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Computational studies (MNDO/PM3 and MMX) were performed towards the selectivity and reactivity of the ringtransformation reactions of the 5-(1-propynyloxyethyl)pyrimidine derivatives A1 -8. Determination of the energy and dipole moments of the transition states of the different possible reaction pathways revealed that the ratio of the product formation was determined by the polarity of the transition states, as expressed by their dipole moments, in combination with the dipole moment of the reaction medium. Also the reactivity of the compounds under study appeared to depend on the polarity of the transition state of the initial Diels-Alder reaction. The differences in dipole moments of the different TS's are ascribed to the geometry of the molecules in the TS's. Furthermore, a comparison of the heats of activation of the initial Diels-Alder reaction and the subsequent retro Diels-Alder reaction showed that the first one is the rate determining step.

Intramolecular Diels-Alder reactions of (2-alkynylphenyl-X)-pyrazines (X = O, NAc, S) under neutral and acidic conditions are described. The isomer distribution of the resulting tricyclic b - and c -annelated pyridines is discussed.

The 5-propynyloxycycloalkane pyrimidines IIIA (17 – 20), IIIB (21 – 24), and IIIC (25, 26) and the 5-(1-propynyloxyethyl) pyrimidines IIID (27,28), easily undergo intramolecular Diels-Alder reactions with inverse electron demand and a subsequent retro Diels-Alder reaction in which R1CN (R1 = H, Me) or X-CH2CN (X = −CH2, −CH2CH2, −H) is expelled. For the compounds IIIA and IIIB the extrusion of X-CH2CN is favoured, yielding 3-(3-cyanopropyl)-1,3 dihydro-6-phenyl-R1-R2-furo[3,4- c ]pyridines (29 – 36). The compounds 17 and 21 also yielded 4-phenyl-2H-6,7,8,8a-tetrahydro-furo[4,3,2- de ]quinoline (38), by expulsion of HCN or MeCN respectively, which constitute a new class of heterocyclic compounds. For the compounds IIIC and IIID the extrusion of HCN is favoured as compared to the extrusion of X-CH2CN. In case of IIIC this also gives a hitherto unknown class of heterocyclic ring systems namely 2H- 1,6,7,8,9,9a-hexahydro-4-phenyl-9a-R1-5-aza-1-oxo-benz[ c , d ]azulenes (39, 40). The reactivity of the compounds III towards the cycloaddition appears to be strongly influenced by the nature of the substituent R2 if R1 = H. However, if R1 = Me the effect of R2 on the reactivity was very small. The ratio of the products V and VI appears to depend mainly on the nature of -X-.

Pyridines being substituted at position 2 or 3 with a silylated propynyloxymethyl side-chain undergo a thermolytic intramolecular Diels-Alder reaction with formation of dihydroisobenzofurans. The 3-substituted pyridines are found to be more reactive than the 2-substituted ones. Substitution of both hydrogens in the methylene group at the (α-position of this side-chain by one methyl as well as one phenyl substituent leads to a considerable increase of the reaction rate. In a similar way, from the N-acetyl derivative of 3-trimethylsilyl-propynylaminomethylpyridine, the isoindoline system is formed. The rate of the reaction is considerably lower than that of the corresponding propynyloxymethyl derivative.

Quaternization of 3-(3-butynylthio) and 3-(4-pentynyltio) substituted 1,2,4-triazines with triethyloxonium tetrafluoroborate in CH2Cl2 at room temperature occurs exclusively at N-1 yielding 3-alkynylthio-1-ethyl-1,2,4-triazinium salts, as unequivocally shown by the 13C NMR and X-ray crystallographic data. 3-Alkynylthio-1-ethyl-5-phenyl-1,2,4-triazinium salts undergo the intramolecular Diels-Alder reaction into the corresponding thieno [2,3-b]- and thiopyrano [2,3-b]pyridines under considerably milder conditions than the corresponding neutral 1,2,4-triazines.

Rate and equilibrium constants for the dissociation of cyanide ion from 1-benzyl-4-cyano-1,4-dihydronicotinamide (BNA-CN) in acetonitrile at 25°C have been evaluated. Compared to water as the solvent, the dissociation constant in acetonitrile, K diss = 3.9(±0.6) × 10 −7 m , is approximately a factor 10 6 lower. This reduction is brought about by a nearly 10 2 slower rate of dissociation ( k 1 = 2.6 × 10 −4 s −1 ) and a 10 4 faster rate of addition of cyanide ion in acetonitrile. Addition of zinc salts, like zinc perchlorate, zinc bromide, and zinc iodide, induce cyanide ion dissociation by both entrapment of cyanide ion and efficient promotion of the cyanide ion expulsion. Remarkably, the latter effect is dependent on the nature of the zinc counterion and increases in the order ClO 4 − − − . It is concluded that the zinc-promoted cyanide expulsion is preceded by complex formation of zinc species with BNA-CN and that both Zn 2+ and monoionized Zn X + species are active. A transition state model for the reaction is proposed.

Thermally induced intramolecular Diels-Alder cyclisations of (alkynyloxyalkyl)pyrazines to dihydropyranopyridines have been studied in the solvent undecane. The introduction of a phenyl group in the α-position of the 3-butynyloxymethyl side chain leads to a 3–4 fold increase of the reaction rate, while the influence of a γ-phenyl group on the rate is negligible. The (3-butynyloxymethyl)pyrazine reacts about 7 times slower than the (3-propynyloxyethyl)pyrazine, the presence of a trimethylsilyl group at the terminus of the alkyne decreases in general the rate of the intramolecular cyclisations. The mechanisms are discussed.

5-Nitropyrimidine undergoes inverse Diels-Alder cycloadditions with ketene_N,N-, -O,O- acetals and enamines resulting in pyridine derivatives. The 1H NMR evidence for the 1 -N,N-diethyl-aminopropyne cycloadduct formation is presented.

Phosphitylation of the allylic hydroxy group in 9-tetrahydropyranyltrans-zeatine with salicyl chlorophosphite gives the allyl phosphonate monoester 5, which can be readily converted into the corresponding phosphate 7, methylphosphate 8 or thiophosphate 9. After cleavage of the tetrahydropyranyl group under mild acidic condition allylic phosphate derivatives of trans-zeatin are obtained.

Zinc 1-(α-2-methyl-1,10-phenanthroline)-1,4-dihydronicotinamide has been synthetized as a model for the enzyme-coenzyme complex of NADH-alcohol dehydrogenase. The model forms with 2-pyridinecarboxaldehyde a ternary complex in which the phenanthroline-bound zinc ion activates the aldehyde group for reduction. Transfer of a hydride equivalent in this complex occurs in an orientation in which the dihydronicotinamide ring lies over the carbonyl group with the carbonyl oxygen pointing to the ring nitrogen. Kinetic data for the reaction are given.