Dimethylformamide Dimethylacetal Research Articles

Errata “Synthesis of Novel Angular and Linear Fused [5-6-5] Heterocycles by the Reaction of Methyl Cyano-(3-cyano-4,5-dihydro-2(3H)-furanylidene)acetate with Hydrazines and Dimethylformamide Dimethyl Acetal” : HETEROCYCLES, 2018, 96, 664, DOI: 10.3987/COM-17-13861

Errata “Synthesis of Novel Angular and Linear Fused [5-6-5] Heterocycles by the Reaction of Methyl Cyano-(3-cyano-4,5-dihydro-2(3H)-furanylidene)acetate with Hydrazines and Dimethylformamide Dimethyl Acetal” : HETEROCYCLES, 2018, 96, 664, DOI: 10.3987/COM-17-13861

Synthesis of Novel Angular and Linear Fused [5-6-5] Heterocycles by the Reaction of Methyl Cyano-(3-cyano-4,5-dihydro-2(3H)-furanylidene)acetate with Hydrazines and Dimethylformamide Dimethyl Acetal

Synthesis of Novel Angular and Linear Fused [5-6-5] Heterocycles by the Reaction of Methyl Cyano-(3-cyano-4,5-dihydro-2(3H)-furanylidene)acetate with Hydrazines and Dimethylformamide Dimethyl Acetal

Synthesis and Characterization of Newly Fused 1,2-Dihydropyrido[3,4-b], Bridged Oxadiazol-2-yl, 4-Substituted-benzylidene Hydrazide and Arylidene 6-Chloroquinoxaline 1,4-Dioxides

Some simple reactions using commercially available chemicals were used in the preparation of new biologically remarkable quinoxaline 1,4-dioxide derivatives. Several steps performed on 4-chloro-2-nitroaniline resulted in a quinoxaline 1,4-dioxide derivative, which reacted with dimethylformamide dimethylacetal (DMF-DMA) to produce an enamine. Transamination of this enamine with anilines gave the fused 1,2-dihydropyrido[3,4-b]quinoxaline 5,10-dioxide derivatives via an addition-elimination mechanism. Basic condensation reaction of quinoxaline active methyl afforded unexpected decarboxylated arylidene derivatives by using different aromatic aldehydes. Bridged oxadiazol-2-yl derivatives were obtained from the reaction of a hydrazide derivative with carbon disulfide and p-nitrobenzoic acid respectively. Whereas, acidic condensation of that hydrazide with aromatic aldehydes afforded the arylidene hydrazides.

Copper‐Catalyzed One‐pot Synthesis of Pyrimidines from Amides, N,N′‐dimethylformamide dimethylacetal, and Enamines

AbstractA versatile copper catalyzed one‐pot synthesis of diversely substituted pyrimidines directly from amides, N,N′‐dimethylformamide dimethylacetal (DMF−DMA) and enamines has been established. The reaction involved the two C−N bonds and one C−C bond formation by formal [2+1+3] annulation approach to pyrimidines. This protocol is based on the use of readily available primary amides, DMF−DMA and enamines to install di‐ and tri‐substituted pyrimidine structure with diverse functionality in one‐pot manner, which makes this strategy to be appealing for the medicinal chemistry.magnified image

One‐pot Synthesis of Benzo[4,5]imidazo[1,2‐a]pyridine Derivatives in Aqueous Conditions

One‐pot reaction of cyclic 1,3‐diketones, dimethylformamide dimethylacetal (DMFDMA) and 2‐(1H‐benzo[d]imidaz‐2‐yl)acetonitrile was found to be a highly selective process leading to 4‐oxo‐1,2,3,4‐tetrahydrobenzo[4,5]imidazo[1,2‐a]quinolin‐6‐yl cyanides. Optimized reaction conditions using water as solvent at room temperature or under microwave heating allowed high yields of the target products required no additional purification.

ChemInform Abstract: Reactions of Silyl Nitronates with Dimethylformamide Dimethyl Acetal as a New General Procedure for the Synthesis of 2‐Nitroenamines.

Silyl nitronates obtained in situ from the corresponding aliphatic nitro compounds react with dimethylformamide dimethyl acetal giving 2-nitroenamines in moderate to good yields. The reaction pathway is discussed.

Synthesis and cycloaddition reactions of 4,4-dimethyl-2,6-dioxocyclohexane-thiocarboxamides with nitrilimines

A new series of 4,4-dimethyl-2,6-dioxocyclohexane-thiocarboxamides were prepared by reaction of aryl isothiocyanate with dimedone. Reaction of N-aryl-4,4-dimethyl-2,6-dioxocyclohexane- thiocarboxamides with hydrazonoyl halides led to th e formation of the corresponding thiadiazoles. Treatment of 2-(5-acetyl-3-phenyl-1,3 ,4-thiadiazol-2(3 H)-ylidene)-5,5- dimethylcyclohexane-1,3-dione with dimethylformamide dimethylacetal (DMF-DMA) in refluxing dioxane afforded (E)-2-(5-(3-(dimethylamino)acryloyl)-3-phenyl-1,3,4-t hiadiazol- 2(3H)-ylidene)-5,5-dimethylcyclohexane-1,3-dione. Reaction of the latter enaminone with hydrazonoyl halides yielded the corresponding 2-(1- aryl-3-substituted-pyrazol-4-carbonyl)-5-(3- phenyl-5-(5,5-dimethylcyclohexane-1,3-dione)-(1,3,4)-thiadiazole) derivatives. The structures of the new compounds were elucidated on the basis of t heir elemental analyses and spectral data.

An efficient synthesis of 1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-carbonitriles

Abstract Ethyl α -(dimethylaminomethylene)-2-cyanomethyl-4-phenylquinoline-3-carboxylate ( 2 ) as new synthons directed to 1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-carbonitriles was obtained by the condensation of ethyl 2-cyanomethyl-4-phenylquinoline-3-carboxylate ( 1 ) and N , N -dimethylformamide dimethyl acetal (DMFDMA). Reaction of this enamine with primary amines ( 3 ) in HOAc-DMF at 120 °C then affords 2-substituted 1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-carbonitrile derivatives ( 4 ) in good yields by a tandem addition–elimination–cyclization reaction.

Synthesis of 4-oxothiazolidine-2,5-diylidenes containing thioamide group based on dithiomalonamides

An approach to the synthesis of 2-(4-oxo-3-arylthiazolidine-2,5-diylidene)-N-arylethanethioamide derivatives from N,N′-diarylmalonodithioamides includes two steps: preparation of thiazoles using the Hantzsch reaction with subsequent modification of the active methylene group by the Knoevenagel condensation or enamination using dimethylformamide dimethyl acetal (DMF-DMA). Configuration and isomerization of the double bonds in 4-oxothiazolidine-2,5-diylidenes were confirmed by 1H NMR and X-ray diffraction analysis and discussed.

ChemInform Abstract: A Strategy for the Synthesis of 2‐Aryl‐3‐dimethylaminopyrazolo[3,4‐c]pyridines that Utilizes [4 + 1] Cycloaddition Reactions of 5‐Arylazo‐2,3,6‐trisubstituted Pyridines.

Abstract In order to explore the viability and generality of a recently uncovered [4+1] cycloaddition based strategy for the preparation of pyrazolo[3,4-c]pyridine derivatives, members of a series of 5-arylazo-2,3,6-trisubstituted pyridines were prepared by reactions of 3-oxo-2-arylhydrazonopropanals with 3-oxo-3-phenylpropionitrile. The results show that 3-oxo-3-phenylpropionitrile reacts with hydrazone substrates, which do not contain electron-withdrawing substituents on the N-aryl ring of the arylhydrazone moieties, to efficiently produce 6-aryl-2-phenyl-5-arylazonicotinonitriles. In contrast, 2-amino-6-aryl-5-arylazo-3-benzoylpyridines are generated in reactions of 3-oxo-2-arylhydrazonopropanals, which contain electron-withdrawing substituents on the N-aryl moiety. In the forecasted manner, the 6-aryl-2-phenyl-5-arylazonicotinonitriles undergo smooth reactions with dimethylformamide dimethylacetal (DMF-DMA) that led to formation of a new class of 2-aryl-3-dimethylaminopyrazolo[3,4-c]pyridines. The mechanism for this process involves a [4+1] cycloaddition reaction that takes place through initial nucleophilic addition of dimethylamino)methoxycarbene, generated from DMF-DMA, to the azadiene moiety of the arylazopyridines followed by cyclization of the formed zwitterionic intermediate.

Carbodiimide Mediated Synthesis of new Thiazolidin-4-Ones and Thiazinan-4-Ones from Thiosemicarbazone Derivatives of 6,7-Dihydro-1H-Indazole-4(5H)-Ones

5,5-Dimethyl-2-[(2-substitutedphenylhydrazinyl)methylene]cyclohexane-1,3-dione, obtained from heating dimedone with N,N‘-dimethylformamide dimethyl acetal (DMF-DMA) and phenyl hydrazines, on cyclisation in ethanol gave 6,7-dihydro-1 H-indazol-4(5 H)-ones. The thiosemicarbazone derivative of 6,7-dihydro-1 H-indazole-4(5 H)-ones, on cyclocondensation with a and (3-haloacids in the presence of N,N‘-dicyclohexylcarbodiimide afforded new thiazolidin-4-ones and 1,3-thiazinan-4-ones respectively. Thiosemicarbazone of 6,7-dihydro-1 H-indazol-4(5 H)-ones on stirring with phenacyl bromides yields 2,4-disubstituted thiazoles. X-ray structure of the intermediate compound 5-dimethyl-2-[(2-phenylhydrazinyl)methylene] cyclohexane-1,3-dione was determined.

Preparation of Polyfunctionally Substituted Pyridine-2(1<i>H</i>)-Thione Derivatives as Precursors to Bicycles and Polycycles

Reaction of acetylacetone with 1 mole of dimethylformamide dimethyl acetal (DMFDMA) affords enamine 2a which reacts with cyanothioacetamide to give pyridinethione 3a. Pyridinethione 3a reacts with methyl iodide, halogenated compounds, aromatic aldehyde and malononitrile/elemental sulfur to yiled compounds 7-10 respectively. Reactions of thioether 7 in ethanolic K2CO3, 1 mole DMFDMA and 4-(dimethylamino)benzaldehyde give compounds 11, 13, 14 respectively. Enaminone 12 can be prepared by reaction of compound 11 with DMFDMA. We have demonstrated some reactions in order to show the potential usefulness of the prepared compounds for the preparation of new bipyridyl compounds 15, 16, 18, bicyclic compounds 17 and uncommon tricyclic compounds 20, 21, 22 and 23 respectively using DMFDMA.

Heterocyclic Synthesis via Enaminones: Synthesis and Molecular Docking Studies of Some Novel Heterocyclic Compounds Containing Sulfonamide Moiety

4-Acetyl-N, N-diethylbenzenesulfonamide (1) was condensed with dimethylformamide dimethy-lacetal (DMF-DMA) to yield the enaminone, which reacts readily with different reagents to give the corresponding pyrazoles, triazolopyrimidine, imidazopyridine, pyrimidopyrimidine, pyrazolopyrimidine, benzofuran, pyranone, pyridine, pyrimidine and pyrazolopyridazine derivatives. These compounds were designed to comply with the general features of sulfonamide pharmacophore which act as Cyclooxygenase (COX-2) inhibitors. Virtual screening using molecular docking studies of the synthesized compounds was performed by (MOE), the molecular docking results indicate that, some synthesized compounds suitable inhibitor against (COX-2) with further modification.

An expeditious and green synthesis of new enaminones and study their chemical reactivity toward some different amines and binucleophiles under environmentally friendly conditions

The condensation reaction of 3-heteroaromatic-3-oxopropanenitriles 3, 4 and 7 with dimethylformamide–dimethylacetal (DMF–DMA) gave the corresponding enaminones 8, 9 and 10, respectively. Nucleophilic substitution of 8 and 9 with different amines resulted in a new derivatives of enaminones 11–18. The reactivity of enaminones 8 and 9 toward some nitrogen nucleophiles was investigated with a view to synthesize new heterocyclic systems. Thus, treatment of compounds 8 and 9 with phenylhydrazine afforded the pyrazole derivatives 19 and 20, respectively. On the other hand, reacting 8 and 9 with guanidine gave the pyrimidines 21 and 22, respectively. Treatment of compound 9 with hydroxylamine hydrochloride afforded the aminoisoxazoles 23. The foregoing reactions were carried out with conventional heating and under green conditions [ultrasound (US) irradiations or ionic liquids (ILs)] and a comparative study was employed. All the new structures are fully characterized.

A strategy for the synthesis of 2-aryl-3-dimethylaminopyrazolo-[3,4-c]pyridines that utilizes [4+1] cycloaddition reactions of 5-arylazo-2,3,6-trisubstituted pyridines

In order to explore the viability and generality of a recently uncovered [4+1] cycloaddition based strategy for the preparation of pyrazolo[3,4-c]pyridine derivatives, members of a series of 5-arylazo-2,3,6-trisubstituted pyridines were prepared by reactions of 3-oxo-2-arylhydrazonopropanals with 3-oxo-3-phenylpropionitrile. The results show that 3-oxo-3-phenylpropionitrile reacts with hydrazone substrates, which do not contain electron-withdrawing substituents on the N-aryl ring of the arylhydrazone moieties, to efficiently produce 6-aryl-2-phenyl-5-arylazonicotinonitriles. In contrast, 2-amino-6-aryl-5-arylazo-3-benzoylpyridines are generated in reactions of 3-oxo-2-arylhydrazonopropanals, which contain electron-withdrawing substituents on the N-aryl moiety. In the forecasted manner, the 6-aryl-2-phenyl-5-arylazonicotinonitriles undergo smooth reactions with dimethylformamide dimethylacetal (DMF-DMA) that led to formation of a new class of 2-aryl-3-dimethylaminopyrazolo[3,4-c]pyridines. The mechanism for this process involves a [4+1] cycloaddition reaction that takes place through initial nucleophilic addition of dimethylamino)methoxycarbene, generated from DMF-DMA, to the azadiene moiety of the arylazopyridines followed by cyclization of the formed zwitterionic intermediate.

Syntheses of 2‐Unsubstituted 1H‐1,3‐Benzazaphospholes from N‐Formyl‐2‐bromoanilides

ABSTRACTThe phosphonylation of 2‐bromo‐formylanilides 1 with triethyl phosphite in the presence of preformed Pd(0)(triethyl phosphite)n catalyst furnished 2‐phosphono‐formanilides 2 in good yields. Reduction with excess LiAlH4 provided mainly N‐methyl‐2‐phosphinoanilines 3 and minor amounts of 1,2‐unsubstituted benzazaphospholes 4. N‐Methyl‐1,3‐benzazaphospholes 5 were synthesized by the cyclocondensation of 3 with dimethylformamide dimethylacetal (DMFA). A more convenient route to 5, avoiding the chromatographic separation of 4, is the reduction of 1 to 2‐bromo‐N‐methylaniline 6, followed by phosphonylation to 7, LiAlH4 reduction, and cyclization with DMFA. The coordination properties at σ2P of benzazaphospholes are characterized by structural data obtained by the crystal structure analysis of (5b)W(CO)5.

Microwave-Assisted Synthesis and Anti-Breast Cancer Activity of 3-Acyl-5-hydroxybenzofurans

A series of four 3-acyl-5-hydroxybenzofuran derivatives (4a-4d) were synthesized by one-pot method under microwave irradiation from aldehydes, dimethylformamide dimethyl acetal (DMFA) and benzoquinone in high yields. These compounds were characterized by IR, NMR and ESI-MS, which were also tested for in vitro anti-proliferative activity against human breast cancer ER(+)-MCF-7 and ER(-)-MDA-MB-231 cell lines. The bioactive compound 4d exhibited the best anti-breast cancer activity against MCF-7 cells with the IC50 values of 43.08 μM. The compound might be used as a potential anti-tumor agent for the further structure modifications and development.

Non-concerted nucleophilic [4+1] cycloaddition of (dimethylamino)methoxycarbene to arylazonicotinates in the synthesis of pyrazolo[3,4-c]pyridines and pyrazolo[4′,3′:4,5]pyrido[2,3-d]pyrimidines

A novel reaction between 2-amino-5-arylazonicotinonitriles 3c–g and dimethylformamide dimethylacetal (DMF-DMA), leading to the formation of a new class of pyrazolo[3,4-c]-pyridine derivatives 8, has been developed. The process is believed to take place via a non-concerted [4+1] cycloaddition pathway involving nucleophilic addition of (dimethylamino)-methoxycarbene, generated from DMF-DMA, to the arylazonicotinates 3c–g. The pyridine derivatives 8 were observed to react with ammonia in refluxing acetic acid to yield novel pyrazolo[4′,3′:4,5]pyrido[2,3-d]pyrimidine derivatives 9. Other members of the pyrido[2,3-d]pyrimidine family 13 were synthesized by reactions between 2-amino-5-arylazonicotinate ethyl esters 3a,b and DMF-DMA, which produce amidine derivatives 10a,b that undergo cyclization to generate the corresponding pyrido[2,3-d]pyrimidines13a,b when treated with ammonia in refluxing acetic acid. Finally, the results of this effort revealed that pyrido[2,3-d]pyrimidines 13a,b also react with DMF-DMA to produce pentaazacyclopenta [a]naphthalene derivatives 14. The structures of all new substances prepared in this investigation were determined by using X-ray crystallographic analysis and spectroscopic methods.

Organocatalysis in heterocyclic synthesis: DABCO as a mild and efficient catalytic system for the synthesis of a novel class of quinazoline, thiazolo [3,2-a]quinazoline and thiazolo[2,3-b] quinazoline derivatives

BackgroundThere are only limited publications devoted to the synthesis of especially thiazolo[3,2-a]quinazoline which involved reaction of 2-mercaptopropargyl quinazolin-4-one with various aryl iodides catalyzed by Pd-Cu or by condensation of 2-mercapto-4-oxoquinazoline with chloroacetic acid, inspite of this procedure was also reported in the literature to afford the thiazolo [2,3-b] quinazoline. So the multistep synthesis of the thiazolo[3,2-a]- quinazoline suffered from some flaws and in this study we have synthesized a novel class of thiazoloquinazolines by a simple and convenient method involving catalysis by 1,4-diazabicyclo[2.2.2]octane (DABCO).ResultsA new and convenient one-pot synthesis of a novel class of 2-arylidene-2H-thiazolo[3,2-a]quinazoline-1,5-diones 9a-i was established through the reaction between methyl-2-(2-thio-cyanatoacetamido)benzoate (4) and a variety of arylidene malononitriles 8a-i in the presence of DABCO as a mild and efficient catalytic system via a Michael type addition reaction and a mechanism for formation of the products observed is proposed. Moreover 4 was converted to ethyl-2-[(4-oxo-3,4-dihydroquinazolin-2-yl)thio]acetate (10) upon reflux in ethanol containing DABCO as catalyst. The latter was reacted with aromatic aldehydes and dimethylformamide dimethylacetal (DMF-DMA) to afford a mixture of two regioselectively products with identical percentage yield, these two products were identified as thiazolo[3,2-a]quinazoline 9,13 and thiazolo[2,3-b]quinazoline 11,12 derivatives respectively. The structure of the compounds prepared in this study was elucidated by different spectroscopic tools of analyses also the X-ray single crystal technique was employed in this study for structure elucidation, Z/E potential isomerism configuration determination and to determine the regioselectivity of the reactions.ConclusionA simple and efficient one-pot synthesis of a novel class of 2-arylidene-2H-thiazolo[3,2-a]quinazoline-1,5-diones 9a-i was established through DABCO catalyzed Michael type addition reaction. In addition many fused quinazoline and quinazoline derivatives were synthesized which appeared as valuable precursors in synthetic and medicinal chemistry.

Selective Methylation of NH-Containing Heterocycles and Sulfonamides Using N,N-Dimethylformamide Dimethylacetal Based on Calculated pKa Measurements

The use of <i>N</i>,<i>N</i>-dimethylformamide dimethylacetal (DMF-DMA) as a suitable methylating agent for the methylation of NH-containing groups and heterocycles has been investigated. Use of ReactArray and calculated p<i>K</i> _a measurements have allowed additional helpful information to be collated to determine optimum reaction conditions for a variety of substrates.