An efficient method for the conversion of aromatic and aliphatic nitriles to the corresponding N-tert-butyl amides: a modified Ritter reaction

Aromatic and aliphatic nitriles react with tert-butyl acetate in the presence of a catalytic amount of sulfuric acid to give the corresponding N-tert-butyl amides in excellent yields.     

Efficient synthesis of 2-alkylidene-3-iminoindoles,indolo[1,2-b]isoquinolin-5-ones,delta-carbolines,and indirubines by domino and sequential reactions of functionalized nitriles

The sodium hydride mediated cyclization of arylacetonitriles with oxalic acid bis(imidoyl) dichlorides, aza-analogues of oxalyl chloride, afforded functionalized 2-alkylidene-3-iminoindoles with very good regio- and E/Z selectivity. Excellent chemoselectivities were observed for functionalized substrates. Based on these results a domino "cyclization-lactamization" reaction of bis(imidoyl) chlorides with methyl 2-(cyanomethyl)benzoate was developed. This process allowed a convenient one-pot synthesis of indolo[1,2-b]isoquinolin-5-ones related to tryptanthrin. A new and convenient synthesis of delta-carbolines by intramolecular electrocyclization-elimination reactions of 2-alkylidene-3-iminoindoles was developed. It was shown that delta-carbolines selectively bind to triplex or duplex DNA (intercalation). Indirubine analogues were prepared by deprotection and lactonization of functionalized 2-alkylidene-3-iminoindoles.     

Co(II)-Mediated and microwave assisted coupling between 2,6-diaminopyridine and nitriles. A new synthetic route to N-(6-aminopyridin-2-yl)carboximidamides

The Chinese-lantern-type Co₂(O₂CBu^t)₄{2,6-(NH₂)₂C₅H₃ N}₂ complex reacts with RCN (R = Me or Prⁿ) under microwave irradiation (MWI) to give the mononuclear amidine complexes Co(O₂CBu^t)₂{H₂N(C₅H₃ N)NHC(R)=NH} (R = Me (4a) or Prⁿ (4c)). Under microwave irradiation, the addition of 2,6-diaminopyridine to acetonitrile in the presence of the pivalate complexes Co₂(μ₂-OH₂)(O₂CBu^t)₄(HO₂CBu^t)₄ (1) or [Co(OH)_n(O₂CBu^t)_2−n ]_x (2) afforded complex 4a in higher yield compared to the corresponding reaction performed earlier without MWI. The use of MWI makes it possible to perform analogous reactions with nitriles RCN (R = Et, Prⁿ, or Ph) giving rise to complexes 4b—d, respectively. Compounds 4a—d were characterized by elemental analysis and IR spectroscopy. The structure of complex 4c was established by X-ray diffraction. Amidines H₂N(C₅H₃N)NHC(R)=NH, which formed in the coordination sphere of cobalt(II), were isolated in the free state from methanolic solutions of complexes 4a—d under the action of Na₂S and were characterized by electrospray mass spectrometry and ¹H and ¹³C{¹H} NMR spectroscopy. The reactions of 2-aminopyridine with both complexes 1 and 2 in acetonitrile under microwave irradiation produced the Co(O₂CBu^t)₂(H₂NC₅H₄N)₂ complex. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 35–42, January, 2006.     

CeCl3/Sm System Induced Reductive Cleavage of the Se‐Se Bond in Diaryl Diselenides: A Novel Method for the Synthesis of β‐Selenoesters and β‐Selenonitriles

The Se‐Se bond in diselenides was reduced by CeCl₃/Sm system to produce selenolate anions, which react with α,β‐unsaturated esters or α,β‐unsaturated nitriles to afford β‐selenoesters and β‐selenonitriles, respectively.     

Hetarylamidines derived from PtIV-mediated coupling of nitriles with aminoheterocycles

The trans-[PtCl₄(EtCN)₂] complex is involved in coupling reactions (CH₂Cl₂, 30–35 °C, 10–15 min) with 2-amino derivatives of heterocyclic compounds (2-NH₂Het, where Het is pyridyl, 4-methylpyridyl, 5-methylpyridyl, 6-methylpyridyl, or thiazolyl) to form the trans-[PtCl₄{ N(H)=C(Et)NHHet}₂] complexes (1–5) with κ¹(N)-coordinated hetarylamidine ligands. The reaction with the use of 2-aminopyrimidine (2-NH₂Pym) produces the [PtCl₄(₂-NH₂Pym)₂] complex (6) as a result of complete replacement of the nitrile ligands in the [PtCl₄(EtCN)₂] complex. The compositions and structures of compounds 1–6 were confirmed by elemental analysis (C, H, N), IR spectroscopy, ¹H, ¹³C{1H}, and ¹⁹⁵Pt{¹H} NMR spectroscopy, and FAB mass spectrometry. Complex 1 was additionally characterized by X-ray diffraction. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1572–1576, September, 2006.     

Silylation as a new strategy of the use of aliphatic nitro compounds in organic synthesis

Silylation of aliphatic nitro compounds is considered as a versatile multistage process. Due to activation of the - and -carbon atoms of the initial nitro substrates, these reactions give rise to a series of products untypical of the traditional chemistry of nitro compounds. A new redox process proposed in the present study involves controlled incomplete reduction of the nitro group with simultaneous oxidation of the carbon skeleton of the initial aliphatic nitro compound.     

A practical synthesis of highly functionalized aryl nitriles through cyanation of aryl bromides employing heterogeneous Pd/C: in quest of an industrially viable process

Preparation of aryl nitrile 2a through classical Rosenmund-von Braun reaction of aryl bromide 1a resulted in a poor yield (61%) due to a high reaction temperature (165 °C) and a lack of efficient procedure for separating 2a from a large quantity of heavy metal waste (Cu salts). To address these issues, a practical synthesis of multifunctional aryl nitriles through cyanation of aryl bromides has been developed with heterogeneous Pd/C used as the catalyst. Treatment of aryl bromides 1 with Zn(CN)₂ in the presence of Pd/C, Zn, ZnBr₂ and PPh₃ in DMA provided aryl nitriles 2 involving those carrying sterically demanding electron-rich substituent in good yields and in highly reproducible manner. The activity of Pd/C is highly dependent on the properties of the Pd/C. Oxidic thickshell type catalyst Pd/C D5 was found to furnish the highest rate acceleration and yield. The use of heterogeneous Pd/C might anchor and disperse Pd over the solid support of the catalyst, at least in the initial stage of the reaction, to assure the formation of monomeric Pd complex without precipitating to inactive Pd black. The use of a slightly excess of Zn(CN)₂ (0.6 equiv) and air oxidation of phosphine ligand, after end of the reaction, converted Pd species to insoluble phosphine-free Pd cyanides, from which Pd was recovered in high yield through simple filtration followed by usual recovery process involving combustion.     

Symmetrical and Unsymmetrical Bis-1,1′-(3,4-dihydroisoquinolines)

3,3,-Dialkyl-1-cyano-3,4-dihydroisoquinolines were prepared by Beckmann defragmentation of ethyl α-(3,3-dialkyl-3,4-dihydroisoquinol-1-yl)-α-hydroximinoacetates and they take part in a Ritter reaction to form substituted bis-1,1′-(3,4-dihydroisoquinolines).__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 558–563, April, 2005.     

Spirocyclohexadienones. 7. Three-component condensation of 1- or 2-methoxynaphthalene with isobutyraldehyde and nitriles

1-R-3,3-Dimethylbenzo[i]-2-azaspiro[4.5]deca-1,6-dien-8-ones or 1-R-3,3-dimethylbenzo[i]-2-azaspiro[4.5]deca-1,7-dien-6-ones were synthesized by three-component condensation of 1- or 2-methoxynaphthalene, isobutyraldehyde (or isobutylene oxide), and nitrile RCN in concentrated sulfuric acid.     

Synthesis of substituted bis(3,3-dialkyl-3,4-dihydro-1-isoquinolyl)methanes

Symmetrical and non-symmetrical substituted bis(3,4-dihydro-1-isoquinolyl)methanes were synthesized by fusion of substituted 1-methylthio-3,4-dihydroisoquinolines with 1-methyl-3,4-dihydroisoquinolines and by the Ritter reaction of 1,1-dialkyl-2-arylethanols with 1-cyanomethylidene-1,2,3,4-tetrahydroisoquinoline or malononitrile.