Oxazine Derivatives

Synthetically, 2,3-dihydro-l,4-benzoxazine-6,7-diones (391) can be prepared from 2,5-bisanilino-3-acetyl- (or methoxycarbonyl)-l,4-benzoquinones and substituted 2-hydroxyethylamines (73T2881). 2-Amino-3-aziridino-1,4-naphthoquinone, when heated in aqueous sodium hydroxide, is claimed to give 392 (69FES732), and the benzo analog was prepared from 2,3-dichloro- 

4- naphthoquinone and tosylated o-aminophenol (21CB259). Compound 392 was prepared from 1,4-naphthoquinone and / -alanine (66MI2). When 

5- dihydroxy-1,4-benzoquinone was condensed with various nitroso compounds, derivatives of 393 were obtained (65T389). 

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The last decade has brought a considerable increase of the number of papers concerned with 1,3-oxazine derivatives. This is due partly to the fact that these compounds show interesting reactivity. Hence, it was suggested recently that 1,3-oxazine derivatives (including benz-l,3-oxazine derivatives) should be used as chemotherapeutic agents. ... 

The compounds with one double bond are dihydro-1,3-oxazines, and the structures shown in Fig. 1 are possible. The conformations of dihydro-1,3-oxazine rings arc based on analogy with cyclohexcne and also on the conformational analysis of several benzo-1,3-oxazine derivatives. 

Oxazine derivatives with two double bonds can exist in three isomeric forms ... 

A general rule can be suggested for one of the principal ways of forming 1,3-oxazine derivatives. They can be formed from 1,3-sub-stituted propane derivatives of general formula ... 

The formation of 1,3-oxazine derivatives was reported for the first time by Kohn. It consisted in cyclizing 3-aminopropan-l-ol derivatives with aldehydes to yield tetrahydro-1,3-oxazine derivatives (1). 

Among various other ways of cyclizing 3-aminopropan-l-ol to a tetrahydro-1,3-oxazine derivative, an interesting reagent is acetylene under pressure ... 

One of the most extensively investigated groups of 1,3-oxazine derivatives is the 5-nitro derivatives of tetrahydro-l,3-oxazine. They were first prepared from 1-nitropropane, aqueous formaldehyde, and ammonia by Hirst et and independently by Senkus from other primary nitroparaffins, formaldehyde, and primary amines. Numerous compounds of the general formula (6) were later prepared from primary nitroparaffins. " ... 

The great tendency of 2-nitro-3-aminopropan-l-ol derivatives to form 1,3-oxazine derivatives (e.g., 12) was demonstrated when it was attempted to acetylate a derivative of 2-nitro-3-aminopropan-l-ol (11). 

A new method of preparing tetrahydro-1,3-oxazine derivatives (13 and 14) consists in reacting olefins with formaldehyde and ammonium chloride or hydrochlorides of primary amines. ... 

Thionotetrahydro-1,3-oxazine derivatives (25) can be formed from dithiocarbamates by the action of carbon disulfide on 3-amino-propanol ... 

Oxazines can form salts with strong acids. The salts vary with regard to their solubility and stability. Some of the hydrochlorides are hydrolyzed by water. Some less common salts are known e.g., dichromates and ferrocyanates, " chloroplatinates and chloroaurates. Sometimes the picrates can also be used to identify the 1,3-oxazine derivatives. " In some instances a special procedure is required to form the picrates, as the heterocyclic ring can open under the action of picric acid. " ... 

If the acid hydrolysis of 1,3-oxazine derivatives is followed by acting with phenyl-isothiocyanate, thiourea derivatives can be formed. ... 

The simple ring opening of tetrahydro-1,3-oxazine derivatives is not the only possible reaction of these heterocyclic compounds catalyzed by mineral acids. An interesting rearrangement of 6-aryl-6-alkyltetrahydro-l,3-oxazines when warmed with concentrated hydrochloric acid was found by Schmiedle and Mansfield ... 

Although all the syntheses of 1,3-oxazine derivatives and their chemical properties left little doubt as to their chemical constitution,... 

Infrared absorption spectra gave more information regarding the structure of 1,3-oxazine derivatives. These studies were mainly concerned with tetrahydro-ljS-oxazine " and dihydro-1,3-oxazine derivatives. - " According to Eckstein et al. a number of bands of frequencies 1150-1050, 955-925, and 855-800 cm characterize the hemiacetal bond C—0—C. Lukes et expressed the view that a triplet of bands at 1143, 1129, and 1083 cm characterized the tetrahydro-1,3-oxazine ring. However, Bergmann and Kaluszyner assigned these bands to the N—C—O system in the tetrahy dro-1,3-oxazines. 

Other functional groups in tetrahydro-1,3-oxazine derivatives, such as N02, qq so,s7,io5 ]s jj (amincs)and NH (amides) give... 

According to Urbanski et al. biological activity of 1,3-oxazine derivatives is due to the active CH2 group in the 2-position. Tne use of tetrahydro-l,3-oxazines was also suggested against some infections in veterinary service. The suggested use of tetrahydro-l,3-oxa-zines as herbicides did not seem to be a success. 

Another line of approach to the practical application of 1,3-oxazine derivatives was the suggested use of tetrahydro-1,3-oxazine derivatives as detergents for textile industry, as anticorrosion chemicals, and polymers from 2-oxo derivatives as additives to improve the properties of paper and textiles. ... 

Both tetrahydro- and dihydro-1,3-oxazine derivatives have been suggested as passive components of azo dyes. ... 

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