A facile synthesis of 3,4-dialkyl-3,4-dihydro-2H-1,3-benzoxazin-2-ones and naphthoxazin-2-ones and their reactions with organolithium and Grignard reagents Preparation of N-[1-(2′-hydroxyphenyl)alkyl]amides

A facile and simple method for the preparation of 3,4-dialkyl-3,4-dihydro-2H-1,3-benzoxazin-2-ones or naphthoxazin-2-ones in high yields from aminoalkylphenols and aminoalkylnaphthols is described. The reactions of the products obtained with organolithium and Grignard reagents were studied, and a method for the preparation of N-[1-(2-hydroxyphenyl)alkyl]-N-alkylamides, which are of pharmaceutical interest, from benzoxazinones was developed. A possible reaction mechanism is also proposed. The relative configuration of chiral products was determined from conformational analysis of 1H NMR spectra.Key words: benzoxazinones, naphthoxazinones, organometallic reagents, amide preparation, aminoalkylphenols.

[1]  Xin Li,et al.  Synthesis of a new type of chiral amino phosphine ligands for asymmetric catalysis , 2002 .

[2]  C. Cimarelli,et al.  Reduction of 4H-chromen-4-ylidene amines: synthesis of 2-[(1-aminoalkyl)-3-aryl-2-propenyl] phenols , 2001 .

[3]  C. Cimarelli,et al.  Ready N-alkylation of enantiopure aminophenols: synthesis of tertiary aminophenols , 2001 .

[4]  G. Palmieri.  A practical o-hydroxybenzylamines promoted enantioselective addition of dialkylzincs to aldehydes with asymmetric amplification , 2000 .

[5]  J. Mindl,et al.  Cyclization of Substituted Phenyl N -(2-Hydroxybenzyl)carbamates in Aprotic Solvents. Synthesis of 4 H -1,3-Benzoxazin-2(3 H )-ones , 2000 .

[6]  Y. Imada,et al.  Highly Diastereoselective Addition of a Chiral Ketene Silyl Acetal to Nitrones: Asymmetric Synthesis of β-Amino Acids and Key Intermediates of β-Lactam Antibiotics , 1999 .

[7]  M. Pérez-Clavijo,et al.  Study of photodegradation of the pesticide ethiofencarb in aqueous and non-aqueous media, by gas chromatography–mass spectrometry , 1999 .

[8]  G. Palmieri.  Synthesis of Enantiopure o‐Hydroxybenzylamines by Stereoselective Reduction of 2‐Imidoylphenols: Application in the Catalytic Enantioselective Addition of Diethylzinc to Aldehydes , 1999 .

[9]  R. Consonni,et al.  Diels–Alder reactions of N-sulfonyl substituted aza-ortho-xylylenes generated from the corresponding 1,4-dihydro-2H-3,1-benzoxazin-2-one derivatives , 1996 .

[10]  D. J. Berrisford,et al.  Ligand‐Accelerated Catalysis , 1995 .

[11]  K. Rieckmann,et al.  Potential Antimalarials. XX. Mannich Base Derivatives of 2-[7-Chloroquinolin-4-ylamino and 7-Bromo(and 7-trifluoromethyl)-1,5-naphthyridin-4-ylamino]-4-chloro(or 4- or 6-t-Butyl or 4- or 5-fluoro)phenols and 4(or 6)-t-Butyl-2-(7-trifluoromethylquinolin-4-ylamino)phenol , 1994 .

[12]  K. Pihlaja,et al.  Studies on the benzoxazine series. Part 3 —Preparation and 13C NMR structural Study of γ Effects of Some N‐substituted 3,4‐dihydro‐2H‐1,3‐benzoxazines , 1990 .

[13]  K. Kubo,et al.  Synthesis and pharmacological evaluation of piperidine derivatives with various heterocyclic rings at the 4-position. , 1985, Chemical & pharmaceutical bulletin.

[14]  K. Hiroi,et al.  Studies on Chiral Organo-Sulfur Compounds. I. Asymmetric Synthesis of Sulfoxides with Optically Active o-Aminoalkylphenol Derivatives , 1983 .

[15]  N. Mishriky,et al.  Carbonyl and thiocarbonyl compounds. XIX. Intramolecular cyclization of (2-nitroetheny1)aryl N-arylcarbamates : synthesis of newer series of 3,4-dihydro-2H-1,3-oxazin-2-ones and their antimicrobial activities , 1982 .