Ketene acetals reaction with 1,2,4-triazines

Table 12 Reactions of Silyl Ketene Acetals (79) with l,3,5-Trialkylhexahydro-l,3,5-triazines (84)...

For preliminary studies on the scope of the [4 + 2] cycloaddition reactions of 1,2,4-triazines with electron-rich dienophiles including enol ethers, enamines, ketene acetals, ynamines and strained or reactive olefins, see Dittmar, W., Sauer, J., and Steigel, A. (1969). Tetrahedron Lett., 5171 Reim, H., Steigel, A., and Sauer, J. (1975). Tetrahedron Lett., 2901. 

Among the reactions of the 1,2,4-triazines, the hetero-DlELS-ALDER reactions with electron-rich alkenes and alkynes are of special importance in preparative chemistry [168]. The heterocyclic ring reacts with enamines, enol ethers and ketene acetals as an electron-deficient 2,3-diazadiene across the ring positions C-3 and C-6 ... 

Even more so than 1,2,4-triazines (see p 441), 1,2,4,5-tetrazines display heterodiene activity in their reactions towards electron-rich, multiply-bonded systems. Enol ethers, enamines, ketene acetals, imido esters, alkynylamines and nitriles undergo [4+2] cycloadditions with inverse electron demand across the ring positions C-3 and C-6 [176]. Olefinic dienophiles lead to diverse products depending on their substituents ... 

The reaction of 1,2,4-triazines with ketene derivatives such as the 0,0-acetals (42la), 0,iV-acetals (421b), Af,Af-aminals (421c) and (V.S-aminals (421d) has been studied extensively. In all cases pyridines (422) were isolated (Scheme 14). These reactions follow the usual cycloaddition route. Again it is found that the orientation is dominated by secondary... 

Investigation of the reaction of l,l-bis(dimethylamino)ethylene 4, ketene N,S- or N,O-acetals, with 1,2,4-triazines and 1,2,4,5-tetrazines has been conducted by Muller and Sauer164. Unlike ketene, N,S- or AT,O-acetals, 1,1-enediamine 4 leads to both... 

When the steric effect is removed, 3 indeed shows higher reactivity than its acyclic analogue 4 or ketene N,S- or AT, 0-acetals. In fact, 3 reacts vigorously at 0 °C with 1,2,4-triazine 206 to give 207, and nitrogen evolution is complete within a few seconds (equation 87). The reaction even occurs at — 20 °C, whereas all other substrates react... 

The 2,5-dihydro-l,2,3-triazines 20, obtained by reaction of 1,2,3-triazines 19 with ketene silyl acetals or silyl enol ethers in the presence of 1-chloroethyl chloroformate, can be readily oxidized and hydrolyzed with ammonium cerium(lV) nitrate (CAN) in acetonitrile/water to afford 5-substituted 1,2,3-triazines 21.3 64... 

Methyl-l,2,4-triazines react with ketene OW-acetals to afford 5-[2-(dimethylamino)-prop-l-enyl]-l,2,4-triazines 10 (see Houben-Weyl, Vol. El5, p 1898). The reactions start with deprotonation of the methyl group by the ketene 0,Ar-acetal followed by combination of the two ions formed. Elimination of alcohol from the adduct 9 yields the isolated product 10.343... 

Triazine 4-oxides with a methyl group in the 5- or 6-position react with ketene 0,iV-acetals to give [2-(dimethylamino)prop-l-enyl]-l,2,4-triazines 4-oxides 11 and 12 with a strong preference for reaction at the methyl group in the 5-position.145... 

In addition to alkenes or compounds with strained double bonds, 1,2,4-triazines react readily with electron-rich dienophiles such as enol ethers, enamines, enaminones, vinyl silyl ethers, vinyl sulfides, vinyl acetate, and ketene derivatives (see also Ilouben-Weyl, Vol. E7b, p 471 ff). It has been shown195,403,404 that oxo compounds and catalytic amounts of amines can be used instead of enamines however, water formed in the reaction can result in the formation of side products.403... 

Aminations which afford 6-aminocarboxylates are of interest in relation to monobactam antibiotics. A secondary aminomethyl group can be introduced at the -position of carboxylic esters by reaction of hexahydro-1,3,5-triazines with ketene silyl acetals in the presence of a catalytic quantity of trifluoromethanesulphonic acid (Scheme 25). The triazine (10) is considered to be converted into an N-silylated methyleneiminium salt which undergoes addition of the ketene silylacetal (11). 

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