aza-Wittig Reaction Of Iminophosphorane Research Articles

A facile synthesis of polysubstituted furo[2,3-d]pyrimidinones and 1,2,4-triazole-fused derivatives

In this paper, a series of polysubstituted furo[2,3- d]pyrimidinones, including 1,2,4-triazole-fused derivatives, are synthesized via aza-Wittig reactions of iminophosphoranes, under mild conditions.

An efficient synthesis of 3-alkyl-2-diversity-substituted benzofuro[3,2-d]pyrimidin-4(3H)-one derivatives

Benzofuro[3,2- d]pyrimidine derivatives are prepared using aza-Wittig reactions of iminophosphoranes with n-butyl isocyanate at 40–50 °C to give carbodiimide intermediates, which are reacted with nitrogen-oxygen-containing nucleophiles to give 3-alkyl-2-amino (aryloxy/alkoxy)-benzofuro[3,2- d]pyrimidin-4(3 H)-ones in satisfactory yields in the presence of a catalytic amount of sodium ethoxide or K2CO3. The iminophosphorane also reacts directly with excess carbon disulfide, followed by n-propylamine; further reaction with alkyl halides or halogenated aliphatic esters in the presence of anhydrous K2CO3 produces the corresponding 2-alkylthio-3-n-propyl-benzofuro[3,2- d]pyrimidin-4(3 H)-ones in good yields. Their structures of the products are confirmed by 1H NMR, 13C NMR, mass spectrometry, infrared and elemental analysis.

Synthesis, characterization and crystal structure of heterocyclic tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidinone derivatives via sequential aza-Wittig/base catalyzed cyclization

Seventeen examples of 7-Benzyl-5,6,7,8-tetrahydropyrido [4′,3′:4,5]thieno [2,3-d]pyrimidin-4(3H) -ones were synthesized by base catalyzed reactions of nucleophilic reagents (aliphatic amines, alcohols or phenols) with carbodiimides 3, which in turn were obtained by the aza-Wittig reaction of iminophosphorane 2 with aromatic isocyanates. The compounds were fully characterized by analytical and spectroscopic techniques (FT-IR, 1H NMR, 13C NMR and MS). Crystal structure determination of three tetrahydropyrido [4′,3':4,5]thieno [2,3-d]pyrimidinone derivatives has been undertaken in order to better understanding the influence of structural modifications upon overall molecular geometry and conformation. 3D supramolecular architectures are formed in the crystals by self-assembly of the molecules via stacking interactions and various hydrogen bonds. Meanwhile, crystal structure of a guanidine intermediate 4a was characterized in order to proclaim the reaction mechanism of the base catalyzed intramolecular cycloaddition.

Synthesis of Pyrrolo[3, 4-d]Pyrimidine Thiono Derivatives via Aza Wittig Reaction

New pyrolo [3,4-d] pyrimidine derivatives were obtained from the aza-Wittig reactions of iminophosphorane with phenylisocyanates via of amino compounds with triphenylphosphine, hexachloroethane and triethyl-amine produced iminophosphorane.

Synthesis of 2-Alkylamino/Alkoxy-3-Arylthieno[3,2-d]Pyrimidin-4(3<i>H</i>)-One Derivatives

The title compounds 2-alkylamino/alkoxy-3-arylthieno [3,2-pyrimidin-4(3H)-ones were synthesized by base catalytic reactions of primary amines or alcohols with carbodiimides,which were obtained from the aza-wittig reaction of iminophosphorane 2 and arylisocyanates.The conditions of cyclization and spectral properties were researched.

Synthesis, Fungicidal Activity, and Sterol 14α-Demethylase Binding Interaction of 2-Azolyl-3,4-dihydroquinazolines on Penicillium digitatum

A series of new 2-azolyl-3,4-dihydroquinazolines 6 was synthesized by direct cyclization of imidazole or 1,2,4-triazole with carbodiimides 4, which were obtained from aza-Wittig reaction of iminophosphorane 3 with isocyanate. The preliminary bioassay results demonstrated that most of the 2-imidazolyl-3,4-dihydroquinazolines 6a-6i exhibited good to significant fungicidal activity against Penicillium digitatum , whereas 2-triazolyl-3,4-dihydroquinazolines 6j-6t exhibited low fungicidal activity. Some of the 2-imidazolyl-3,4-dihydroquinazolines 6a-6i also exhibited strong binding interaction with the cytochrome P450-dependent sterol 14α-demethylase (CYP51). For example, compound 6e showed the best fungicidal activity against P. digitatum with IC(50) = 4.14 μg/mL and the best CYP51 binding activity with K(d) = 0.34 μg/mL, both superior to those of the agricultural fungicide triadimefon.

ChemInform Abstract: Synthesis of 1,2,4,5‐Tetrasubstituted Imidazoles by a Sequential Aza‐Wittig/Michael/Isomerization Reaction.

Carbodiimides 4, obtained from aza-Wittig reactions of iminophosphorane 3 with aryl isocyanates, reacted with secondary amines in the presence of a catalytic amount of sodium alkoxide to give 1,2,4,5-tetrasubstituted imidazoles 7 in good yields. However, 4-acylimidazoles 11 were obtained, as phenols were used in the presence of a catalytic amount of potassium carbonate due to further air oxidation of the expected products 10.

Synthesis and Antitumor Activity of Some 2-Amino-furo[2,3-d]- yrimidin-4(3H)-one Derivatives

In this paper, a novel series of 2-aminofuro(2,3-d)yrimidin-4(3H)-one derivatives were prepared via aza-Wittig reaction of iminophosphorane 3 with aromatic isocyanate and subsequent reaction with various amine under mild condition in 78%~90% yields. The structures of these compounds were confirmed by mass spectral data, 1 H NMR, IR and elemental analysis. Compound 5c was further analyzed by single crystal X-ray diffraction. The in vitro antitumor activities of com- pounds 5 were analyzed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) standard method, and compound 5f showed the best inhibition activities against A459 with IC50 18.4 μmol/L. Keywords furo(2,3-d)pyrimidin-4(3H)-one; synthesis; antitumor activity 稠合嘧啶酮衍生物具有丰富的和多样性的化学性

Efficient Synthesis of Thieno [2,3-<i>d</i>] Pyrimidin-4(4<i>H</i>)-ones by the Aza-Wittig Methodology

The carbodiimides 4, obtained from the aza-Wittig reaction of iminophosphorane 3 with aromatic isocyanates, reacted with aliphatic amines or alcohols to give 2-substituted thieno [2,3-d] pyrimidin-4(4H)-ones 6 in the presence of catalytic amount of sodium alkoxide in good yields.

Efficient Synthesis of Thieno [2,3-<i>d</i>] Pyrimidin-4(4<i>H</i>)-ones by the Aza-Wittig Methodology

The carbodiimides 4, obtained from the aza-Wittig reaction of iminophosphorane 3 with aromatic isocyanates, reacted with aliphatic amines or alcohols to give 2-substituted thieno [2,3-d] pyrimidin-4(4H)-ones 6 in the presence of catalytic amount of sodium alkoxide in good yields.

Efficient synthesis of thieno[2,3-d]pyrimidin-4(3H)-ones by a sequential aza-Wittig reaction/base catalyzed cyclization

Abstract7-Benzyl-5,6,7,8-tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidin-4(3H)-ones were synthesized by base catalyzed reactions of nucleophilic reagents (aliphatic amines, alcohols or phenols) with carbodiimides4, which in turn were obtained by the aza-Wittig reaction of iminophosphoranes3with aromatic isocyanates.

Synthesis of 1,2,4,5-Tetrasubstituted Imidazoles by a Sequential Aza-Wittig/Michael/Isomerization Reaction

Carbodiimides 4, obtained from aza-Wittig reactions of iminophosphorane 3 with aryl isocyanates, reacted with secondary amines in the presence of a catalytic amount of sodium alkoxide to give 1,2,4,5-tetrasubstituted imidazoles 7 in good yields. However, 4-acylimidazoles 11 were obtained, as phenols were used in the presence of a catalytic amount of potassium carbonate due to further air oxidation of the expected products 10.

Efficient Synthesis of 7-benzyl-5,6,7,8-tetrahydropyrido[4',3':4',5]thieno [2,3-d]pyrimidin-4(3H)-Ones Via Aza-Wittig Reaction

7-benzyl-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4(3H)-ones were synthesized by base catalytic reactions of nucleophilic reagents (aliphatic amines, alcohols or phenols) with carbodiimides 4, which were obtained from the aza-Wittig reaction of iminophosphoranes 3 with aromatic isocyanates. Keywords: Aza-Wittig reaction, carbodiimide, iminophosphorane, thieno[2, 3-d]pyrimidin-4(3H)-one, alkyl, antianxiety, antiarrhythmic, antiprotozoal, benzene

An efficient route for synthesis of 2-alkylamino benzo[b]thieno[3,2-d]pyrimidin-4(3H)-one

Abstract The carbodiimide 2 , obtained from the aza-Wittig reactions of iminophosphorane 1 with alkyl isocyanates, reacted with primary amino to give 2-alkylamino benzo[b]thieno[3,2- d ]pyrimidin-4(3 H )-ones 4 and 5 . The formation mechanism of the title compounds has been investigated.

Efficient synthesis and biological evaluation of some 2,4-diamino-furo[2,3- d]pyrimidine derivatives

The carbodiimides 2, obtained from aza-Wittig reactions of iminophosphorane 1 with aromatic isocyanates, reacted with ammonia to give ethyl 3,4-dihydro-6-methyl-4-oxo-2-arylamino-furo[2,3- d]pyrimidine-5-carboxylate 3. Further reaction of 3 with POCl 3 and various amines generated ethyl 4-alkylamino-2-arylamino-6-methyl-furo[2,3- d]pyrimidine-5-carboxylate 5 in good yields. Their structures were confirmed by 1H NMR, EI-Ms, IR and elemental analysis. Compound 5b was further analyzed by single crystal X-ray diffraction. Compound 5 exhibited cytotoxicity against two lung cancer cell lines. For example, compound 5a showed the best inhibition activities against A459 with IC 50 0.8 μM.

ChemInform Abstract: Heterocycles by Intramolecular Aza-Wittig Reactions of Iminophosphoranes Obtained from 2-Azidobenzoyl and 2-Azidobenzylidene Derivatives.

ChemInform Abstract: Heterocycles by Intramolecular Aza-Wittig Reactions of Iminophosphoranes Obtained from 2-Azidobenzoyl and 2-Azidobenzylidene Derivatives.

ChemInform Abstract: A Straightforward and Practical Formal Synthesis of Lavendamycin Ethyl Ester.

Abstract Aza Wittig reaction of iminophosphorane derived from ethyl α-azido-β-(3-indolyl)butyrate and 8-benzyloxy-7-bromo-2-formylquinoline is the key step in a new synthesis of lavendamycin ethyl ester.

Application of iminophosphorane in heterocyclic synthesis

Recent work of our group on the synthesis of heterocycles via aza-Wittig reaction of iminophosphorane was reviewed. We have developed a new efficient synthesis of various imidazolones or oxazoles by utilizing a consecutive cyclization of α-ethoxycarbonyl iminophosphorane, isocynate (or carbon disulfide) and various nucleophilic reagents. New derivatives of (fused) quinazolinones and pyrimidinones were prepared from the tandem reaction of β-ethoxycarbonyl iminophosphorane, isocynate (or carbon disulfide) and various nucleophilic reagents. Indole derivatives were also obtained in good yields from the sequential reaction of β-phenylethynyl iminophosphorane, isocynate and various nucleophilic reagents in the presence of a catalytic amount of Ag+. Recently the iminophosphorane was applied in post-condensation modifications of Ugi and Passerini reactions to prepare multisubstituted benzoxazines and quinazolines.

Facile Synthesis of 2-Alkylthio-5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidin-4(3H)-ones

Isothiocyanate 2, obtained from aza-Wittig reaction of iminophosphorane 1 with CS2, reacted with amine to give 2-thioxo-2,3,5,6,7,8-hexahydrobenzothieno[2,3-d]pyrimidin-4(1H)-ones 4 in the presence of sodium ethoxide. S-Alkylation of 4 produced 2-alkylthio-5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidin-4(3H)-ones 5 in good yields.

Efficient Synthesis and Fungicidal Activities of 2-Alkylthiobenzofuro[3,2-d]Pyrimidinones

2-Alkylthiobenzofuro[3,2-d]pyrimidinones 5 and 6 were synthesized by S-alkylation of 2,3-dihydro-2-thioxobenzofuro[3,2-d]pyrimidin-4(1H)-ones 4, which were obtained via aza-Wittig reaction of iminophosphorane 2 with CS2 and further reaction of the product with various amines. Compounds 5 and 6 exhibited fungicidal activity. For example, compound 6a, which has a small N-substituted methyl group, showed the best inhibitive activity (91%) against Dothiorella gregaria at 50 mg/L. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.