New Approaches to the Synthesis of 4‐(2‐Aminophenyl)‐1,3‐dihydro‐2H‐imidazol‐2‐ones and 3‐Ureidoindoles and a Study of Their Interconversion

3‐Alkyl/aryl‐3‐ureido‐1H,3H‐quinoline‐2,4‐diones ( 2 ) and 3a‐alkyl/aryl‐9b‐hydroxy‐3,3a,5,9b‐tetrahydro‐1H‐imidazo[4,5‐c]quinoline‐2,4‐diones ( 3 ) react in boiling concentrated HCl to give 5‐alkyl/aryl‐4‐(2‐aminophenyl)‐1,3‐dihydro‐2H‐imidazol‐2‐ones ( 6 ). The same compounds were prepared by the same procedure from 2‐alkyl/aryl‐3‐ureido‐1H‐indoles ( 4 ), which were obtained from the reaction of 3‐alkyl/aryl‐3‐aminoquinoline‐2,4(1H,3H)‐diones ( 1 ) with 1,3‐diphenylurea or by the transformation of 3a‐alkyl/aryl‐9b‐hydroxy‐3,3a,5,9b‐tetrahydro‐1H‐imidazo[4,5‐c]quinoline‐2,4‐diones ( 3 ) and 5‐alkyl/aryl‐4‐(2‐aminophenyl)‐1,3‐dihydro‐2H‐imidazol‐2‐ones ( 6 ) in boiling AcOH. The latter were converted into 1,3‐bis[2‐(2‐oxo‐2,3‐dihydro‐1H‐imidazol‐4‐yl)phenyl]ureas ( 5 ) by treatment with triphosgene. All compounds were characterized by ¹H‐ and ¹³C‐NMR and IR spectroscopy, as well as atmospheric pressure chemical‐ionisation mass spectra.     

New Methods for the Synthesis of 3‐Amino‐6,7‐Dihydro‐5H‐Cyclopenta[c]Pyridine‐4‐Carbonitriles and Cyclopenta[d]Pyrazolo[3,4‐b]Pyridines via a Smiles‐type Rearrangement

By reaction with sodium ethoxide and as a function of their structures, 2‐[(1‐alkyl(aryl)‐4‐cyano‐6,7‐dihydro‐5H‐cyclopenta[c ]pyridin‐3‐yl)oxy]acetamides 11 gave 1‐amino‐5‐alkyl(aryl)‐7,8‐dihydro‐6H‐cyclopenta[d ]furo[2,3‐b ]pyridine‐2‐carboxamides 10 and/or 1‐alkyl(aryl)‐3‐amino‐6,7‐dihydro‐5H‐cyclopenta[c ]pyridine‐4‐carbonitriles 12 .     

Reactions of 2‐amino‐3‐cyano‐4,5,6,7‐tetrahydrobenzo[b]thiophene and 2‐amino‐3‐cyano‐4,7‐diphenyl‐5‐methyl‐4H‐pyrano[2,3‐c] pyrazole with phenylisocyanate,carbon disulfide,and thiourea

2‐Amino‐3‐cyano‐4,5,6,7‐tetrahydrobenzo[b]thiophene 1a or 2‐amino‐3‐cyano‐4,7‐di‐ phenyl‐5‐methyl‐4H‐pyrano[2,3‐c]pyrazole 2a reacted with phenylisocyanate in dry pyridine to give 2‐(3‐phenylureido)‐3‐cyanobenzo[b]thiophene 1b or 2‐disubstituted amino‐3‐cyanopyranopyrazole 2b derivative. However, when 1a and 2a were refluxed with carbon disulfide in 10% ethanolic sodium hydroxide solution, they afforded the thieno[2,3‐d]pyrimidin‐2,4‐dithione derivative 5 in the former case, 2,4‐dicyano‐1,3‐bis(dithio carboxamino)cyclobuta‐1,3‐ diene 6 and pyrazolopyranopyrido[2,3‐d]pyrimidin‐ 2,4‐dithione derivative 7 in the latter one. Treatment of 2a with thiourea in refluxing ethanol in the presence of potassium carbonate gave 2,2′‐dithiobispyrimidine derivative 9 (major) in addition to pyranopyrazole derivative 10 and 2,2′‐dithiobis ethoxypyrimidine derivative 11 in minor amounts. The structures of all products were evidenced by microanalytical and spectral data. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:6–11, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20070     

Synthese und Reaktivität von 2‐Brom‐1,3‐diethyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborol Molekülstruktur von Bis(1,3‐diethyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborol‐2‐yl)

Synthesis and Reactivity of 2‐Bromo‐1,3‐diethyl‐2,3‐dihydro‐1 H ‐1,3,2‐benzodiazaborole Molecular Structure of Bis(1,3‐diethyl‐2,3‐dihydro‐1 H ‐1,3,2‐benzodiazaborol‐2‐yl The reaction of a slurry of calcium hydride in toluene with N,N′‐diethyl‐o‐phenylenediamine ( 1 ) and boron tribromide affords 2‐bromo‐1,3‐diethyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborol ( 2 ) as a colorless oil. Compound 2 is converted into 2‐cyano‐1,3‐diethyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborole ( 3 ) by treatment with silver cyanide in acetonitrile. Reaction of 2 with an equimolar amount of methyllithium affords 1,3‐diethyl‐2‐methyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborole ( 4 ). 1,3,2‐Benzodiazaborole is smoothly reduced by a potassium‐sodium alloy to yield bis(1,3‐diethyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborol‐2‐yl] ( 7 ), which crystallizes from n‐pentane as colorless needles. Compound 7 is also obtained from the reaction of 2 and LiSnMe₃ instead of the expected 2‐trimethylstannyl‐1,3,2‐benzodiazaborole. N,N′‐Bis(1,3‐diethyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborol‐2‐ yl)‐1,2‐diamino‐ethane ( 6 ) results from the reaction of 2 with Li(en)C≡CH as the only boron containing product. Compounds 2 – 4 , 6 and 7 are characterized by means of elemental analyses and spectroscopy (IR, ¹H‐, ¹¹B{¹H}‐, ¹³C{¹H}‐NMR, MS). The molecular structure of 7 was elucidated by X‐ray diffraction analysis.     

2,4,5‐Substituted furan‐3(2H)‐ones: Synthesis,reactions with amino acid and hydrazine derivatives

Furan‐3(2H)‐ones ( 3 ) were obtained from some 2,3‐dihydro‐furan‐2,3‐diones with a few Wittig reagents ( 2 ). The compounds of 3 with glycin and hydrazines ( 4a,b ) produced 2,3‐dihydro‐1H‐pyrrol‐3‐ones ( 5a–d ). All the reaction mechanisms were discussed by utilizing the similar reaction pathways. Structures of these compounds were determined by the IR, NMR, elemental analysis, and X‐ray diffraction method. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:235–241, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20115     

Hydriodic Acid‐Mediated Cyclization of α‐Substituted Secondary 2‐Ethenylbenzamides: Synthesis of 2‐Substituted 2,3‐Dihydro‐3,3‐dimethyl‐1H‐isoindol‐1‐ones and 3,3‐Disubstituted (E)‐1‐(Arylimino)‐1,3‐dihydroisobenzofurans

A new and facile method for the preparation of 2‐substituted 2,3‐dihydro‐3,3‐dimethyl‐1H‐isoindol‐1‐ones 3 and 3,3‐disubstituted (E)‐1‐(arylimino)‐1,3‐dihydroisobenzofurans 6 has been developed. Thus, treatment of N‐alkyl(or aryl)‐2‐(1‐methylethen‐1‐yl)benzamides 2 with concentrated hydriodic acid (HI) in MeCN at room temperature afforded 3 . Similar treatment of N‐aryl‐2‐(1‐phenylethen‐1‐yl)benzamide 5 with concentrated HI at 0° afforded 6 .     

Cyclization vs. Elimination Reactions of 5‐Aryl‐5‐hydroxy 1,3‐Diones: One‐Pot Synthesis of 2‐Aryl‐2,3‐dihydro‐4H‐pyran‐4‐ones

2‐Aryl‐2,3‐dihydro‐4H‐pyran‐4‐ones were prepared in one step by cyclocondensation of 1,3‐diketone dianions with aldehydes. The use of HCl (10%) for the aqueous workup proved to be very important to avoid elimination reactions of the 5‐aryl‐5‐hydroxy 1,3‐diones formed as intermediates. The TiCl₄‐mediated cyclization of a 2‐aryl‐2,3‐dihydro‐4H‐pyran‐4‐one with 1,3‐silyloxybuta‐1,3‐diene resulted in cleavage of the pyranone moiety and formation of a highly functionalized benzene derivative.     

Facile synthesis of 2‐alkylthio‐3‐amino‐4 H‐imidazol‐4‐ones and 2H‐imidazo[2,1‐b]‐1,3,4‐thiadiazin‐6(7H)‐ones via N‐vinylic iminophosphorane

2‐Alkylthio‐3‐amino‐4H‐imidazol‐4‐ ones 5 were synthesized by S‐alkylation of 2‐thioxo‐3‐amino‐4‐imidazolidinones 4 , which were obtained via cyclization of isothiocyanates 2 with hydrazine hydrate. 5l–n reacted with Ph₃P, C₂Cl₆, and NEt₃ to give 2H‐imidazo[2,1‐b]‐1,3,4‐thiadiazin‐ 6(7H)‐ones 7a–c in good yields. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:76–80, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20069     

A Novel Diastereoselective Synthesis of 6‐Aryl‐5‐hydroxy‐2,3‐dihydropyrano[2,3‐c]pyrazol‐4(1H)‐ones

A novel one‐pot diastereoselective synthesis of trans‐6‐aryl‐5‐hydroxy‐2,3‐dihydro[2,3‐c]pyrazol‐4(1H)‐ones 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h is described via the Darzens condensation reaction of 2‐chloro‐1‐(5‐hydroxy‐3‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl)ethanone ( 2 ) with different aromatic aldehydes in aqueous basic medium. The structures of the compounds prepared were determined by analytical and spectral analyses.     

Nickel boride mediated reductive desulfurization of 2‐thioxo‐4(3H)‐quinazolinones: A new synthesis of quinazolin‐4(3H)‐ones and 2,3‐dihydro‐4(1H)‐quinazolinones

A novel one‐pot approach for the synthesis of aryl substituted quinazolin‐4(3H)‐ones and 2,3‐dihydro‐4(1H)‐quinazolinones has been reported based on the reductive desulfurization of 3‐aryl‐2‐thioxo‐4(3H)‐quinazolinones with nickel boride in dry methanol at ambient temperature.     

Thermal cycloaddition reaction of symmetrical and unsymmetrical α‐diazo‐β‐diketones with 4‐aryl‐2‐methyl‐2,3‐dihydro‐1,5‐benzothia/diazepines

Symmetrical and unsymmetrical α‐diazo‐β‐diketones undergo thermal Wolff rearrangements to generate α‐carbonylketenes to participate as dienes in Diels–Alder reactions with 4‐aryl‐2‐methyl‐2,3‐dihydro‐1,5‐benzothia/diazepines to give, whereapplicable, regiospecific cycloadducts, 4a,5,6,12‐tetrahydro‐1H/1H,7H‐1,3‐oxazino[3,2‐d][1,5]benzo‐thia/diazepin‐1‐ones. A mechanism of formation of the regiospecific cycloadducts is suggested. © 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 35–40, 1999     

Convenient synthesis and biological activities of pyridine derivatives of 3,4‐dihydropyrimidin‐2(1H)‐ones

2‐Chloro‐5‐(chloromethyl)‐pyridine reacted with 3,4‐dihydropyrimidin‐2(1H)‐ones 1 to afford 1‐[6‐aryl‐1‐(6‐chloropyridin‐3‐yl‐methyl)‐2‐(6‐chloropyridin‐3‐yl‐methylthio)‐4‐methyl‐1,6‐dihydropyrimidin‐5‐yl] carboxylates or ethanones 2 in good yields. The structure of the target compounds 2 was confirmed by IR, ¹H NMR, EI‐MS, and elemental analyses, and compound 2a was further characterized by single crystal X‐ray diffraction. The preliminary bioassay indicated that some of the title compounds possess moderate insecticidal and fungicidal activities. J. Heterocyclic Chem., (2011).     

Condensation products of 1‐aryl‐4‐carboxy‐ 2‐ pyrrolidinones with o‐diaminoarenes,o‐aminophenol,and their structural studies

A series of 2‐substituted benzimidazoles, benzoxazoles were synthesized by the condensation reactions of 1‐aryl‐4‐carboxy‐2‐pyrrolidinones and aromatic ortho‐diamines or ortho‐aminophenol. Alkylation of benzimidazoles with iodoalkanes led to 1‐aryl‐4‐(1‐alkyl‐1H‐benzimidazol‐2‐yl)‐2‐pyrrolidin‐ ones or 1,3‐dialkylbenzimidazolium iodides. N‐Subs‐ tituted γ‐amino acids were prepared by the hydrolysis of 1‐aryl‐4‐(1H‐benzimidazol‐2‐yl)‐2‐pyrrolidinones in sodium hydroxide solution, followed by treatment with acetic acid. The structure of the synthesized pro‐ ducts was investigated using IR and ¹H, ¹³C NMR spectra, MM2 molecular mechanics, and AM1 semi‐ empirical quantum mechanical methods. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:47–56, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20171     

Pinacol Rearrangement of 3,4‐Dihydro‐3,4‐dihydroxyquinolin‐2(1H)‐ones: An Alternative Pathway to Viridicatin Alkaloids and Their Analogs

3‐Alkyl/aryl‐3‐hydroxyquinoline‐2,4‐diones were reduced with NaBH₄ to give cis‐3‐alkyl/aryl‐3,4‐dihydro‐3,4‐dihydroxyquinolin‐2(1H)‐ones. These compounds were subjected to pinacol rearrangement by treatment with concentrated H₂SO₄, resulting in 4‐alkyl/aryl‐3‐hydroxyquinolin‐2(1H)‐ones. When a benzyl (Bn) group was present in position 3 of the starting compound, its elimination occurred during the rearrangement, and the corresponding 3‐hydroxyquinolin‐2(1H)‐one was formed. The reaction mechanisms are discussed for all transformations. All compounds were characterized by IR, ¹H‐ and ¹³C‐NMR spectroscopy, as well as mass spectrometry.     

Azinoiminophosphorane mediated 4H,8H‐1,2,4‐triazolo[1,5‐C]‐[1,3]oxazepin‐4‐ones and 5,6‐dihydro‐7H, 12H‐naphtho[2,1‐f]‐[1,2,4]triazolo[1,5‐c][1,3]oxazepin‐7‐ones synthesis

The aza‐Wittig reactions of benzaldehyde‐, acetophenone‐ and benzophenone 1‐[(triphenylphosphor‐anylidene)amino]ethylidenehydrazones ( 1 ) with 2,3‐furandiones 6 provide a new route to 4H,8H‐1,2,4‐triazolo[1,5‐c][1,3]oxazepin‐4‐ones 14 or 5,6‐dihydro‐7H,12H‐naphtho[2,1‐f|[1,2,4]triazolo[1,5‐c]‐[1,3]oxazepin‐7‐ones 17 via the thermal reaction of the expected azinoimine vinylogous lactones.     

New 7‐phosphanorbornenes derived from 2‐methyl‐1‐phenyl‐ and 1‐cyclohexyl‐3‐ methyl‐2,5‐dihydro‐1H‐phosphole 1‐oxides

Novel 7‐phosphanorbornene derivatives, such as 4, 5, 10 , and 11 were synthesized utilizing 1‐phenyl‐2‐methyl‐2,5‐dihydro‐1H‐phosphole oxide ( 1 ) and 1‐cyclohexyl‐3‐methyl‐2,5‐dihydro‐1H‐phosphole oxide ( 7 ) as the starting materials. Products 4 and 10 were prepared by trapping the corresponding phosphole oxide intermediates ( 3 and 9 , respectively) by N‐phenylmaleimide, while 5 and 11 were obtained by the dimerization of 3 and 9 , respectively. The trapping reaction was studied in details; on one hand, bromo‐2,3‐dihydro‐1H‐phosphole oxides ( 6‐1 and 6‐2 ) were pointed out as the intermediates, on the other hand, the trapping reaction was optimized. Bri‐ dged P‐heterocycles 4, 5, 10 , and 11 were tested in the fragmentation‐related phosphorylation of methanol. Hydrogenation of phosphanorbornenes 4 and 5 led to the corresponding phosphanorbornanes ( 12 and 14 , respectively) and to a reductive type of retro cycloaddition. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:320–326, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20097     

Synthesis of 2‐Aryl‐2,3‐dihydro‐1,8‐naphthyridin‐4(1H)‐ones by Deprotective Cyclization of N‐{3‐[(2E)‐3‐Arylprop‐2‐enoyl]pyridin‐2‐yl}‐2,2‐dimethylpropanamides in Water

A new and convenient method for the preparation of 2‐aryl‐2,3‐dihydro‐1,8‐naphthyridin‐4(1H)‐ones 4 has been developed. Thus, N‐{3‐[(2E)‐3‐arylprop‐2‐enoyl]pyridin‐2‐yl}‐2,2‐dimethylpropanamides 3 are synthesized from commercially available pyridin‐2‐amine using an easily performed three‐step sequence and are subjected to cyclization with deprotection under acidic conditions in H₂O to give the desired products. Similarly, 2‐aryl‐2,3‐dihydro‐1,7‐naphthyridin‐4(1H)‐ones 8 and 2‐aryl‐2,3‐dihydro‐1,6‐naphthyridin‐4(1H)‐ones 12 can be prepared from pyridin‐3‐amine and pyridin‐4‐amine, respectively.     

Reduction of 3‐Aminoquinoline‐2,4(1H,3H)‐diones and Deamination of the Reaction Products

3‐Aminoquinoline‐2,4‐diones were stereoselectively reduced with NaBH₄ to give cis‐3‐amino‐3,4‐dihydro‐4‐hydroxyquinolin‐2(1H)‐ones. Using triphosgene (=bis(trichloromethyl) carbonate), these compounds were converted to 3,3a‐dihydrooxazolo[4,5‐c]quinoline‐2,4(5H,9bH)‐diones. The deamination of the reduction products using HNO₂ afforded mixtures of several compounds, from which 3‐alkyl/aryl‐2,3‐dihydro‐1H‐indol‐2‐ones and their 3‐hydroxy and 3‐nitro derivatives were isolated as the products of the molecular rearrangement.     

Spiro[4H‐2,3‐dihydropyran‐3,3′‐oxindoles] derived from 1,2,3,4‐tetrahydroquinoline

Knoevenagel condensation of 5,6‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinoline‐1,2‐dione 3 with aryl cyanomethyl ketones 9 generates 3‐(aroyl(cyano)methylidene)oxindoles 10 that react with cyclic 1,3‐diketones 11 to generate polycyclic hemiacetal spiro[4H‐2,3‐dihydropyran‐3,3′‐oxindoles] 13 .     

Microwave‐assisted synthesis of some 1,2,4‐triazol‐5‐one derivatives

A series of 3‐alkyl(aryl)‐4‐(p‐hydroxy‐phenyl)‐4,5‐dihydro‐1H‐1,2,4‐triazol‐5‐ones 2 were obtained from the reaction of alkyl (aryl) ester ethoxycarbonyl hydrazones 1 with p‐hydroxy aniline. The reaction of 1 with 1,4‐diamino benzene (1:1) to afford 3‐alkyl(aryl)‐4‐(p‐aminophenyl)‐4,5‐dihydro‐1H‐1,2,4‐triazol‐5‐ones 3 . The reaction of 3 with benzaldehyde gave 3‐alkyl(aryl)‐4‐(4′‐benzilidenamino)‐4,5‐dihydro‐1H‐1,2,4‐triazol‐5‐ones 4 . All of the above reactions occurred under microwave heating and conventional methods. Their structures were confirmed by ¹H NMR, ¹³C NMR, IR, and elemental analyses. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:38–42, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20381