Isoquinoline analogues

The reaction of the fused 5,7-dihalopyrimidine (19) to form the 7-methoxy derivative (20) also shows that the more readily displaced chlorine is next to the azole ring (67T675). Hydrazinolysis of the isoquinoline analogue (21) is stepwise with initial 4-substitution (22). The difference in reactivity at C-4 and C-6 in (22) is sufficient for selective acid hydrolysis of the hydrazino group in (22). Reductive cleavage of the hydrazino C—N bond is achieved in the usual manner by the reaction of its tosyl derivative with alkali (75JCS(Pi)2l90). 

Lactams, e.g. (26) (67T681), can be chlorinated in the usual manner with phosphorus oxychloride. Phenylphosphonic dichloride is often a preferable reagent in this type of reaction, especially if the reaction requires a relatively high temperature for complete conversion, e.g. for the isoquinoline analogue (27) (75JCS(P1)2190). 

The cyano-substituted Ai-aminopyridinium salt (119) dimerized to (120) with the participation of the cyano group (Equation (18)), but the quinoline and isoquinoline analogues reacted differently <89JOC3062>. The dimerization of (119) could be suppressed by treatment with triethyl orthoformate. The iminoformate formed could then be cyclized with amines <90H(31)289). 

Recently the interesting prospect of making isoquinoline analogues of yohimbine has appeared with our discovery that an alternative rearrangement of methyl secoxyloganin aglucone can be induced (Brown and Pratt 1980). At pH7 a highly stereose-... 

Bridging the gap between pure nthetic chemistry and biosynthetic studies is the area of biomimetic syntheses. The Ipecacuanha alkaloids can be obtained from substituted dopamines and secologanin. Similar studies have resulted in the isoquinoline analogues of the heteroyohimbine alkaloids which have not yet been isolated as natural products. 

When two fused six-membered rings (naphthalene analogues) are considered, possibilities become very numerous, partly on account of the reduced symmetry of naphthalene, compared with benzene, and also because of the larger number of positions available for substitution. Thus, there are two monoazanaphthalenes, quinoline (8) and isoquinoline (9), four benzodiazines [cinnoline (10), phthalazine (11), quinazoline (12) and quinoxaline(13)], with the two nitrogen atoms in the same ring, and six naphthyridines (e.g. (14), named and... 

The Pictet-Spengler reaction has been carried out on various solid support materials " and with microwave irradiation activation.Diverse structural analogues of (-)-Saframycin A have been prepared by carrying out the Pictet-Spengler isoquinoline synthesis on substrates attached to a polystyrene support. Amine 20 was condensed with aldehyde 21 followed by cyclization to give predominantly the cis isomer tetrahydroisoquinoline 22 which was further elaborated to (-)-Saframycin A analogues. 

Fluorination. Attention has been focused on the direct fluorination of isoquinolines activated by conversion into 2-methylisocarbostyril (80). With gaseous fluorine (diluted to 10% with argon) in acetic acid a 54% yield of the 4-fluoro derivative was obtained. (Scheme 40). With methylene chloride as the solvent, only the 4-chloro analogue was formed [82H( 17)429]. Fluoroisoquinolines have also been made by displacement of nitro groups, and from diazonium fluoroborates (87JHC181). Hepta-chloroisoquinoline was converted into a perfluoro derivative by heating it in an autoclave with anhydrous potassium fluoride [66JCS(C)2328]. 

Scheme 1.35 Test reaction with l-(2-methylthio-l-naphthyl)isoquinoline ligand and its N/O-analogue.

In a recent study, the group of Moser has described the use of a polymer-bound borohydride in reductive aminations of tetrameric isoquinolines (Scheme 7.101) [122]. These tetrameric isoquinolines, which represented lead compounds in a search for antibacterial distamicyn A analogues, were prepared from the appropriate... 

The ESR hyperfine coupling constants have been established experimentally (67MI20402) for the pyridinyl radical (134 R = H) and deuterated analogues, produced by y irradiation of a solid solution of pyridine in ethanol at 77 K, but the signs of the couplings are not known experimentally and are made solely on the basis of Huckel MO calculations. INDO MO calculations on this radical, together with the radical anions of quinoline, isoquinoline and acridine h ve also been carried out (740MR(6)5). 

Thiol-thione tautomerism is similar to that exhibited by the oxygen analogues but with the a- and y-thiones, e.g. (129), slightly more favoured than the corresponding a- and y-oxo compounds. UV and other data have indicated the predominance of the thione forms of quinoline-2- and -4-thione, e.g. (130), isoquinoline-1- and -3-thione, e.g. (131), and acridine-9-thione (132) (76AHC(S1)144>. 

The HMO method has been used to study models of all the aza analogues of pyridine, quinoline, isoquinoline, the monoazaanthra-cenes, and 1- and 9-azaphenanthrenes as well as of their derivatives such as aminopyridines and aminoquinolines.28 Again their energy characteristics are correlated with those of the parent systems. 

Electron-attracting substituents facilitate electrochemical reduction. The reduction potentials for the polarographic reduction of quinoline and isoquinoline derivatives are much less negative than those for the pyridine analogues. Diazines are reduced electrochemically stepwise, usually as far as tetrahydro derivatives (70AHC(12)262). 

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