1.2- Dihydroisoquinolines stability

Evidently, the stability of 3-hydroxy-3,4-dihydroisoquinolines 137, formed as the result of heterocyclization, is also determined by the anne-lated benzenoid ring. The lower tendency toward aromatization for these compounds, compared to monocyclic analogs, leads to the ability of 137 to react as a cyclic azomethine. The addition of a molecule of nucleophile to the C=N bond causes opening of the isoquinoline ring and formation of a new ring system (for instance, a-naphthols 141 in alkaline aqueous solutions). Such conversions occur even under conditions of the recyclization reaction of 2-benzopyrylium salts, namely, on heating 137 in alcoholic ammonia a mixture of isoquinoline 138 and a-naphthylamine 140 results (88MI1). 

The double bond is kept in the exocyclic position by conjugation with the carbonyl group (the free base absorbs at 3270 cm-1). The free base of l-(a-picolyl)-6,7-methylenedioxy-3,4-dihydroisoquinoline also possesses the stabilized enamine structure, whereas the imino structure is exhibited by the 1-methyl analog, as shown by comparison of the... 

Although 3,4-dihydroisoquinolines are well known, and are reasonably stable, easily characterizable compounds, the isomeric 1,2-dihydroisoquinolines have often been considered12,17, Z2,61,62 to be unstable and difficult to isolate in a pure state. This is certainly true in some cases, but stability does depend on (a) whether the nitrogen is secondary or tertiary, (b) the position and nature of... 

There is a discrepancy in the literature concerning 1,2-dihydro-isoquinoline itself. Thus, Huckel and Graner54 report its trimerization to 31 (m.p. 138°, the same melting point that Packham and Jackman11 ascribe to the monomer). It is thought63 that in a nonpolar solvent, 1,2-dihydroisoquinoline is relatively stable, but in methanol, protonation and trimerization occur certainly the mass spectrum of the compound (m.p. 138°) described by Packham and Jackman indicates that it is trimeric.63 The series of 1,2-dialkyl-1,2-dihydroisoquinolines described by Bradley and Jeffry30 was purified by distillation under reduced pressure. The stability of these compounds is quite remarkable in view of the known tendency for 1,2-dihydroisoquinolines to undergo disproportionation. Some other 1,2-dialkyl-1,2-dihydroisoquinolines have been described,7 as well as 1-aryl derivatives.7 The derivative (32) when heated with triethyl phosphite is transformed by an unknown mechanism, in 37% yield, into 33.64... 

The relative stabilities of some 1,2-dihydroisoquinolines may be related to their ease of protonation at C-4. Thus, introduction of a C-3 methyl group,12,41 a C-4 methyl group,53 a C-4 benzyl group,18, 65... 

Similar anti-azomethine ylides 76 (EWG = COOR, R = MeO) bearing an ylide-stabilizing ester moiety are involved in the diastereoselective cycloadditions to 3,4-dihydroisoquinolines and N-(arylmethylene)methylamines to provide stereoselective imidazolidine-fused cycloadducts 259 and 260 (82LA924, 82LA2146). As imines and ylides 76 bear extremely different LUMO and HOMO coefficients on each termini, uniformly high regioselec-tion is not surprising. endo-Approach of the dihydroisoquinolines to the... 

Nucleophilic reactions take place on the hetero ring of isoquinoline, preferably in the 1-position. For instance, the Chichibabin amination with NaNH2 in liquid ammonia yields 1-aminoisoquinoline 5. The Ziegler reaction with w-butyllithium furnishes the 1-substituted product 7 as with quinoline, benzene ring annulation stabilizes the primary addition product 6 (1,2-dihydroisoquinoline), which can be isolated and dehydrogenated to 7 by nitro compoxmds ... 

In the isoquinoline series, we were able to demonstrate clearly that a carboxyl group in the 1-position was lost quantitatively at the oxidation potential of a phenol in the ring (3ff). The products were 3, -dihydroisoquinolines such as 39 which were reduced to tetrahydroisoquinolines for isolation. When no phenol group was present, the oxidation potential was much higher, but the decarboxylation did take place. In a sense, the reaction is a Hofei—Moest reaction where the cation is stabilized by the electron pair on the neighboring nitrogen. This does not explain the relationship between the oxidation potential of the phenol and the decarboxylation, but it has been established that phenylacetic... 

Combination of the hydroxyl ion with the mesomeric cation involves the removal of a double bond. For the quaternary pyridinium compounds this causes the total loss of the aromaticity. For quaternary quinolinium and isoquinolinium compounds, the aromatic character of one of the two rings is lost, and for the quaternary acridinium compounds that of one out of three. Hence., the order of stabilities of these compounds (determined by Hantzsch= ) is explained. - Comparison of quaternary 3,4-dihydroisoquinolinium compounds and their isoquinolinium analogs with respect to the equilibrium (5) (4) shows that a much higher hydroxyl ion concentration is necessary for the isoquinolinium ions to form the carbinolamine. This is because the transition from the quaternary 3,4-dihydroisoquinolin-ium ions into the undissociated carbinolamine involves significantly smaller loss of mesomeric energy than that for the quaternary isoquinolinium hydroxides. ... 

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