Aromatic Compounds Through Intramolecular Electrophilic Substitution

Aromatic Compounds Through Intramolecular Electrophilic Substitution 

A simple example to illustrate the procedure is the thermal dehydration of 2-biphenyl-methylphosphonic acid (311) to the cyclic acid 312 whilst the thermolysis of the di(phos-phonomethyl)biphenyl (313) yields two cyclic phosphinic acids in 30% overall yield with 314 as the major product 2-Biphenylvl- and 2-phenoxyphenyl-phosphinic acids fail to cyclize under a variety of conditions, nor does (2-biphenylyl)phenylphosphinic acid cyclize with H2SO4 or polyphosphoric acid, although the corresponding phosphinic chloride does so in nitrobenzene. 

When a vinylphosphonic ester (315) (R = CH2CH2R ) is heated with polyphosphoric acid or with phosphoric acid in toluene, cyclization occurs with the elimination of R CH2CH20H. The reaction, thought to proceed through the steps illustrated, provides 17-70% yields of 2H-1,2-benzoxaphosphorin 2-oxides (316) . 

---

B. Aromatic Compounds Through Intramolecular Electrophilic Substitution... 

Detailed mechanistic studies by Fodor revealed that the reaction is initiated by a nucleophilic attack of phenylethylamide to the dehydrating agent to afford intermediate imidoyl chlorides. Upon heating, these compounds are converted to nitrilium salts, which were cyclized through an intramolecular electrophilic aromatic substitution, providing the desired dihydroisoquinolines." Fodor prepared imidoyl chlorides using mild condition and promoted their cyclization to dihydroisoquinolines by using Lewis acids. His results supported the intermediacy of nitrilium salts as the key intermediates for the synthesis of dihydroisoquinolines. ... 

---