Cu(I) mediated one-pot synthesis of azobenzenes from bis-Boc aryl hydrazines and aryl halides

N,N^′-bis-Boc aryl hydrazines underwent Cu(I) catalyzed couplings with aryl halides to provide N,N^′-bis-Boc diaryl hydrazines. The resulting N,N^′-bis-Boc diaryl hydrazines are readily oxidized to the azobenzenes in the presence of Cu(I) and a base. A prolonged heating of the initial coupling reactions directly provides the corresponding azobenzenes in one pot.     

A new method for the synthesis of N-substituted 1,3,5-dithiazinanes via the catalytic recyclization of 1,3,5-trithiane with aryl(benzyl) hydrazines and aryl amines

An efficient method for the synthesis of N-substituted 1,3,5-dithiazinanes based on the amination reaction of 1,3,5-trithiane with aryl(benzyl) hydrazines and N-aryl amines in the presence of Ti and Fe catalysts has been developed.     

Efficient synthesis of 3-aryl(hetaryl)-1,5,3-dioxazepanes involving catalysts containing Sm and Co

Efficient synthetic procedure was developed for 3-aryl(hetaryl)-1,5,3-dioxazepanes consisting in the transamination of 3-tert-butyl-1,5,3-dioxazepane with arylamines and also by the reaction of 1,2-ethanediol with N,N-bis(methoxymethyl)aryl(hetaryl)amines in the presence of catalytic amounts of Sm and Co compounds.     

Stereochimie de l'action des organomagnesiens et des organolithiens sur les dimethyl-1,2 alcoxy-1 silacyclobutanes

The reaction of organomagnesium organolithium compounds (alkyl, aryl, allyl and benzyl derivatives) with 1,2-dimethyl-1-alkoxy-l-silacyclobutanes proceeds with retention of configuration at the silicon atom. Stereochemical results are discussed in terms of the S_N2Si mechanism. The proposed configurations are supported by ¹H and ¹³C NMR data.     

Stereoisomerism in the series of isoindole-based quaternary salts

Steric structure of quaternary ammonium salts of the 3-[alkyl(aryl)amino]-1-[alkyl(aryl)iminio]-1H-isoindole series was studied by ¹H NMR spectroscopy and X-ray analysis. The examined salts are characterized by E,E configuration of substituents with respect to the exocyclic C-N bonds, and the presence of ortho- and meta-substituents in the benzene rings on the nitrogen atoms gives rise to atropisomers. Sterically hindered N-(2,4,6-trimethylphenyl) derivative was found to exist as Z,Z isomer which undergoes irreversible thermal isomerization into the more stable E,E isomer through intermediate Z,E structure. The reactions of 1,1,3-trichloro-1H-isoindole with secondary aromatic amines having an electron-withdrawing substituent in the ortho position in the presence of organic bases (triethylamine, N,N-dimethylbenzylamine) are accompanied by decomposition of the latter and formation of unsymmetrically substituted salts of the 3-[alkyl(aryl)amino]-1-(dialkyliminio)-1H-isoindole series, which contain both arylamine residue and dialkylamino group and are also characterized by atropisomerism.     

Synthesis of aryl benzyl NH-sulfoximines

Efficient synthesis and characterisation of a series of aryl benzyl NH-sulfoximines are described. While N-protected versions of aryl benzyl sulfoximines have been previously described, reports of their deprotection are very limited, presumably due to lability under the typically harsh deprotection conditions which can be employed with the less reactive aryl alkyl derivatives. Use of N-cyanosulfoximines as key intermediates overcomes these difficulties leading to an effective synthetic route to these compounds.     

Hydrazines in the synthesis of 1,5,3-dithiazepane and 1,5,3-dithiazocane derivatives in the presence of catalysts under the action of d- and f-elements

A method of synthesis was developed for 1,5,3-dithiazepan(dithiazocan)-3-ylamines and 3,3′-bi-1,5,3-dithiazepane(dithiazocane) by hydrazines cyclocondensation with formaldehyde and α,ω-alkanedithiols (1,2-ethanedithiol, 1,3-propanedithiol) involving catalysts based on d- and f-elements.     

The formation of 3‐ferrocenylpyrazole‐4‐carboxylates and alkylhydrazine insertion products from α‐ferrocenylmethylidene‐β‐oxocarboxylates

The reactions of α‐ferrocenylmethylidene‐β‐oxocarboxylates ( 1 , 2 , 3a , and 3b ) with N‐methyl‐ and N‐(2‐hydroxyethyl)hydrazines ( 5a , 5b ) afford ethyl 1‐alkyl‐5‐aryl(methyl)‐3‐ferrocenylpyrazole‐4‐carboxylates ( 6a , 6b , 6c , 6d , 6e ) (～50%) and N‐alkylhydrazine insertion products, viz., ethyl (N′‐acyl‐N′‐alkylhydrazino)‐3‐ferrocenylpropanoates ( 7a , 7b , 7c , 7d , 7e ) (～20%) and 1‐acyl‐2‐(N′‐alkyl‐N′‐ethoxycarbonylhydrazino)‐2‐ferrocenylethanes ( 8a , 8b , 8c , 8d , 8e ) (～10%). The structures of the compounds obtained were established based on the spectroscopic data and X‐ray diffraction analysis (for pyrazoles 6a and 6b ). J. Heterocyclic Chem., (2011).     

Synthesis and Characterization of Novel Methyl (3)5-(N-Boc-piperidinyl)-1H-pyrazole-4-carboxylates

Series of methyl 3- and 5-(N-Boc-piperidinyl)-1H-pyrazole-4-carboxylates were developed and regioselectively synthesized as novel heterocyclic amino acids in their N-Boc protected ester form for achiral and chiral building blocks. In the first stage of the synthesis, piperidine-4-carboxylic and (R)- and (S)-piperidine-3-carboxylic acids were converted to the corresponding β-keto esters, which were then treated with N,N-dimethylformamide dimethyl acetal. The subsequent reaction of β-enamine diketones with various N-mono-substituted hydrazines afforded the target 5-(N-Boc-piperidinyl)-1H-pyrazole-4-carboxylates as major products, and tautomeric NH-pyrazoles prepared from hydrazine hydrate were further N-alkylated with alkyl halides to give 3-(N-Boc-piperidinyl)-1H-pyrazole-4-carboxylates. The structures of the novel heterocyclic compounds were confirmed by ¹H-, ¹³C-, and ¹⁵N-NMR spectroscopy and HRMS investigation.     

A novel synthesis of 4,5-diaryl-6-arylamino-2,3-benzo-1,3a,6a-triazapentalenes

Treatment of N-alkyl- and N-aryl-imines of 2,3-diaryl- and 2-alkyl-3-aryl-3-(benzotriazol-1-yl)propenals with trifluoroacetic anhydride in THF at room temperature gave 5-alkyl-4-aryl-6-[N-alkyl (and aryl)-N-trifluoroacetyl]amino-2,3-benzo-1,3a,6a-triazapentalenes in moderate to good yields. On heating triazapentalenes having R²=aryl in MeOH at reflux, detrifluoroacetylation of triazapentalene occurred to give title compounds in good yields. However, the same treatment of triazapentalenes having R²=alkyl did not give the corresponding detrifluoroacetylation product. The title compounds and 5-alkyl-4-aryl-6-(N-alkyl-N-trifluoroacetyl)amino-2,3-benzo-1,3a,6a-triazapentalenes were found to be good precursors for the synthesis of 1-(o-aminophenyl)-3-arylamino-4-alkyl (and aryl)-5-arylpyrazoles and 1-(o-aminophenyl)-3-(N-alkyl-N-trifluoroacetyl)amino-4-alkyl (and aryl)-5-arylpyrazoles, respectively.     

Pinacol Rearrangement of 3,4‐Dihydro‐3,4‐dihydroxyquinolin‐2(1H)‐ones: An Alternative Pathway to Viridicatin Alkaloids and Their Analogs

3‐Alkyl/aryl‐3‐hydroxyquinoline‐2,4‐diones were reduced with NaBH₄ to give cis‐3‐alkyl/aryl‐3,4‐dihydro‐3,4‐dihydroxyquinolin‐2(1H)‐ones. These compounds were subjected to pinacol rearrangement by treatment with concentrated H₂SO₄, resulting in 4‐alkyl/aryl‐3‐hydroxyquinolin‐2(1H)‐ones. When a benzyl (Bn) group was present in position 3 of the starting compound, its elimination occurred during the rearrangement, and the corresponding 3‐hydroxyquinolin‐2(1H)‐one was formed. The reaction mechanisms are discussed for all transformations. All compounds were characterized by IR, ¹H‐ and ¹³C‐NMR spectroscopy, as well as mass spectrometry.     

Amidrazones. 6 . Synthesis of 1,2,4-thiadiazoles by thermolysis of N3-thiocarbamoylamidrazone ylides

Reaction of N³-unsubstituted amidrazone ylides ( 1a and 1b ) with alkyl or aryl isothiocyanates gives N³-thiocarbamoylamidrazone ylides ( 2 ). Thermolysis of 2 gives 3-alkyl(or aryl)-5-alkyl(or aryl)amino-1,2,4-thiadiazoles ( 3a-i ).     

Synthesis of N-(1,5,3-dithiazepan-3-yl)- and N-(1,5,3-dithiazocan-3-yl)amides in the presence of lanthanide catalysts

A new method was developed for preparation of N-(1,5,3-dithiazepan-5-yl)- and N-(1,5,3-dithiazocan-5-yl)amides by transamination of N-tert-butyl-1,5,3-dithiazepane and N-tert-butyl-1,5,3-dithiazocane, and also by recyclization of 1-oxa-3,6-dithiacycloheptane and 1-oxa-3,7-dithiacyclooctane with carboxylic acids hydrazides in the presence of catalysts based on rare earth elements.     

Diastereoselective LiAlH4 reduction of chiral ketone hydrazones derived from (R)-(–)-2-aminobutan-1-ol

Various chiral N,N-dialkylhydrazines were prepared in four to five steps from (R)-(–)-2-aminobutan-1-ol 6. They reacted with various prochiral ketones, thus giving the corresponding hydrazones. Reduction of the latter by means of LiAlH₄ afforded N,N,N′-trisubstituted hydrazines whose d.e.s were in the range 43–100%. Interestingly, LiAlH₄ reduction of the four N-trifluoroethylhydrazones 34 and 38–40 yielded the hydrazines 46 and 48–50, respectively, and with d.e.s=100% by ¹H and ¹³C NMR.     

Synthesis of azepino[3,4b]indoles via the Plancher rearrangement

The reaction of benzyl 3-formylpiperidine-1-carboxylate and aryl hydrazines under standard Fisher Indole conditions followed by reductive work-up affords azepino[3,4b]indoles in moderate to good yields. The products are proposed to be derived via a Plancher rearrangement [(a) Plancher, G. Gazz. Chim. Ital. 1898, 28, II, 374; (b) Plancher, G. Atti. Accad.Lincei1900, 9, 5, 115; (c) Boyd-Barrett, H. S. J. Chem. Soc.1932, 321].     

Synthesis and Antimicrobial Activity of Novel Iminophosphocin Derivatives

Iminophosphocins 8a – 8e and 9a – 9e were synthesized in four‐step reactions via Staudinger reaction. 3‐(Bromomethyl)‐1,2,3,4,5‐pentahydro‐3λ⁵‐naphtho[1,8‐f,g][1,5,3]diazaphosphocin‐3‐one ( 3 ) was prepared by reacting tris(bromomethyl)phosphineoxide ( 1 ) with 1,8‐diaminonaphthalene ( 2 ) in the presence of triethylamine (TEA) in dry tetrahydrofuran (THF), and treated with L‐valine methyl ester ( 4 ) and bis(2‐chloroethyl)amine ( 5 ) in the presence of TEA in dry THF to get 3‐methyl‐2‐[(3‐oxo‐1,2,3,4,5‐pentahydro‐3λ⁵‐naphtho[1,8‐f,g][1,5,3]diazaphosphocin‐3‐yl)methylamino]butanoate ( 6 ) and 3‐[di(2‐chloroethyl)aminomethyl]‐1,2,3,4,5‐pentahydro‐3λ⁵‐ naphtho[1,8‐f,g][1,5,3]diazaphosphocin‐3‐one ( 7 ). The compounds 6 and 7 were treated with trichlorosilane (SiCl₃H) in dry tetrahydrofuran (THF) to form the trivalent P(III) intermediates 8 and 9 , which were further treated with various alkyl azides in dry THF in 55–60°C to afford the title compounds 8a – 8e and 9a – 9e . Their structures were established by multi‐nuclear NMR and mass spectra. All the newly synthesized compounds were found to possess moderate anti‐microbial activity.     

Lithium and sodium N,N′-di(2,6-dialkylphenyl)formamidinate complexes

A study has been undertaken of the lithium and sodium metallation of N,N′-di(aryl)formamidines with alkyl groups at the 2- and 6-aryl position. ¹H NMR and X-ray diffraction data indicate an increase in steric bulk from 2,6-dimethylphenyl to 2,6-diethylphenyl to 2,6-diisopropylphenyl incites incremental changes in amidinate binding and nuclearity. In selected instances, this invokes the first lithium and sodium amidinate/guanidinate complexes to exhibit metal-arene contacts.     

Distinguishing Features of reactions of 2-chloro-and 2,2-dichloro(bromo)vinyl ketones with alkyl-and arylhydrazines

2-Chlorovinyl alkyl ketones react with alkylhydrazines to give mixtures of 1-R-3-R′- and 1-R-5-R′-pyrazoles: The 1-R-3-R′-pyrazoles form through the heterocyclization of 2-chlorovinyl ketone alkylhydrazones whereas in the heterocyclization into 1-R-5-R′-pyrazoles N ¹-alkyl-N ²-(2-acylvinyl)hydrazines are involved. The regiospecific heterocyclization of 2-chloro-and 2,2-dichlorovinyl ketones with arylhydrazines and also of 2,2-dichloro(bromo)vinyl trifluoromethyl ketones with C alkylhydrazines into pyrazoles and 5-chloro(bromo)-pyrazoles proceeds through a stage of haloenones hydrazones formation. The study of the structure of the obtained 1-alkyl-3(5)-alkylpyrazoles by means of two-dimenaional ¹H and ¹³C NMR spectroscopy and GC-MS method made it possible to assign the proton and carbon signals of isomeric pyrazoles and to establish the diagnostic ions for the pair of 1,3-and 1,5-isomers.     

Sequential azomethine imine cycloaddition-palladium catalysed cyclisation processes

In situ generation of azomethine imines from aryl/heteroaryl aldehydes and N,N′-disubstituted hydrazines followed by cycloaddition to N-methylmaleimide generates pyrazolidines, which undergo Pd(0) catalysed cyclisation involving the aldehyde and hydrazine substituents, with formation of 6-8 membered rings in good yield. AMI calculations indicate the preferred configuration of the azomethine imines involved and identify the most likely cycloaddition transition states.     

Synthesis of 1,6-dihydro-5-hydroxy-6-oxo-3-(trifluoromethyl)-4-pyridazinecarboxylates

The reaction of 2-(alkylamino)-3-(trifluoroacetyl)butenedioates 2a-b with alkyl and aryl hydrazines in ether provides 1,6-dihydro-6-oxo-3-(trifluoromethyl)-4-pyridazinecarboxylates as their alkylamine salts 3a-g . The structures of these products are substantiated using 2D nmr and ¹⁵N nmr techniques.