Dimethylformamide Dimethylacetal Research Articles

Studies with enaminones and enaminonitriles: synthesis of 3-aroyl and 3-heteroaroyl-pyrazolo-[1,5- a]pyrimidines

The reaction of electron rich aromatics with cyanoacetic acid and acetic anhydride afforded 3-oxoalkanenitriles. Indium trichloride was used as a Lewis acid catalyst when the aromatic ring was not sufficiently reactive. The synthesized 3-oxoalkanenitriles were subsequently condensed with dimethylformamide dimethylacetal (DMFDMA) to yield enaminones that reacted readily with hydrazine hydrate to yield 4-aroylpyrazole-3-amines. The 4-aroylpyrazole-3-amines were condensed with enaminones to yield 3-aroylpyrazolo[1,5- a]pyrimidines.

Utility of p‐phenylenediformamidine in the synthesis of bisazoles and phenanthroline

Abstract magnified imagep‐Phenylenediformamidine 1 is readily obtained upon treating p‐phenylenediamine with dimethylformamide dimethyl acetal (DMFDMA) by heating or by microwave irradiation. Compound 1 was treated with active methylene nitriles followed by hydrazine hydrate derivatives to give bisaminopyrazole derivatives. Other bisazoles can be obtained by reacting 1 with aminoazole derivatives. Cyclization of Bis [2‐(p‐phenelyeneimino)malononitrile] to 1,10‐diaminophenanthroline‐2,9‐dicarbonitrile is also reported. J. Heterocyclic Chem., (2009).

Synthesis of novel pyrazolo[3,4‐d]pyridazine, pyrido[1,2‐a]benzimidazole, pyrimido[1,2‐a]benzimidazole and triazolo[4,3‐a]pyrimidine derivatives

Abstractmagnified image4‐Acetyl‐5‐methyl‐1‐phenyl‐1H‐pyrazole reacts with dimethylformamide dimethylacetal (DMF‐DMA) to afford the corresponding (E)1‐(5‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐3‐(N,N‐dimethylamino)‐2‐propen‐1‐one. The latter product undergoes regioselective 1,3‐dipolar cycloaddition with nitrilimines and nitrile oxides to afford the novel 3‐aroyl‐4‐(5‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl)carbonyl‐1‐phenylpyrazole and 3‐aroyl‐4‐(5‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl)carbonyl isoxazole derivatives, respectively. It reacts also with 1H‐benzimidazole‐2‐acetonitrile, 2‐aminobenzimidazole and 3‐amino‐1,2,4‐triazole to afford the novel pyrido[1,2‐a]benzimidazole, pyrimido[1,2‐a]benzimidazole and the triazolo[4,3‐a]pyrimidine derivatives, respectively. The reaction of 3‐aroyl‐4‐(5‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl) carbonyl‐1‐phenylpyrazole derivatives with hydrazine hydrate led to a new pyrazolo[3,4‐d]pyridazine derivatives.

First synthesis of selenadiazolo[3,4‐i] Benzazepine derivatives

Abstractmagnified image5‐Methyl‐4‐nitro‐2,1,3‐benzoselenadiazole (1) was converted into (E)‐5‐(2‐dimethylamino)vinylbenzo‐[c](1,2,5)selenadiazole‐4‐amine (4) by initial treatment with dimethylformamide dimethyl acetal (DMFDMA) (2) followed by selective reduction using ammonium bromide in methanol. Compound 4 afforded the selenadiazolo[3,4‐i][1]benzazepine derivatives (7, 10, 13, 15) upon treatment with malononitrile (5), ethyl cyanoacetate (8) and cyanoacetamide (11) respectively.

3-Amino- and 3-acylamido-2-phosphonopyridines: synthesis by Pd-catalyzed P–C coupling, structure and conversion to pyrido[ b]-anellated P [dbnd]C–N heterocycles

Palladium catalyzed cross-coupling of 3-amino- and 3-acylamido-2-bromopyridines 1a– f with triethyl phosphite allowed the synthesis of 3-amino- and 3-acylamido pyridine-2-phosphonic acid diethyl esters 2a– f, whereas nickel catalysts, although providing access to related anilido-2-phosphonates, proved inactive. Reduction of the aminophosphonate 2a with LiAlH 4 afforded 3-amino-2-phosphinopyridine ( 3a), which was cyclocondensed with dimethylformamide dimethyl acetal (DMFA) via phosphaalkene intermediates 4a to the novel pyrido[ b]-anellated 1,3-azaphosphole 5a. Reaction of amidophosphonates 2b– f with LiAlH 4 did not result in the expected reductive cyclization, as shown by closely related anilido-2-phosphonates, but led to product mixtures containing N-secondary 3-amino-2-phosphinopyridines 3b– f as the main or major component. The conversion of 3b, d, e with DMFA to 5b, d, e provides first examples of N-substituted pyrido[ b]-anellated azaphospholes. Structures were confirmed by multinuclear NMR and X-ray crystallography (for 2c, 3b).

Synthesis and Antimicrobial Evaluation of Novel Pyrazolo[1,5-a]pyrimidine, Pyrimido[1,2-a]benzimidazole, Triazolo[4,3-a]pyrimidine and Pyrido[1,2-a]benzimidazole Derivatives Incorporated Phenylsulfonyl Moiety

Phenylsulfonylacetonitrile (1) reacts with dimethylformamide dimethyl acetal (DMF-DMA) to afford 3-(dimethylamino)-2-(phenylsulfonyl)acrylonitrile (2). Enaminonitrile 2 reacts with 5-aminopyrazole derivatives 3a-e, 5-amino-l,2,4-triazole (7) and 2-aminobenzimidazole (11) to afford new pyrazolo[1,5-a]pyrimidine, triazolo[4,3-a]pyrimidine and pyrimido[1,2-a]benzimidazole derivatives 4a-e, 9 and 12, respectively. Also, 3-(dimethylamino)-2-(phenylsulfonyl)acrylonitrile (2) reacts with 2-(1H-benzimidazol-2-yl)acetonitrile (13) to give the corresponding pyrido[1,2-a]benzimidazole derivative 15. Some of the newly synthesized compounds were tested in vitro for their antibacterial and antifungal activities, and showed promising results.

Microwaves in organic synthesis: Facile synthesis of biologically active pyridazinone and iminopyridazine derivatives

Abstractmagnified imageCondensation of Wittig reagents 1a,b with arylhydrazones 2a,b by conventional and by microwave heating techniques furnished the corresponding pyridazines 3a‐e. The arylhydrazones 7a,b were allowed to react with 1a,b under the same conditions to produce the pyridazinones 10a,b and iminopyridazines 11a,b respectively. On the other hand, the arylhydrazones 12a‐c reacted with 1a to afford the pyridazinones 13a‐c. Treatment of 3b with dimethylformamide dimethyl acetal (DMFDMA) produced the adduct 15. The utility of microwave heating technique led to the reduction of the reaction times to few minutes and to the improvement of the yields of the products. The in vitro biological activity of some newly prepared compounds against four types of fungi was studied.

Dimethylformamide Dimethyl Acetal in Heterocylic Synthesis: Synthesis of Polyfunctionally Substituted Pyridine Derivatives as Precursors to Bicycles and Polycycles.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Synthesis of a deuterium‐labelled standard of bufotenine (5‐HO‐DMT)

AbstractThe Batcho–Leimgruber strategy was employed to synthesize 3‐(2‐dimethylamino‐[2H4]‐ethyl)‐1H‐indol‐5‐ol (bufotenine, 5‐HO‐DMT) (8) from commercial 3‐methyl‐4‐nitro‐phenol (1), benzyl bromide and N,N–dimethylformamide–dimethylacetal. Compound 4 was synthesized from compound 3 using the Batcho–Leimgruber strategy in the presence of Raney nickel and hydrazine hydrate. Compound 4 was treated with oxalyl chloride, dimethylamine and lithium aluminum [2H4]‐hydride to yield [2‐(5‐benzyloxy‐1H‐indol‐3‐yl)‐[2H4]‐ethyl]‐dimethyl‐amine (7). The benzyl ether in compound 7 was cleaved by hydrogenolysis to give bufotenine 8. Copyright © 2007 John Wiley & Sons, Ltd.

A convenient synthesis of linear pyridinoimidazo[1,2- a]pyridine and pyrroloimidazo[1,2- a]pyridine cores

Two new imidazo[1,2- a]pyridine derivatives, pyridinoimidazo[1,2- a]pyridine ( 10) and pyrroloimidazo[1,2- a]pyridine ( 16), were synthesised from 2-amino-4-methyl-5-nitropyridine ( 1) by linear cyclisation, making use of dimethylformamide dimethylacetal (DMFDMA) as an agent of vinylamine functionalisation. This report describes first the formation of pyridine and pyrroloimidazopyridine from ( 1), and then the formation of pyridine-fused and pyrrolo-fused pyridine by the Friedländer method and reductive cyclisation followed by treatment of the resulting adduct with chloroacetaldehyde.

Microwave Assisted Condensation Reactions of 2-Aryl Hydrazonopropanals with Nucleophilic Reagents and Dimethyl Acetylenedicarboxylate

The reaction of methyl ketones 1a-g with dimethylformamide dimethylacetal (DMFDMA) afforded the enaminones 2a-g, which were coupled with diazotized aromatic amines 3a,b to give the corresponding aryl hydrazones 6a-h. Condensation of compounds 6a-h with some aromatic heterocyclic amines afforded iminoarylhydrazones 9a-m. Enaminoazo compounds 12a,b could be obtained from condensation of 6c with secondary amines. The reaction of 6e,h with benzotriazolylacetone yielded 14a,b. Also, the reaction of 6a,b,d-f,h with glycine and hippuric acid in acetic anhydride afforded pyridazinone derivatives 17a-f. Synthesis of pyridazine carboxylic acid derivatives 22a,b from the reaction of 6b,e with dimethyl acetylenedicarboxylate (DMAD) in the presence of triphenylphosphine at room temperature is also reported. Most of these reactions were conducted under irradiation in a microwave oven in the absence of solvent in an attempt to improve the product yields and to reduce the reaction times.

Utility of Cyanoacetamides as Precursors to Pyrazolo[3,4-d]pyrimidin-4-ones, 2-Aryl-6-substituted 1,2,3 Triazolo[4,5-d]pyrimidines and Pyrazolo[1,5-a]pyrimidine-3-carboxamides

Cyanoacetamides (7a-c) were prepared via reacting cyanoacetic acid (5) with amines in the presence of acetic anhydride. Compounds (7a-c) coupled with benzenediazonium chloride to yield the phenylhydrazones (8a-c). These reacted with chloroacetonitrile to yield aminopyrazolecarboxamides (lla-c). Reaction of (8a,b) with hydroxylamine hydrochloride in DMF in presence of anhydrous sodium acetate afforded the amino-l,2,3-triazolecarboxamides (36a,b). Also compounds (7a-c) reacted with dimethylformamide dimethylacetal (DMFDMA) to yield the enamines (9a-c) which react with hydrazine hydrate to afford the aminopyrazoles (16a-c). Compounds (16) and (36) reacted with DMFDMA to yield the title heterocyclic derivatives.

Facile Synthesis of 5, 6, 7, 8-Tetrahydropyrimido [4, 5-b]-quinoline Derivatives

2-Amino-4-phenyl-5,6,7,8-tetrahydroquinoline-3-carbonitrile (3) was synthesized by treating cyclohexanone (1) with 2-benzylidenemalononitrile (2) in the presence of ammonium acetate. The reactivity of compound 3 towards dimethylformamide dimethyl acetal (DMF-DMA), carbon disulfide, urea, thiourea, formamide, formic acid, acetyl chloride and isothiocyanate were studied. In addition, the antimicrobial activity of some selected derivatives is reported.

Studies with Heteroaromatic Amines. A New Route to 2‐Azolylamino‐2‐thiazolin‐4‐ones.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Studies with heteroaromatic amines. A new route to 2-azolylamino-2-thiazolin-4-ones

Heteroaromatic chloroacetamides 3a–c on treatment with potassium thiocyanate afforded the thiazolylamino-thiazolines 6a–c via intermediacy of 4a–c and 5a–c. Compounds 6a–c condensed with dimethylformamide dimethylacetal (DMFDMA) to yield the Z–enamines 7a–c. The enamines 7a and 7b could be converted into the enamines 8a–e and 9a,b on treatment with amines. However, reacting 10c with morpholine afforded 11b. Compounds 9a,b, as well as 9c, were also obtained on reacting 6a–c with triethyl orthoformate and piperidine in DMF. The structures of 6a and 11b were confirmed by X-ray crystal structure determination.

Studies with Enaminones: Synthesis and Chemical Reactivity of 2‐(4‐Dimethylamino‐2‐oxobut‐3‐enyl)‐isoindole‐1,3‐dione and of 4‐(4‐Dimethylamino‐2‐oxobut‐3‐enyloxy)‐2H‐phthalazin‐1‐one.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Studies with enaminones: Synthesis and chemical reactivity of 2‐(4‐dimethylamino‐2‐oxobut‐3‐enyl)‐isoindole‐1,3‐dione and of 4‐(4‐dimethylamino‐2‐oxobut‐3‐enyloxy)‐2H‐phthalazin‐1‐one

AbstractThe title compounds were synthesized via condensing acetonylphthalimide and 4‐acetonyloxyphthalazine‐1‐one with dimethylformamide dimethylacetal (DMFDMA). The reaction of these enaminones with electrophiles and nucleophiles is reported as a route to polyfunctional heteroaromatics.

New Routes to Pyridino[2,3-d]pyrimidin-4-one and Pyridino-[2,3-d]triazolino[4,5-a]pyrimidin-5-one Derivatives

2-Thioxopyrimidinyl-5-(N,N-dimethylamino)formamidine (5) and 1,3-diphenyltriazolo[3,4-d]pyrimidinyl-N,N-dimethylformamidine (14) were prepared by condensation of 6-amino-2-thioxo-1,3-dihydropyrimidin-4-one (2) and 7-amino-1,3-diphenyl-1,2,4-triazolo[4,3-a]pyrimidin-4-one (13) with dimethylformamide dimethyl- acetal (DMFDMA). Compound 5 reacts with acetophenone and 2-acetylthiophene to give the 2-thioxo-1,3-dihydropyridino[2,3-d]pyrimidin-4-ones 3a and 3b, respectively. Compounds 3a,b react with hydrazonoyl halides 6,7 to give pyridino[2,3-d]triazolo[4,5-a]pyrimidin-4-ones 11a-d and not the isomeric structures 12a-d. Formamidines of type 14 react with ethyl cyanoacetate, malononitrile and benzoyl acetonitrile to give the 1,3-diphenyl-3a-hydropyridino[2,3-d]1,2,4-triazolo[4,5-a]pyrimidin-4-one derivatives 15a,b and 18, respectively. The structures of the newly synthesized compounds are established on the basis of chemical and spectroscopic evidences as well as their synthesis by alternative methods.

Analysis of amino acids as formamidene butyl esters by electrospray ionization tandem mass spectrometry.

Amino acid formamidene butyl esters are optimally prepared by heating amino acids with dimethylformamide dimethylacetal (DMF-DMA) for 2 minutes at 65 degrees C and then with n-butanol/hydrogen chloride for 15 minutes at 65 degrees C. The formamidene butyl esters of simple alpha-amino acids and beta-amino acids afford between 1.1 and 20 times the signal intensity of the corresponding butyl esters during electrospray ionization tandem mass spectral analysis. Complex alpha-amino acids, such as ornithine, arginine and citrulline, and gamma-amino acids are better analyzed as butyl esters. Secondary alpha-amino acids, such as proline and sarcosine, give a mixture of two iminium salts with the DMF-DMA derivatization method. A derivative incorporating two molecules of the amino acid predominates at higher derivatization temperatures. Contrary to a previous report, N-formylamino acids were not detected. The presence of secondary amino acids in amino acid mixtures, derivatized as formamidene butyl esters, affords derivatives that incorporate two different amino acids. The new formamidene butylation method is unlikely to replace the butylation procedure used by neonatal blood spot screening programs for amino acid disorders, since a much poorer response was obtained with formamidene butyl esters of arginine and citrulline, important in the diagnosis of arginase deficiency and citrullinaemia.

Studies with enaminones: synthesis of new coumarin‐3‐yl azoles, coumarin‐3‐yl azines, coumarin‐3‐yl azoloazines, coumarin‐3‐yl pyrone and coumarin‐2‐yl benzo[b]Furans

Abstract3‐Acetylcoumarine was condensed with dimethylformamide dimethylacetal (DMFDMA) to yield the enaminone, which reacts readily with hydroxylamine and with hydrazines to yield coumarin‐3‐ylisoxazoles and coumarin‐3‐ylpyrazoles respectively. Reaction of the enaminone with benzamidine hydrochloride and 3‐amino‐1,2,4‐1H‐triazole affords the pyrimidine and triazolo[3,4‐b]pyrimidine. The enaminone reacts with hippuric acid and with the dithiocarboxylic acid to yield pyranones. The reaction of the enaminone with 3‐amino‐1H‐1,2,4‐triazole gives the triazolo[3,4‐b]pyrimidine. The enaminone underwent self dimerization on reflux in acetic acid ammonium acetate to yield the coumarinyl pyridines and reacted with ketone under the same conditions to yield the pyridine. The reaction of the enaminone with 1,4‐benzoquinone and 1,4‐naphthoquinone gives benzofuryl coumarine derivatives.