Alkylation of Tautomeric Cinnolinones

Tautomeric cinnolinones usually undergo A -alkylation to afford regular N-alkylcinnolinones, zwitteiionic Al-alkylcinnoliniumolates, or a mixture of both 0-alkylation to afford alkoxycinnolines is rare but not unknown. These possibilities are illustrated in the following classified examples. 

3(2/i)-Cinnolinone (19) gave 2-methyl-3(2f/)-cinnoUnone (20, R = Me) (substrate, NaOH, H2O, EtOH, then Me2S04, mild exotherm, 90 min 80% or CH2N2, Et20, 30 min 71%) or 2-benzyl-3(2//)-cinnoUnone (20, R = CH2Ph) (substrate, KOH, EtOH, reflux, then PhCH2Cli dropwise, reflux, 12 h 62%). 2 

7-Phenyl-5,6-dihydro-3(2//)-cinnolinone (21, R = H) gave 2-ethoxycarbonyl-methyl-7-phenyl-5,6-dihydro-3(2//)-cinnolinone (21, R = CH2C02Et) (Et02-CCHjBr, K2CO3, AcMe, reflux, 24 h 40%).  

Ethyl 7-methoxy-4-oxo-l,4-dihydro-3-cinnolinecarboxylate (22, R = H) gave ethyl 1-ethyl-7-methoxy-4-oxo-l,4-dihydro-3-cinnolinecarboxylate (22, R = Et) [Etl, K2CO3 (1 equiv), AcMe, reflux, 8 h 78% (as hydriodide salt) then Et3N, CH2CI2, 20°C, 48 h 91% (as base)].  

3-Triphenylphosphoranylidene-3,4-dihydro-4-cinnolinone (25) gave l-methyl-3-triphenylphosphonio-4(lfl)-cinnolinone iodide (26) (neat Mel, reflux, h 95%) and thence l-methyl-4(17/)-cinnolinone (27) (NaOH, MeOH, H2O, 

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Note The formation of these ethers by primary synthesis Chapter 1), by alcoholysis or phenolysis of halogenocinnolines (Section 3.2), and by alkylation of tautomeric cinnolinones (Section 4.1.2.1) has been covered already. Other routes appear to be unrepresented. 

Note A few such products have been made by primary synthesis (see Chapter 1) but most, by alkylation of tautomeric cinnolinones (see Section 4.1.2.1). Minor routes are exemplified here. 

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