Tandem aza-Wittig Research Articles

Synthesis of 3-methylthio-1-phenyl-pyrazolo[3,4-d][1,2,4]triazolo[1,5-a]pyrimidin-4-one derivatives via tandem aza-Wittig reaction

An efficient and convenient procedure for the synthesis of 3-methylthio-1-phenyl-pyrazolo[3,4-d][1,2,4]triazolo[1,5-a]pyrimidin-4-one derivatives (4a–m) via tandem aza-Wittig and annulation reactions with iminophosphoranes 1, aryl isocyanate, and substituted 2-phenoxyacetohydrazide is described. This protocol provides a simple and facile approach to synthesize pyrazolo[3,4-d][1,2,4] triazolo[1,5-a]pyrimidine derivatives under mild conditions.

Design, synthesis, and herbicidal activity of novel 2-(arylamino)-5-methyl-4-methylene-7-(methylthio)-4H-pyrido[4,3-d][1,3]oxazine-8-carbonitrile derivatives

A series of 5-methyl-4-methylene-7-methylthio-2-arylmino-4 H-pyrido[4,3- d][1,3]oxazine-8-carbonitrile derivatives were synthesized via tandem aza-Wittig and annulation reactions with { N-[3-acetyl-5-cyano-2-methyl-6-(methylthio)pyridin-4-yl]imino}triphenylphosphorane and aryl isocyanate in dry dichloromethane. Their structures were clearly confirmed by infrared, 1H NMR, 13C NMR, high-resolution mass spectrometry, and X-ray single-crystal diffraction. All newly synthesized compounds were screened for herbicidal activities against monocotyledonous and dicotyledonous plants. The results indicated that the target compound 2-[(4-methoxyphenyl)amino]-5-methyl-4-methylene-7-(methylthio)-4 H-pyrido[4,3- d][1,3]oxazine-8-carbonitrile showed 100% inhibition rate to grain sorghum (monocotyledonous) at the concentration of 100 mg L−1.

New efficient synthesis of 1H-imidazo-[4,5-c]quinolines by a sequential Van Leusen/Staudinger/aza-Wittig/carbodiimide-mediated cyclization

A new efficient synthesis of multisubstituted 1H-imidazo-[4,5-c]quinoline derivatives via sequential van Leusen/Staudinger/aza-Wittig/carbodiimide-mediated cyclization was developed. Azides 4, obtained from Van Leusen reaction of 2-azidobenzaldehyde 1, amine 2 and TosMIC (tosylmethyl isocyanide) 3, reacted with triphenyl phosphine to produce iminophosphorane 5. A tandem aza-Wittig reaction of iminophosphorane 5 with isocyanate generated 1H-imidazo-[4,5-c]quinoline 7 through carbodiimide intermediate 6 in moderate to good yield.

Synthesis and herbicidal activity of novel 6-arylthio-3-methylthio-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones

GRAPHICAL ABSTRACT

New Facile Synthesis of 2-Alkylthiopyrimidin-4(3H)-ones by Tandem Aza-Wittig Reaction Starting from the Baylis–Hillman Adducts

Iminophosphoranes reacted with CS2 at –5 °C to produce the isothiocyanates, which were treated with primary amine to give thioureas in 73–91% yields. The subsequent reaction of thioureas with alkyl bromides in the presence of solid K2CO3 produced 2-alkylthiopyrimidin-4(3H)-ones in 68–88% yield via tandem intramolecular cyclization–isomerization–S-alkylation.

Synthesis, Characterization, and Fungicidal Activity of New Thienopyridopyrimidine Derivatives

Iminophosphorane 3 is a important intermediate in organic synthesis. A series of new 2-substituted tetrahydrobenzo[4′,5′]thieno[3′,2′:5,6]pyrido[4,3-d]pyrimidin-4(3H)-ones 5 have been designed and synthesized via the tandem aza-Wittig reaction in 58–92% yields. Iminophosphorane 3 reacted with phenyl isocyanate (or 4-chlorophenyl isocyanate, 4-fluorophenyl isocyanate) to give carbodiimide 4, which was further treated with amines to cyclize in the presence of a catalytic amount of EtONa. The structures of compounds 5 have been confirmed by 1H NMR, electron-impact mass spectrometry, infrared spectroscopy, and elemental analyses. The results of preliminary bioassay indicated that some compounds possess inhibition activities against Rhizoctonia solani and Botrytis cinereapers at a dosage of 50 mg/L.

Synthesis and Characterization of New 2-Methoxy-Thieno[2,3-<i>d</i>]pyrimidin-4(3<i>H</i>)-One

An efficient method is described for the synthesis of 2-methoxy-thieno[2,3-d]pyrimidin- 4(3H)-one (5) via Gewald reaction, a tandem aza-Wittig reaction and cyclization process. The key step is an aza-Wittig reaction between iminophosphorane (2), 4-chlorophenyl isocyanine and nucleophilic reagent CH3OH. Its structures were determined by means of MS, IR and 1H NMR spectra.

New Efficient Synthesis of 5,6-Disubstituted-3-phenyl-1,2,3-triazolo[4,5-d]pyrimidin-7-ones via a Tandem Aza-Wittig Reaction

Twelve novel 5,6-disubstituted-3-phenyl-1,2,3-triazolo[4,5-d]pyrimidine-7-ones 5a–5l were designed and successfully synthesized via tandem aza-Wittig and annulation reactions of the corresponding iminophosphorances 2, aromatic isocyanate, and substituted thiophenols in satisfactory yields. The results from the preliminary bioassay indicated that some of these compounds possess inhibitory activities against the root and stalk of Brassica napus(rape) as well as Echinochloa crusgalli (barnyard grass) at the dosages of 100 mg/L and 10 mg/L, respectively.

New efficient synthesis of 1,2,4-trisubstituted imidazoles and imidazo[1,2- c]quinazolines by a tandem aza-Wittig/electrocyclic ring-closure process

A series of 1,2,4-trisubstituted imidazoles 5 were synthesized efficiently by a tandem aza-Wittig/1,5-electrocyclic ring-closure reaction of vinyliminophosphoranes 3 with aldehydes. Reactions of 5s, t with triphenylphosphine produced iminophosphoranes 7. A tandem aza-Wittig reaction of iminophosphorane 7 with isocyanate generated imidazo[1,2-c]quinazolines 9 in high yields.

ChemInform Abstract: Synthesis of Isoquinoline Derivatives by a Tandem Aza-Wittig/ Electrocyclization Strategy and Preparation of the Unknown 1,9- Diazaphenalene Ring by a Consecutive Electrocyclic Ring Closure/ Claisen Rearrangement/ Intramolecular Amina

Treatment of iminophosphrane 3, derived from ethyl α-azido-2-(allyloxy) cinnamate, with aromatic isocyanates in toluene at 150 o C leads to the corresponding isoquinoline derivatives 5 by a tandem electrocyclic ring closure/Claisen rearrangement of the intermediate carbodiimide. Fremy's salt promoted oxidation of compounds 5 yields the 5,8-isoquinolinequinone allides 6, which by heating undergo cyclization to 2H-pyrano [2,3-f] isoquinolines isocyanates to give the corresponding carbodiimides, which by thermal treatment at 150 o C undergo a consecutive electrocyclic ring closure/Claisen rearrangement/intramolecular amination process to give 1,9-diazaphenalene derivatives

New efficient synthesis of pyrimido[1,6-c]quinazolin-4-ones by a Biginelli 3CC/Staudinger/aza-Wittig sequence

Dihydropyrimidinone azides 1, obtained from trimethylsilyl chloride-catalyzed Biginelli reaction of 2-azidobenzaldehyde, ethyl acetoacetate, and urea (or thiourea) at room temperature, reacted with triphenylphosphine to give iminophosphorane 2. A tandem aza-Wittig reaction of iminophosphorane 2 with isocyanate, acyl chloride or CS2 in the presence of K2CO3 or NEt3 generated pyrimido[1,6-c]quinazolin-4-ones 4, 6 or 8 in moderate to good yield.

Facile Method for the Synthesis of Pyrazolo[3,4-b]-pyrido[4,3-d]-pyrimidine-4-ones via a Tandem Aza-Wittig Reaction

Fifteen novel pyrazolo[3,4-b]-pyrido[4,3-d]-pyrimidine-4-ones (7a–o) were designed and have been successfully synthesized via tandem aza-Wittig and annulation reactions of the corresponding iminophosphorances 5, phenylisocyanate, and substituted phenols in 60–77% isolated yields. Their structures were clearly verified by infrared (IR), 1H NMR, electron impact–mass spectrometry (EI-MS), and elemental analysis. The results of a preliminary bioassay indicated that some compounds possess inhibition activities against the root of Brassica napus (rape) and Echinochloa crusgalli (barnyard grass) at a dosage of 100 mg/L and 10 mg/L.

ChemInform Abstract: New 3,7‐Dihydro‐4H‐pyrazolo[3′,4′:2,3]pyrido[4,5‐d]pyrimidin‐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 of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

New Efficient Synthesis of 5-Ethoxyoxazoles and Oxazolo[3,2-c]quinazolines via Aza-Wittig Reaction

5-Ethoxyoxazoles or 2-acylamino propanoates were synthesized by aza-Wittig reaction of iminophosphorane with acyl chloride in the presence of triethylamine. Reactions of 5-alkoxyoxazole with triphenyphosphine produced iminophosphoranes. A tandem aza-Wittig reaction of iminophosphorane with isocyanate or carbon disulfide generated oxazolo[3,2-c]quinazolines in satisfactory yields.

New 3,7-dihydro-4H-pyrazolo[3′,4′:2,3]pyrido[4,5-d]pyrimidin-4-ones

Thirteen novel pyrazolo[3″,4″:2,3]pyrido[4,5-d]pyrimidin-4-ones 7a–m were synthesised via tandem aza-Wittig and annulation reactions of the corresponding iminophosphoranes 5, phenylisocyanate, and substituted amine in 56–86% yields. Their structures were verified by IR, 1H NMR, EI-MS spectroscopy and elemental analysis. Preliminary bioassay indicated that some compounds possess inhibition activity against Brassica napus (rape) and Echinochloa crusgalli (barnyard grass).

Synthesis and Antifungal Activities of Novel 5-Amino-6-arylamino- 1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one Derivatives

A novel approach was developed to regioselectively synthesize new 5-amino-6-arylamino-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one 5 derivatives via a tandem aza-Wittig and annulation reactions of iminophosphorane 2, aromatic isocyanates, and hydrazine in 52-92% isolated yields. The compounds 5 reacted with triethyl orthoformate to give 1,8-2H-pyrazolo[3,4-d][1,2,4]triazolo[1,5-a]pyrimidin-4-ones 6 in good yields (62-94%). Their structures were clearly confirmed by spectroscopy data (IR, (1)H NMR, MS), elemental analysis, or X-ray diffraction crystallography. The results of preliminary bioassay indicated that the compounds 5 and 6 possessed high antifungal activity against Botrytis cinerea Pers and Sclerotinia sclerotiorum. Compounds 5 showed much better antifungal activities when R was Me instead of PhCH 2. Especially, compounds 6c, 6g, and 6i inhibited Sclerotinia by 100% at the concentration of 50 mg/L and by 83, 83, and 82% at the dosage of 10 mg/L, respectively.

Application of the aza-Wittig reaction to the synthesis of pyrazinothienotriazolopyrimidinones: a new tetracyclic ring system

A simple one-pot and efficient method is described for the synthesis of pyrazinothienopyrimidines 6 by domino processes involving aza-Wittig/intermolecular nucleophilic addition/intramolecular cyclization. A tandem aza-Wittig reaction of phosphazenes 7, derived from 6, with heterocumulenes (isocyanates, carbon disulfide or carbon dioxide) generates the pyrazinothienotriazolopyrimidinones 9, 11 and 12, respectively. Pyrazino[2′,3′:4,5]thieno[3,2- d]-1,2,4-triazolo[1,5- a]pyrimidin-4(3 H)-ones 15 and bis(pyrazinothienotriazolopyrimidinones) 17 were synthesized by the intermolecular aza-Wittig reaction of phosphazenes 7 with acyl chlorides or α,ω-dichlorides followed by heterocyclization via imidoyl chloride intermediate 16. Further S-alkylation of 11 and reaction of 6 with phosgeniminium chloride produce 2-alkylthio- and 2- N, N-dimethylaminopyrazinothienotriazolopyrimidinones 13 and 19, respectively.

A Facile Synthesis and Herbicidal Activities of Novel Fluorine‐Containing Thiazolo[4,5‐d]pyrimidin‐7(6H)‐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.

A facile synthesis and fungicidal activities of novel fluorine-containing pyrido[4,3- d]pyrimidin-4(3 H)-ones

Sixteen novel 2-substituted-5,8,9-trimethyl-3-(4-fluoro-substituted)phenyl-thieno[3′,2′-5,6] pyrido[4,3- d]pyrimidin-4(3 H)-ones 5a–5p were designed and have been successfully synthesized via tandem aza-Wittig and annulation reactions of the corresponding iminophosphorances 1, para-fluoro phenyl isocyanate, and substituted phenols or amines in 73–90% isolated yields. Their structures were clearly verified by IR, 1H NMR, EI-MS spectroscopy and elemental analysis, and in the case of compound 5a, analyzed by single-crystal X-ray diffraction further. The results of preliminary bioassay indicated that some compounds possess inhibition activities against Rhizoctonia solani and Botrytis cinereapers at a dosage of 50 mg/L.

3-(4-Chlorophenyl)-2-(diisobutylamino)-4-oxo-5-phenyl-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidine-7-carbonitrile

A tandem aza-Wittig reaction of ethyl 3-triphenyl­phospho­ranylideneamino-4-cyano-1-phenyl-1H-pyrrole-2-carboxyl­ate with 4-chloro­phenyl isocyanate and diisobutyl­amine produced the title compound, C27H28ClN5O. In the mol­ecule, the angles between the fused-ring system and the two benzene rings are 51.66 (2) and 65.79 (2)°. Intra­molecular C—H⋯N hydrogen bonds determine the conformation of the mol­ecule. The packing of the mol­ecules in the crystal structure is governed mainly by inter­molecular C—H⋯N hydrogen-bonding inter­actions. There are no π–π inter­actions.