Synthesis,psychotropic and anticancer activity of 2,2‐dimethyl‐5‐[5′‐trialkylgermyl(silyl)‐2′‐hetarylidene]‐1,3‐dioxane‐4,6‐diones and their analogues

A series of 2,2‐dimethyl‐5‐(5′‐R‐hetarylidene)‐1,3‐dioxane‐4,6‐diones has been synthesized for examing a structure–activity relationship. Furyl and thienyl derivatives of Meldrum's acid possess neurotropic activity comprising both depriming and activating components. Comparison of acute toxicity of carbon, silicon and germanium analogues in the furan series of the compounds has demonstrated that the germanium derivative is 11.5 times less toxic than the carbon analogue and four times less toxic than the silicon derivative. 2,2‐Dimethyl‐5‐(5′‐triethylsilyl‐2′‐thenylidene)‐1,3‐dioxane‐4,6‐dione has moderate toxicity with the highest neurotropic and cytotoxic activity Copyright © 2003 John Wiley & Sons, Ltd.     

A Simple One-pot Synthesis of Indeno[2,1-f]quinolin-3-one Derivatives under Microwave Irradiation

A series of new indeno[2,1‐f]quinolin‐3(2H)‐one derivatives were synthesized by a reaction of aromatic aldehyde with Meldrum's acid (2,2‐dimethyl‐1,3‐dioxane‐4,6‐dione) and 9H‐fluoren‐2‐amine under microwave irradiation without catalyst in glacial acetic acid. This reaction has notable advantages of short reaction time, high yield and convenient operation.     

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.     

PPh3‐catalyzed knoevenagel condensation: A facile synthesis of 5‐(1H‐indol‐3‐yl)Meth‐ ylene)‐2, 2‐Dimethyl‐1, 3‐Dioxane‐4, 6‐dione,and their N‐alkyl derivatives by using peg‐600 as the reaction medium

Triphenylphosphine (TPP) has been utilized as a novel and efficient catalyst for the Knoevenagel condensation of indole‐3‐carboxaldehydes 1(a–e) , 1‐methyl‐1H‐indole‐3‐carboxaldehydes 4(a–e) , and 1‐ethyl‐1H‐indole‐3‐carboxaldehydes 6(a–e) with the active methylene compound, that is, meldrum's acid ( 2 ), to afford substituted derivatives 5‐((1H‐indol‐3‐yl) methylene)‐2,2‐dimethyl‐1,3‐dioxane‐4,6‐dione 3(a–e) , 2,2‐dimethyl‐5‐((1‐methyl‐1H‐indol‐3‐yl)methylene)‐1,3‐dioxane‐4,6‐dione 5(a–e) , and 2,2‐dimethyl‐5‐((1‐ethyl‐1H‐indol‐3‐yl)methylene)‐1,3‐dioxane‐4,6‐dione 7(a–e) , respectively, in ethanol medium at RT just within 1 h in excellent yields. The products 3(a–e) were reacted independently with alkylating agents, that is, DMS and DES in the presence of PEG‐600 as an efficient and green solvent, to afford the corresponding N‐substituted methyl and ethyl derivatives 5(a–e) and 7(a–e) , respectively. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 23:41–48, 2012; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.20750     

Microwave induced synthesis of the thiazolidine‐2,4‐dione motif and the efficient solvent free‐solid phase parallel syntheses of 5‐benzylidene‐thiazolidine‐2,4‐dione and 5‐benzylidene‐2‐thioxo‐thiazolidine‐4‐one compounds

Novel microwave induced method for the synthesis of thiazolidine‐2,4‐dione motif under solvent phase conditions is developed. Further we report an efficient, microwave assisted method for the parallel syntheses of biologically important 5‐benzylidene‐thiazolidine‐2,4‐dione and 5‐benzylidene‐2‐thioxothiazolidine‐4‐one compounds under solid‐phase and solvent‐free conditions. A comparative study between the developed microwave methods and the conventional methods is described. We have also illustrated the possible mechanism behind to address the reason why piperidine, acetic acid and silica gel enhanced the Knoevenagel condensation reaction.     

A Novel Route for the Diastereoselective Synthesis of Dispiro[tetrahydroquinoline‐bis(2,2‐dimethyl[1,3]dioxane‐4,6‐dione)] Derivatives via a One‐Pot Domino Multicomponent Reaction of Arylamines,Aromatic Aldehydes,and Meldrum's Acid

A protocol has been developed for the diastereoselective synthesis of dispiro[tetrahydroquinoline‐bis(2,2‐dimethyl[1,3] dioxane‐4,6‐dione)] derivatives via a one‐pot domino multicomponent reaction of arylamines, aromatic aldehydes, and Meldrum's acid for the first time. The products, with remarkable diastereoselectivity, were successfully synthesized in acetic acid media in ambient temperature along with the suggested mechanism through combination of domino Knoevenagel, Michael, and Diels–Alder reactions. The products have been characterized by IR, mass, ¹H NMR, ¹³C NMR spectroscopy, and elemental analyses. The stereoselectivity of compounds was established with crystallography and NMR spectroscopy.     

Synthesis and intramolecular cyclization of 2‐methylsulfany‐4‐oxo‐3(4H)‐quinazolinyl)acetohydrazide

Treatment of ambident sodium salt of 2‐methylsulfanyl‐4(3H)‐quinazolinone with methyl bromoacetate resulted in N₍₃₎‐alkyl ester formation. Reaction of the resulted ester with hydrazine hydrate gave 2‐methylsulfanyl‐4‐oxo‐3(4H)‐quinazolinyl)acetohydrazide, which underwent intramolecular cyclization under heating in dimethylformamide to give 1‐aminoimidazo[2,1‐b]quinazoline‐2,5(1H,3H)‐dione. The latter took place in acylation reaction and in condensation with aromatic aldehydes.     

New route to pyrimido[4,5‐ e][1,3,4]thiadiazine derivatives

5‐Bromo‐2‐chloro‐4‐methyl‐6‐(1‐methylhydrazino)pyrimidine is readily obtained from the recently reported 5‐bromo‐2,4‐dichloro‐6‐methylpyrimidine by treatment with methylhydrazine in chloroform. Treatment of this compound with carbon disulfide and several alkyl halides gave an intermediate which was successfully converted to its corresponding 3‐(alkylsulfanyl)‐7‐chloro‐1,5‐dimethyl‐1H‐pyrimido[4,5‐e][1,3,4]thiadiazine derivatives in basic acetonitrile. The latter compounds were reacted with secondary amines in boiling ethanol to afford the related 7‐amino derivatives.     

Synthesis of 4‐amino‐5,6,7,8‐tetrahydrothieno[2,3‐b]quinolin‐5‐ol derivatives

This paper describes the synthesis of 4‐amino‐5,6,7,8‐tetrahydrothieno[2,3‐b]quinolin‐5‐ol derivatives ( 3a‐h ) and 4‐amino‐5,6,7,8‐tetrahydrothieno[2,3‐b]quinoline ( 8a ) in good yield by three‐step procedures starting from 2‐aminothiophene‐3‐carbonitrile and 5‐substituted cyclohexane‐1,3‐dione.     

无外加催化剂条件下芳香醛与活性亚甲基化合物的缩合反应和迈克尔加成反应

在DMF溶剂中,不外加催化剂使芳香醛(1)与2,2-二甲基-1,3-二氧六环-4,6-二酮(2)发生缩合反应生成2,2-二甲基-5-芳亚甲基-1,3-二氧六环-4,6-二酮(3a～f)。在同样条件下,芳香醛与5,5-二甲基-1,3-环己二酮(4)则发生缩合和迈克尔加成反应生成2,2’-芳亚甲基双(3-羟基-5,5-二甲基-2-环己烯-1-酮)(5a～h)。用单晶X-射线分析法确定了产物5b的晶体结构。     

An efficient one‐pot synthesis of 5‐aryl substituted 2‐amino‐5,8‐dihydropyrido[2,3‐D] pyrimidin‐4,7‐diones under microwave irradiationl without catalyst

A series of 5‐aryl substituted 2‐amino‐5,8‐dihydropyrido[2,3‐d]pyrimidin‐4,7‐diones were synthesized through one‐pot condensation of 2,6‐diaminopyrimidin‐4‐one, aldehyde and Meldrum's acid using glycol as energy transfer agent under microwave irradiation without catalyst. The one‐pot protocol in the absence of catalyst has the advantage of good yield (86‐95%), short route and reaction time (3‐6 min) and environmentally friendly.     

An efficient one‐pot synthesis of polyhydrobenzoacridine‐1‐one derivatives under microwave irradiation without catalyst

A series of 3,3‐dimethyl‐9‐substituted‐1,2,3,4,9,10‐hexahydrobenzo[c] acridine‐1‐ones and 3,3‐dimethyl‐9‐substituted‐1,2,3,4,9,10‐hexahydrobenzo[a] acridine‐1‐ones were synthesized by the reaction of an aldehyde, α‐naphthylamine or β‐naphthylamine and dimedone under microwave irradiation with short times and high yields.     

Facile three‐component one‐pot synthesis of indeno‐[1,2‐b]quinolin‐9,11(6H,10H)‐dione derivatives

One‐pot three‐component cyclocondensation of aldehydes, 1,3‐indanedione and enaminones proceeds in the presence of acetic acid to afford Indeno[1,2‐b]quinolin‐9,11(6H,10H)‐dione derivatives, The method has the advantage of excellent yields(85‐94%) and simple workup procedure.     

Reactions of aroylthioureas with acetylenic esters and dibenzoyl ethylene. Selectivity towards the formation of new 1,3‐thiazines

A series of 1,3‐thiazines has been synthesized by the reactions of N‐aroylsubstituted thioureas with ethyl propiolate, dimethyl but‐2‐ynedioate and (E)‐1,4‐diphenyl‐but‐2‐ene‐1,4‐dione. The reaction of antipyrinylphenyl thiourea with π‐deficient acetylenic reagents did not afford the corresponding 1,3‐thiazines, whereas pyrrolo‐pyrazolopyrimidines were obtained.     

Synthesis of alicyclic N‐substituted 1,3‐amino alcohols via 1,3‐oxazines

Alicyclic N‐substituted 1,3‐amino alcohols 13‐18 were prepared in a facile way in a one‐pot procedure from 1,3‐oxazines 5‐8 in the presence of a ketone 9‐12 . The complex reaction involves palladium‐catalyzed reduction, debenzylation and/or transimination and further reduction.     

Preparation of Pseudo‐Peptide Building Blocks with retro‐Thioamide Bond Mediated via Thiocarbamoyl Meldrum's Acid

An easy and efficient synthesis of pseudo‐tripeptide containing a thiomalonamide moiety was developed. Isothiocyanate derivatives of amino acids react smoothly with 2,2‐dimethyl‐1,3‐dioxane‐4,6‐dione (Meldrum's acid) to yield new thiocarbamoyl derivatives of Meldrum's acids. Thermal decomposition of these new derivatives leads to thiocarbamoyl ketenes, which acylate amino acid esters to give pseudo‐tripeptides.     

A simple two steps ytterbium triflate‐catalysed preparation of 2,2‐dimethyl‐2h‐chromenes from salicylaldehydes and 2‐methylpropene

The preparation of various 2,2‐dimethyl‐2H‐chromenes was achieved in two steps via an ytterbium triflate‐catalysed reaction between salicylaldehydes, trimethylorthoformate and 2‐methylpropene. From salicylaldehyde, two reaction products were characterised: 4‐methoxy‐2,2‐dimethylchroman and 2‐(1,3‐dimethoxy‐3‐methylbutyl)phenol. The former compound probably results from a Lewis acid‐catalysed [2+4] cycloaddition between the intermediate quinonemethide and 2‐methylpropene whereas the latter may occur via a reaction related to a carbonyl‐ene reaction between the quinonemethide and 2‐methylpropene. Both compounds were subjected to a catalytic acidic treatment leading to 2,2‐dimethyl‐2H‐chromene. Starting from various salicylaldehydes, the scope of this method was investigated.     

Synthesis of substituted 1,2,4‐oxadiazoles from substituted acid chlorides and amidoximes under mild conditions

Substituted amidoximes have been synthesized, isolated and converted into substituted oxadiazoles as a novel heterocyclic compounds under mild conditions in good to excellent yield.     

An efficient microwave‐assisted synthesis of 3,5‐unsubstituted 4‐substituted‐6‐aryl‐3,4‐dihydropyridin‐2(1H)‐ones derivatives

Small libraries of 3,5‐unsubstituted 4‐substituted‐6‐aryl‐3,4‐dihydropyridin‐2(1H)‐ones derivatives were synthesized from the condensation‐products of aldehydes with Meldrum's acid, aromatic ketones and ammonium acetate using acetic acid as energy transferring‐agent under microwave irradiation without catalyst. This method has the advantages of excellent yields (65‐90%), short reaction time (5‐10 min) and being environmentally friendly. It aimed to provide new series of potential biologically active compounds for biomedical screening.