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This paper reports synthesis and characterization, by spectroscopic methods, of three new N-methyl-5-phenyl-7-chloro-1,2,3-triazolo[4,5-d]pyrimidine isomers 3a, 3b and 3c. For comparison purpose the 3-benzyl-5-phenyl-7-chloro-1,2,3-triazolo[4,5-d]pyrimidine (7) was also prepared. Starting from the isomer mixture 3a-c and the chloroderivative 7, by nucleophilic substitution reaction with ethyl carbazate and subsequent intramolecular cyclization, the new tricyclic derivatives 5a-c and 9 were prepared and tested towards the benzodiazepine and adenosine A1 and A2A receptors.

New tricyclic 1,2,3-triazolo-1,2,4-triazolo-pyridazine derivatives, bearing a methyl substituent on the 1,2,3-triazole ring, were prepared as potential biological agents. N-Methylation of dimethyl 1,2,3-triazole-4,5-dicarboxylate allowed synthesis of the isomeric 1-methyl-4,7-dihydroxy and 2-methyl-4,7-dihydroxy triazolo-pyridazines 4a and 4b which, by a chlorination reaction, gave the corresponding 1-methyl-4-chloro-(6a), 1-methyl-7-chloro- (6b) and 2-methyl-4-chloro- (9) substituted 1,2,3-triazolo-pyridazines. The nucle-ophilic substitution with hydrazine hydrate and the suitable cyclization to form the 1,2,4-triazole ring, provided the expected tricyclic isomeric derivatives 8a, 8b and 11 respectively. The p-methoxybenzyl substituent, introduced as a leaving group to obtain either v-triazolo-pyridazine or v-triazolo-s-triazolo-pyri-dazine derivatives unsubstituted on the 1,2,3-triazole ring, appeared inadequate. Some compounds underwent binding assays toward the adenosine A1and A2A receptors.

This paper reports the synthesis of a series of new 5-substituted-1-(2-hydroxybenzoyl)-benzotriazoles, which have been tested for their activity as possible activators of potassium channels. In rat aortic rings, the 'opened' derivatives 1a-f, intermediates of synthesis, showed vasorelaxing properties, with appreciable values of potency. However, the most remarkable effects were recorded for the 2-hydroxybenzoylbenzotriazoles 3a-f, which showed full vasorelaxing efficacy and high potency values. The introduction of a 2-hydroxybenzyl substituent in the 1 position of the benzotriazole ring (compound 7) strongly decreased the activity, showing the importance of the electron-acceptor carbonyl function. The best compound, 3b, was further investigated, in order to evaluate the possible mechanism of action involved in the vasodilator activity. In the vascular model, different potassium channel blockers inhibited the effects of the compound, and an increase of the levels of membrane depolarisation induced a significant reduction of the recorded responses. Compound 3b was also tested in a model of isolated rat heart, retroperfused through the aorta and submitted to a global ischemia/reperfusion cycle. In such an experimental condition, 3b showed an interesting cardioprotective activity. All the above observations are in agreement with the hypothesis of a mechanism linked to the activation of potassium channels.

Synthesis and reactions of 6-chloro-7-fluoro-4-oxo-4H-chromene-3-carboxylic acid are described. The molecular structure of its achiral heterotopic 3-diethoxy-methyl precursor has been determined by NMR spectroscopy and X-ray crystallography. C14H14ClFO4 is monoclinic, space group P21/a, with unit cell dimensions a = 14.923(5), b = 6.615(2), c = 14.921(5) Å, β = 101.44(3)°, V = 1443.7(8) Å3, Z = 4, D calc. = 1.383 g/cm3.

The inosose derivative 3 was obtained with high stereoselectivity by intramolecular aldol condensation of the aldohexos-5-ulose derivative 2 , and it was selectively reduced and debenzylated to give epi -inositol in high yield. The stereochemistry and the preferred conformations of compounds 3 – 7 were determined through 1D and 2D NMR experiments.

The unreported title compound and its 2,6-di-O-benzyl derivative have been prepared from methyl β-D-galactopyranoside through a sequence involving the bisglycoside methyl 2,6-di-O-benzyl-5-O-methoxv-β-D-galactopyranoside 8, the precursor of L-orabino-hexos-5-ulose, that was converted to the L-lyxo series by inversion at C-3. The inversion was achieved in acceptable yields by selective triflation, followed by displacement with benzoate, and by an oxidation/reduction sequence. Whereas 2,5-di-O-benzyl-L-lyxo-hexos-5-ulose exists entirely as a mixture of the two anomeric 1,4-furanosic forms, the unprotected hexos-5-ulose involves at equilibrium in CD3CN/D2O at least eight tautomers, one of which is predominant.

This paper continues the synthesis of new 1,2,3-triazolo[1,2-a]benzotriazoles or 2,3-benzo-1,3a,6,6a-tetrazapentalenes to submit to biological assays. The derivatives were obtained by deoxycyclization reactions of appropriate nitrophenyl-1,2,3-triazole derivatives and by thermal decomposition of appropriate azidophenyl-1,2,3-triazoles (Schemes 1 and 2). Some attempts to extend these synthetic routes to the preparation of 1,2,4-triazolo[1,2-a]benzotriazoles (Scheme 3) and 1,2,3-triazolo[1,2-b]-4H-1,2,3-benzo-triazines (Scheme 4) completely failed.

Efficient preparations both of 2,3:5,6:3′,4′-tri-O-isopropylidenelactose dimethyl acetal (5, 95% yield) and its 6′-O-(1-methoxy-1-methylethyl) derivative (65% yield), useful intermediates for the conversion of lactose into biologically relevant oligosaccharides, by ‘one-pot’ acetonation procedures with 2,2-dimethoxypropane are reported. The acetonation of 5 with 2-methoxypropene in the presence of pyridinium tosylate and 4 A molecular sieves unexpectedly revealed the formation, in a first kinetic reaction phase, of similar amounts of the 2′-O- and 6′-O-(1-methoxy-1-methylethyl) acetals. The structures of all new products were fully characterized by NMR analyses, which also allowed some deductions on the conformation of the galactopyranosyl rings.

Some new v-triazolo[1,2-a]benzotriazoles or 2,3-benzo-1,3a,6,6a-tetraazapentalenes were prepared according to previously employed synthetic routes concerning deoxycyclization reactions of appropriate nitrophenyl-1,2,3-triazole derivatives and/or thermal decompositions of appropriate azidophenyl-1,2,3-triazoles. The nitration of 9-phenyl-1,2,3-triazolo[1,2-a]benzotriazoles allowed the isolation of some mononitro- and trinitro-derivatives, whose structures were assigned by chemical and spectroscopic methods.

Several new 1,2,3-triazolo[4,5-b][1,4]diazepines were prepared starting from 1-benzyl-1 and 1-phenethyl-4,5-diamino-1,2,3-triazole 2 (Scheme 1), by condensation reactions with β-diketones (Scheme 2), β-ketoesters (Scheme 3), and diethyl malonates (Scheme 4). In the first case we obtained compounds 3 and 4 with basic properties, while the ester function condensations gave cyclic amide derivatives 7, 8, 10, 12 and 13 with acid properties. Some N-methyl derivatives 11, 14 and 15 were obtained from the cyclic amide compounds. Most of compounds were tested for their ability to displace [3H]flunitrazepam from bovine brain membranes but no compound showed benzodiazepine receptor binding affinity.

3,4-Epoxytetrahydrofuran is hydrolyzed by rabbit liver microsomal epoxide hydrolase (MEH) with a high preference for the attack by water at the (S) epoxide carbon to give the (R,R)-diol with an e.e. of 96.5±0.3%. In the acid catalyzed hydrolysis of trans-3,3a-epoxyoctahydrobenzofuran the oxirane ring is opened with inversion exclusively on the tertiary carbon atom to give the corresponding trans-diol, whereas hydrolysis of the cis isomer is less regioselective, the ratio of attack at the tertiary and secondary carbons being 81:19. The MEH catalyzed hydrolysis of the same two substrates occurs exclusively at their secondary epoxide carbons and with a very high enantioselectivity: only enantiomers of configuration (3S,3aR) of the cis- and trans-epoxide are substrates for the enzyme and give the corresponding (3R,3aR)-diols with at least 98% e.e., the corresponding (3R,3aS)-epoxides being totally resistant to enzymatic hydrolysis. These results agree well with previously formulated rules on steric requirements of MEH subtrates. Absolute configurations and optical purities of new chiral compounds were obtained by chiroptical, NMR and chiral chromatographic techniques. Conformations of the octahydrobenzofuran derivatives were derived from coupling constants and found to be in fairly good agreement with those deduced from molecular mechanics calculations.

3,4-Epoxytetrahydrofuran is hydrolyzed by rabbit liver microsomal epoxide hydrolase (MEH) with a high preference for the attack by water at the (S) epoxide carbon to give the (R,R)-diol with an e.e. of 96.5±0.3%. In the acid catalyzed hydrolysis of trans-3,3a-epoxyoctahydrobenzofuran the oxirane ring is opened with inversion exclusively on the tertiary carbon atom to give the corresponding trans-diol, whereas hydrolysis of the cis isomer is less regioselective, the ratio of attack at the tertiary and secondary carbons being 81:19. The MEH catalyzed hydrolysis of the same two substrates occurs exclusively at their secondary epoxide carbons and with a very high enantioselectivity: only enantiomers of configuration (3S,3aR) of the cis- and trans-epoxide are substrates for the enzyme and give the corresponding (3R,3aR)-diols with at least 98% e.e., the corresponding (3R,3aS)-epoxides being totally resistant to enzymatic hydrolysis. These results agree well with previously formulated rules on steric requirements of MEH subtrates. Absolute configurations and optical purities of new chiral compounds were obtained by chiroptical, NMR and chiral chromatographic techniques. Conformations of the octahydrobenzofuran derivatives were derived from coupling constants and found to be in fairly good agreement with those deduced from molecular mechanics calculations.

Some new v-triazolo[1,2-a]benzotriazoles or 2,3-benzo-1,3a,6,6a-tetraazapentalenes were prepared according to previously employed synthetic routes concerning deoxycyclization reactions of appropriate nitrophenyl-1,2,3-triazole derivatives and/or thermal decompositions of appropriate azidophenyl-1,2,3-triazoles. The nitration of 9-phenyl-1,2,3-triazolo[1,2-a]benzotriazoles allowed the isolation of some mononitro- and trinitro-derivatives, whose structures were assigned by chemical and spectroscopic methods.

A new 4-(benzotriazol-1-yl)-1,2,3-triazole structure was obtained by the diazotization reaction of either of 1-(2-aminophenyl)-4-carboxamido-5-amino-1H-1,2,3-triazole (1c) or of the corresponding Dimroth isomer 1d. It underwent some common reactions to evaluate its chemical behaviour and structure. An analogous reaction sequence was carried out from the 2-nitro-4-methylphenyl azide, to assign the structure to the nitro derivatives prepared. The structure of the new compounds prepared was confirmed by chemical and spectroscopic methods.

This paper reports the synthesis of new 1,2,3-triazolo[1,4]benzodiazepine and 1,2,3-triazolo[1,5]benzodiazepine derivatives and their evaluation toward benzodiazepine receptors. Receptor affinity gradually and remarkably increases by moving the nitrogen atom of the central ring from position 3 through 4 to position 5, to give the most effective compound 6a (Ki=150 nM). N-methylation of the diazepine ring (7a) lowers receptorial binding. Introduction of a chlorine atom on the benzene ring doubles the Ki value (6b) which remains unaltered by the N-methylation (7b).

This paper reports the synthesis and evaluation of the biological affinity towards benzodiazepine and A(1) and A(2A) adenosine receptors of some 3-ethoxycarbonyl or 3-phenyl-substituted 1,2, 3-triazolo[1,5-a]quinazolines. Starting from the appropriate chloro-substituted phenylazides, the series of 7 or 8 chloro-substituted triazoloquinazolines were prepared. Nitration reactions of the triazoloquinazoline ring and chlorination reactions of the hydroxyl group in the 5 position of the same ring are also reported. By nucleophilic displacement of halogen, the corresponding 5-amino derivatives and some analogous derivatives bearing cyclohexylamino and p-toluidino substituents were obtained. The binding assays showed a generalized decrease in the affinity towards the benzodiazepine receptors and confirmed a moderate affinity towards the A(1) adenosine receptors in comparison with the previously studied triazoloquinazoline derivatives.

3,4-O-Isopropylidene derivatives of the title compounds have been prepared by new methods and found to exhibit a high preference for tautomeric forms deriving from hemiacetalization between 6-CH2OH, or 6-CH(OH)2, and 2-CO functions.

1,5-Anhydro- d -galactitol, easily available from d -galactose, was selectively protected in positions 2, 3 and 4 and converted into 5-O-acetyl-2,6-anhydro-3-deoxy l -threo-hex-2-enonic acid methyl ester, which, on reaction with MCPBA in acetic acid gave 2,5-di-O-acetyl-α- l -lyxo-hex-2-ulopyranosonic acid methyl ester. Reaction of the latter with sodium methoxide produced sodium l -ascorbate in high yield. Several side-reactions and the conformations of some of the intermediates are also discussed.

This paper reports the synthesis and evaluation of the biological affinity towards benzodiazepine and A(1) and A(2A) adenosine receptors of some 3-ethoxycarbonyl or 3-phenyl-substituted 1,2, 3-triazolo[1,5-a]quinazolines. Starting from the appropriate chloro-substituted phenylazides, the series of 7 or 8 chloro-substituted triazoloquinazolines were prepared. Nitration reactions of the triazoloquinazoline ring and chlorination reactions of the hydroxyl group in the 5 position of the same ring are also reported. By nucleophilic displacement of halogen, the corresponding 5-amino derivatives and some analogous derivatives bearing cyclohexylamino and p-toluidino substituents were obtained. The binding assays showed a generalized decrease in the affinity towards the benzodiazepine receptors and confirmed a moderate affinity towards the A(1) adenosine receptors in comparison with the previously studied triazoloquinazoline derivatives.

A series of 1,8-naphthyridine derivatives (12-36), bearing a phenyl group in position 2 and various substituents in positions 4 and 7, were synthesized in an attempt to obtain potent, selective antagonists for the A1 adenosine receptor subtype. The compounds were tested to evaluate their affinity for A1 compared with A2A and A3 adenosine receptor subtypes. In binding studies in bovine brain cortical membranes, most of the compounds showed an affinity for A1 receptors in the low nanomolar range and two in the subnanomolar range with an interesting degree of A1 versus A2A and A3 selectivity. Comparison of the 4-substituted derivatives indicated that 4-OH substitution, with a 4-quinoid structure, causes an increase in the A1 and A2A affinity and generally also in A1 selectivity. The kind of substitution in position 7 can greatly modulate the affinity: the most interesting substituents in this position seemed to be electron-withdrawing groups; in particular the 7-chloronaphthyridine 25d showed a remarkable selectivity (A2A/A1 ratio of 670, A3/A1 ratio of 14,000) associated with a higher A1 affinity (Ki = 0.15 nM). NMR studies on these compounds 12-36 indicated that the 4-OH-substituted ones prefer the tautomer in which the oxygen in position 4 is in the quinoid form and the nitrogen in position 1 is protonated. Theoretical calculations are in agreement with the NMR data.

The title compound, previously unreported in either enantioform, and its 2,6-di-O-benzyl derivative have been synthesized through a stereocontrolled epimerization at C-2 of 6-O-protected methyl 3,4-O-isopropylidene-5-C-methoxy-β-D-galactopyranosides. The epimerization, performed through a high yielding sequence of oxidation-reduction owing to the cooperative role of the equatorial C-1 aglycon and the steric hindrance of the isopropylidene group, turned out to be completely diastereoselective. Whereas the unprotected L-ribo-hexos-5-ulose exists, as proved by NMR in D2O, in five main tautomeric forms in a ratio of about 4:2:2:1:1, only two anomeric 1,4-furanosic forms are present at equilibrium in its 2,6-di-O-benzyl derivative, in ratios ranging from 10:1 to 7:3, depending on the prevalence of D2O or CD3CN in the solvent mixture.

This paper reports the synthesis of new 1,2,3-triazolo[1,4]benzodiazepine and 1,2,3-triazolo[1,5]benzodiazepine derivatives and their evaluation toward benzodiazepine receptors. Receptor affinity gradually and remarkably increases by moving the nitrogen atom of the central ring from position 3 through 4 to position 5, to give the most effective compound 6a (Ki=150 nM). N-methylation of the diazepine ring (7a) lowers receptorial binding. Introduction of a chlorine atom on the benzene ring doubles the Ki value (6b) which remains unaltered by the N-methylation (7b).

The Pseudomonas sp. (LPS) promoted acyl transfer from vinyl acetate to selected 3,4-O-isopropylidene-D-galactopyranosides takes place in a completely selective manner giving in high yield the corresponding 6-O-acetates. The acetylation rate is strongly dependent on the type and the orientation of the aglycon, varying from a maximum of reactivity for the 1-deoxy derivative, 1,5-anhydro-3,4-O-isopropylidene-D-galactitol (1d), to a minimum for β configurated alkyl glycosides and showing a complete loss of reactivity for 3′,4′:2,3:5,6-tri-O-isopropylidenelactose dimethyl acetal (1e). The latter compound is, however, selectively 6′-O-esterified in good yield by lipase from Candida Antarctica and vinyl acetate. Also the course of the enzymatic hydrolysis of 2,6-di-O-acetyl-3,4-O-isopropylidene-D-galactopyranosides 2 is dependent on the type of the aglycon, both for the reaction rate and the selectivity. The 2-O-acetates 4 are selectively obtained in good yields with porcine pancreatic lipase (PPL) prom...

The double reductive amination of l - arabino -hexos-5-ulose with benzhydrylamine and NaBH 3 CN takes place in a diastereospecific manner giving in moderate chemical yield (36 %) the galactosidase inhibitor 1-deoxy- d -galactostatin. The aminocyclization of 2,6- di -O- benzyl- l -arabino- hexos-5-ulose is more complicated giving results dependent from the type of amine: with ammonia or methylamine a mixture of C-5 epimeric 1-deoxyazapyranoses ( d -galacto l -altro ratio ≈ 4:1 ) is obtained in 45–65% combined yield, while with benzhydrylamine substantial amounts of an acyclic 1-deoxy-1-benzydrylamino-hexitol (10 % yield) is isolated together with the expected 1-deoxy-azasugars of the d - galacto and l - altro series.

A new 4-(benzotriazol-1-yl)-1,2,3-triazole structure was obtained by the diazotization reaction of either of 1-(2-aminophenyl)-4-carboxamido-5-amino-1H-1,2,3-triazole (1c) or of the corresponding Dimroth isomer 1d. It underwent some common reactions to evaluate its chemical behaviour and structure. An analogous reaction sequence was carried out from the 2-nitro-4-methylphenyl azide, to assign the structure to the nitro derivatives prepared. The structure of the new compounds prepared was confirmed by chemical and spectroscopic methods.

3,4- O -Isopropylidene- d - lyxo -hexopyranosid-2-ulose derivatives, obtained by oxidation of 3,4,6-protected d -galactopyranosides, can be alkylated in their anionic 2,6-pyranose forms to produce bis-glycosides containing the 2,5-dioxabicyclo[2.2.2]octane ring system. The 1-benzyl-2-methyl bis-glycoside 4b , when subjected to catalytic hydrogenolysis, produces the methyl d - lyxo -hexopyranos-2-uloside 10 , existing as an 8:2 mixture of 1,5-pyranose anomers 9 . Computational and NMR evidence is presented in favour of the hypothesis that the major anomer has the α configuration. Reduction of 9/10 with NaBH 4 gives methyl 3,4- O -isopropylidene-β- d -tagatopyranoside, that can be hydrolyzed to d -tagatose. A simple synthesis of 1,5-anhydro- d -tagatose, starting from 1,5-anhydro- d -galactitol, is also presented. All new compounds were fully characterized by elemental analysis and by 1 H and 13 C NMR spectroscopy.

Several 9-(2′,3′-O-isopropylidene)- and 9-(2′,3′-dihydroxypropyl)-8-azahypoxanthines and 8-azaadenines were synthesized by a “one pot” method starting from the acetonide of racemic or (S)-1-azido-2,3-dihydroxypropane, obtained from D-mannitol. 9-(2′,3′-Dihydroxypropyl)-8-azapurines were tested as adenosine deaminase inhibitors.

1 H N.m.r. spectra of [14N]- and [15N]-pyridine partially oriented in nematic phase IV in the presence of iodine show dipolar couplings (Dij) increasing linearly as a function of iodine concentration. The spectral changes induced by iodine can be rationalized, to a first approximation, by assuming that the pyridine molecule is in equilibrium, in the oriented phase, with the pyridine–iodine charge transfer complex so that a considerable variation in the mean orientation of the pyridine moiety occurs. Attempts to reproduce the measured dipolar couplings of the exchanging complex on the basis of an average geometry and orientation afforded only dramatic distortion effects on the apparent geometry. Looking, moreover, at the geometry of [15N]pyridine in phase IV and in other liquid crystals geometrical distortions were also found, probably due to solute–solvent interactions, except for the ZLI 1167 phase, where an rα structure in close agreement with gas-phase microwave measurements was observed. The results suggest that, for pyridine in the nematic phase in the presence of iodine, at least a three-site mechanism is operating, one of the sites being the complexed pyridine.

A new simple method for the synthesis of title compounds is described starting from malononitrile, benzyl-azide and an aliphatic or aromatic nitrile.

A series of (η6-arene)(η4-cyclo-octa-1, 5-diene)ruthenium(0) complexes have been readily prepared by reaction of (η4-cyclo-octa-1,5-diene)(η6-cyclo-octa-1, 3, 5-triene)ruthenium(0) with arene compounds, under 1 atm H2[arene = C6H6, CH3 C6H5, 1, 4-Me2C6H4, 1,3,5-Me3C6H3, C2H5C6H5, Me2CHC6H5, Et2CHC6H5, C6H5(CH2)3 C6H5,C6H5C6H5, C2H5CH(Me)C6H5, Me2CHCH(Me)C6H5, NH2CH(Me)C6H5, CH3OC6H5, or CH3COC6H5]. These complexes react with aqueous HCI to give in almost quantitative yield the corresponding (η6-arene)-dichlororuthenium(II) complexes.

Kinetically controlled reaction of 4.5 equiv. of 2-methoxypropene with some alkyl α- and β- d -galactopyranosides gave the 2,3:4,6-di- O -isopropylidene derivatives in high yields (80–85%). With 2 equiv. of 2-methoxypropene, benzyl β- d -galactopyranoside gave the 4,6- and the 3,4-monoacetals in the ratio 30:1 together with ∼20% of the 2,3:4,6-diacetal. The structures of methyl 2,3:4,6-di- O -isopropylidene-α- and -β- d -galactopyranosides were determined by X-ray analysis. The former crystallised in the orthorhombic system, P 2 1 2 1 2 1 , with a = 5.503, b = 16.105, c = 16.822 A, and Z = 4, the latter in the monoclinic system, P 2 1 , with a = 10.400, b = 13.344, c = 11.647 A, β = 111.50, and Z = 4. The α anomer and the two molecules of the β anomer had the d -galactopyranoside and the 1,3-dioxane rings in twist-chair conformations and the dioxolane ring in a half-chair conformation. N.m.r. spectroscopy suggested the occurrence of similar conformations in solution.

Racemic isobutyl 3,4-anhydro-2,6-dideoxy-α- lyxo -hexopyranoside, 3, was prepared starting from the cycloadduct between 3-buten-2-one and isobutyl vinyl ether, through a sequence involving hydroboration-oxidation, mesylation, anomeric equilibration, elimination and epoxidation. The intermediate isobutyl 2,3,4,6-tetradeoxy-α-3-DL-hexenopyranoside, 10 was not stable under the conditions used for its preparation ( t -BuOK in DMSO), being converted in part into the corresponding 2-hexenopyranoside. Under the same conditions the -anomer of 10 was stable. Complete hydrolysis of DL-3 with aqueous NaOH, or with microsomial epoxide hydrolase (MEH) gave exclusively the xylo -diol (isobutyl DL-α-boivinopyranoside 5). When the hydrolysis with MEH was stopped near 50% conversion and the product diol was separated from the unchanged epoxide, both were optically active, the former having the L and the latter the D configuration. An ee of at least 96% was found for both the diol and the epoxide by the use of a chiral shift reagent.

The title compounds gave carbocations in acid media. The electrophilic aromatic substitution of those carbocations was studied.

The reaction of 1,2-epoxy-1-(p-nitrophenyl)cyclohexane with boron trifluoride–diethyl ether exhibits a pronounced solvent dependence: in benzene it gives a 9 : 1 ratio of cis-2-fluoro-2-(p-nitrophenyl)cyclohexanol to 1-(p-nitrophenyl)cyclopentanecarbaldehyde, which does not change with reaction time; in dichloromethane the cis-fluorohydrin is again the main primary product, but is rapidly converted into the aldehyde in the reaction medium; and in ether about equimolar amounts of cis- and trans-2-fluoro-2-(p-nitrophenyl)cyclohexanol are formed. The presence of small amounts of water in the dichloromethane solvent causes the formation of a ca. 6 : 4 mixture of cis-fluorohydrin and aldehyde, the composition of which changes little with reaction time. This solvent dependence of the reaction can be useful for preparative purposes. A reaction mechanism is suggested.

A careful reinvestigation on reductive butylation of N-β-diethylaminoethyl aminophthalimides showed that this reaction yields the corresponding butylaminophthalimides together with the 1-hydroxy butylaminophthalimidines. The same reaction carried out on N-β-diethylaminoethyl aminophthalimides hydrochlorides gave the corresponding butylamino phthalimidines. The 1-hydroxy butylaminophthalimidines 5 and 6, tested for their local anesthetic properties, exhibited interesting activity comparable to that of Novesine, showing hence a potential therapeutic efficacy.

Reaction of several α- and β-galactopyranosides with 2,2-dimethoxypropane produced up to five types of mono-, bis-, and tris(isopropylidene)acetals, among which the 3,4-0-iso-propylidene-6-0-(2-methoxyisopropyl) derivatives can be obtained in high yield and be useful intermediates for selective syntheses of 2-, 6-, and 2,6-0-substituted galactose derivatives.

The NMR spectrum of a bromine—pyridine charge-transfer complex oriented in a nematic phase has been obtained and analyzed. The orientational parameters suggest relative positions of donor and acceptor molecules similar to those found in the solid state analogous halogenpyridine complexes.

The reaction of (1–2 : 5–6-η-cyclo-octa-1,5-diene)(1–6-η-cyclo-octa-1,3,5-triene)ruthenium with P(OMe)3 yielded the title compound which has been structurally characterized by X-ray diffraction studies. The complex crystallizes in the monoclinic space group P21/n with unit-cell dimensions a= 13.306(5), b= 9.628(3), c= 16.382(20)A, β= 111.62(6)°, and Z= 4. The co-ordination geometry around the ruthenium is a distorted square pyramid whose vertices are occupied by the phosphite ligand, the butadiene moiety of cyclo-octatriene, and the two double bonds of cyclo-octadiene.

A new simple method for the synthesis of title compounds is described starting from malononitrile, benzyl-azide and an aliphatic or aromatic nitrile.