Rearrangement of 1,2-Dihydroisoquinolines

A further reaction of 1,2-dihydroisoquinolines with acids is the elimination of the C-1 substituent. An isoquinolinium salt (29) and a toluene derivative (30) are formed from (28) (70AP255). The reaction can occur if the C-1 substituent is a benzyl or a heteroanalogous benzyl group. In 1,2-dihydroisoquinolines that are able to rearrange, the elimination reaction only is... 

In an effort to define the scope of the benzyl migration reaction, and to elucidate its mechanism, Knabe et al.1 have treated a series of 1-substituted 1,2-dihydroisoquinolines with acids. The following reactions have been observed (a) rearrangement, (b) elimination of the C-l substituent, (c) disproportionation without rearrangement, (d) disproportionation after rearrangement, and (e) recovery of starting material (Scheme VIII). The results are summarized in... 

AP831). Product 74 was obtained in only 10% yield, and a considerable part of the starting material (22a) was found to be resinified under the acidic conditions. The iminium salts 75 and 76 form in 23 and 49% yields, respectively. In both cases, disproportionation products could be isolated from 23a the compounds 77 and 78 in low yields and from 24a the compounds 79 and 80 in yields of about 15%. These findings demonstrate that the furo-(22a) and thienodihydropyridines (23a and 24a) under the rearrangement conditions behave similarly to the corresponding l-allyl-1,2-dihydroisoquinolines. 

In order to study the stereochemical course of the rearrangement of 1-benzyl-l,2-dihydroisoquinolines, the optically active acetal (-f-)-106 was synthesized, starting with the amine (-i-)-105. Compound (-f-)-106 is a precursor of an optically active l-benzyl-l,2-dihydroisoquinoline possessing an asymmetric center in the 1 position. The ring closure of the acetal (-f- )-106, performed with 6 N HCl, leads to 1,2-dihydroisoquinolines or, in compounds that can be rearranged under acidic conditions, via 107 to the 3-substituted... 

In order to demonstrate the transfer of a benzyl group to an acceptor under the rearrangement conditions, a mixture of the l-benzyl-3-ethyl-l,2-dihyd-roisoquinoline 110, a 3-substituted 1,2-dihydroisoquinoline that does not rearrange, and the l-ethyl-l,2-dihydroisoquinoline 111, which normally gives disproportionation, was treated with dilute acid. The 3,4-dihydroisoquino-linium salt 112 was obtained in 5% yield. This experiment demonstrated that the transfer of a benzyl group from a 1,2-dihydroisoquinoline (110), existing as a 1,4-dihydroisoquinolinium salt in acidic solution, to form the 3,4-dihydroisoquinolinium salt 112 is possible. The low yield of 112 can be... 

The 1-benzyl-1,2-dihydroisoquinoline [(138) R = OH, R = OMe] has been rearranged,146 and the structure of the product (140) proved by synthesis.147 The threshold for pavine formation versus migration... 

The 1,2-dihydroisoquinoline (141) cyclizes very readily to 142 rearrangement to 143 could only be observed under special conditions of acid treatment.148... 

Methyl-1,2-dihydropapaverine (175, R = OMe) rearranges to the 2-methyl-3-(3,4-dimethoxybenzyl)-6,7-dimethoxy-3,4-dihydroisoquinolin-ium salt (176, R = OMe) under very mild conditions (treatment with 2% hydrochloric acid). A similar rearrangement of l-(3,4-methyl-enedioxybenzyl) - 2 - methyl - 6,7 - dimethoxyisoquinoline (175, R, R = —O—CHj—O—) affords 3-(3,4-methylenedioxybenzyl)-2-methyl-6,7-di-methoxy-3,4-dihydroisoquinolinium chloride (176, R, R = O—CHj—O—) (256). The reaction was shown to be an allylic rearrangement with internal return (275,275). 

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