Isoquinolines as Substrates

The conversion of an isoquinoline to a phthalazine is represented by only one example 3-oxo-2-phenyl-2,3-dihydro-1,4-isoquinolinequinone (287) in ethanolic hydrazine hydrate at 20°C during 2h afforded 4-oxo-3 4-dihydro-1-phthalazine-carbohydrazide (288) but in only 9% yield after separation from an isoindolinone the mechanism remains unclear. o 

The conversion of these substrates into phthalazines clearly has synthetic potential. For example, 4-phenylpyridazino[4,5- i]pyridazin-l(2F/)-oiie (290) and A -(l-ethylprop-l-enyl)pyrrolidine (289) in refluxing dioxane for 1 h gave a mixture of the Diels-Alder adducts (291) and (292) that lost nitrogen and pyrrolidine on refluxing in dilute propanolic acetic acid during 24h to afford a 1 2 mixture (61%) of 7-ethyl-6-methyl-4-phenyl-l(2//)-phthalazinone (293) and 6-ethyl-7-methyl-4-phenyl-l(27/)-phthalazinone (294), from which only the latter could be obtained in 

Primary Syntheses of Phthalazines 8.6.10. Thieno[3,4- l]pyridazines as Substrates 

These substrates have been used extensively with two-carbon synthons to make phthalazines, apparently via nonisolable cyclic adducts that are degraded spontaneously with or without loss of hydrogen sulfide. Some typical examples follow. 

Ethyl 5-amino-4-oxo-3-p-tolyl-3,4-dihydrothieno [3,4-d] pyridazin-l-carboxylate (295) and p-dimethylaminopropiophenone (presumably converted by loss of dimethylamine into phenyl vinyl ketone under the reaction conditions) probably gave the intermediate adduct (296) that lost H2S to afford ethyl 5-amino-7-benzoyl-4-oxo-3-p-tolyl-3,4-dihydro-1 -phthalazinecarboxylate (298) (Mc2NCHO, trace AcOH, reflux, 2h 61%) the same substrate (295) with p-methoxy-p-nitrostyrene likewise gave ethyl 5-amino-7-p-methoxyphenyl-6-nitro-4-oxo-3-p-tolyl-3,4-dihydro-l-phthalazinecarboxylate (297) (80%) and many analogs were made similarly.  

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From Heterobicyclic Derivatives as Substrates 8.6.8. Isoquinolines as Substrates... 

The same oxidants can be used with quinoline or isoquinoline as substrates. In most of these reactions Se metal is used in catalytic amounts and is continuously regenerated by the other oxidants present. 

Allenic sulphoxides ArSOCH=C==CR R are available through the reaction of sulphenyl halides with propargyl alcohols HC CCR R OH. Friedel-Crafts reactions with toluene>p-sulphinyl chloride in the presence of AICI3, SnCh, or SbCl, give aryl p-tolyl sulphoxides, and an analogous product is obtained unexpectedly, using toluene-p-sulphonyl chloride with isoquinoline as substrate in the presence of excess NaH. ... 

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