Studies on the syntheses of analgesics. Part XXXII. An alternative synthesis of 1,2,3,4,5,6-Hexahydro-8-hydroxy-6,11-dimethyl-3-(3-methyl-2-butenyl)-2,6-methano-3-benzazoeine [Studies on the syntheses of heterocyclic compounds. Part CDLXXX]

Bischler-Napieralski reaction of the amides (VIII and IX), derived from the 3-methyl-3-pentenylamine (III) with the phenylacetic acid derivatives (V ～ VII), gave the 5,6-dihydropyridines (XII and XIII), which were reduced, followed by N-benzylation, to afford the 1,2,5,6-tetrahydropyridines (XIX ～ XXI). Grewe-type cyclization of these compounds gave 3-benzyl-3-benzazocine (II), which was already converted into pentazocine (Ic). Moreover, the 1,2,5,6-tetrahydropyridines (XIX ～ XXI) were also obtained from the 2-benzylidene-1,2,5,6-tetrahydropyridine (XVII ～ XVIII) from the N-benzylamine (IV) of III via the amides (X and XI).     

SYNTHESIS AND REACTIONS OF SOME NEW THIENO[2,3-b]-PYRIDINES AND THE ANTIMICROBIAL EFFECTS

Abstract

3,5-Dicyano-6-mercapto-4-phenylpyridin-2(1H)-one (1) was reacted with ethyl chloroacetate to give compound (II) which on reaction with hydrazine hydrate gave the corresponding hydrazide derivative (III). Acylation of (III) with acetic acid, phenylisocyanate, or phenylisothiocyanate gave different monoacyl derivatives (IV-VI). Condensation of III with aromatic aldehydes and acetylacetone gave compounds VII_a-c, VIII respectively. Compound I was reacted with chloroanilides, bromoacetone and phenacyl bromide to yield the IX-XI; these and compound II gave thieno[2,3-b]-pyridines (XU-XV) on treatment with sodium ethoxide solution. Reaction of XII with acetic anhydride gave the diacetyl derivative XVI. Hydrolysis of compound XII with sodium hydroxide gave the corresponding acid (XVII) which on treatment with acetic anhydride gave the oxazine derivative (XVIII). Reaction of oxazine compound XVIII with ammonium acetate and hydrazine hydrate gave pyrido[3′,2′:4,5] thieno[3,2-d]pyrimidin-4.7-dione derivative (XIX) and (XX) respectively. The N-amino derivative (XX) was reacted with 4-nitrobenzaldehyde to give the corresponding azomethine (XXI).

Significant in vitro gram-positive and gram negative antibacterial activities as well as anti-fungal effect were observed for some members of the series.     

Reactions with 2-mercaptopyrimidines. Synthesis of some new thiazolo[3,2-a]- and triazolo[4,3-a]pyrimidines

Alkylation of 5-cyano-4-oxo-6-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine I with methyl iodide, chloroacetic acid or 3-chloro-2,4-pentanedione, afforded the S-alkyl derivatives IIa-c. 2-Carboxymethylthio and 2-(2′,4′-dioxopentan-3-ylthio) derivatives IIb and IIc could be cyclised by acetic anhydride or polyphosphoric acid to give 6-cyano-3,5-dioxo-5H-7-phenylthiazolo[3,2-a]pyrimidine III and 2-acetyl-6-carboxamido-5H-3-methyl-7-phenylthiazolo[3,2-a]pyrimidine-5-one IX , respectively. Benzoylation of 2-hydrazinopyrimidine derivative XII , in anhydrous dioxan, afforded the N-benzoyl derivative XIII , which could be cyclised by heating in dimethylformamide to give 5-amino-6-cyano-3,7-diphenyl-s-triazolo[4,3-a]pyrimidine ( XIV ). The 2-hydrazinopyrimidine derivatives XII and XV reacted with benzoyl isothiocyanate in dioxane to yield 4-benzoylthiosemicarbazide derivatives XVI and XVII , which were converted into the 2-s-trizolopyrimidine derivatives XVIII and XIX , respectively. Also, XVI and XVII reacted with 2,4-pentanedione and 3-chloro-2,4-pentanedione to yield 2-pyrazolopyrimidine derivatives XX and XXI , respectively.     

Reactions of tetrafluoroethylene oligomers. Part 1. Some pyrolytic reactions of the pentamer and hexaher and of the fluorine adducts of the tetramer and pentamer

Pyrolyses of these highly branched fluorocarbons over glass beads caused the preferential thermolyses of CC bonds where there is maximum carbon substitution. Fluorinations of perfluoro-3,4-dimethylhex-3-ene (tetramer) (I) and perfluoro-4-ethyl-3,4-dimethylhex- 2-ehe (pentamer) (II) over cobalt (III) fluoride at 230° and 145° respectively afforded the corresponding saturated fluorocarbons (III) and (IV), though II gave principally the saturated tetramer (III) at 250°. Pyrolysis of III alone at 500—520° gave perfluoro-2-methylbutane (V), whilst pyrolysis of III in the presence of bromine or toluene afforded 2-bromononafluorobutane (VI) and 2H-nonafluorobutane (VII) respectively. Pyrolysis of perfluoro-3-ethyl-3, 4-dimethylhexane (IV) alone gave a mixture of perfluoro-2-methylbutane (V), perfluoro-2-methylbut-1-ene (VIII), perfluoro-3-methylpentane (IX), perfluoro-3,3-dimethylpentane (X), and perfluoro-3,4- dimethylhexane (III). Pyrolysis of IV in the presence of bromine gave (VI) and 3-bromo-3-trifluoromethyl-decafluoropentane (XI): with toluene, pyrolysis gare VlI and 3H-3-trifluoromethyldecafluoropentane (XII). Pyrolysis of II at 500° over glass gave perfluoro-1,2,3-trimethylcyclobutene (XIII) and perfluoro-2,3-dimethylpenta-1,3(E)- and (Z)-diene (XIV) and (XV) respectively. The diene mixture (XIV and XV) was fluorinated with CoF₃ to give perfluoro-2,3-dimethylpentane (XVI) and was cyclised thermally to give the cyclobutene (XIII). Pyrolysis of perfluoro-2- (1′-ethyl-1′-methylpropyl)-3-methylpent-1-ene (XVII) (TFE hexamer major isomer) at 500° gave perfluoro-1-methyl-2-(1′-methylpropyl)cyclobut-1-ene (XVIII) and perfluoro-2-methyl-2-(1′-methylpropyl)buta-1,3-diene (XIX). Fluorination of XVIII over CoF₃ gave perfluoro-1-methyl-2- (1′-methylpropyl)cyclobutane (XX), which on co-pyrolysis with bromine gave VI. XIX on heating gave XVIII. Reaction of XVIII with ammonia in ether gave a mixture of E and Z 1′-trifluoromethyl-2-(1′-trifluoromethyl- pentafluoropropyliden-1′-yl)tetrafluorocyclobutylamine (XXI) which on diazotisation and hydrolysis afforded 2-(2′trifluoromethyl- tetrafluorocyclobut-1-en-1′-yl)-octafluorobutan-2-ol (XXII).     

Synthesis of vitamin b6 derivatives. II. 3-Hydroxy-4-hydroxymethyl-2-methyl-5-pyridine acetic acid and related substances

The syntheses of 3-hydroxy-4-hydroxymethyl-2-methyl-5-pyridineacetic and -5-pyridine-propionic acids and several related compounds are described. Although acid hydrolysis of α⁴,3-O-isopropylidene-5-pyridoxic acid gives 5-pyridoxic acid lactone (α-pyracin), its higher homolog α⁴,3-O-isopropylidene-pyridoxylformic acid gave a corresponding free alcohol whose carboxylic acid proton was shown to be exchanged rapidly with the 3-phenolic and -4-alcoholic - protons in nuclear magnetic resonance studies. Inter-molecular hydrogen bonding between the side chain carboxylic acid and pyridine nitrogen atoms is suggested in the solid state.     

Syntheses of benzomorphan and related compounds. Part III. An alternate synthesis of 3-substituted-1,2,3,4,5,6-hexahydro-8-hydroxy-2,6-methano-6,11-dimethyl-3-benzazocine

Reduction of the appropriate Schiff bases gave 5-benzylamino-3-methyl-2-pentene (XVII) and l-benzylamino-3-methylpentane (XVIII), the condensation of which with methyl 3-(4-methoxyphenyl)-2,3-epoxypropionate afforded a mixture of the isomeric 1-benzyl-2-(4-methoxy-benzyl)-3,4-dimethyl-4-hydroxypiperidines (XIXa and XIXb). The piperidinols were heated with hydrobromic acid, respectively, to afford 3-benzyl-1,2,3,4,5,6-hexahydro-8-hydroxy-2,6-methano-6,11-dimethyl-3-benzazocine (II). Since the conversion of II to pentazocine (Ic) had already been accomplished, an alternate synthesis of Ic was achieved.     

Synthesis of a 2-Methyl-4-sulfanilamido-s-triazine derivative

An attempt to obtain 2-methyl-4-sulfanilamido-s-triazine (XXI) by condensation of 2-amino-4-methyl-s-triazine (II) with p-acetamidobenzenesulfonyl chloride (III) in pyridine and in benzene containing trimethylamine gave instead the unexpected products, guanidine N-acetylsulfanilate (IV) (after hydrolysis) and N¹,N¹-dimethylsulfanilamide (V), respectively. On the other hand, 2-methyl-4-methylthio-6-sulfanilamido-s-triazine (XIX) was obtained from 4,6-dimethylthio-s-triazine (XVII), but the reduction of XIX with Raney nickel in aqueous sodium hydroxide solution also gave an unexpected compound, sulfaguanidine (XX).     

The synthesis of ω-dialkylaminoalkylaminopyrazino[2,3-d]-, pyrido[2,3-d]-, imidazo[4,5-c]- and imidazo[4,5-d]pyridazines

The synthesis of 5-chloro-8-(ω-dialkylaminoalkylamino)pyrazino[2,3-d]pyridazine (II) proceeded smoothly when 5,8-dichloropyrazino[2,3-d]pyridazine (I) was allowed to react with ω-dialkylaminoalkylamines. Similarly, the reaction of 5,8-dichloropyrido[2,3-d]pyridazine (IV) with ω-dialkylaminoalkylamines gave the two expected products 8-chloro-5-(ω-dialkylaminoalkylamino)pyrido[2,3-d]pyridazine (V) and 5-chloro-8-(ω-dialkylaminoalkylamino)pyrido[2,3-d]pyridazine (VI) in a 2:3 ratio. 4,7-Dichloroimidazo[4,5-d]pyridazine (XII) was found to be much less reactive towards nucleophilic substitutions and more vigorous conditions resulted in disubstituted products (XIII). 7-Chloroimidazo[4,5-c]pyridazine (XVIII) was also found to be much less reactive towards nucleophilic substitution. In both of these cases one of the imidazole nitrogen atoms was blocked by a tetrahydropyranyl group which increased the reactivities and led to the desired monosubstituted products XVII from XII and in the latter case the expected products (XIX).     

The synthesis of pyridazino[4,5-d] pyridazines,pyrazino [2,3-d] pyridazines and a pyrimido [4,5-d] pyridazine

The synthetic chemistry of the relatively unknown pyridazino [4,5-d]pyridazine ring system has been extended. 1,4-Diaminopyridazino [4,5-d]pyridazine (VIII) has been prepared by two routes, the most interesting of these being the one-step conversion of 4,5-dicyanopyridazine into VIII with hydrazine. Upon nitration VIII gave only the mononitramine (X). Attempts to prepare 1,4-dichloropyridazino [4,5-d]pyridazine gave only 4-chloro-2H-pyridazino [4,5-d]pyridazin-1-one (XII). Pyrimido [4,5-d]pyridazine-1,3-dione (XIV) was prepared from pyridazine-4,5-dicarboxamide (IV). The hydrolysis of 5,8-dichloropyrazino [2,3-d]pyridazine (XV) gave 5-chloropyrazino [2,3-d]pyridazin-8-one (XVII) and likewise the ammonolysis of XV gave 5-amino-8-chloropyrazino [2,3-d]pyridazine (XX). As expected the hydrolysis of 5,8-dibromo-pyrazino [2,3-d]pyridazine (XXI) gave 5-bromopyrazino [2,3-d]pyridazin-8-one (XXII). Attempted catalytic dechlorination of 5-chloropyrazino [2,3-d]pyridazin-8-one (XVII) gave 1,2,3,4-tetrahydropyrazino [2,3-d]pyridazin-5-one (XIX).     

Studies on the syntheses of heterocyclic compounds. Part CCLXXIII. Synthesis of C-nordihydrocorynantheol and its related compounds

Mannich reaction of tryptamine with 3,3,4-triethoxycarbonylhexaldehyde (IV) gave the cyclized product (VIII), whose hydrolysis, followed by decarboxylation, afforded the acid (IX). After esterification of IX, reduction of ester (X) with lithium aluminum hydride gave the C-nordihydrocorynantheol (II). The syntheses of IV and XV were also described. Furthermore, the Mannich reaction of L-N-benzyl-1-methyltryptophan methyl ester (XV) with IV was also examined. This reaction gave the ester (XVII), which was hydrolyzed and decarboxylated to give the acid (XVIII). Esterification of XVIII, followed by catalytic hydrogenation, gave the lactam (III).     

Antifilarial and antimalarial agents. Basically substituted 10-aminobenzo[b] [1,5] naphthyridines, 10-Aminobenzo[b] [1,5] naphthyridine N-Oxides,and 8-Amino-1,5-naphthyridines

Various 2-alkoxy 7-chloro-10-[[[(dialkylamino)alkyl]amino]]benzo[b][1,5]naphthyridines (XI) and N-oxides (XV, XVII, XVIII, XXII), 4-[(2-alkoxy-7-chlorobenzo[b][1,5]naphthyridin-10-yl)-amino]-α-(diethylamino)-o-cresol derivatives (XII-XIV, XXI) and N-oxides (XIX, XX, XXV), 2-butoxy-8-[[[(dialkylamino)alkyl]amino]]-1,5-naphthyridines (XXVIa and b), and 2-butoxy-8–[[3-[(diethylamino)methyl]-p-anisidino]]-1,5-naphthyridine (XXVII) were synthesized for antifilarial and antimalarial evaluation. The compounds were obtained in 13–91% yield by the condensation of 2-alkoxy-7,10-dichlorobenzo[b][1,5]naphthyridines, 2-alkoxy-7,10-dichlorobenzo[b][1,5]naphthyridine 5-oxides, and 2-butoxy-8-chloro-1,5-naphthyridine with the appropriate diamine in phenol, or by perbenzoic acid oxidation of the parent 10-amino-7-chlorobenzo-[b][1,5] naphthyridines in chloroform. Among them, eight compounds killed adult Litomosoides carinii in gerbils when administered in daily gavage doses of 25–400 mg./kg. for 5 days. Azacrine 5-oxide (XVII), the most active compound, was equipotent with amodiaquine (1a), azacrine (IX), and quinacrine 10-oxide (VI). Twelve substances were active orally against Plasmodium berghei in mice at doses ranging from 3.8–155 mg./kg./day for 6 days. 7-Chloro-10-[[-3-[(diethylamino)-methyl]-p-anisidino]]-2-methoxybenzo[b][1,5]naphthyridine 5-oxide dihydrochloride (XX) was approximately 12 times as potent as quinine against P. berghei, but was highly cross-resistant with chloroquine (IV). Structure-activity relationships are discussed.     

Synthesis of Terminal Oligosaccharides from Type Specific Lipooligosaccharide of Mycobacterium Tuberculosis

Abstract

The coupling reaction between 1,3-di-O-acetyl-4-O-benzyl-2-O-methyl-α-L-rhamnopyranose (9) and methyl 4-O-benzyl-2-O-methyl-α-L-rhamno-pyranoside (4) was carried out in the presence of boron trifluoride-etherate followed by deacetylation to give the disaccharide (11) containing a free 3′ position. The second glycosylation reaction with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide in the presence of mercuric salts followed by removal of benzyl and acetyl groups provided the trisaccharide 2. The boron trifluoride catalysed condensation of 1,3,4-tri-O-acetyl-2-O-methyl-L-fucopyranose (14) and methyl 2,4,6-tri-O-benzyl-α-d-glucopyranoside (15) gave the disaccharide (16) from which the protecting groups were removed to form the disaccharide (3).     

Synthesis and ring-opening polymerization of new 1,4-anhydro-glucopyranose derivatives

Three new 1,4-anhydro-glucopyranose derivatives having different hydroxyl protective groups such as 1,4-anhydro-2,3,6-tri-O-methyl-α-D -glucopyranose (AMGLU), 1,4-anhydro-6-O-benzyl-2,3-di-O-methyl-α-D -glucopyranose (A6BMG), and 1,4-anhydro-2,3-di-O-methyl-6-O-trityl-α-D -glucopyranose (A6TMG) were synthesized from methyl α-D -glucopyranoside in good yields. Their polymerizability was compared with that of 1,4-anhydro-2,3,6-tri-O-benzyl-α-D -glucopyranose (ABGLU) reported previously. The trimethylated monomer, AMGLU, was polymerized by a PF₅ catalyst to give 1,5-α-furanosidic polymer having number-average molecular weights (M̄_n) in the range of 2.8 × 10³ to 6.8 × 10³. The ¹³C-NMR spectrum was compared with that of methylated amylose and cellulose. Other anhydro monomers, A6BMG and A6TMG, gave the corresponding 1,5-α furanosidic polymers having M̄_n = 17.1 × 10³ and 1.8 × 10³, respectively. Thus, the substituents at the C2 and C6 positions were found to play an important role for the ring-opening polymerizability of the 1,4-anhydro-glucose monomers. In addition, debenzylation of the tribenzylated polymer gave free (1 → 5)-α-D -glucofuranan. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 841–850, 1998     

Studies on the syntheses of analgesics. Part XXXIX . Synthesis of 1,2,3,4,5,6- Hexahydro-8-hydroxy -2,6-methane-3,6,1 1-trimethyl-2,3-benzo|g| diazocine and 1,2,3,4,5,10,11,12-Octahydro-7-hydroxy-1,5-dimethylpyridazino|2,3-b| isoquinoline |studies on the syntheses of heterocyclic compounds. Part LXI |

1,2,3,4,5,6-Hexahydro-8-hydroxy-2,6-methano-3,6,1 1-trimethyl-2,3-benzo |g| diazocine (IV) and 1,2,3,4,5,10,11,12-octahydro-7-hydroxy-1,5-dimethylpyridazino |2,3-b| isoquinoline (VI) were synthesized from a common intermediate, 3-(3-methoxyphenyl)-2-butanone (VII), through several steps. Reaction of VII with ethyl bromoacetate gave the mixture of ethyl 4-keto-3-(3-methoxyphenyl)-3-methylpentanoate (XIV) and ethyl 4-keto-5-(3-methoxyphenyl)hexanoate (XV) which were hydrolyzed and condensed with methylhydrazine to give the 4,5-dihydro-5-(3-methoxyphenyl)-2,5,6-trimethyl- (XVIII) and 4,5-dihydro-6-(3-methoxy-α-methylbenzyl)-2-methylpyridazine-3(2H)one (XIX). Reduction of XVIII and XIX followed hy cyclization afforded the 2,3-benzo |g| diazocine (XXII) and the pyridazino |2,3-b| isoquinoline (XXIII) which on treatment with 47% hydrobromine acid afforded the phenolic bases (IV and VI), respectively. The mass spectrum of IV, VI, XXII and XXIII was also discussed.     

Chemistry of sulfonyl isocyanates and sulfonyl isothiocyanates. X. Possible routes to substituted imidazolidinethiones and hexahydropyrimidinethiones

4-Toluenesulfonyl isocyanate (I) reacted with 2-aminoethanol and 3-amino-l-propanol to give 2:1 isocyanate/amino alcohol addition products. 1-Amino-2-propanol and I gave 1:1 and 2:1 adducts while 2-amino-2-methyl-l-propanol afforded only a 1:1 adduct. 4-Toluenesulfonyl isothio-cyanate (III) gave 1:1 adducts with 2-aminoethanol, l-amino-2-propanol and 3-amino-l-propanol, the first two of which were cyclized by concentrated sulfuric acid to 1-(4-toluenesulfonyl)-imidazoline-2-thiones and the third to 1-(4-toluenesulfonyl)hexahydropyrimidine-2-thione. A 1:2 adduct was obtained from III and 2-amino-2-methyl-l-propanol. Amino acids reacted with I and with 4-chlorobenzenesulfonyl isocyanate (II) to give N-(arylsulfonyl)-N¹-(carboxylic acid)-ureas. N-(4-Toluenesulfonyl)-N¹-(acetic acid)-urea (XVI) was converted to the methyl ester (XIX) by concentrated sulfuric acid and methanol and to water-soluble unrecoverable products by sulfuric acid alone. Glycine and III gave N-(4-toluenesulfonyl)-N¹-(acetic acid)-thiourea (XX) which was converted to the methyl ester (XXII) by concentrated sulfuric acid/methanol and to the cyclic 1-(4-toluenesulfonyl)imidazolin-5-one-2-thione (XXI) by sulfuric acid alone.     

γ- And δ-lycorane

Hydrogenation of -anhydrodihydrocaranine (V) or anhydrocaranine (VII) with Adams catalyst in acetic acid or the Hauptmann reduction of -dihydrocaranone (XX) yielded (—)γ-lycorane (XVII). Catalytic reduction of β-anhydrodihydrocaranine (IX) with palladium-carbon in ethanol gave (+)γ-lycorane (XVIII), while with Adams catalyst in acetic acid it afforded (+)δ-lycorane (XIX) along with (—)β-lycorane (III). Reduction of anhydrocaranine in ethanol gave (±)γ-lycorane which was also obtained by hydrogenation of anhydrolycorine (X). Based on these findings, the configurational structures of -, β-, γ- and δ-lycorane were established and the configuration of dihydrolycorine was confirmed.     

Application of Phenyl 1-Selenoglycosides in the Synthesis of a Cell-Wall Tetrameric Fragment of Proteus Vulgaris Strain 5/43

Abstract

DAST-assisted rearrangement of 3-O-allyl-4-O-benzyl-α-l-rhamnopyranosyl azide followed by treatment of the generated fluorides with ethanethiol and BF₃·OEt₂ gave glycosyl donor ethyl 3-O-allyl-2-azido-4-O-benzyl-2,6-dideoxy-1-thio-α/β-l-glucopyranoside. Stereoselective glycosylation of methyl 4,6-O-benzylidene-2-deoxy-2-phthalimido-β-D-glucopyranoside with ethyl 3-O-allyl-2-azido-4-O-benzyl-2,6-dideoxy-1-thio-α/β-l-glucopyranoside, under the agency of NIS/TfOH afforded methyl 3-O-(3-O-allyl-2-azido-4-O-benzyl-2,6-dideoxy-α-l-glucopyranosyl)-4,6-O-benzyli-dene-2-deoxy-2-phthalimido-β-D-glucopyranoside. Removal of the allyl function of the latter dimer, followed by condensation with properly protected 2-azido-2-deoxy-glucosyl donors, in the presence of suitable promoters, yielded selectively methyl 3-O-(3-O-[6-O-acetyl-2-azido-3,4-di-O-benzyl-2-deoxy-α-D-glucopyranosyl]-2-azido-4-O-benzyl-2,6-dideoxy-α-l-glucopyranosyl)-4,6-O-benzylidene-2-deoxy-2-phthalimido-β-D-glucopyranoside. Deacetylation and subsequent glycosylation of the free HO-6 with phenyl 2,3,4,6-tetra-O-benzoyl-1-seleno-β-D-glucopyranoside in the presence of NIS/TfOH furnished a fully protected tetrasaccharide. Deprotection then gave methyl 3-O-(3-O-[6-O-{β-D-glucopyranosyl}-2-acetamido-2-deoxy-β-D-glucopyranosyl)-2-acetamido-2,6-dideoxy-α-L-glucopyranosyl)-2-acetamido-2-deoxy-β-D-glucopyranoside.     

Ylides du soufre dérivés de sucres Communication préliminaire

S-Methylation of 6-S-benzyl-6-deoxy-1,2-O-isopropylidene-3-O-methyl-α-D-xylo-6-thiohexofuranos-5-ulose ( 1 ) gave the expected sulfonium salt 2 which on alcaline treatment yielded the stable sulfur ylide 3 . This compound constitutes an useful synthetic intermediate in carbohydrate chemistry. On heating in 1,2-dimethoxyethane, it underwent a Stevens rearrangement which led to an extension of the carbon chain of the sugar and, reacted with Michael acceptors, it gave cyclopropanation reactions.     

Syntheses and interconversions of some s-triazolo[3,4-a]isoquinolines

s-Triazolo[3,4-a]isoquinoline (II) and its 3-methyl analogue (III) have been synthesized from 1-isoquinolylhydrazine (I) by cyclisation with formic and acetic acid. The 3-hydroxy derivative (IV) has been shown to exist in the lactam form. Methylation with methyl iodide gave the N-methyl derivative (V). Dimethyl sulphate and diazomethane also led exclusively to the same product. The O-methyl derivative (IX) could be obtained only through the 3-chloro compound (VIII). The chlorine atom in VIII undergoes nucleophilic replacement easily. The 3,6-dichloro derivative (X) has also been prepared. Several interconversions in the series are described. Aryl hydrazones (XVIII) prepared from (I) have been oxidatively cyclised to give 3-aryl-s-triazolo[3,4-a]isoquinolines (XIX). U.V., I.R. and P.M.R. spectra have been recorded and used for assignment of structures in some cases.     

Preparation of 2-Azido-4-O-benzoyl-2,6-dideoxy-3-O-methyl-β-D-allopyranose and Its Disaccharide Derivative

Abstract

2-Azido-4-O-benzoyl-2,6-dideoxy-3-O-methyl-D-allopyranose, needed as one of the building blocks for construction of a novel cyclodextrin-like compound, was prepared in the form of crystalline β-anomer 6 from methyl 2-azido-4,6-O-benzylidene-2-deoxy-α-D-allopyranoside 1. As a model of α-glycosidation necessary for formation of a cyclic structure, 6 was converted into the corresponding β-glycosyl trichloroacetimidate and coupled with methyl 6-O-benzyl-2,3-di-O-methyl-α-D-glucopyranoside 8, giving α(1→4)-linked disaccharide derivative 9.