Cyclization of Substituted Phenyl N-(2-Hydroxybenzyl)carbamates in Aprotic Solvents. Synthesis of 4H-1,3-Benzoxazin-2(3H)-ones

Abstract

The kinetics of cyclization of substituted phenyl N-(2-hydroxybenzyl)carbamates and their N-methyl analogs, prepared by the reaction of 2-(aminomethyl)phenols with substituted phenyl chloroformates, was studied in dioxane or toluene at the temperatures 110-180 °C. Electron-withdrawing substituents in the leaving phenoxy group strongly accelerate the rate of cyclization (ρ = 2.45 ± 0.15) while the substituents in the other ring have virtually no effect. The cyclization was catalyzed with triethylamine in toluene but not in dioxane. On the basis of these results, the most convenient method for preparation of substituted 4H-1,3-benzoxazin-2(3H)-ones was a one-hour reflux of substituted 4-nitrophenyl N-(2-hydroxybenzyl)carbamates in dioxane. Based on the influence of substituents, solvents (dioxane and toluene) and triethylamine, the reaction mechanism and structure of the transition state were proposed.

An Efficient Synthesis of 3,3′,4,4′‐Tetrahydro‐4,4′‐bibenzo[e][1,3]oxazine‐2,2′‐dione Derivatives with the Aid of Low‐valent Titanium

“…Melting points are uncorrected. IR spectra were recorded on a Tensor 27 spectrometer in KBr with absorptions in cm H NMR (400 MHz) and 13 C NMR (100 MHz) spectra were recorded on a Bruker DPX 400 MHz spectrometer in DMSO-d 6 solution with TMS as internal standard. HRMS were obtained on a microma GCT-TOF instrument.…”

“…The fight against HIV, by developing more efficacious drugs than Efavirenz, has been the prime driving force for benzoxazinone derivatisation which has received considerable attention. [1][2][3][4][5][6] Figure 1 Structure of Sustiva.…”

Transformation reactions of the betti base analog aminonaphthols

“…Similar ring closures of the analogous 2-aminomethylphenol were recently investigated [14]. The reactions of 1-3 with ethyl benzimidate in boiling EtOH gave the desired 1,3-oxazine derivative 6 only in the case of the unsubstituted aminophenol 2; with the phenyl-substituted regioisomers 1 and 3, only decomposition of the starting aminonaphthols was observed (Scheme 1).…”

Solvent-free preparation of primary carbamates using silica sulfuric acid as an efficient reagent

“…8 These materials are most commonly prepared from amines and alcohols by carbonylation using phosgene in organic solvents which are also toxic and flammable. [1][2][3] These procedures seem to be efficient, pose environmental and operational concerns since highly harmful and corrosive reagents are used. Efforts have been continuously made for the replacement of the phosgene with carbon dioxide and organic carbonates.…”

“…Carbamates (urethanes) are compounds of growing interest because of their applications in the agrochemicals industry [1][2][3][4][5] as herbicides, fungicides and pesticides, in the pharmaceuticals industry 1,2,6 as drug intermediates and in the polymer industry, 1,2,7 in the synthesis of polyurethane and peptides. In addition, among the various amine-protecting groups, carbamates are commonly used due to their chemical stability towards acids, bases and hydrogenation.…”