Practical One‐Pot Procedure for the Synthesis of 1,2,3,4‐Tetrahydroquinolines by the Imino‐Diels‐Alder Reaction

A novel‐one‐pot procedure for the synthesis of tetrahydroquinolines via the imino‐Diels‐Alder reaction is described. This procedure gives better yields and exhibits better versatility for alkene substrates than the existing hemi‐aminal based methodologies.     

Evaluation of the (Allyl alcohol 1,2‐butoxylate‐block‐etoxylate)‐b‐PMMA Copolymers Composition by the Dielectric Measurements

Redox initiated free‐radical polymerization of methyl methacrylate (MMA) with allyl alcohol 1,2‐butoxylate‐block‐etoxylate (AABE) was carried out to yield AABE‐b‐PMMA copolymers at elevated temperatures. The composition of the copolymers depending on the polymerization temperature was qualitatively estimated by the dielectric measurements. It has been seen that AABE segment quantity decreased and PMMA segment quantity increased with increasing the polymerization temperature. The dielectric constant and the dissipation factor of the copolymers were investigated as a function of frequency and temperature. The dielectric constant and the dissipation factor were found to be strongly affected by the polymerization temperature. The highest dielectric constant in all studied temperatures and frequencies was obtained in the case of the copolymer which was prepared at 313 K. The dipolar C‐O and OH groups of the AABE segment have the primary effect on the dielectric constant. The copolymer which was prepared at 323 K, showed the highest dissipation factor near the relaxation temperature of PMMA.     

Synthesis of the Aliphatic Subunit of the Macrolide LL‐Z 1640‐2 via Vasella Ring Opening of a 6‐Iodo‐4‐deoxy‐D‐mannose

The synthesis of the aliphatic subunit 9 of the macrolide LL‐Z1640‐2 (I), starting from a 4‐deoxy‐D‐mannose derivative 2a, is described. The procedure includes the first successful application of a Vasella ring opening reaction for a 4‐deoxypyranoside. Nucleophilic addition of an alkynyllithium reagent to the aldehyde 4 led to the propargylic alcohol 7, which was converted to the advanced building block 9 in two further steps.     

Application of Dichlorovinyl Xyloside for the Novel Synthesis of 2,3,4‐Tri‐O‐methyl‐D‐xylono‐1,5‐lactone

A novel synthesis of 2,3,4‐tri‐O‐methyl‐D‐xylopyranose, 4, and its oxidation product 2,3,4‐tri‐O‐methyl‐D‐xylono‐1,5‐lactone, 5, are reported. The new synthesis applies a regioselective Wittig‐like reaction of tetra-O-acetyl-D-xylopyranase, 1, with triphenylphosphine and carbon tetrachloride to yield an O‐dichlorovinyl xyloside protected at C‐1, 2. The protecting group facilitates the permethylation of xylose and is removed under the methylation conditions, to yield tetra-O-acetyl-D-xylopyranase, 3. The anomeric methyl group was removed under mildly acidic conditions to give 2,3,4‐tri‐O‐methyl‐D‐xylopyranose, 4, in good yield. Compound 4 was oxidized using pyridinium chlorochromate to give the title compound, 5, in 95% yield.     

New Method for the Synthesis of 2‐Aza‐1,3‐Butadienes

2‐Aza‐1,3‐butadienes have been synthesized from carbonyl compounds and 1,1,1,3,3,3‐hexamethyl‐disilazane in the presence of cobalt‐containing catalysts. The best yields (up to 95%) were achieved in the case of aldehydes branched in the α-position and 2-methylcyclohexanone. In the case of two α,β‐unsaturated ketones, pyridine derivatives were found as the main products.     

Sydnones as Masked Hydrazines for the Synthesis of 4‐Arylazo‐1,2‐dihydro‐pyrazol‐3‐one Derivatives

A simple and convenient one‐pot synthesis of 4‐(4‐chlorophenylazo)‐5‐methyl‐2‐aryl‐1,2‐dihydro‐pyrazol‐3‐ones (4a–j) has been carried out from 3‐arylsydnones (3a–j) by reaction with 2‐(4‐chlorophenyl)‐hydrazono‐3‐oxo‐butyric acid ethyl ester (2b). The 3‐arylsydnones are used as masked hydrazines in this reaction. Similarly, the 4‐arylazo‐2‐(7‐hydroxy‐4‐methyl‐2‐oxo‐2H‐chromen‐8‐ylmethyl)‐5‐methyl‐1,2‐dihydro‐pyrazol‐3‐ones (7a–j) were synthesized from 3‐[(7‐acetoxy‐4‐methyl‐8‐methylene)coumaryl]sydnone (5). All the newly synthesized compounds exhibited antimicrobial activity greater than the reference drugs used.     

Two‐dimensional step‐scan FTIR: a tool to unravel the OH‐valency‐range of the spectrum of Cellulose I

This article presents the results of the first application of dynamic mechanical analysis (DMA) coupled with 2D stepscan Fourier transform infrared (FTIR) spectroscopy, to cellulose. It is demonstrated that the broad hydroxyl infrared absorption band between 3700 and 3000cm^–1 in the cellulose infrared spectra could be separated into distinct bands by this dynamic rheooptical investigation using FTIRspectroscopy as detecting system. The responses of the OHgroups to an external perturbation were recorded as inphase and outofphase spectra. The cross correlation of these spectra gave the 2D synchronous and asynchronous plots, which showed clearly separated bands in the OHvibration range and the relation of the OHgroups to each other. It is demonstrated that it is possible to establish relations between the OHbands and the cellulose structure.     

One‐Pot Synthesis of 2‐Arylthio‐2‐cyclohexenone Derivatives by the Diels–Alder Reaction of 4‐Arylthio‐3‐hydroxy‐2‐pyrones

The base‐catalyzed Diels–Alder reactions of 4‐arylthio‐3‐hydroxy‐2‐pyrones are reported. Treatment of 4‐arylthio‐3‐hydroxy‐2‐pyrones and dienophiles with triethylamine gave 2‐arylthio‐2‐cyclohexenone derivatives by the Diels–Alder reaction involving a decarboxylation in excellent to reasonable yields.     

Synthesis of 9‐Methyl‐11H‐pyrido[2,1‐b]quinazolin‐11‐one Using the Ullmann Condensation

The Ullmann condensation between 2‐chlorobenzoic acid and 2‐amino‐6‐methyl pyridine in DMF as solvent yielded 2‐[(6‐methyl‐2‐pyridinyl)amino] benzoic acid. The cyclization of this acid gave two isomers, the 9‐methyl‐11H‐pyrido[2,1‐b]quinazolin‐11‐one and, in a minor quantity, 2‐methylbenzo[b][1,8]naphtyridin‐5(10H)‐one. Using ultrasound irradiation the pyridoquinazolin‐11‐one was obtained as the sole product.     

Novel Methods for the Synthesis of 4‐Arylisoquinolinium Perchlorates and 4‐Arylisoquinolin‐1‐ones

2‐Benzylamino‐1‐phenyl‐ethanones 1 were converted to the corresponding isoquinolinium perchlorates 2 in high yields using 70% HClO₄‐FeCl₃ mixture as a cyclization and oxidation reagent. A mild and high yielding method for the oxidation of perchlorates 2 to isoquinolin‐1‐ones 3 involving the treatment of 2 with KOH and K₃[Fe(CN)₆] in THF‐H₂O two‐phase system at room temperature was developed. Compounds 2a–g were shown to be disproportionate to 3 and the corresponding 1,2‐dihydroisoquinoline 4 in the presence of base, which in turn is oxidized by K₃[Fe(CN)₆] to 2.     

Studies Towards the Synthesis of the β‐D‐Xyl‐(1 → 3)‐L‐ara Disaccharide Moiety of OSW‐1 from Ornithogalum saundersiae

Abstract

The OSW‐1 disaccharide having 2‐O‐p‐methoxybenzoyl‐β‐D‐xylopyranosyl‐(1 → 3)‐L‐arabinopyranoside structure was obtained as the benzylated 4‐O‐acetyl derivative 19. Also, the 4,2′‐di‐O‐acetate 18 was synthesized by a short synthetic approach. The arabinose acceptor 15 was obtained in a three step‐one pot sequence from easily available benzyl β‐L‐arabinopyranoside.     

A Convenient Approach to the Synthesis of Dialkyl 5‐Oxo‐1,2‐dihydro‐5H‐chromeno [4,3‐b]pyridine‐2,3‐dicarboxylates

Coumarin and its analogs are considered privileged scaffolds in the current synthetic and pharmacological research. The chemical behavior of enaminocarbaldehydes of the coumarin moiety under intramolecular Wittig reaction conditions in the presence of triphenylphosphine and dimethyl or diethyl acetylenedicarboxylates has been studied, resulting in the isolation of a series of dimethyl and diethyl 5‐oxo‐1,2‐dihydro‐5H‐chromeno[4,3‐b]pyridine‐2,3‐dicarboxylates in good to high yields.     

Convenient Synthesis of Nucleoside‐5′‐Diphosphates from the Corresponding Ribonucleoside‐5′‐phosphoroimidazole

The reaction of ribonucleoside‐5′‐phosphoroimidazolide with a tributylammonium orthophosphate in anhydrous dimethylformamide at room temperature provides a general method for the synthesis of nucleoside‐5′‐diphosphates. The novelty of the approach is to use the triethylammonium salt of 5′‐monophosphate nucleoside derivative prior to the imidazolate reaction with imidazole, triphenylphosphine, and 2,2′‐dithiodipyridine. Deprotection, followed by displacement of the imidazole moiety using tributylammonium orthophosphate and a catalytic amount of zinc chloride in dimethylformamide gave the desired 5′‐diphosphate products. The triethyl ammonium salt of 5′‐diphosphate nucleosides was purified by flash chromatography using DEAE (diethylaminoethyl weak anion exchange resin) Sepharosa fast flow packed in an XK 50/60 column on an Akta FPLC (Fast Protein Liquid Chromatography). Synthesis procedures are reported for adenosine‐5′‐diphosphate, uridine‐5′‐diphosphate, cytidine‐5′‐diphosphate, and guanosine‐5′‐diphosphate. Yields for the displacement reactions ranged from 95 to 97%. Thus, this method offers the advantages of shorter reaction time, greater product yield, and a more cost‐effective synthetic route.     

Strategies towards the Synthesis of 6‐N,N‐Diethylcarbamyloxy‐1,4‐dimethoxy‐ 7‐naphthylboronic Acid

After acetylation, condensation between Danishefsky's diene and benzoquinone afforded a stable methoxytriacetoxydihydronaphthalene intermediate, which was subsequently transformed by the Snieckus DOM protocol into the regiospecific 7‐naphthylboronic acid.     

Alternative Route for the Synthesis of 6‐Methoxy‐5‐methyl‐α‐tetralone and 6‐Methoxy‐2,5‐dimethyl‐α‐tetralone

The ketoesters 3 and 4, obtained by the condensation of 2‐cyclohexanone carboxylate and 1‐chloro‐3‐pentanone, were heated with 2,3‐dichloro‐5,6‐dicyanobenzoquinone (DDQ) to yield the dienones 5 and 6, which on hydrolysis with potassium t‐butoxide and dimethyl sulfoxide afforded tetralin 8. These were converted to tetralone 10 by methylation and oxidation respectively. Further methylation of 10 yielded tetralone 11.     

Utility of 1‐Chloro‐3,4‐dihydronaphthalene‐2‐carboxaldehyde in the Synthesis of Novel Heterocycles with Pharmaceutical Interest

Ethyl α‐cyano‐β‐(1‐chloro‐3,4‐dihydronaphthalene‐2‐yl) acrylate (2) was prepared by the Knoevenagel condensation of 1 with ethyl cyanoacetate. Compound 2 was used as the key intermediate to prepare Schiff bases (3a, b), benzo[c]acridine (4), naphthyl thiopyrimidine (5), and pyrazolo[2,3‐a]‐benzo[h]quinazoline (6) derivatives through its reaction with hydrazines, p‐ansidine, thiourea, and 3,5‐diamino‐4‐phenylazopyrazole, respectively. Base‐catalyzed cyclocondensation of 1 with hippuric acid gives oxazolone derivative (7). Reaction of compound 7 with aniline gave imidazolone derivative (9). Treatment of compound 1 with different types of diaminopyrazoles gave 6,7‐dihydro‐pyrazolo[2,3‐a]‐benzo[h]quinazoline (10–13) derivatives. The multicomponent reaction of compound 1 with pyrazolone and malononitrile in the presence of ammonium acetate furnished pyrazolo[3,4‐b]‐benzo[h]quinoline (14) while in the presence of piperidine afforded benzo[h]chromeno[2,3‐c]pyrazole derivative 15.     

Solid‐Phase Synthesis of N‐Aryl‐N′‐Carboalkoxy Guanidines by the Mitsunobu Reaction of Fmoc‐Guanidines

Abstract

A new method for the solid‐phase synthesis of N‐aryl‐N′‐carboalkoxy guanidines is described. Aromatic amines were reacted with Fmoc‐isothiocyanate to provide Fmoc‐thioureas, which were coupled with Rink amide resin to provide the corresponding resin‐bound Fmoc‐guanidines. Subsequent Mitsunobu alkylation with a variety of alcohols delivered N‐aryl‐N′ carboalkoxy guanidines in good to high purity after resin cleavage.     

Improved Procedure for the Preparation of cis‐2,4‐Dimethylglutaranhydride

Addition of 2.5 mol% DBU to a mixture of isomeric 2,4‐dimethylglutaric anhydrides in ethyl acetate promotes crystallization‐induced transformation, affording the pure cis‐2,4‐dimethylglutaric anhydride in 87% yield.     

Application of Sulfinyl bis(2,4‐dihydroxythiobenzoyl) in the Synthesis of N‐Substituted 2‐Amino‐5‐(2,4‐dihydroxyphenyl)‐1,3,4‐thiadiazoles

One‐stage synthesis of N‐substituted 2‐amino‐5‐(2,4‐dihydroxyphenyl)‐1,3,4‐thiadiazoles is described. The compounds were prepared by the reaction of the sulfinyl bis(2,4‐dihydroxythiobenzoyl) (STB) with 4‐substituted 3‐thiosemicarbazides. STB was obtained from 2,4‐dihydroxybenzenecarbodithioic acid and thionyl dichloride. The structure of compounds was confirmed by IR, ¹H NMR, ¹³C NMR, and EI‐MS data.     

Nitroimidazoles,Part 1. An Unexpected Reactivity During the Cyclization of 3‐(4‐Amino‐1‐benzyl‐2‐ethyl‐1H‐imidazol‐5‐ylsulphanyl)‐propionic Acid Methyl Ester

Nucleophilic substitution of the 5‐bromo group in 1 by methyl 3‐mercaptopropionate gave the 5‐alkyl‐mercapto derivative 2. Reduction of 2 with H₂/Pd led to the amine 3, meanwhile reduction with Fe/HOAc afforded the 5‐acetamido derivative 4 and not the cyclized derivative 1,3,8‐triaza‐azulen‐7‐one 6, as expected. Treatment of 3 with NaOMe/MeOH furnished the racemic mixture 5a and 5b via an unexpected reactivity.