Nucleophilic addition of enaminones to the S-S dimer of 2-aminobenzenethiol

Nucleophilic addition of β -amino α , β -unsaturated ketones and esters to the S-S dimer of 2-aminobenzenethiol which acts as an electrophile, followed by cyclization, lead to 4H-1


Introduction
At present the chemistry of enaminones is a developing field of organic synthesis. 1,2 hese compounds are versatile synthetic intermediates that combine the ambident nucleophilicity of enamines with the ambident electrophilicity of enones. 3There are many reports on functionalization of enaminone in the literature by the introduction of different substituents on the nitrogen, the α-carbon and the β-carbonylic carbon atoms.These derivatives have been extensively used for the preparation of a variety of heterocyclic systems including some natural products and analogues. 4,5 ecently, β-dimethyl amino-α,β-unsaturated ketones and nitriles have been transformed into pyridine, isoquinoline, 6 pyrazole, isoxazole, pyrimidine 7 and pyranone derivatives. 8As part of our current studies on the development of new routes to the synthesis of heterocyclic compounds, by using 1,3-bielectrophiles and binucleoplies such as 1,3-dicarbonyl compounds and enaminones, [9][10][11] we now turn our attention to the reactivity of enaminones by nucleophilic addition of β-amino α,β-unsaturated ketones and esters on the S-S dimer of 2aminobenzenethiol.

Results and Discussion
Many useful and interesting reactions of disulfides are known. 12,13Disulfides, especially diaryl disulfides, are very commonly used as electrophiles in the sulfenylation of enolates anions. 14,15 lfenamides and sulfenylimines have been prepared from nucleophilic addition of amines 16 and ketimines 17 to the S-S of disulfide compounds respectively.Enaminones have two electrondeficient centers at C-1 and C-3, while the C-2 and amino functions are electron rich.Thus they can react with both electrophils and nucleophiles.In order to study the reactivity of the enaminones with electrophiles, we have chosen dimer of 2-aminobenzenethiol, which acts as electrophile (sulfur atoms) and nucleophile (amino group) (Scheme 1).
The formation of these compounds was unexpected and it can be considered to proceed by a nucleophilic attack of the C α of the β-amino α,β-unsaturated esters on the sulfur of dimer of 2aminobenzenethiol, followed by Michael addition of the 2-amino nitrogen (NH 2 ) on the C=C double bond.
A possible pathway accounting for the formation of the compounds 3a-c is depicted in Scheme 2. On the basis of the well established chemistry of enaminones and diaryl disulfides 1,19,20 it is reasonable to assume that compounds 3a-c result from nucleophilic addition of enaminones on the S-S dimer of 2-aminobenzenethiol which acts as an electrophile, followed by cleavage of disulfide bond to form of an α-(2-amino phenyl sulfonyl)enaminone intermediate and 2-amino-benzenethionl anion which the thiolate anion is easily oxidized by oxygen (air) to yield the dimer of 2-aminobenzenethionl. Thus only 0.5 equivalents of dimer 2 is needed.Successively, formation of the 2-acyl-3-methyl-4H-1,4-benzothiazines could occur by intermolecular Michael addition of α-(2-amino phenyl sulfonyl)enaminone intermediate, followed by the loss of the aryl or alkyl amino group (Scheme 2).
1,4-Benzothiazines are usually prepared by the reaction of 2-aminobenzenethiol with αhaloketones or α-haloesters and oxidative cyclocondensation of 2-aminobenzenethiol with 1,3dicarbonyl compounds 20,21 4H-1,4-benzothiazines 3a-c are known and their melting points and spectral data are in good agreement with those reported in the literature. 22,23  should be stressed that all starting enaminones are readily available. 24,25 he dimer of 2aminobenzenethiol is easily obtained in a one pot reaction by oxidizing the alkaline solution of the 2-aminobenzenethionl with hydrogen peroxide. 26lthough enaminones have three nucleophilic sites of the reaction (nitrogen, C α and oxygen) and two electrophilic sites (C β and carbon of carbonyl), the reaction of β-amino α,β-unsaturated ketones and esters on the S-S dimer of 2-aminobenzenethiolo have been produced only one product.These processes are highly regioselective, and the yields of formation of compounds 3a-c depend on the size of the R 1 , R 2 and R 3 (Table 1).

Experimental Section
General Procedures.Melting points were measured on a calibrated Gallenkamp melting point apparatus.IR spectra were measured on a Mattson 1000 FT-IR spectrometer. 1 H and 13 C NMR spectra were measured with a BRUKER DRX-500 AVANCE spectrometer at 500 and 125.77MHz, respectively.Mass spectra were recorded on a MS-QP2000A Shimadzu mass spectrometer operating at an ionization potential of 70 eV.