Studies of some bioactive N-p-methacrylamidobenzoic esters

Preparations of four typical bioactive esters of N-p-methacrylamidobenzoic monomers and their reactive polymers as immobilized trypsin carriers are described. N-p-methacrylamidobenzoic active ester monomers containing ? COONB, ? COOSu, ? COOObt, or ? COOBT group can react with an aliphatic amine such as benzylamine at room temperature to give an identical product, N-benzyl-p-methacrylamidobenzamide. However, only monomers with ? COOObt or ? COOBT group can also react with an aromatic amine such as aniline to give N-phenyl-p-methacrylamidobenzamide. These monmoers polymerized readily in solution with azobisisobutyronitrile as free-radical initiator; the polymers were used to immobilize trypsin. Among the four different active esters for the immobilization of trypsin, thE HONB and HOSu active ester showed rather higher bioactivities than the HOObt or HOBT active ester under the same conditions. Both P(MABONB)-trypsin and P(MABOSu)-trypsin matrices possess higher biological activities by about four or three times that of P(MABOObt)-trypsin or P(MABOBT)-trypsin matrices, respectively. It is proposed that these rather high bioactivities may be attributed to the “specific” aminolysis of reactive polymer with ? COONB or ? COOSu active ester group by aliphatic amino substituents.     

Photopolymerization of N-substituted phenyl maleimide initiated with N,N-dimethyl-4-toluidine

Several N-phenyl maleimides with different p-substituents have been synthesized from the maleic anhydride and relevant aromatic amine. In the presence of N,N-dimethyl-4-toluidine (DMT), the N-substituted phenyl maleimide (4-XPhMIs) could be polymerized under UV irradiation. It was observed that a new absorption appeared on the UV-Vis spectrum of the mixture solution of 4-XPhMI and DMT, which reveals the formation of charge-transfer complex in the ground state. It was found that the fluorescence of DMT was quenched by 4-XPhMI and the quenching constant of 4-XPhMI, obtained from the Stern–Volmer plot, increases with the electron-deficiency of ethylene double bond of 4-XPhMI. The dynamic quenching of the fluorescence of DMT by 4-XPhMI suggests the formation of exciplex in excited state between DMT and 4-XPhMI. The radicals formed in the systems have been detected by spin-trapping techniques and electron paramagnetic resonance (EPR) spectrometer. Based on all of these results, it has been proposed that the initiation process of the polymerization involves the formation of exciplex and the initial radicals were produced by proton-transfer in the exciplex from DMT to 4-XPhMI. © 1997 John Wiley & Sons, Inc.     

Cu-mediated selective bromination of aniline derivatives and preliminary mechanism study

A simple and efficient bromination of aniline, aniline derivatives, and analogs have been developed. Forty three examples were given and the highest yield reached was 98%. Different substrates including substituted aniline, pyridin-amine, N-substituted aniline, N,N-disubstituted aniline, N-phenyl-amide, N-phenyl-sulfonamide, and nitrogen-containing heterocycles were all reactive and selectively generated desired bromo-products. The method can be applied to synthesize drug intermediate and quinoxaline derivatives.     

Cyclopolymerization of amine-linked diacrylate monomers

New diacrylate monomers for cyclopolymerization were synthesized from the reaction of ethyl α-chloromethylacrylate (ECMA) and t-butyl α-bromomethyl acrylate (TBBr) with aniline, adamantyl amine, t-butyl amine, cyanamide, and 4-tetradecyl aniline in yields of ca. 50–70%. Bulk and solution polymerizations with azobisisobutyronitrile (AIBN) at 60–85°C gave soluble cyclopolymers with M_n and M_w ranging from 10,000–30,000 and 12,000–40,000, respectively. The ECMA–cyanamide derivative only gave crosslinked polymers. ¹H and ¹³C solution NMR indicated high cyclization efficiency (>93%). A prototype NLO polymer was synthesized from the reaction of the TBBr–aniline cyclopolymer with tetracyanoethylene. The p-hydroxyaniline derivative of ECMA was synthesized and used for further derivatizations; for example, the benzoate ester was made and polymerized (M_n = 21,260 and M_w = 40,317). The ester groups of the TBBrndash;aniline polymer were hydrolyzed completely to give a polymer with both acid and base moieties. DSC thermograms showed glass transitions of 132°C for the ECMA–aniline derivative, 192°C for the ECMA–adamantyl derivative, 53°C for the TBBr–tetradecylaniline derivative, and 120° for the ECMA–p-benzoylaniline derivative. The ECMA–t-butyl amine polymer showed no obvious T_g. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35 : 2111–2121, 1997     

Synthesis and spectral properties of 2,3-dihydro-2-[(o- and p-substituted)anilinylidene]-1H-4-(p-methylphenyl)-7-[(o- and p-methyl)phenoxy]-1,5-benzodiazepines

A series of twelve new 2,3-dihydro-2-[(o- and p-substituted)anilinylidene]-1H-4-(p-methylphenyl)-7-[(o- and p-methyl)phenoxy]-1,5-benzodiazepines, which have potentially useful pharmacological properties, has been synthesized by condensing the 3,3-dimercapto-1-(p-methylphenyl)-2-propen-1-one with 3,4-diaminophenyl-R-phenyl ethers. Subsequently the 1H-1,5-benzodiazepine-2-thiones obtained were treated with the (o- and p-substituted)aniline. The structure of all products was corroborated by ir, ¹H nmr, ¹³C nmr and ms.     

A ruthenium(II) complex with p‐cymene and (S)‐2‐(anilinomethyl)pyrrolidine

The title compound, [(S)‐2‐(anilino­methyl)­pyrrolidine‐N,N′]‐chloro(η⁶‐para‐cymene)­ruthenium(II) chloride, [RuCl‐(C₁₀H₁₄)(C₁₁H₁₆N₂)]Cl, has been synthesized by the reaction of [RuCl₂(p‐cymene)]₂ (p‐cymene is para‐iso­propyl­toluene) with (S)‐2‐(anilinomethyl)­pyrrolidine in triethyl­amine/2‐propanol. The Ru atom is in a pseudo‐tetrahedral environment coordinated by a chloride ligand, the aromatic hydro­carbon is linked in a η⁶ manner and the amine is linked via its two N atoms. The chloride anion is involved in hydrogen bonding with the di­amine moieties through N—H?Cl interactions, with N?Cl distances of 3.273 (4) and 3.352 (4) Å.     

Synthesis and characterization of N-phenylated aromatic polyamides from N-silylated dianilino compounds and aromatic diacid chlorides

N-Phenylated aromatic polyamides of high molecular weights were synthesized by the hightemperature solution polycondensation of N,N′ -di(trimethylsilyl)-substituted dianilino compounds derived from p-dianilinobenzene, bis(4-anllinophenyl) ether, and α,α′-dianilino-p-xylene, with isophthaloyl and terephthaloyl chloride. Almost all of the N-phenylated polyamides were amorphous, and soluble in a variety of organic solvents including dimethylformamide, m-cresol, and chloroform. Transparent and flexible films of these polymers could be cast from the dimethylformamide solutions. Four wholly aromatic polyamides had glass transition temperatures in the range of 195–255°C, and began to lose weight around 400°C in air.     

N‐Glycosyl‐N′‐[p‐(isoamyloxy)phenyl]‐thiourea Derivatives: Potential Anti‐TB Therapeutic Agents

Thiocarlide (THC; N,N′‐bis[p‐(isoamyloxy)phenyl]‐thiourea; also known as Isoxyl^®) has been used in the past as an anti‐tuberculosis agent. In an effort to improve the therapeutic value of THC, several N‐glycosyl‐N′‐[p‐(isoamyloxy)phenyl]‐thiourea derivatives were synthesized by coupling an aniline derivative and glycosyl isothiocyanates. The minimum inhibitory concentration (MIC) values of the new products against M. tuberculosis were determined.     

Acceleration of amine/epoxy reactions with N‐methyl secondary amines

Kinetic studies established that the monomethylation of a primary amine leads to significantly higher reaction rates with glycidyl ethers. The relative rates for approximately 25 amines were determined in an alcohol solvent under pseudo‐first‐order conditions (excess epoxy). The rates were referenced to aniline. For the aliphatic amines, reactivity consistently increased upon going from a primary amine to the corresponding N‐methyl secondary amine. This acceleration effect was not seen for aniline. The enhanced reactivity was also seen in curing systems, both with pure methylated amine curing agents and with complex mixtures obtained from the partial methylation of polyamines. Economically viable partially methylated amine curing agents were obtained by the reductive alkylation of commercial polyamines with formaldehyde and by the reaction of monomethylamine with 3‐(N‐methylamino)propionitrile in the presence of hydrogen and a hydrogenation catalyst. Although actual cure performance is based on a complex combination of several factors, the acceleration due to monomethylation could be a useful tool for enhancing amine/epoxy curing reactions. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 921–930, 2000     

超声法合成新型3-(5-氯/苯氧基-3-甲基-1-苯基-4-吡唑基)异噁唑N-取代苯基去甲去氢斑蝥酰亚胺衍生物

去甲去氢斑蝥素与取代芳胺反应得到了一系列N-取代苯基去甲去氢斑蝥酰亚胺, 再与5-氯/苯氧基-4-(α-氯-α-肟基甲基)-3-甲基-1-苯基吡唑甲酰基氯代肟发生1,3-偶极环加成反应生成一系列未见报道的3-(5-氯/苯氧基-3-甲基-1-苯基-4-吡唑基)异噁唑N-取代苯基去甲去氢斑蝥酰亚胺衍生物. 所合成化合物经元素分析, IR, ¹H NMR, ¹H-¹HCOSY, NOESY确证结构.     

Synthesis of 2-amino-4-imino-4,5-dihydrothiazoles from N-sulfonyl-α-chloroamidines and thiourea

A number of new and interesting 2-amino-4-(N-substituted)imino-4,5-dihydrothiazoles were synthesized by reacting thiourea (or thiourea hydrochloride) with N-alkyl- or N,N-dialkyl-N′-p-toluenesulfonyl-α-chloroacetamidines, where the N,N-alkyl groups were ethyl, cyclohexyl, benzyl, β-phenethyl, (3,5-dimethyl-1-adamantyl)-methyl, as well as N,N-dimethyl- and N,N-pentamethylene. Reactions of N-alkyl-N-p-toluenesulfonyl-2-chloroacetamidines (substituents being N-ethyl, N-benzyl and N,N-dimethyl) with thiourea hydrochloride in hot 2-propanol furnished 2-amino-4-(p-toluenesulfonyl)imino-4,5-dihydrothiazole (in 51, 60 and 65% yields, respectively) and the corresponding amine hydrochloride. In hot acetone or butanone, the reactions of these N-sulfonyl-2-chloroacetamidines with excess thiourea provided 2-amino-4-N-(alkyl or N,N-dialkyl)imminium-4,5-dihydrothiazole chlorides in 25–80% yield. The by-product from these reactions was p-toluenesulfonamide. The structures of the products were established by chemical transformations and spectral methods (nmr and mass spectra).     

Synthesis of N-substituted bisitaconimide monomers for use as thermosetting polyimide resins

Two monomeric N-substituted bisitaconimides, N,N′-bisitaconimido-p,p′-diphenylmethane and N,N′-bis(itaconimido-p,p′-diphenyl ether), were synthesized from the corresponding diamines. The synthesis was accomplished by reaction of the diamine with itaconic anhydride and cyclocondensation of the resultant bisitaconamic acid. Attempts to use p,p′-diaminodiphenylsulfone as the diamine gave N,N′-biscitraconimido-p,p′-diphenylsulfone and N-citraconimido-N′-itaconimido-p,p′-diphenylsulfone instead of the bisitaconimide. The two bisitaconimides polymerize thermally at 180°C and 225°C, respectively, and yield tough polymers with very high thermal stability.     

Copper-Mediated monochlorination of anilines and nitrogen-containing heterocycles

A simple and selective copper(II) chloride-mediated monochlorination of anilines and nitrogen-containing heterocycles has been developed. Stirring a mixture of aniline, copper(II) chloride, lithium chloride in EtOH under reflux condition produced 4-chloroaniline with high yield. Eighteen substrates including substituted anilines, N-substituted anilines, N,N-disubstituted anilines, 5-nitroindole and carbazole were all reactive and afforded desired products in moderate to excellent yields (52%–98%).     

Thermal latency and structure–activity relationship of aminimides in the polymerization of epoxide

1,1-Dimethyl-1-(2-hydroxypropyl)amine p-substituted benzimide (“aminimide”) derivatives were prepared by the reaction of p-substituted methyl benzoates with equimolar amounts of 1,1-dimethylhydrazine and propylene oxide. These ylide compounds are shown to be useful as thermally latent initiators for the polymerization of glycidyl phenyl ether (GPE). Bulk polymerization of GPE with 3 mol % of these aminimides was carried out at 40–150°C for 8 h, showing ≥ 100°C was required for an effective rate. No consumption of the monomer could be observed at temperatures lower than 80°C. p-Methoxy substituted 1 showed the largest thermal latency among four aminimides tested. The activities of the aminimides increased with an increase of electron-donating ability of the substituents on the benzene ring, according to the following order: 1 (p-MeO) > 2 (p-Me) > 3 (H) > 4 (p-NO₂). © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35: 689–694, 1997     

A novel synthetic strategy to develop second‐order nonlinear optical polysilanes for potential photorefractive effects

A novel strategy to develop polysilanes functionalized with a high density of nonlinear optical chromophores has been explored. Thus a polysilane with phenyl and N,N‐dialkylsubstituted aniline as pendant groups was synthesized under standard conditions for the Wurtz reductive coupling, and the post azo coupling of p‐nitrobenzenediazonium fluoroborate towards the aniline groups afforded a dispersed red (DR) chromophore‐functionalized polysilane (P2). The poled film of P2 reveals a resonant d₃₃ value of 19 pm/V by second harmonic generation (SHG) measurements.     

Facile One-Pot Synthesis of 1,2,3-Triazoles Featuring Oxygen,Nitrogen, and Sulfur Functionalized Pendant Arms

A practical and efficient one-pot synthesis of novel 1,2,3-triazoles featuring nitrogen, oxygen, and sulfur functionalized pendant arms has been developed. The click reaction of mono-propargyl derivatives supported by aniline, thiophenol, and benzyl alcohol, with sodium azide and p-substituted benzyl halogenides, renders a series of N-substituted-1,2,3-triazoles in good yields under mild reaction conditions. The catalyst system was based in Cu(OAc)₂ · H₂O, sodium L-ascorbate, and 1,10-phenanthroline monohydrate, and all reactions were performed in a mixture H₂O–ethanol (4:1 v/v). Additionally, the preparation of bis-1,2,3-triazoles supported by di-propargylated aniline was carried out, demonstrating the versatility of the present methodology.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Studies on the imidization of N-substituted polymaleamic acids

A spectral method for determining the imidization from maleamic acid to maleimide was described. The formation condition and mechanism of polymaleimide compared with N-phenyl-maleimide ( I ) and 4,4′-bis(N-maleimido)-diphenylmethane ( II ) were investigated. A series of N-substituted maleimides were synthesized by the reaction of their corresponding maleamic acids with acetic anhydride and sodium acetate as a catalyst. The rate of dehydration reaction of N-phenylmaleamic acid with Ac₂O was determined at a mole ratio 0.1:1 of NaOAc to N-phenyl-maleamic acid and a second-order constant K of 1.38 × 10^?2 (mL/mol s) was obtained. The activation energies for the ring-closure reaction of N-phenylmaleamic acid and polyphenylene-methylenemaleamic acid were 1.26 × 10⁴ (cal/g mol) and 1.32 × 10⁴ (cal/g mol), respectively. The decreasing order for the rate of N-substituted maleimide formation was N-(p-methylphenyl)maleimide > I ≒ II > N-(p-chlorophenyl)maleimide. The result was attributed to the para-substituent effect. These imidization reaction were observed qualitatively by IR spectra and analyzed quantitatively by ¹H-NMR spectra.     

Radical polymerization of 4-methylene-4H-1,3-benzodioxin-2-ones: Cyclic α-substituted styrenes

4-Methylene-4H-1,3-benzodioxin-2-one (MBDOON), an α-substituted cyclic styrene derivative, was synthesized and polymerized readily with 2,2′-azobis(isobutyronitrile) (AIBN) as an initiator in solution. The kinetics of the MBDOON homopolymerization with AIBN was investigated in N-methyl-2-pyrrolidone (NMP). The rate of polymerization, R_p, can be expressed by R_p ? k[AIBN]^0.52[MBDOON]^1.1 and the overall activation energy has been calcualted to be 75.7 kJ/mol. Monomer reactivity ratios in copolymerization of MBDOON (M₂) with styrene (M₁) are r₁ = 0.31 and r₂ = 3.20, from which Q and e values of MBDOON can be calculated as 3.0 and ?0.7, respectively. Ring-substituted MBDOON monomers such as 6-chloro, 6-methyl, and 7-methoxy derivatives were synthesized and polymerized with AIBN. The 6-substituted MBDOON's readily underwent radical polymerization while the 7-methoxy-MBDOON was slower to polymerize. Poly(MBDOON) is predominantly heterotactic. (rr = 35, mr = 46, and mm = 19%). The polymer releases carbon dioxide at about 200°C and is converted with some depolymerization to poly[(o-hydroxyphenyl)acetylene]. The thermolysis temperature is very much affected by the ring substituent. The onset of carbon dioxide liberation was observed at 140°C in the case of the 7-methoxyl derivative while the 6-substituents had a smaller effect on the decarboxylation temperature. © 1993 John Wiley & Sons, Inc.     

Electrochemical synthesis of a novel sulfonated polyaniline and its electrochemical properties

A novel N-substituted aniline, N-(4-sulfonicbutyryl)aniline was synthesized and subsequently to be electropolymerized to yield a new conductive polymer, poly(N-(4-sulfonicbutyryl)aniline). X-ray photoelectron spectrum (XPS) of the polymer film was examined to propose the polymer molecular structure. The sulfonated polyaniline was also characterized by ¹H NMR, TGA, DTA, FTIR, and UV–vis spectra. The sulfonated polyaniline showed high conductivity in neutral aqueous solutions, which is two orders of magnitude higher than that of poly(N-acetylaniline) (PNAANI).     

SOME REACTIONS OF CHOLESTERYL N-PHENYL-PHOSPHORAMIDIC CHLORIDE AND RELATED COMPOUNDS

Abstract

Cholesteryl N-phenylphosphoramidic chloride has been converted to the corresponding phosphoramidic hydrazide and azide. The former compound was characterised by the preparation of a number of hydrazones, while the latter has been reacted with norbornene, dimethylsulphoxide, and triphenylphosphine. However, the azide did not react with decane, o-anisole, or butylamine. 17-Oxoandrost-5-ene-3β-yl N-phenylphosphoramidic chloride was prepared and was converted to the hydrazide, but a pure sample of the azide could not be isolated. Cholesteryl N-phenyl phosphoramidic triphenylphosphinimine has been reacted with eight carbonyl compounds and the structures of the products investigated. Cholesteryl N-cyclohexylphosphoramidic chloride was converted to the azide and the triphenylphosphinimine; the latter was reacted with acetone and p-nitrobenzaldehyde.

Cholesteryl phosphorodichloridate has been condensed with phenol, p-nitrophenol, and p-methoxyphenol to give the corresponding O-arylphosphorochloridates. The O-phenyl and O-p-methoxyphenyl phosphorochloridates have been converted to the corresponding azides, but the azide from the p-nitrophenyl derivative could not be isolated. The reactions of cholesteryl phosphorodichloridate with diethylamine, hydrazine, and sodium azide have also been examined; and cholesteryl phosphorodichloridothioate has been condensed with aniline and benzylamine.