4//-l,3-Oxazinium salts

The situation was changed by the discovery of a novel approach to the synthesis of 5,6-dihydro-4//-l,3-oxazinium salts consisting in a polar 1,4-... 

A moderately intense band at 1665-1700 cm appears in the IR spectra of 4//-l,3-oxazinium salts 2a which can be ascribed to C=C double bond of the ring (90S763 91KGS568). 

Simultaneously and independently, similar results were obtained by the author s group47,49. It was observed that a short reflux (1-2 min) of an equimolecular mixture of chalcone 291 and A -ethylbenzonitrilium salt 35 in 1,2-dichloroethane furnishes the 2,4,6-triphenyl-3-ethyl-4//-l,3-oxazinium salt 38 (equation 81) obtained also by reaction of benzaldehyde with 35 and phenylacetylene (equation 15). If the salt 35 reacts with benzoylacetone 137 under the same conditions, 4-methylene-4//-l,3-oxazinium hexa-chloroantimonate 301 is formed47 (equation 82). 

This assumption was confirmed by the reactions of nitrilium salts prepared before-hand ° with both aldehydes (see Section II.B) and ketones. According to Jochims and coworkers , Af-isopropylnitrilium hexachloroantimonates 290 react with chalcone 291 to yield 3-A -isopropyl-4//-l,3-oxazinium salts 293 (equation 78). 1,3-Oxazinium salts having another structure 297 are obtained by the reaction of both crotonaldehyde 294a and (. )-2-methyl-2-butenaI 294b with nitrilium salts 290 (equation 79). Besides, the reactions of cinnamaldehyde 298 with nitrilium salts 290 lead under the same conditions to the A(-acyIiminium salts 300 having an open-chain structure (equation 80). 

It is well known that nitriles react with j8-chlorocarbonyl compounds in the presence of a Lewis acid to yield 4//-l,3-oxazinium salts, but now it has been shown that nitrilium salts combine with enones to give similar products. Thus enones and nitrilium hexachloroantimonates (150) combine to produce 4/f-l,3-oxazinium salts (152), but in some cases 6//-l,3-oxazinium salts (154) are formed instead and, while tautomerism between the 4H- and 6//-forms cannot be ruled out, oxetenium salts may participate in the reactions as common intermediates. One type of bond cleavage may give the carbocations (151) (especially when R = Ar), which cyclize to the 4//-tautomers and another may lead to A-acyliminium salts (153) (Scheme 41). The latter then ring close to 6//-l,3-oxazines. Evidence that such reactions do occur is provided, since A-acyliminium salts can be isolated in some cases <90S763>. 

There are two types of benzo derivatives differently annulated namely, benzo-4//-l,3-oxazinium 42 and benzo-4//-3,l-oxazinium salts 46. Some information about uncharged benzoxazine systems has been summarized in a review [62HC(17)341]. The chemistry of the corresponding salts has been almost unknown. 

As mentioned above, the polar 1,4-cycloaddition of N-acyliminium ions 14 and 18 to olefins gives 5,6-dihydro-4H-l,3-oxazinium salts 16 (Section fI,A,l), or forms the 1,3-oxazinium salts with acetylenes (Section III, A). The same ions 89 and 91 add nitriles to furnish 1,3,5-oxadiazinium salts 90 and 92, little investigated until now (65CB334 88ZOR230). Salts 92 are unstable and can dissociate at elevated temperatures with nitrile liberation. Therefore, they may serve as original reservoirs for active jV-acyliminium cations. 

The 4-oxo-l,3-oxazinium salts and their benzo derivatives are characterized by a very strong band at 1730-1770 cm attributed to C = 0 bond vibrations. Such an abnormally high frequency was explained by an increase in the C = 0 bond order due to an electron-density shift from the carbonyl oxygen to the ring (80TH1). 

Methyl-l,3-oxazinium salts may be deprotonated to methylene derivatives (70) by bases such as triethylamine (Scheme 23). 

The assumption that the azomethine 34 is formed by an intermolecular hydride transfer from aldehyde 30 to the nitrilium salt 31 is not confirmed because the different Schiff bases 34 obtained carry the group R which are originated from the aldehyde 30. In this way, the process described in equation 14 can be reversed and applied as an enamide synthesis by acylation of imines . However, the A -ethylbenzonitrilium salt 35 reacts with benzaldehyde to give the more stable Af-benzoyl-A -ethyliminium ions 36 which add to trimethylethylene to form 5,6-dihydro-4/f-l,3-oxazinium salt 37. On the other hand, the reaction of ions 36 with phenylacetylene leads to another type of 1,3-oxazinium heterocycle, namely to 47/-l,3-oxazinium hexachloroantimonate 38 (equation 15). 

Theoretical calculations (B3LYP/6-31G ) were reported for geometries (bond lengths and bond angles) and chemical shifts of 3-methyl- and 3-phenyl-4-hydroxy-2-oxo-2/7-pyrido[2,l-f>][l, 3]oxazinium inner salts (00JCS(P2)2096). 

The reactive cation (101) may be generated either by protonation and dehydration of the A-hydroxymethylamide (100) or by the Lewis acid-catalyzed removal of a chloride ion from an A-chloromethylamide (102). Addition of the cation (101) to benzonitrile afforded a 2,6-diphenyl-4jy-l,3,5-oxadiazinium salt (103) in 39% yield, while addition to phenylacetylene gave 2,6-diphenyl-4.ff-l,3-oxazinium hexachloro-stannate (104) in 99% yield. 

The resin-bound 1,3-oxazinium salt 116, obtained by oxidation of 4//-l,3-oxazines 115 with 2,3-dicyano-5,6-dichloro-p-benzoquinone (DDQ), behaved as /3-diketone equivalents and formed pyrazoles 117 through a functionalizing release process on treatment with hydrazines (Scheme 18). When the hydrazines were substituted (R = Me, Ph), the oxazinium salts reacted selectively to afford one regioisomer 117 <2004JC0846>. 

The cyclization reactions of chloro-substituted 2-azonioallene hexachloroantimonate salts with dimethylbarbituric acid (204) give highly substituted pyrimido[5,4-e][l,3]oxazinium hexachloroantimonate salts (205) and (207). Some of them could be converted into pyrimido[4,5-c/]pyrimidines (206) (Scheme 35) <92S59i>. 

The 5,6-dihydro-4/f-l,3-oxazinium cations 18 formed can be isolated as salts of stable non-nucleophilic anions (e.g. SbClg). Usually, the reaction mixtures are treated with water or with alkali solutions, and 5,6-dihydro-4//-l,3-oxazines 19 are obtained by deprotonation (equation 9, R = H). This reaction can be carried out as a two-... 

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