A simple and an efficient approach to the synthesis of a specific tautomer of 1,3-thiazinones and 1,3-oxazinones

A specific tautomer of 1,3-thiazinone and 1,3-oxazinone derivatives were prepared in a one step procedure from condensation of chlorocarbonyl ketenes (CCKs) such as (chlorocarbonyl)phenyl ketene and (chlorocarbonyl)benzyl ketene with thiobenzamide, thioacetamide , cinnamide , benzamide, 2-phenylacetamide and acetamide . This method provides an easy route to prepare 2,5-disubstituted 4-hydroxy-1,3-thiaizin-6-ones and 2, 5-disubstituted 4-hydroxy 1, 3-oxazin-6-ones in good to excellent yields in a short experimental time.


Introduction
The study of α-oxoketenes (acyl ketenes) and their reactions, were investigated because these compounds contain two active functional groups.][3][4] However, some of these ketenes can be stabilized both sterically and electronically.For example ketenes containing carboxylic acid derivatives such as chlorocarbonyl ketenes (CCKs) are extraordinarily stable.These ketenes are currently of considerable interest, not only because of mechanistic and theoretical considerations, 5 but also due to their use as synthetic building blocks in the preparation of organic compounds. 6,7 hlorocarbonyl ketenes have been found to be a very effective 1,3-bielectrophile reagents and react with a wide variety of nucleophiles under a mild experimental conditions, and have been used mainly for the synthesis of five-and six-membered heterocycles functionalized with oxo and hydroxyl groups in 1,3-positions. 8,9  have recently reported the reaction of (chlorocarbonyl)phenyl ketene with 1,3-diketones as 1,3-dinucleophiles to produce 2-pyrone derivatives. 104][15] In continuing our interest in the synthesis of heterocyclic compounds, now we wish to report a one-pot synthesis of a specific tautomer of 1,3-thiazinone and 1,3-oxazinone derivatives.However, the attempted reaction of (chlorocarbonyl)phenyl ketene and (chlorocarbonyl)benzyl ketene with several N-unsubstituted amides and thioamides at ambient temperature or even in boiling solvent such as dry THF have been mostly unsuccessful.Therefore the reactions were performed in a boiling solvent such as toluene or xylene.The simplicity and efficient one-pot procedure is one aspect of particular interest, in comparison to the other multi-step methods.On the other hand, readily available starting materials such as (chlorocarbonyl)phenyl ketene and (chlorocarbonyl)benzyl ketene, 16 shorten experimental time, and high yield of the final products are the other advantages of this method.
The same reaction with N-unsubstituted aliphatic amides such as 6a and 6b afforded a mixture of two tautomers of corresponding 1,3-oxazinones (Scheme 4).

Scheme 4
It is not clear to us why the products of the cycloaddition reaction of chlorocarbonyl ketenes with N-unsubstituted α , β-unsaturated amides or aromatic amides are different from the products of the cycloaddition reaction of chlorocarbonyl ketenes with N-unsubstituted aliphatic amides.As it is shown (Scheme 2 , 3 and 4) N-unsubstituted aliphatic amides produce mixture of two tautomers, while α, β-unsaturated amides or aromatic amides give different tautomers.Apparently the conjugation of the 1,3-oxazinone ring with α, β-unsaturated parts of the amides or aromatic rings of the amides might play an important role in these reactions.
Thus the cycloaddition reactions presented in schemes 2 and 3 accomplished by mixing the equimolar quantities of (chlorocarbonyl) ketenes and thioamides or amides in a dry boiling solvent.On the basis of our results, a plausible mechanism has been proposed for the reactions of chlorocarbonyl ketenes 19 to yield 1,3-thiazinone and 1,3-oxazinone derivatives, as shown in scheme 5.However, the formation of compounds 3a-d, 5a-b and 7a-b can be explained by tautomerization of A to give small amount of intermediate B at high temperature.Attack of the SH as a good nucleophile 20 or OH groups of the latter onto the acyl chloride of ketene, followed by cyclization of intermediate C and finally by proton shift from nitrogen to the oxygen atom.The final product was produced and was further characterized.
The structures of compounds 3a-d, 5a-b and 7a-b were deduced from their elemental analyses and their IR, high-field 1 H and 13 C NMR spectra.The 1 H NMR and 13 C NMR spectra of 1, 3-thioxazinones 3a-d and 1,3-oxazinones 5a-d exhibited only one tautomer.Based on the 1 H NMR and 13 C NMR a mixture of two tautomers obtained from the reaction of aliphatic Nunsubstituted amides such as acetamide and phenyl acetamide with (chlorocarbonyl)phenyl ketene.Quantitative analysis of mixtures is achieved by evaluating the integration peaks of 1 H NMR spectra.
The the enol form.The 13 C NMR and mass spectra of compound 3a are also in accordance with the proposed structure.The tautomer I is ruled out because in the high field 1 H NMR spectra of compounds 3a-d, the chemical shifts due to the methine proton were not detected.The 13 C NMR spectrum of C=O attached to the sulfur atom revealed at about δ 180 ppm, whereas the carbon number 6 attached to sulfur (tautomer No. III) should revealed at approximately δ 160-170 ppm.
Ziegler and coworkers, have reported 36% yield of 4-hydroxy-2,5-diphenyl-6H-1,3-thiazin-6one 3a by treating phenyl malonic acid and PCl 3 with thiobenzamide at 80 ˚C. 21On the bases of these information the tautomer No II was formed as the only product.In general all of the spectral data support the structures of compounds 3a-d.The 1 H NMR spectrum of 5a showed four different kinds of proton signals.One signal at (δ 7.85 ppm) which was identified as βolefinic proton of styryl group appear as a doublet ( 3 J HH =15 Hz), the other doublet signal appears at δ = 6.85 ppm due to α-olefinic proton of styryl group ( 3 J HH =15 Hz) and a multiplet (δ = 7.79-7.23)for the aromatic protons (10 H) along with one signal quite downfield (δ 12.62 ppm) which is the proton of enol OH.The 13 C NMR spectrum of 5a displayed 14 distinct resonances in agreement with the proposed structure.The 1 H NMR and 13 C NMR spectra of 5b are similar to those of 5a, except for the presence of a peak due to CH 2 group, and the absence of signals due to olfenic region.The 1 H and 13 C NMR spectroscopic data for compounds 7a-b are also consistent with the presence of two tautomers.

Experimental Section
General Procedures.Thioacetamide, thiobenzamide, benzamide, cinnamide, 2-phenylacetamide, acetamide, phenyl malonic acid and benzylmalonic acid were obtained from Merck Chemical Co. and were used without further purification.Melting points were measured on a Gallenkamp melting point apparatus and are uncorrected.IR spectra were measured on a Mattson 1000 FT-IR spectrometer.The proton and carbon NMR spectra were recorded 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.Elemental analyses were performed by National Iranian Oil Company lab (Tehran) using a Heracus CHN-O-Rapid analyzer.

18
Scheme 1 1  H NMR spectrum of 3a indicated two kinds of proton signals related to two different aromatic rings along with one signal quite downfield (δ 12.51 ppm) which is the OH proton of

The 1 H
NMR spectrum of compound 7 indicated five kinds of proton signals in agreement with the mixture of 7(I)a and 7(II)b.