (1 : 2 : 1) afforded 5,5′-(ethane-1,2-diyl)bis(1,3,5-triazinane-2-thione) and 5,5′-(butane-1,4-diyl)bis(1,3,5-triazinane-2-thione), respectively.     

Transformations of 5-chloro-2-hydrazino-4-<Emphasis Type="Italic">p</Emphasis>-tolylsulfonyl-1,3-thiazole

Accessible 2,2-dichloro-1-p-tolylsulfonylethenyl isothiocyanate reacted with hydrazine hydrate to give 5-chloro-2-hydrazino-4-p-tolylsulfonyl-1,3-thiazole whose reactions with thiols and amines followed a complicated pattern. Treatment of 5-chloro-2-hydrazino-4-p-tolylsulfonyl-1,3-thiazole with acetylacetone led to the formation of previously unknown 5-chloro-2-(3,5-dimethyl-1H-pyrazol-1-yl)-4-p-tolylsulfonyl-1,3-thiazole which reacted with O-, S-, and N-centered nucleophiles at the C⁵ atom with high regioselectivity.     

Synthesis of tertiary amines containing <Emphasis Type="Italic">gem</Emphasis>-dichlorocyclopropane and cycloacetal fragments

Reactions of secondary amines containing gem-dichlorocyclopropane and cycloacetal fragments with allyl chloride, trans-1,3-dichloropropene, benzyl chloride, and chloromethyl-gem-dichlorocyclopropane were studied. The corresponding tertiary amines were obtained in 20–85% yield. Microwave radiation stimulates N-alkylation of the secondary amine containing the heterocyclic moiety. The structures of the tertiary amines prepared were studied. The configuration of the double bond in the trans-1,3-dichloropropene derivative is retained.     

Reactions of internal perfluoroolefin oxides with urea

Internal perfluoroolefin oxides reacted with urea to give, depending on the solvent nature, two types of new fluorine-substituted nitrogen-containing heterocycles. 1,5-Bis(perfluoroalkyl)tetraazabicyclo[3.3.0]octane-3,7-diones were formed in dimethyl sulfoxide, N,N-dimethylacetamide, and acetonitrile, while the reaction in dioxane resulted in the formation of unexpected products, 2-amino-5-fluoro-4,5-bis(perfluoroalkyl)-4,5-dihydrooxazol-4-ols, existing mainly as trans isomers. trans Orientation of perfluoroalkyl substituents in these compounds was determined by analysis of ¹⁹F-¹⁹F spin-spin coupling constants in the ¹⁹F NMR spectra. The molecular structure of trans-2-amino-5-fluoro-4,5-bis(trifluoromethyl)-4,5-dihydrooxazol-4-ol was studied by X-ray analysis.     

N-trifluoroacyl lysine derivatives in the synthesis of L-Lysyl-L-glutamic acid

Conditions were developed for simultaneous preparation of N ^å-trifluoroacetyl-L-lysine and N ^α,N ^å-bis(trifluoroacetyl)-L-lysine at overall conversion of initial lysine monohydrochloride up to 82%. By reaction of dimethyl L-glutamate with N ^α,N ^å-bis(trifluoroacetyl)-L-lysyl chloride in the presence of triethylamine or with N ^α-carboxyanhydride of N ^å-trifluoroacetyl-L-lysine with subsequent removing protecting groups in the formed dipeptides by treating with water-ethanol solution of sodium hydroxide we obtained L-lysyl-L-glutamic acid. Physicochemical characteristics of samples obtained coincided with characteristics of L-lysyl-L-glutamic acid described in the literature thus suggesting that no racemization occurred either at the stage of peptide bond formation or at deprotection.     

Fusion of 2-(furan-2-yl)thiazole to 1-methyl-1<Emphasis Type="Italic">H</Emphasis>-benzimidazole

Methylation of 5(6)-nitro-1H-benzimidazole with methyl iodide in the presence of potassium hydroxide and N-methylpyrrolidin-2-one gave a mixture of isomeric 1-methyl-5-nitro- and 1-methyl-6-nitro-1H-benzimidazoles which were reduced with tin in concentrated aqueous HCl on heating. The resulting amines reacted with furan-2-carbonyl chloride in N-methylpyrrolidin-2-one to give furan-2-carboxamides which were treated with excess P₂S₅ in pyridine. Oxidation of isomeric furan-2-carbothioamides with K₃[Fe(CN)₆] in alkaline medium afforded a mixture of intramolecular cyclization products, 2-(furan-2-yl)-6-methyl-6H-imidazo[4,5-g][1,3]benzothiazole and 2-(furan-2-yl)-8-methyl-8H-imidazo[4,5-g][1,3]benzothiazole which were separated by column chromatography and identified.     

Reaction of <Emphasis Type="Italic">N</Emphasis>-aryl-3-oxobutanethioamides with 2-amino-1,3-thiazole and 2-amino-1,3-benzothiazole

N-Aryl-3-oxobutanethioamides react with 2-amino-1,3-thiazole (2-amino-1,3-benzothiazole) in acetic acid to give mixtures of 7-methyl-5H-[1,3]thiazolo[3,2-a]pyrimidine-5-thione (2-methyl-4H-pyrimido-[2,1-b][1,3]benzothiazole-4-thione) and 5-arylimino-7-methyl-5H-[1,3]thiazolo[3,2-a]pyrimidines (4-arylimino-2-methyl-4H-pyrimido[2,1-b][1,3]benzothiazoles), whose ratio depends on the nature of the aryl substituent in the initial butanethioamide.     

Nitration of 1,3-dihydro-2<Emphasis Type="Italic">H</Emphasis>-imidazo[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridin-2-one derivatives

Nitration of 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one and its N-methyl derivatives at 0–5°C and 60°C gives 5-nitro-and 5,6-dinitro-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones, respectively. The latter can also be obtained by nitration of 5-mononitro derivatives under similar conditions. The nitration of 6-chloro-and 6-bromo-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones and their N-methyl-substituted analogs leads to the formation of the corresponding 6-chloro(bromo)-5-nitro compounds. The same products are formed in the nitration of 5,6-dichloro-and 5,6-dibromo-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones. In this case, the process involves replacement of the halogen atom in position 5 of the pyridine fragment by nitro group. The nitration of 6-bromo-5-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one is accompanied by oxidation of the 5-methyl group to carboxy.     

Synthesis of Macrocyclic Stereoisomers Substituted with Oligolactide Fragments

Acylation of cone and 1,3-alternate stereoisomers of hydrazides of p-tert-butylthaicalix[4]arene tetrasubstituted at the lower rim with S,S-lactide in dimethylsulfoxide has afforded the macrocyclic oligolactide derivatives containing 16 (cone) to 24 (1,3-alternate) lactide fragments. It has been shown that nanosized aggregates (80 nm) are formed with silver nitrate in the case of the cone stereoisomer containing the oligolactide fragments at one side of the macrocyclic rim, whereas submicron particles (400 nm) are formed in the case of the 1,3-alternate conformation when the substituents are at different sides of the macrocycle.