Transformation of methyl N-methyl-N-(6-substituted-5-nitro-4-pyrimidinyl)aminoacetates into 4-methylamino-5-nitrosopyrimidines and 9-methylpurin-8-ones

N-Methyl-N-(6-substituted-5-nitro-4-pyrimidinyl)aminoacetic acid methyl esters under the treatment of sodium alkoxides, depending on the nature of substituents in 6 position of the pyrimidine ring, undergo ring closure and rearrangement to give 6-substituted-4-methylamino-5-nitrosopyrimidines or 9-methylpurin-8-ones.     

One-pot palladium-catalyzed C-I and C-H bond activation and subsequent Suzuki-Miyaura cross-coupling of 2-aryl-3-iodo-4-(phenylamino)quinolines with arylboronic acids

The 2-aryl-3-iodo-4-(phenylamino)quinolines undergo one-pot palladium-mediated C-I and C-H bond activation and subsequent Suzuki-Miyaura cross-coupling with arylboronic acids under anhydrous conditions to afford mixture of 2,3-diaryl-4-(phenylamino)quinolines (minor) and 2-aryl-4-([(1,1′-biaryl)-2-yl]amino)quinoline derivatives (major). The 2,3-diaryl-4-(phenylamino)quinolines were isolated as major products when 2 M K₂CO₃ was used as a base. A plausible mechanism, which implicates a six-membered palladacycle intermediate is proposed for the formation of the observed mixture of products. The prepared compounds were characterized using a combination of spectroscopic and X-ray crystallographic techniques.     

A highly enantioselective synthesis of 5-(l-menthyloxy )-4-substituted-3-chloro-2(5H )-furanones

In this paper, stereocontrolled tandem Michael addition-elimination reaction of the novel chiral source, 5-(l-menthyloxy)-3,4-dichloro-2(5H)-furanone, with various thiols and amines has been investigated. A series of new enantiomerically pure compounds, 5–(l-menthyloxy)-4-substituted-3-chloro-2(5H)-furanones, were obtained in good yields with d. e. ? 98% under mild conditions.     

Friedländer reaction/quinoxalinone–benzimidazole rearrangement sequence: expeditious entry to diverse quinoline derivatives with the benzimidazole moieties

A protocol has been developed for the efficient synthesis of structurally diverse 4-(benzimidazol-2-yl)quinolines via reactions of 3-(2-aminophenyl)quinoxalin-2(1H)-ones and ketones, including acetone, acetophenones, 1,3-pentanedione and ethyl acetoacetate. The selective formation of the very different quinoline derivatives depends on the structure of ketones. The key steps are proposed to involve the new acid-catalyzed rearrangement of the spiro-quinoxalinone derivatives formed in situ from the reaction of 3-(2-aminophenyl)quinoxalin-2(1H)-ones and ketones under the modified Friedländer reaction. This transformation would facilitate the synthesis by short reaction times, large-scale synthesis, simple and prompt isolation of the products, which are the main advantages of this procedure.     

Synthesis of Some New 2-(4-Methoxybenzothiazol-2′-yl amino)-4-(2-chloro-4-trifluoromethylanilino)-6-(substituted thioureido)-1,3,5-triazine as Antifungal Agents

2,4,6-Trichloro 1,3,5-triazine was selectively reacted with new nucleophilic reagents such as 4-methoxy-2-aminobenzothiazole, 2-chloro-4-trifluoromethyl-aniline, and phenylsubstituted thiourea in alkaline medium to give 2-(4-methoxybenzothiazol-2′-ylamino)-4-(phenylthioureido)-6-(substitutedthioureido)-1,3,5-triazines. The structures of these compounds were confirmed by IR, ¹H NMR, ¹⁹F NMR, mass spectral data, and elemental analysis. The compounds show fungicidal activity against Alternaria alternata, Aspergillus niger, and Macrofomina.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Synthesis of some novel pyrazolo[1,5-a]quinazolines and their fused derivatives

New pyrazolo[1,5-a]quinazoline-3-carbonitriles 4a,b were obtained via cyclocondensation of 5-amino-3-cyanomethyl-1H-pyrazole-4-carbonitrile (1) with enaminones of 1,3-cyclohexanedione derivatives 2a,b in refluxing glacial acetic acid. Condensation of compounds 4a,b with various aromatic aldehydes furnished the corresponding arylidene derivatives 6a–j. On the other hand, condensation of 4a,b with o-hydroxybenzaldehydes yielded the polyheterocyclic compounds 10a–h. Coupling of compounds 4a,b with aryldiazonium chlorides led to formation of 2-arylhydrazono derivatives 12a–h. Also, reaction of compounds 4a,b with phenyl isothiocyanate, followed by addition of ethyl chloroacetate and chloroacetonitrile, afforded the polyheterocyclic compounds based on pyrazolo[1,5-a]quinazoline core. The reaction of compounds 4a,b with phenyl isothiocyanate and elemental sulfur gave the thiazole-2-thione derivatives 25a,b. The reaction of enamines of compounds 4a,b with each of hydrazine hydrate and guanidine hydrochloride afforded pyrazolo[4″,3″:5′,6′]pyrido[4′,3′:3,4]pyrazolo[1,5-a]quinazolin-8-ones 30a,b and pyrimido[5″,4″:5′,6′]pyrido[4′,3′:3,4]pyrazolo[1,5-a]quinazolin-9(10H)-ones 33a,b, respectively. The structures of all the newly synthesized compounds were elucidated by elemental analyses and spectral data. The plausible mechanisms have been postulated to account for their formation.     

Syntheses of spiro[indazole-3,3′-indolin]-2′-ones and spiro[indazole-3,3′-indolin]-2′-imines via 1,3-dipolar cycloadditions of arynes and studies on their isomerization reactions

A 1,3-dipolar cycloaddition reaction of arynes with 3-diazoindolin-2-ones under mild conditions in excellent yields has been developed, which allows facile access to a library of labile spiro[indazole-3,3′-indolin]-2′-ones. Spiro[indazole-3,3′-indolin]-2′-imines could be obtained as well following the same protocol. The isomerization reaction of spiro[indazole-3,3′-indolin]-2′-ones under thermal or acidic conditions has been efficiently achieved to afford a wide range of indazolo-[2,3-c]quinazolin-6(5H)-ones and the one-pot synthesis of indazolo-[2,3-c]quinazolin-6(5H)-ones from arynes and 3-diazoindolin-2-ones is also described. Whereas, spiro[indazole-3,3′-indolin]-2′-imines could not undergo the same rearrangement.     

Aroyl[bis(4-hydroxycoumarin-3-yl)]methanes in reactions with 1,2-diaminobenzenes

The reaction of aroyl[bis(4-hydroxycoumarin-3-yl)]methanes with 1,2-phenylenediamines in PrⁱOH is accompanied by the recyclization to 8-R-or 7-R-4-(2-hydroxyphenyl)-1,5-benzodiazepin-2-ones, whereas the reaction with o-phenylenediamine and its 4-methyl-substituted derivatives in MeOH produces organic ionic salts of the bis-coumarin anion with monoprotonated o-phenylenediamine as the cation. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2200–2205, November, 2007.     

An improved process for the synthesis of nintedanib esylate

Nintedanib esylate is synthesized via novel intermediates of (Z)-methyl 3-(acetoxy-phenyl)methylene)-1-acetyl-2-oxoindoline-6-carboxylate and N-(4-aminophenyl)-2-chloro-N-methylacetamide in good yields.     

Synthesis of 1H-pyrrolo[3,2-c]quinoline derivatives via palladium-catalyzed heteroannulation of 2-aryl-3-iodo-4-(phenylamino)quinolines and 4-(N,N-allylphenylamino)-2-aryl-3-iodoquinolines

Palladium(0)/copper iodide catalyzed Sonogashira cross-coupling of 2-aryl-3-iodo-4-(phenylamino)quinolines with terminal alkynes afforded series of 1,2,4-trisubstituted 1H-pyrrolo[3,2-c]quinolines in a single-step operation. Conversely, the 4-(N,N-allylphenylamino)-2-aryl-3-iodoquinoline derivatives were found to undergo PdCl₂(PPh₃)₂/CuI catalyzed intramolecular Heck reaction to yield the corresponding 1,3,4-trisubstituted 1H-pyrrolo[3,2-c]quinolines.     

Nitrosation of methyl 2-cinnamoylamino-3-dimethylaminopropenoates. Alkyl N-cinnamoyloxalic acid hydroxyimidic amides,intermediates in the synthesis of alkyl 5-styryl-1,2,4-oxadiazole-3-carboxylates

Alkyl 2-(substituted cinnamoylamino)-3-dimethylaminopropenoates 5, prepared either from glycine ( 1 ) and substituted cinnamoyl chlorides 2 via oxazol-5(4H)-ones 4 , or from cinnamoylglycinate with t-butoxy-bisdimethylaminomethane, were transformed by nitrosation into 5-substituted-1,2,4-oxadiazole-3-carboxylates 8 . The formation of alkyl N-cinnamoyloxalic acid hydroxyimidic amides 7, which were isolated as intermediates, represent a novel synthesis of N-acyl substituted hydroxyimidic amides.     

Halogen effects in Robinson-Gabriel type reaction of cyclopropanecarboxylic acid N′-substituted-hydrazides with PPh3/CX4

We found that the reaction of cyclopropanecarboxylic acid N′-substituted-hydrazides with PPh₃/CCl₄ proceeded smoothly to give the corresponding normal Robinson-Gabriel type product 2-cyclopropyl-5-substituted-[1,3,4]-oxadiazoles in good yields. Using CBr₄ or CI₄ instead of CCl₄ in the above system, the ring opening of cyclopropane occurred after dehydration to give the corresponding 2-(3-halopropyl)-5-substituted-[1,3,4]-oxadiazoles (4 or 5) in good yields.     

The investigations in 2,3′-biquinoline series. 25*. Synthesis of 4-(2-quinolinyl)-pyrrolo[1,2-<Emphasis Type="Italic">a</Emphasis>]quinolines and 4-(2-quinolyl)-imidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]quinolines

A method has been developed for the synthesis of 4-(2-quinolinyl)-1,2,3,3a-tetrahydropyrrolo-[1,2-a]quinolines based on the 1,3-dipolar cycloaddition reaction of α,β-unsaturated carbonyl compounds to 2,3′-biquinolinium salts. Oxidation in benzene using MnO₂ gave 4-(2-quinolinyl)-pyrrolo[1,2-a]quinolines. It was found that a side product of the 1,3-dipolar cycloaddition is 7,14-di-benzoyl-6,13-di(2-quinolyl)-6a,7,13a,14-tetrahydro-7a,14a-diazadibenzo[a,h]anthracene. Reaction of 1′-phenacyl-2,3′-biquinolinium salts with hydroxylamine in acetic acid gave 4-(2-quinolyl)imidazo-[1,2-a]quinolines. *For Communication 24 see [1]. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 433–439, March, 2009.     

Synthesis of Alkyl and Aryl Substituted Benzo[h]Naphtho[1,2-b][1,6]naphthyridines

The reaction of 4-chloro-2-methylquinolines and 1-naphthylamine under neat conditions yielded 2-methyl-N-(1-naphthyl)quinolin-4-amines. These potential intermediates on reaction with aliphatic and aromatic carboxylic acids yielded the respective 7-alkyl and -aryl substituted benzo[h]naphtho[1,2-b][1,6]naphthyridines. The highly deshielded protons in the final compounds were assigned on the basis of 2D NMR studies.     

Thioureas from 3-aminoquinazolin-4(3H)-one. 2. Unusual alkaline recyclization of 3-(N",N",S-trialkylisothioureido)quinazolin-4(3H)-ones into new 1,3,4-oxadiazoles

3-(N",N",S-trialkylisothioureido)quinazolin-4(3H)-ones obtained by the reactions of 3-(N",N"-dialkylthioureido)quinazolin-4(3H)-ones with alkyl halides undergo unusual recyclization into 5-(2-aminophenyl)-2-dialkylamino-1,3,4-oxadiazoles under the action of aqueous solutions of alkali, hydrazine, and primary aliphatic amines. A plausible mechanism of the recyclization was proposed.     

Nitrosation of methyl 2-acylamino-3-dimethylaminopropenoates. A simple conversion of n-acylglycines into 5-substituted 1,2,4-Oxadiazole-3-carboxylates

A novel simple synthesis of 5-substituted-1,2,4-oxadiazole-3-carboxylates 5 from N-acylglycines 1 , which are transformed with DMF in the presence of phosphorus oxychloride into 2-substituted-4-dimethyl-aminomethyleneoxazol-5(4H)-ones 2 , followed by opening into 2-aroylamino-3-dimethylamino-propenoates 3 , and nitrosation to give the oximes 4 as intermediates, which cyclize spontaneously into 5-substituted-1,2,4-oxadiazole-3-carboxylates 5 . The compounds 2 can be transformed into 5 without isolation of 3 and 4 .     

Reaction of 3-trifluoroacetylchromones with diamines

Reaction of 3-(trifluoroacetyl)chromones with ethylenediamine and o-phenylenediamine depending on the nature of substituents and the reaction conditions afforded either mono-adducts, 3-[(2-aminoethyl)aminomethylidene]-and 3-[(2-aminophenyl)aminomethylidene]-2-hydroxy-2-(trifluoromethyl)chroman-4-ones, or bis-adducts, N,N′-ethylenebis-and N,N′-o-phenylenebis[3-aminomethylidene-2-hydroxy-2-(trifluoromethyl)chroman-4-ones]. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1548–1551, August, 2007.     

Synthesis of 2,3‐Disubstituted Quinolines via Ketenimine or Carbodiimide Intermediates

Cyclopenta[b]quinolines and cyclohexa[b]quinolines were prepared via the reactions of α‐diazo ketones with N‐(2‐cyclopropylidenemethylphenyl)phosphanimines and N‐(2‐cyclobutylidenemethylphenyl) phosphanimine, respectively. The reaction proceeds in a cascade involving ketenimine formation, 6 π‐electron ring closure, and 1,3‐alkyl shift. A similar approach was developed for the synthesis of dihydropyrrolo‐[2,3‐b]quinolines from N‐(2‐cyclopropylidenemethylphenyl)phosphanimines and isocyanates.     

Reactions of 4-Aryl-2-hydrazino-3-nitro-6-R-quinolines with HNO2

The reaction of 4-aryl-2-hydrazino-3-nitro-6-R-quinolines with NaNO₂ in AcOH gives the corresponding tetrazolo[1,5-a]quinolines. In contrast to tetrazolo[1,5-c]pyrimidines they cannot be converted to 6-R-4-phenyl[1,2,5]oxadiazolo[3,4-b]quinoline-3-oxides by heating in THF, toluene, or AcOH. Total energy quantum-chemical calculations using the MINDO/3 and MNDO methods show that [1,2,5]oxadiazolo[3,4-b]quinoline-3-oxides are significantly higher in energy (230-280 kcal/mol) than the mentioned tetrazolo[1,5-a]quinolines and hence their formation is unlikely.     

SYNTHESIS AND CHARACTERISATION OF TIN(IV) AND ORGANOTIN(IV) COMPLEXES OF [N′-2-HYDROXYPHENYL-6-METHYLPYRIDINE-2-CARBALDIMINE. X-RAY CRYSTAL STRUCTURES OF n-BUTYLDICHLORO[N′-2-HYDROXYPHENYL-6-METHYLPYRIDINE-2-CARBALDIMINATO(1-)N,N′,O]TIN(IV) AND DIPHENYLCHLORO [N′-2-HYDROXYPHENYL-6-METHYL-PYRIDINE-2-CARBALDIMINATO(1-) N,N′,O]TIN(IV)

Abstract

The reactions of N′-2-hydroxyphenyl-6-methylpyridine-2-carbaldimine (LH) with tin(IV) chloride and organotin(IV) chlorides result in the formation of the corresponding tin(IV) and organotin(IV) complexes in which LH behaves as a uninegative tridentate ligand coordinating to the central tin atom via an N,N,O donor set. Crystal structure determinations of two of the compounds, n-butyldichloro[N′-2-hydroxyphenyl-6-methylpyridine-2-carbaldiminato(l-)N,N′,O]-tin(IV) (BuSnCl₂.L) and diphenylchloro[N′-2-hydroxyphenyl-6-methylpyridine-2-carbaldiminato(l-)N,N′,O]tin(IV) (Ph₂SnCl.L), have been performed and both structures feature distorted octahedral geometries about the tin centres. Systematic differences in the Sn-ligand separations are rationalised in terms of the reduced Lewis acidity of tin in Ph₂SnCl.L.