The reaction of organophosphorus reagents with substituted‐1,3‐diphenylpropanetrione: New synthesis of azaphospholene derivatives

The reaction of 1,3‐diphenyl‐2‐(phenylimino)‐3‐(ylidenemethyl‐acetate)‐1‐propanone (5) with trisdialkylaminophosphines (6a,b) in refluxing toluene afforded the new oxazaphospholene products (7a–b) . On the other hand, the cyclic azaphospholene adducts 8a–b were isolated from the reaction of 5 with 6a,b without solvent. Trialkyl phosphites 1b–c react with compound 5 to give the respective dialkyl phosphate products (9a,b) . Moreover, trisdialkylaminophosphines (6a,b) react with 2a and 2b to give the dipolar adducts 10a,b and the phosphonate products 11a,b, respectively. Possible reaction mechanisms are considered, and the structural assignments are based on compatible analytical and spectroscopic results. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:511–517, 2001     

Studies with polyfunctionally substituted heteroaromatics: A facile route for the synthesis of polyfunctionally substituted N-aminopyridines, 1,2,4-triazolo[1,5-a]pyridines and isoquinolines

The reactions of formaldehyde and acetaldehyde with active methylene compounds, followed by reaction with cyanoacetic acid hydrazide 2, afforded N-aminopyridine-2-one derivatives 5a-f. In contrast, the reactions of cyanoacetic acid hydrazide 2 with aliphatic aldehydes and cyanothioacetamide afforded pyridinethione derivatives 11a-b. Also, the reactions of active methylene compounds with formaldehyde and cyanoacetamide afforded pyridin(1H)-2-one derivatives 12a-c. The reactions of 5b with aldehydes and ketones afforded compounds 13a, b, 14, and 15, respectively. The reactions of 5b with arylidinemalononitriles 16a,b afforded isoquinoline derivatives 19a,b. Compound 19b by hydrolysis gave the final product 20. Compound 20 could also be formed by hydrolysis of 5b to give 21, followed by the reaction with 16b. © 1997 John Wiley & Sons, Inc.     

Synthesis and Reaction of Novel Spiro Pyrimidine Derivatives

2‐Mercapto‐6‐[(pyridin‐4‐ylmethylene)‐amino]‐3H‐pyrimidin‐4‐one 1 was synthesized from Schiff base reaction of 6‐amino‐2‐thiouracil with isonicotinaldehyde. The reaction of 1 with hydrazonyl chloride 2a , 2b , 2c , 2d afforded the novel pyrimidin‐4‐one 3a , 3b , 3c , 3d . Compounds 3a , 3b , 3c , 3d reacted with methyl iodide to give 4a , 4b , 4c , 4d . Subsequently, reaction of 4a , 4b , 4c , 4d with triethylamine as a catalyst in dry chloroform yielded tetraaza‐spiro[4.5]deca‐2, 8‐dien‐7‐one 5a , 5b , 5c , 5d . In addition, reaction of 1 with acrylonitrile gave pyrimidin‐propionitrile 6 . The cyclization of 6 by reacting with sodium ethoxide to give pyrimido [2, 1‐b] [1,3] thiazin‐6‐one 7 . The refluxing of 1 with bromine in acetic acid yielded 2‐bromo‐pyrimidin‐4‐one 8 . The latter compound 8 reacted with sodium azide gave tetrazolo‐pyrimidine 10 . The chemical structures of the newly synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, and mass spectral analysis.     

Copolymerization of cyclic ketene N,O-acetals with phenylisothiocyanate via zwitterionic intermediates

The reaction of 3-methyl-2-methylene-1,3-oxazolidine ( 1a ) and phenylisothiocyanate (PhNCS) gives 3-methyl-2-(phenylthiocarbamoyl)methylene-1,3-oxazolidine ( 3 ) whereas that of 2-isopropylidene-3-methyl-1,3-oxazolidine ( 1b ) and PhNCS gives 1:1 alternating copolymers. It is assumed that the reaction of 1b and PhNCS forms a zwitterionic intermediate ( 2b ), followed by the successive combination of 2b to give 1:1 alternating copolymers 4 and/or 5 . Consequently, it was demonstrated that the copolymerization of 1b and PhNCS proceeds via a zwitterionic mechanism with complete ring-opening to afford the 1:1 alternating copolymer 5 .     

Reactions of some benzofuran derivatives with amides,nitriles and hydrazines

When 6-acetoacetyl-5-methoxy- ( 1b ) and 5-acetoacetyl-6-methoxy-2,3-diphenylbenzofuran ( 2b ) were treated with cyanoacetamide, the corresponding pyridinecarbonitriles were obtained. Compounds 1b and 2b reacted with ethyl cyanoacetate in the presence of ammonium acetate to give the benzofuranyl-pyrone derivatives. This reaction, when carried out in presence of diethylamine, led to the formation of furochromones. Hydrazine hydrate, phenylhydrazine and semicarbazide hydrochloride reacted with 1b and 2b with the formation of the corresponding pyrazoles. The corresponding isoxazole derivatives were formed by the reaction of 1b and 2b with hydroxylamine hydrochloride.     

Synthesis and Antimicrobial Activity of Some Novel Substituted Bis‐Pyridone,Pyrazole, and Thiazole Derivatives

A variety of novel bis‐heterocyclic derivatives were synthesized via the reaction of bis‐cyanoacetanilide derivative 3 with various aromatic aldehydes (1:2 molar ratio), to give the corresponding bis‐arylidene derivatives 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j , 5k , 5l , 5m . On the other hand, reacting compound 3 with substituted 2‐hydroxybenzaldehydes 6a , 6b , 6c afforded 2‐iminochromene‐3‐carboxamides 7a , 7b , 7c . The reaction of compound 5 with malononitrile afforded the novel bis‐pyridones 9a , 9b , 9c , 9f , 9g , 9h . The reaction of 5 with hydrazine derivatives afforded pyrazoles 11a , 11b , 11c , 11d , 11e , 11f , respectively. Compound 3 reacts with phenyl isothiocyanate in the presence of potassium hydroxide at room temperature followed by addition of some different halo‐carbonyl compounds to afford bis‐poly‐functionalized thiazole derivatives 13a , 13b , 13c . The bis‐enamine derivative 15 reacts also with hydrazine hydrate, guanidine, and hydroxylamine to give bis‐pyrazole 17 , pyrimidine 19 , and isoxazole 21 derivatives, respectively. Some of the newly synthesized compounds show moderate to high antimicrobial activity.     

Thermal ring expansion of 2-azidoselenochromenes: first synthetic examples of 1,3-benzoselenazepines

The thermolysis of 2-azido-2-tert-butyl-2H-selenochromenes (2a, b), which were easily obtained by the reaction of the corresponding 1-benzoselenopyrylium salts (1) with sodium azide, resulted in a ring expansion to give the novel stable 1,3-benzoselenazepines (5a, b) with denitrogenation in good yields.     

Synthesis of Some Pyrimidine 2-Oxo(Thio)-4,6-Dione Derivatives

5-Arylidenes 1a and 1b, on reaction with ethyl cyanoacetate and diethyl malonate in the presence of ammonium acetate under Michael condensation, yield pyridine derivatives 2 and 3, respectively. Cyclopentapyrimidine derivative 4 can also be obtained by the reaction of 1a with malononitrile in the presence of piperidine. The reaction of 5-arylidene lb with monochloroacetic acid in an alkaline medium gives the thiazol derivative 5. Also, spiro-[3′, 5′]cyclohexenyl pyrimidine derivative 6 could be obtained from the reaction of 1d with maleic anhydride. On the other hand, 5-arylidene 1e reacts with maleic anhydride to give 2-thiobarbituric acid derivative 7. The condensation reaction of 2-thiovioluric acid 8 with some hydrazines affords the triazole derivatives 9a-d. Finally, barbituric acid condenses with isatin to give 5-arylidene 1f, which can be cyclized with phosphorous pentoxide to afford 10.     

叶绿素-a及其衍生物的Qy轴向氧化反应和E-环重排反应

在酸碱性条件下对叶绿素-a (1)进行空气氧化反应, 分别得到卟吩衍生物2b～4b; 通过酯交换和去金属镁离子, 将叶绿素-a转化为脱镁叶绿酸-a甲酯(MPa) (5), 其3-位碳碳双键与氯化氢的加成生成卟吩醇(6), 经碱性空气氧化和E-环重排则转化成紫红素-18衍生物7. 选用四氧化锇和高碘酸钠将5氧化成卟吩醛(8), 在丁醇中以丁醇钠作催化剂, 8的氧化和重排反应给出3-甲酰基紫红素-18酯(9)和紫红素-7三甲酯衍生物10. 异构体4的空气氧化和重排反应也生成紫红素-18酯(3), 进一步与2-甲基丁胺进行缩合反应, 得到N-烷基紫红素-18酰亚胺(11a)以及氧化重排产物3-甲酰基-N-烷基紫红素-18酰亚胺(11b). 所得叶绿素衍生物均经UV, IR, 1H NMR及元素分析证明其结构, 并对相应的反应提出可能的反应机理.     

Zirconium complexes having a chiral phosphanylamide in the co-ordination sphere

The chiral phosphanylamido ligand, (N(CHMePh)(PPh2))-, has been introduced into co-ordination chemistry. As starting material the oily amines HN(R-*CHMePh)(PPh2)(1a) and HN(S-*CHMePh)(PPh2)(1b) were used. To reconfirm their absolute structure, 1b was oxidized with H2O2 in air to obtain HN(S-*CHMePh)(P(O)Ph2)(2) as a solid compound. The solid-state structure of 2 was established by single-crystal X-ray diffraction. The lithium salts of both enantiomers Li(N(R-*CHMePh)(PPh2))(3a) and Li(N(S-*CHMePh)(PPh2))(3b) were prepared by deprotonation reaction of 1a,b. Compounds 3a,b were further reacted with zirconocen dichloride to give the chiral metallocenes [(eta5-C5H5)2Zr(Cl)(eta2-N(R-*CHMePh)(PPh2))](4a) and [(eta5-C5H5)2Zr(Cl)(eta2-N(S-*CHMePh)(PPh2))](4b). In an alternative approach to give chiral zirconium compounds, the neutral amine 1b was reacted with [(PhCH2)4Zr] to give the enantiomeric pure complex [(PhCH2)3Zr(eta2-N(S-*CHMePh)(PPh2))](5). The solid-state structures of all zirconium complexes were determined by single-crystal X-ray diffraction.     

Synthesis of new visnagen and khellin furochromone pyrimidine derivatives and their anti-inflammatory and analgesic activity

6-[(4-Methoxy/4,9-dimethoxy)-7-methylfurochromen-5-ylideneamino]-2-thioxo-2,3-dihydropyrimidin-4-ones 1a,b were prepared by reaction of 6-amino-2-thiouracil with visnagen or khellin, respectively. Reaction of 1a,b with methyl iodide afforded furochromenylideneaminomethylsulfanylpyrimidin-4-ones 2a,b. Compounds 2a,b were reacted with secondary aliphatic amines to give the corresponding furochromen-ylideneamino-2-substituted pyrimidin-4-ones 3a-d. Reaction of 3a-d with phosphorus oxychloride yielded 6-chlorofurochromenylidenepyrimidinamines 4a-d, which were reacted with secondary amines to afford furochromenylideneamino-2,6-disubstituted pyrimidin-4-ones 5a-d. In addition, reaction of 5a-d with 3-chloropentane-2,4-dione gave 3-chloro-furochromenylpyrimidopyrimidines 6a-d. The latter were reacted with piperazine and morpholine to give 1-(furochromenyl)-pyrimidopyrimidine-3,6,8-triylpiperazines or -3,6,8-triylmorpholines 7a-d. The chemical structures of the newly synthesized compound ware characterized by IR, 1H-NMR, 13C-NMR and mass spectral analysis. These compounds were also screened for their analgesic and anti-inflammatory activities. Some of them, particularly 3-7, exhibited promising activities.     

Chemistry of Phosphorus Ylides. Part 37. The Reaction of Phosphonium Ylides with Indoles and Naphthofurans. Synthesis of Phosphanylidenes,Pyrans, Cyclobutenes,and Pyridazine as Antitumor Agents

The reaction of the stabilized phosphonium ylides 2a , 2b with indolinones 1a , 1b and naphthofuranone 13 afforded the corresponding propylidene and ethylidene derivatives 4a , 4b , 4c , 4d and 14a , 14b . On the other hand, the active phosphacumulenes 5a , 5b react with compounds 4a , 4b , 4c , 4d by [4 + 2]‐cycloaddition to give the stable phosphanylidene indole pyranones 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h . Although compounds 14a , 14b afforded the naphthofuropyrans 16a , 16b , 16c , 16d and triphenylphosphane. Moreover, the phosphallene ylide 7 react with compounds 4a , 4b , 4c , 4d and 14a , 14b to give phosphanylidenecyclobuteneindoline 9a , 9b , 9c , 9d and naphthalenones 18a , 18b , respectively. In addition, the naphthofuropyridazine 21 was obtained from the reaction of the hydrazone 19 and the phosphacumulene 5a . The antitumor activity of some of the new compounds was evaluated, in vitro, against colon and hepatocellular carcinoma cell lines. They showed values closed to that recorded by the reference drug Doxorubicin.     

Hydroxylation de l''estrone et de son acétate par le peroxyde d''hydrogéne en milieu superacide

Estrone 1a and its acetate 1b react with hydrogen peroxide in SbF₅-HF to give hydroxylated compounds. The formation of the dienone 2 can be accounted for by reaction of the electrophile H₃O₂⁺ on the neutral substrate, whereas formation of compound 3b implies electrophilic attack on the protonated ester 1b. Higher acidity favours rearrangement of the resulting ion 9 to yield, through a spiro intermediate, the ester 4b. Under the reaction conditions esters 3b and 4b]are slowly converted into the corresponding phenols 3a and 4a.     

Mesoionic dimethyl derivatives of some 1,2,4-triazinones. The course of the reaction of 3,5-dimethoxy, 3-methoxy-5-methylthio, 5-methoxy-3- methylthio and 3,5-bis(methylthio)-1,2,4-triazine with methyl iodide

Treatment of 3,5-dimethoxy-1,2,4-triazine ( 1a ) with methyl iodide was found to give depending on the reaction time triazinium iodide 2a , triaziniumolates 4a and 6a as well as methoxytriazinones 7a and 8a . Thermolysis of 2a gave triaziniumolates 4a and 6a . Reaction of 2a , 4a or methoxytriazinone 9a with methyl iodide in acetonitrile yielded as the sole product 6a . Reaction of 3-methoxy-5-methylthio-1,2,4-tri-azine (1b ) with methyl iodide gave triazinium iodide 2b and methylthio triazinone 7b . Hydrolysis of 2a,b afforded 4a . Reaction of 5-methoxy-3-methylthio-1,2,4-triazine ( 1c ) with methyl iodide gave triazinium iodide 2c , triaziniumolate 4b , triazinium iodide 5b and triazinone 8b . Hydrolysis of 2c yielded 4b and its thermolysis gave a mixture of 4b and 5b . Reaction of 2c , 4b and triazinone 9b with methyl iodide afforded 5b . Treatment of 3,5-bis(methylthio)-1,2,4-triazine ( 1d ) with methyl iodide was found to give a mixture of N1 and N2 methiodides 2d and 3d which gave on hydrolysis 4b and 8b , respectively. Methylation of 6-methyl derivatives 1c-g gave analogous results, however the proportions of N1 methylated products were lower and the reaction rates higher in comparison to their respective lower homologues 1a,c,d . The structures of the mesoionic dimethyl derivatives were assigned from uv, ir, ¹H nmr and electron impact mass spectra. The structural assignments were eventually confirmed by quantum chemical calculations of net charge distributions, bond lengths and ipso angles of the C5?O bonds.     

Zur Lenkung der intramolekularen Diels-Alder-Reaktion von Cyclopentadienen mit olefinischen Substituenten

On the Course of the Intramolecular Diels-Alder-Reaction of Cyclopentadienes with Olefinic Substituents The 1:3 mixture of 4-bromobicyclo [3.2.0]hept-2-en-6-one and -7-one ( 1/2 ), available by N-bromosuccinimide bromination of bicyclo [3.2.0]hept-2-en-6-one, reacted rapidly with the organo-magnesium and -zinc reagents 3, 10a, 10b and 10d by cyclobutanone ring opening and bromide ion expulsion to give the 5-substituted cyclopentadienes 5, 12a, 12b/12c , and 12d as non-isolated intermediates. Further transformation occured in situ either by a direct intramolecular Diels-Alder reaction (path a) or by a [1,5]-H-migration prior to the intramolecular Diels-Alder reaction (path b). The intermediate 5 followed only path a to give the bridged norbornene derivative 7 , the intermediates 12a, 12b and 12c followed only path b to give the annellated norbornene derivatives 15a, 15b and 15c , respectively, and the intermediate 12d followed both paths to give the bridged 14d and the annellated norbornene derivative 15d (in the ration of about 1.4:1). These observations are discussed in terms of the relative velocities of [1,5]-H-migrations and intramolecular Diels-Alder reactions. The major conclusions are: (1) bridged norbornene derivatives with a six-membered ring C (such as 14d ) can be prepared by an intramolecular Diels-Alder reaction from 5-alkenyl-cyclopentadienes 12 , as long as the dienophilic double bond is activated by an appropriate substituent (as in 12d ); (2) such 5-alkenyl-cyclopentadienes 12 are available from the reaction of the bromo-bicyclo-heptenones 1/2 with suitable C-nucleophiles 10 .     

N,N-addition of frustrated Lewis pairs to nitric oxide: an easy entry to a unique family of aminoxyl radicals

The intramolecular cyclohexylene-bridged P/B frustrated Lewis pair [Mes(2)P-C(6)H(10)-B(C(6)F(5))(2)] 1b reacts rapidly with NO to give the persistent FLP-NO aminoxyl radical 2b formed by P/B addition to the nitrogen atom of NO. This species was fully characterized by X-ray diffraction, EPR and UV/vis spectroscopies, C,H,N elemental analysis, and DFT calculations. The reactive oxygen-centered radical 2b undergoes a H-atom abstraction (HAA) reaction with 1,4-cyclohexadiene to give the diamagnetic FLP-NOH product 3b. FLP-NO 2b reacts with toluene at 70 °C in an HAA/radical capture sequence to give a 1:1 mixture of FLP-NOH 3b and FLP-NO-CH(2)Ph 4b, both characterized by X-ray diffraction. Structurally related FLPs [Mes(2)P-CHR(1)-CHR(2)-B(C(6)F(5))(2)] 1c, 1d, and 1e react analogously with NO to give the respective persistent FLP-NO radicals 2c, 2d, and 2e, respectively, which show similar HAA and O-functionalization reactions. The FLP-NO-CHMePh 6b derived from 1-bromoethylbenzene undergoes NO-C bond cleavage at 120 °C with an activation energy of E(a) = 35(2) kcal/mol. Species 6b induces the controlled nitroxide-mediated radical polymerization (NMP) of styrene at 130 °C to give polystyrene with a polydispersity index of 1.3. The FLP-NO systems represent a new family of aminoxyl radicals that are easily available by N,N-cycloaddition of C(2)-bridged intramolecular P/B frustrated Lewis pairs to nitric oxide.     

The reactions of tetrafluoroethylene oligomers: V. The reactions of perfluoro-3,4-dimethyl-4-ethylhexene-(2) with thionucleophiles and the chemical transformations of reaction products

The reactions of perfluoro-3,4-dimethyl-4-ethylhexene-(2) (1) with s-nucleophiles such as benzylthiol, allylthiol, phenylthiol and the chemical transformations of these reaction products were reported. 1 reacted with S-nucleophiles to give four types of isomeric products. At ?30～ ?60°C, in ether, kinetically controlled product 2 (a, b, c) were formed. Compound 2 might be converted directly into the thermodynamically stable products 3 (a, b,) in DMF-KF at r.t., At 100°C, 2 was converted to 4 (a, b, c) via intramolecular rearrangement. In KF-DMF at r.t., 4 was isomerized to 5 (a, b, c). 2a also reacted with another mole of thiol to give the corresponding disulfide 6 and hydrogen-containing olefin 7a as well as the disubstituted product 8a in DMF, but only give 3a and 9a in ether-Et₃N. The reaction of 2a with methyl alcohol gave only a small amounts of 3a and 10a. The reaction of 2b with dimethylamine was complex and 3b and 11 were obtained in low yield.     

Reactions of substituted furan-2-carboxaldehydes and furo[b]pyrrole type aldehydes with benzothiazolium salts

A series of new push-pull compounds were synthesised by reaction of 5-aryl- furan-2-carboxaldehydes and furo[b]pyrrole type aldehydes with benzothiazolium salts. These new condensation products represent highly conjugated systems that have potential biological activity. The reaction of furo[b]pyrrole type aldehydes with benzothiazolium salts give potential precursors of cyanine dyes.     

The behavior of 2‐substituted‐1,3‐diphenylpropane‐1,3‐tione toward organophosphorus reagents

The reaction of 2‐benzylidene‐1,3‐diphenylpropanetrione ( 1a ) with phosphorus ylides 2a–c afforded the new phosphonium ylides 4a–c . Trialkyl phosphites 3a–c react with 1a to give the respective dialkyl phosphonate products 5a–c . On the other hand, the olefinic compounds 6 and 7 were isolated from the reaction of 1b with Wittig reagents 2 . Moreover, trialkyl phosphites reacted with 1b to give products 8a–c . Possible reaction mechanisms are considered, and the structural assignments are based on analytical and spectroscopic evidence. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:57–64, 2000     

Synthesis of furo[3,2-g]chromones under microwave irradiation and their antitumor activity evaluation

A series of furo[3,2-g]chromone derivatives were synthesized via the reaction of furochromone carbaldehyde 1 with amines 3a - d and thioglycolic acid to give thiazolidinones 4a - d . The later react with benzaldehyde/thiourea or hydroxylamine and DMF-DMA in glacial acetic acid to give thiazolopyrimidines 5a - d or thiazoloisoxazoles 6a - d , respectively. Also, the synthesis of α-aminophosphonates via the one-pot reaction of 1 and amines 3a , b were trapped by dialkylphosphites 7a - c afforded the corresponding α-aminophosphonates 8a - f . Applying hexaalkyltriamidophosphites 9a , b to 1 gives alkylidenephosphorane ylides 11a , b in an open structure form. In the present investigation, the in vitro inhibition capacity of compounds ( 4a , 4c , 5b , 5c , 6b - d , 8a - f , and 11a ) was screened in three human cancer cell lines HCT-116, MCF-7, and HepG2. The anticancer activity results revealed that 8b and 8e had more potent cytotoxic inhibition activity against HCT-116 cell line; however, all the tested compounds had obviously less cytotoxic activity against MCF-7 cell line, while 5b , 5c , and 6d were potent against HepG2 cell line compared with that of doxorubicin.