Addition of 1,8-diaminonaphthalene1 to dimethylacetylene dicarboxylate (DMAD) leads to the perimidine4a and the naphthodiazepine3a. A similar reaction with the diethyl ester (DEAD) gave rise to3b and4b. The latter product has been incorrectly formulated as naphthodiazepine2b in the literature. 1,8-Dihydroxynaphthalene8 and DMAD gives rise to the naphthodioxane9, which is hydrolysed to the diacid11. 8-Hydroxy-1,2,3,4-tetrahydroquinoline (14) and acetylenic esters form pyridobenzoxazines15, which exist as equilibrium mixture of15 and16 in solution. The ethyl ester is hydrogenated to the dihydroderivative18b.¹H and more particularly¹³C NMR spectra are used to assign structures to various products.

Solutions of 3,4-dihydro-6,7-methylenedioxyisoquinoline (1) and analogues2–5 and9 as well as isoquinolines7 and8 in certain samples of CDCl₃, CCl₄, DMSO-d₆ or acetone-d₆ gave rise to anomalous¹Hnmr spectra with extreme line broadening, signals due to protons at C-l and C-3 most often not being seen. The spectra of1 and3 were most striking in this respect.¹Hnmr spectra of the quaternary salt10 and the model schiff base11 were normal. Several hypotheses for the observed line broadening have been considered and rejected, a slow equilibrium1 ⇆13 being one of them. NaBH₄ reduction of1 and2 followed by mass spectrometric analysis of the crude tetrahydroisoquinolines16 and17 ruled out a slow equilibrium1 ⇆14 and2 ⇆15 as contributory cause for line broadening. The crude reduction products unexpectedly contained N-ethyl species22 and25. Their formation is rationalised

Recent synthetic routes to the tetrahydro, hexahydro and octahydro derivatives of indoles are reviewed. An interesting one is the formation of 3-amino-4-oxo-4,5,6,7-tetrahydroindoles in the reaction of 2-phenacyl cyclohexane-l,3-diones with 1,1-disubstituted hydrazines. Antifertility, cns depressant and antiinflammatory activities have been encountered for perhydroindoles besides other biological activities. Hexahydrocinnolines are obtained from the reaction of 2-phenacyl (acetonyl) cyclohexanones and cyclohexane-1,3-diones with hydrazines, while octahydrocinnolines are formed from cyclohexanone-2-acetic acids and hydrazines in two steps. 5-oxo-5,6,7,8-hexahydrocinnolines and their oximes undergo anomalous and interesting aromatisation reactions. Some hexahydrocinnolines are cns depressants while octahydrocinnolines are analgesics. More importantly, they are precursors for interesting azamorphinans.

The usefulness of¹³CNMR spectral data in solving otherwise intractable structural problems in heterocyclic chemistry is illustrated with ring systems such as imidazoles, pyrazoles, thiazoles, pyrimidines, benzodioxoles, benzodioxanes, benzoxazines, benzothiazines, quinoxalines, imidazopyrazoles, imidazothiazoles, pyridobenzoxazines, thiazolobenzimidazoles, thiazinobenzimidazoles, pyrimidobenzimidazoles, naphthodioxanes and perimidines. For example, using both chemical shifts and coupling constants, especially the one across three bonds, it has been possible to assign unique structures to the addition products of acetylenedicarboxylic esters to a variety of dinucleophiles such as thioureas, guanidines, 2-aminophenol, 2-aminothiophenol, 1,8-dihydroxy and 1,8-diaminonaphthalenes and 8-hydroxy-1,2,3,4-tetrahydroquinoline. These parameters also allow easy differentiation of isomeric imidazoles arising from N-alkylation of nitroimidazoles or nitration of imidazoles and of isomeric pyrazoles obtained from the reaction of hydrazines with ethoxymethylene derivatives of 1,3-dicarbonyl compounds.

IR, UV, NMR and mass spectral data for the title compounds are discussed. The EI mass spectra of4. and the analogues5–9 and11–15 display major (M-Cn₂H₃O₂)⁺ fragment ions that correspond to the loss of a structural element not present in the parent molecules. These (M-59)⁺ ions have no equivalent in the model compound l-phenyl-2,6,6-trimethyl-4-oxo-4, 5,6,7-tetrahydroindole (27). The unusual fragmentation is thought to be initiated by α-cleavage within the alicyclic 1,3-diketone moiety (ring C) under concomitant formation of a benzylic radical site. Reclosure of this ‘open’ intermediate to a lactone-type molecular ion provides two O-atoms in the proximity required for an ejection of a CH₂COOH radical as the neutral species in question. The¹H NMR spectra of4 and its methyl ether16 reveal restricted rotation of substituents at positions 1 and 3 of the pyrrole ring, the eight methylene protons becoming fully anisochronous at 500 MHz. X-ray studies on single crystals of8 confirmed its structure.

2-Amino-2-arylethylamides1 carrying electron-donating substituents in thepara position are transformed by hot POC1₃ to the the title compounds2, presumably via iminochlorides 7 and imidazolium derivatives8. Amides lacking this para-substituent give rise to chloroamidines11 under these conditions.m-Methoxyphenethylamide1t and POCl₃ form, besides11f, an isoquinoline derivative3. The involvement of an imidazolium compound8 in the formation of ethenamidines has been verified by the synthesis of2a from10. Reaction of amide1w with PCl₅ in the cold leads to, besides the chloroamidine11c, thecis-ethenamidine12 which equilibrates with thetrans-isomer2o in hot toluene. Thienylethyl urea13 converted by hot POCl₃ to the imidazoline16, while phenylpropylamide17 forms only the iminochloride18a.

Cyclization of N-(2-haloacyl)-8-hydroxy-l,2,3,4-tetrahydroqumolines4–7 and9 with alkali affords pyridobenzoxazinones21–24 and26 respectively and of the 4-chlorobutyramide13 with NaH, the benzoxazocinone31. Exposure of 3-chloropropionamide12 to NaH affords acrylamide15, benzoxazepinone28 or methyl benzoxazinone22 or mixtures thereof under various conditions.28 undergoes rapid base-catalysed ring contraction to22. NaH-catalysed ring closure of acrylamide15 affords mixtures of22 and28, while from the crotonamides16 and17, the methylbenzoxazepinones29 and30 are obtained preponderantly, the former amide yielding only traces of the ethyl benzoxazinone23.29 shows no propensity for ring contraction to give23. The cinnamoyl derivatives18,19 and20 are cyclized to benzyl benzoxazinones24,27 and25, respectively. The intermediacy of the phenyl benzoxazepinone39 in the formation of24 has been established by deuteration studies. Benzylidene benzoxazinone41 is obtained from dibromocinnamamide14 and propiolamide40. Dichloracetamides8 and10 undergo interesting ring closure to compounds45–54 upon treatment with amines. The course of electrophilic reactions of the lactams depends upon the ring size.