6‐Polyfluoroacyl‐ and 6‐trichloroacetylnorkhellins: Synthesis and reaction with aromatic amines

Five new 6‐polyhaloacylnorkhellins were synthesized in high yields from diethoxymethyl acetate and the condensation products of khellinone with R_FCO₂Et and CCl₃COCl. Reaction of 6‐polyfluoroacylnorkhellins with primary aromatic amines yielded 6‐(arylaminomethylene)‐7‐hydroxy‐4,9‐dimethoxy‐7‐(polyfluoroalkyl)furo[3,2‐g]chroman‐5‐ones. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:99–103, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20174     

Oxidation of 7,8‐diaminotheophylline with lead tetraacetate and reaction of the oxidation product, 6‐cyanoimino‐5‐diazo‐1,3‐dimethylpyrimidine‐2,4‐dione with alcohols or amines

Oxidation of 7,8‐diaminotheophylline (1) with lead tetraacetate in refluxing toluene gave a mixture of 3‐amino‐5,7‐dimethylpyrimido[4,5‐e][1,2,4]triazine‐6,8‐dione ( 2 ) and 6‐cyanoimino‐5‐diazo‐1,3‐dimethylpyrimidine‐2,4‐dione ( 4 ). The latter was transformed to 2 by the reaction with 1‐propanethiol in quantitative yield. The reaction of 4 with methanol, ethanol and 1‐propanol in the presence of rhodium ( II ) acetate gave 5‐alkoxy‐6‐(2‐alkyl‐3‐isoureido)‐1,3‐dimethylpyrimidine‐2,4‐diones ( 7a‐c ). A similar reaction of 4 with alkylamines such as n‐propylamine, n‐butylamine, isobutylamine and n‐hexylamine gave a mixture of 7‐alkyl‐8‐aminotheophyllines ( 8a‐d ) and (5‐alkylamino‐1,3‐dimethyl‐2,4‐dioxopyrimidin‐6‐yl)cyanamides ( 9a‐d ).     

Preparation of pyrimidine derivatives as potential medicinal agents by the reaction of 2‐amino‐4‐chloro‐6‐methylpyrimidine with primary and secondary amines

Thirteen derivatives of pyrimidine were prepared as potential medicinal agents by the reaction of 2‐amino‐4‐chloro‐6‐methylpyrimidine with primary and secondary amines in the absence of a solvent. Six of the derivatives are piperazinylpyrimidines. The compounds prepared in this work may prove to be efficacious in the treatment of inflammation, hypertension, anxiety, depression, or cancer.     

Synthesis of 1‐substituted 3,5‐diaryl‐2‐pyrazolines by the reaction of α,β‐unsaturated ketones with hydrazines

1‐Acetyl‐, 1‐propionyl‐ and 1‐phenyl‐3,5‐diaryl‐2‐pyrazolines have been synthesized by the reaction of the appropriate α,β‐unsaturated ketones with hydrazine or phenylhydrazine in hot acetic acid or propionic acid. Structures of all new 2‐pyrazolines 16‐40 have been elucidated by microanalyses, ¹H and ¹³C nmr spectroscopies.     

Synthesis of 3‐aryl‐5‐styryl‐2‐pyrazolines by the reaction of (E,E)‐cinnamylideneacetophenones with hydrazines and their oxidation into pyrazoles

New 3‐aryl‐5‐styryl‐2‐pyrazolines have been synthesized by the reaction of (E,E)‐cinnamylideneace‐tophenones with hydrazines. These 2‐pyrazolines have also been converted into the corresponding pyrazoles by oxidation with chloranil. Structures of all new compounds have been elucidated by elemental analysis, mass spectrometry, ir and nmr spectroscopic measurements.     

A new polymorph of 2‐methyl‐6‐nitroaniline

A new crystal form of 2‐methyl‐6‐nitroaniline, C₇H₈N₂O₂, crystallizing with Z′ = 2 in the space group P2₁/c, has been identified during screening for salts and cocrystals. The different N—H...O hydrogen‐bonding synthons result in linear V‐shaped chains in the new polymorph, rather than the helical chain arrangement seen in the known form where Z′ = 1. The presence of a second component during crystallization appears to have determined the resultant crystal form of 2‐methyl‐6‐nitroaniline.     

A new reagent for incorporating the 2‐(1‐adamantyl)‐2‐propyloxycarbonyl protecting group into amines

A new reagent to incorporate the 2‐(1‐adamantyl)‐2‐propyloxycarbonyl (Ad‐POC) protecting group into amines, 2‐(1‐adamantyl)‐2‐propyl p‐nitrophenylcarbonate, was prepared in two steps from the commercially available 1‐adamantylcarbonyl chloride. The Ad‐POC group was introduced into a variety of amines and amino acid derivatives. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:192–195, 2000     

Synthesis of new 2,3‐dihydrofuran‐3‐one derivative and its reactions with some primary amines

The Wittig reaction of 2,3‐dihydro‐4‐(4‐methoxybenzoyl)‐5‐(4‐methoxyphenyl)‐furan‐2,3‐dione (1) with methyl (triphenylphosphoranylidene)acetate (2) stereo‐ and regioselectively afforded methyl (Z)‐[2,3‐dihydro‐4‐(4‐methoxybenzoyl)‐5‐(4‐methoxyphenyl)‐3‐oxofuran‐2‐ylidene]acetate (3) in good yield. The reactions of 3 with primary amines (4a‐k) gave corresponding 1‐substituted 2,3‐dihydro‐1Hpyrrol‐3‐ones (5a‐k).     

Synthesis of 1‐substituted 5‐aryl‐3‐(3‐coumarinyl)‐2‐pyrazolines by the reaction of 3‐aryl‐1‐(3‐coumarinyl)propen‐1‐ones with hydrazines

1‐Acetyl‐ and 1‐propionyl‐2‐pyrazolines 11‐27 have been synthesized by the reaction of (3‐coumarinyl)chalcones 1‐10 with hydrazine in hot acetic acid or propionic acid. While 5‐aryl‐3‐(3‐coumarinyl)‐1‐phenyl‐2‐pyrazolines 28‐35 have been prepared by the reaction of (3‐coumarinyl)chalcones 1,3,5‐10 with phenylhydrazine in hot pyridine. Structures of all new compounds have been elucidated by microanalyses, ¹H and ¹³C nmr spectroscopies.     

Synthesis of 1‐substituted 5‐aryl‐3‐styryl‐2‐pyrazolines and 3‐aryl‐5‐styryl‐2‐pyrazolines by the reaction of dibenzylideneacetones and E,E‐cinnamylideneacetophenones with hydrazines

The reaction of dibenzylideneacetones or E,E‐cinnamylidene‐ acetophenones and hydrazine hydrate provided 1‐propionyl derivatives of 5‐aryl‐3‐styryl‐2‐pyrazolines and 3‐aryl‐5‐styryl‐2‐pyrazolines. These unsaturated ketones afforded 1‐(2‐carboxyphenyl) or 1‐(4‐carboxyphenyl) 5‐aryl‐3‐styryl‐2‐pyrazolines and 1‐(4‐carboxyphenyl) derivatives of 3‐aryl‐5‐styryl‐2‐pyrazolines on treatment with (2‐carboxyphenyl)‐hydrazine or (4‐carboxyphenyl)hydrazine in hot acetic acid. Structures of all new 2‐pyrazolines have been elucidated by microanalyses and a combined utilization of various spectroscopic methods.     

New synthesis and reactivity of 3‐bromoacetyl‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one with binucleophilic amines

3‐(Bromoacetyl)‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one was synthesized by the reaction of dehydroacetic acid (DHAA) with bromine in glacial acetic acid. Novel heterocyclic products were synthesized from the reaction of bromo‐DHAA with alkanediamines, phenylhydrazines, ortho‐phenylenediamines, and ortho‐aminobenzenethiol. The obtained new products 3‐(2‐N‐substituted‐acetyl)‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐ones, 4‐hydroxy‐3‐[1‐hydroxy‐2‐(2‐phenylhydrazinyl)vinyl]‐6‐methyl‐2H‐pyran‐2‐one, 1‐(2,4‐dinitrophenyl)‐7‐methyl‐2,3‐dihydro‐1H‐pyrano[4,3‐c]pyridazine‐4,5‐dione, 3‐(3,4‐dihydroquinoxalin‐2‐yl)‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one/3‐(3,4‐dihydroquinoxalin‐2‐yl)‐6‐methyl‐2H‐pyran‐2,4(3H)‐dione, 6‐methyl‐3‐(3,4‐dihydroquinoxalin‐2‐yl)‐2H‐pyran‐2,4(3H)‐dione, and (E)‐3‐(2H‐benzo[b][1,4]thiazin‐3(4H)‐ylidene)‐6‐methyl‐2H‐pyran‐2,4(3H)‐dione were fully characterized by IR, ¹H and ¹³C NMR, and mass spectra. J. Heterocyclic Chem., 2011.     

Synthesis of 3‐(2‐benzyloxy‐6‐hydroxyphenyl)‐1‐methylpyrazoles by the reaction of chromones with methylhydrazine

The 3‐(2‐benzyloxy‐6‐hydroxyphenyl)‐5‐(methyl, phenyl or styryl)pyrazoles were prepared from the reaction of 2‐(methyl, phenyl or styryl)chromones with methylhydrazine. The structure of these compounds has been determined by several nmr techniques, and the reaction mechanism is discussed.     

A general and efficient route to 6‐methyl‐pyrazin‐2‐yl‐amines: Alkylation of 2,6‐dichloropyrazine via malonate derivatives

We have developed a convenient two‐stage process for the synthesis of 6‐methylpyrazine‐2‐yl‐amines from commercially available materials. The procedure involves the synthesis of (6‐chloro‐pyrazin‐2‐yl)‐acetic acid via arylation of diethyl malonate and in situ hydrolysis/decarboxylation. A second decarboxylation takes place under the subsequent amination conditions allowing simple and efficient access to the intended pyrazines.     

Reaction of 2‐Alkoxy‐4,5‐diphenyl‐1,3‐oxazin‐6‐one with different alcohols and elucidation of the products

Reaction of 2‐methoxy‐4,5‐diphenyl‐1,3‐oxazin‐6‐one 1a with methanol was studied, and the product of the reaction was determined by spectroscopic data and X‐ray analysis. In addition, a series of (Z)‐alkyl 3‐(alkoxycarbonylamino)‐2,3‐diphenylacrylate 4 was synthesized and characterized. J. Heterocyclic Chem., (2012).     

Biginelli‐like three component reaction: Synthesis of some new ethyl 6‐ethoxycarbonylmethyl‐4‐aryl‐2‐oxo‐1,2,3,4‐tetrahydropyrimidine‐5‐carboxylate derivatives

In the context of our high‐throughput organic synthesis program, we have studied the reactivity of special β‐keto esters toward the Biginelli reaction. We have found that a diethyl‐3‐oxoglutarate reacts with one molecule of urea and one molecule of aldehyde under solvent‐free conditions to give a new family of 3,4‐dihydropyrimidin‐2(1H)‐ones in good yields.     

Formation of aryl‐bis (6‐amino‐1,3‐dimethyluracil‐5‐yl) methanes by reaction of 6‐amino‐1, 3‐dimethyluracil with aromatic aldehydes

The synthesis of aryl‐bis(6‐amino‐1,3‐dimethyluracil‐5‐yl)‐methanes 3a‐m by condensation of 6‐amino‐1,3‐dimethyluracil ( 1 ) with aromatic aldehydes 2a‐m at room temperature is reported. The structures of the compounds were established using various spectroscopic analyses and X‐ray crystallography. The crystal structures of two aryl‐bis (6‐amino‐1,3‐dimethyluracil‐5‐yl) methanes are presented.     

Synthesis and self‐assembly behavior study of α,ω‐dicarboxyl‐poly(ethylene glycol)–permethyl‐6‐amino‐6‐deoxy‐β‐cyclodextrin‐monoamide: A new β‐cyclodextrin conjugate

A new type of amphiphilic macromolecule was synthesized through the attachment of a poly(ethylene glycol) chain to a permethyl‐amino‐β‐cyclodextrin ring. The structure of the product was studied with 1D and 2D NMR experiments and with MALDI‐TOF MS. The resulting comet‐shaped molecule showed self‐assembly behavior in polar solvents. The presence of supramolecular structures in aqueous media was detected with dynamic light scattering and proven also by 2D NOESY and DOSY experiments. The supramolecular structures that formed could serve as starting materials for new types of drug delivery bioconjugates containing two independent dopable sites, that is, the cyclodextrin ring and the core of the supramolecular structure. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5149–5155, 2007     

A new direction in the alkylation of 5‐acetyl‐2‐amino‐6‐methyl‐4‐phenyl‐4H‐pyran‐3‐carbonitrile with active methylene reagents

In this paper, we report a new synthesis route to 4H‐pyran derivatives and a plausible reaction mechanism. The interaction of 5‐acetyl‐2‐amino‐6‐methyl‐4‐phenyl‐4H‐pyran‐3‐carbonitrile with different active methylene reagents gives rise to the cleavage and subsequent recyclization of the pyran ring to afford the corresponding 4H‐pyran derivatives.     

6‐Nitro‐1,2,3,4‐tetrahydroquinolines by a tandem reductive amination‐SNAr reaction

A tandem reductive amination‐S_NAr reaction has been developed for the synthesis of 6‐nitro‐1,2,3,4‐tetrahydroquinolines. Treatment of 4‐(2‐fluoro‐5‐nitrophenyl)‐2‐butanone or 3‐(2‐fluoro‐5‐nitrophenyl)‐propanal with primary amines and sodium cyanoborohydride in methanol at room temperature provided good to excellent yields of the substituted tetrahydroquinolines. The reaction proceeded best with the ketone substrate using primary amines that were unbranched at the α‐carbon. The aldehyde also produced the target heterocycles, but these were accompanied by 10‐15% of the uncyclized side chain reductive amination products.     

Facile synthesis of new imidazoles from direct reaction of 2,3‐diamino‐1,4‐naphthoquinone with aldehydes

New imidazoles were easily prepared from 2,3‐diamino‐1,4‐naphthoquinone and stoichiometric quantities of the appropriate aldehydes in dimethyl sulfoxide as a solvent. The reaction proceeded for few hours. The procedure can be generalized to different classes of aldehydes. 2‐Methyl‐1H‐naphtho[2,3‐d]imidazole‐4,9‐dione was also obtained in good yield during refluxing of 2,3‐diaminonaphthoquinone in acetic acid. The structure of the newly synthesized imidazoles was extensively investigated using NMR experiments. J. Heterocyclic Chem., (2011).