Phthalazinecarbonyl halides

Like most acyl halides, these useful intermediates are moisture-sensitive and unsuitable for storage. Accordingly, they are usually prepared and then used immediately as crude intermediates. However, it is quite possible to purify and characterize such halides with the obvious precautions. Their chemistry is illustrated by the following classified examples. 

Note Phthalazinecarbonyl halides may be made by Reissert reactions (see Section 9.1.3) but usually from phthalazinecarboxylic acids with thionyl chloride or the like (see Section 14.1.2). 

Note The conversions of phthalazinecarbonyi halides into the corresponding esters, amides, or diazoacetates are iiiustrated here also their cyclizations. 

4-Oxo-3,4-dihydro-5-phthaIazinecarbonyl chloride (33, R = Cl) [crude, from the acid (31, R=OH) with thionyl chloride] gave ethyl 4-oxo-3,4-dihydro-5-phthalazinecarboxylate (33, R = OEt) (EtOH, reflux, 18 h 85%) or methyl 4-oxo-3,4-dihydro-5-phthalazinecarboxyIate (33, R = OMe) (MeOH, likewise 97%).  

4-Oxo-3-phenyl-3,4-dihydro-6-phthalazinecarbonyl chloride (34, R = C1) gave 4-oxo-3-phenyl-3,4-dihydro-6-phthalazinecarboxamide (34, R = NH2) [crude substrate, CH2CI2, NH3, solvent ( ), 20°C, 4h 60%], lVA -dunethyl-4-oxo-3-phenyl-3,4-dihydro-6-phthalazinecarboxamide (34, R = NMe2) (Mc2NH, likewise 52%), or analogs.  

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Note Esterification may be done indirectly via phthalazinecarbonyl halides or directly (as illustrated here) by treatment with alcoholic sulfuric acid, a diazoalkane, or some other alkylating agent. l-(5-Ethylthien-2-yl)-4-oxo-3,4-dihydro-6-phthalazinecarboxylic acid (21, R = H) gave ethyl l-(5-ethylthien-2-yl)-4-oxo-3,4-dihydro-6-phthalazinecarboxy-late (21, R = Et) (EtOH, H2SO4, reflux, 12 h 88%). °... 

Most of the routes to such amides have been covered already by primary synthesis (Chapter 8), by aminolysis of phthalazinecarboxylic acids (Section 14.1.2), by aminolysis of phthalazinecarbonyl halides (Section 14.2), by aminolysis of phthalazinecarboxylic esters (Section 14.3.2), and by passenger introduction (most chapters). One major and several minor preparative methods are illustrated in the following examples. 

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