| dc.description.abstract | The thesis entitled "Synthesis of Heterocycles" consists of three chapters.
An unusual reaction wherein potassamide in liquid ammonia converts substituted 5,6-dihydroisoquinolines to the corresponding stable 1,2-dihydroisoquinolines and isoquinoline derivatives has been reported from our laboratory. With a view to study the generality of this reaction, several 7- and 8-substituted 5,6-dihydroisoquinoline derivatives (1) were synthesized. Reaction of the 5,6-dihydroisoquinolines (1) with potassamide in liquid ammonia gave the corresponding 1,2-dihydroisoquinolines (2) (as a major product) and isoquinoline derivatives (3) (as a minor product). An intramolecular disproportionation mechanism is postulated. These results are discussed in Chapter I.
The literature concerning the Vilsmeier reaction on N-heterocycles is reviewed in Section 1 of Chapter II. Section 2 of Chapter II deals with the study of Vilsmeier reaction on dihydro-, tetrahydro-, and fully aromatic isoquinoline derivatives. A one-step transformation of 3-alkoxy-5,6-dihydroisoquinoline derivatives (4) to the corresponding 3-chloro compounds (5) instead of the expected aldehyde (6) under Vilsmeier reaction conditions is reported. Similarly, 3-alkoxy-5,6,7,8-tetrahydroisoquinoline derivatives (7) gave the corresponding 3-chloro compounds (8). Variation in the nature of the substituents (aryl, alkyl, or hydrogen) at C-1 does not alter the course of the reaction. On the basis of available chemical evidence, a tentative mechanism involving the initial attack of Vilsmeier complex on the oxygen of the alkoxy group followed by the attack by chloride ion at C-3 and cleavage of the ether is proposed. The presence of an alkoxy group at C-1 in addition to C-3 alkoxy group changes the course of this reaction and yields three products, 10, 11, and 12 depending on the molar ratio of substrate/Vilsmeier reagent employed. All these products were characterized on the basis of spectral (UV, IR, NMR, and mass) data. Structures of compounds 13 and 14 were confirmed by independent synthesis. Several mechanisms for the above transformations are considered; on the basis of some experimental evidence, tentatively, a ketenimine-type intermediate is proposed. Part of the work reported in this chapter has been accepted for publication in Synthesis.
Chapter III describes the attempted synthesis of 8-substituted-7,8-dihydropterins. Condensation of aminoacetone dimethyl ketal with propanal, butanal, and methoxyethanal followed by sodium borohydride reduction of the Schiff bases gave N-propylaminoacetone dimethyl ketal (13), N-butylaminoacetone dimethyl ketal (14), and N-methoxyethylaminoacetone dimethyl ketal (15) respectively. Condensation of 13 with 2-amino-6-chloro-5-nitro-4(3H)-oxopyrimidine (16) followed by hydrogenation and cyclization led to 7,8-dihydro-6-methyl-8-propylpterin (R = n-propyl). Similar reactions of 14 and 15 did not give the corresponding pterins (17). Sodium borohydride reduction of nitropyrimidine (16, R = H) followed by cyclization gave 7,8-dihydro-6-methylpterin (18, R = H) in excellent yield. Phase-transfer alkylation of 7,8-dihydro-6-methylpterin (18, R = H) using benzo-15-crown-5-ether as catalyst gave 6-methyl-7-substituted pterins (19) regiospecifically. | |
