Synthesis of Isatin Derivatives

Reactions were studied of isatin sodium salt with bromocyclohexane, p-ethoxyphenyl chloroethyl ketone, 4,4'-di(chloromethyl)biphenyl, and 4,4'-(dichloromethyl)diphenylmethane. N-cyclohexylisatin, p-ethoxyphenyl N-isatinoethyl ketone, 4,4'-di(N-isatinomethyl)biphenyl, 4-chloromethyl-4'(N-isatinomethyl)biphenyl, 4,4'-di(N-isatinomethyl)diphenylmethane, 4-chloromethyl-4'(N-isatinomethyl)diphenylmethane, and 4-(N-morpholinomethyl)-4'-(N-isatinomethyl)diphenyl were synthesized.     

Synthese von N-Methyl- und N,N-Dimethylmerucathin sowie von N-Methyl- und N,N-Dimethylpseudomerucathin aus L-Alanin

Synthesis of N-Methyl- and N,N-Dimethylmerucathine and of N-Methyl- and N,N--Dimethylpseudomerucathine Starting from L -Alanine Starting form L -alanine, N-methylmerucathine (= (3R,4S)-4-(methylamino)1-phenyl-1-penten-3-ol; (3R,4S,)- 6 ), N,N-dimethylmerucathine (= (3R,4S)-4-(dimethylamino)-1-phenyl-1-penten-3-ol; (3R,4S)- 9 ), N-methylpseudomerucathine (= (3S,4S)-4-(methylamino)-1-phenyl-1-penten-3-01; (3S,4S)-6), and N,N-dimethylpseudomerucathine (= (3S,4S)-4-(dimethylamino)-1-phenyl-1-penten-3-ol; (3S,4S)- 9 ) were synthesized. The four compounds were analyzed by HPLC and compared with a natural khat extract.     

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).     

N-(4-Nitrophenyl)oxamic Acid and Related N-Acylanilines Are Non-competitive Inhibitors of vibrio cholerae sialidase but do not inhibit trypanosoma cruzi or trypanosoma brucei trans-sialidases

N-(4-Nitrophenyl)oxamic acid 1 , N-(2-fluoro-4-nitrophenyl)oxamic acid 7 , N-(4-nitrophenyl)-trifluoroacetamide 3 , and N-(2-methoxy-4-nitrophenyl)trifluoroacetamide 9 are non-competitive inhibitors of Vibrio cholerae sialidase with K_i-values ranging from 2.66 to 5.18 · 10^?4 M . These compounds, and the N-acetylneuraminic-acid analogues 11–13 do not inhibit the sialidase and trans-sialidase activities from Trypanosoma cruzi; nor does N-(4-nitrophenyl)oxamic acid ( 1 ) inhibit the corresponding enzyme activities from T. brucei.     

Allgemeiner Zugang zu Polyaminen mit Ethan-1,2-diamin-Einheiten: Synthese von nicht natürlich vorkommenden homologen und isomeren N1,4-Di(4-cumaroyl)sperminen

█tl="American"█The synthesis of the three N,N′-di(4-coumaroyl)tetramines, i.e., of (E,E)-N-{3-[(2-aminoethyl)amino]propyl}-3,3′-bis(4-hydroxyphenyl)-N,N′-(ethane-1,2-diyl)bis[prop-2-enamide] ( 1a ), (E,E)-N-{4-[(2-aminoethyl)amino]butyl}-3,3′-bis(4-hydroxyphenyl)-N,N′-(ethane-1,2-diyl)bis[prop-2-enamide] ( 1b ), and (E,E)-N-{6-[(2-aminoethyl)amino]hexyl}-3,3′-bis(4-hydroxyphenyl)-N,N′-(ethane-1,2-diyl)bis[prop-2-enamide] ( 1c ), is described. It proceeds through stepwise construction of the symmetric polyamine backbone including protection and deprotection steps of the amino functions. Their behavior on TLC in comparison with that of 1,4-di(4-coumaroyl)spermine (=(E,E)-N-{4-[(3-aminopropyl)amino]butyl}-3,3′-bis(4-hydroxyphenyl)-N,N′-(propane-1,3-diyl)bis[prop-2-enamide]; 2 ) is discussed.     

Isolation and characterisation of products from the reactions between [Co2(nta)2(μ-OH)2]2− and different ligands. The crystal structure of [Co(nta)(N,N-Et2en)]

The crystal structure of [Co(nta)(N,N-Et₂en)] (nta = nitrilotriacetate and N,N-Et₂en = N,N-diethylethylenediamine) was determined from three-dimensional X-ray diffraction data. The substituted nitrogen of N,N-diethylethylenediamine is bonded trans to the nta nitrogen with the Co—N_{(N,N Et2en)}= 2.011(5) and Co—N_(nta) = 1.950(4) Å while the cis Co—N bond is 1.953(4) Å. The Co—O bond lengths are 1.905(2) and 1.884(4) Å respectively.     

A study concerning the synthesis,basicity and hydrolysis of 4‐amino‐2‐(N,N‐diethylamino)quinazoline derivatives

A group of 2‐(N,N‐diethylamino)‐4‐aminoquinazoline derivatives have been synthesized in the reaction of N¹,N¹‐diethyl‐N²‐arylchlorocarboxyamidines with cyanamide in the presence of T1Cl₄ as a catalyst. Such quinazolines decompose into the corresponding quinazolones in dilute aqueous HC1 solutions at higher temperature. Hydrolysis rates of 2‐(N,N‐diethylamino)‐4‐aminoquinazoline and 2‐(N,N‐diethylamino)‐4‐(N,N‐dimethylamino)‐quinazoline have been determined to observe the influence of substituents at the 4‐amino group upon the hydrolysis. pK_a values have been also determined for these compounds and analyzed in conjunction with the Hammett σ constants.     

Synthesis and activity of four (N,N‐dimethylamino)benzamide nonsteroidal anti‐inflammatory drugs based on thiazole and thiazoline

Four compounds derived from 2‐aminothiazole and 2‐amino‐2‐thiazoline were prepared by coupling the respective bases with the acid chlorides of either 3‐ or 4‐(N,N‐dimethylamino)benzoic acid. Products were identified using infrared spectroscopy, ¹H NMR spectroscopy and electrospray mass spectroscopy and in two cases by single‐crystal X‐ray diffraction. Of the four, N‐(thiazol‐2‐yl)‐3‐(N,N‐dimethylamino)‐benzamide (1), N‐(thiazolin‐2‐yl)‐4‐(N,N‐dimethylamino)benzamide (2), N‐(thiazolin‐2‐yl)‐3‐(N,N‐dimethylamino) benzamide (3) and N‐(thiazolin‐2‐yl)‐4‐(N,N‐dimethylamino)benzamide (4), the hydrochloride salts of compounds 3 and 4 showed anti‐inflammatory activity across a concentration range of 10^?2?5 × 10^?4 M while 3 (at a concentration of 10^?5 M) was found to have no adverse effect on myocardial function. The X‐ray crystal structure of 2 and the 1:1 adduct structure of 3 with 3‐(N,N‐dimethylamino)benzoic acid are reported.     

Thermochemical study of the trans- and cis-isomeric forms of 4-(4-methoxystyryl)pyridine N-oxide

The trans and cis form of 4-(4-methoxystyryl)pyridine N-oxide were studied. The spectral characteristics of cis-4-(4-methoxystyryl)pyridine N-oxide were determined in acetonitrile. The melting and thermal decomposition processes of the trans and cisforms of 4-(4-methoxystyryl)pyridine N-oxide were studied by thermochemical methods. It was establish that the thermal decomposition of 4-(4-methoxystyryl)pyridine N-oxide begins with the cleavage of the bond between the pyridine and benzene rings.

     

Anionic synthesis of aromatic amide and carboxyl functionalized polymers. Chain-end functionalization of poly(styryl)lithium with N,N-diisopropyl-4-(1-phenylethenyl)benzamide

The novel syntheses of N,N-diisopropyl-4-benzoylbenzamide, N,N-diisopropyl-4-(1-hydroxy-1-phenylethyl)benzamide, and N,N-diisopropyl-4-(1-phenylethenyl)benzamide ( 1 ) are described. ω-Amidopolystyrene ( 2 ) was synthesized in quantitative yields by the reaction of poly(styryl)lithium with stoichiometric amounts of N,N-diisopropyl-4-(1-phenylethenyl)benzamide ( 1 ) in toluene/tetrahydrofuran (4 : 1 v/v) at −78°C. Deblocking of the amide protecting group by acid hydrolysis quantitatively provides the corresponding aromatic carboxyl chain-end functionalized polystyrene ( 3 ). The functionalization agent and functionalized polymers were characterized by HPLC, thin-layer chromatography, size exclusion chromatography, vapor phase osmometry, spectroscopy (¹H-NMR, ¹³C-NMR, and FTIR), potentiometry, and elemental analysis. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 1233–1241, 1998     

The solvent effect on the isotropic hyperfine interaction in some aliphatic polyamine copper(II) complexes

ESR and optical absorption studies are described for a number of copper(II) chelates with aliphatic polyamines, exhibiting both square pyramidal and square bipyramidal coordination around the copper ion. The complexes studied were bis(N,N′-dimethylethylenediamine)copper(II) sulphate tetrahydrate, bis(N,N′-diethylethylenediamine)copper(II) nitrate, diaquosulphato(N,N,N′,N′-tetramethylethylenediamine)copper(II) hydrate, dinitrato(N,N,N′,N′-tetramethylethylenediamine)copper(II), dichloro(N,N,N′,N′-tetramethylethylenediamine)copper(II) and dithiocyanato(N,N,N′,N′-tetramethylethylenediamine)copper(II). The ESR measurements were carried out in methanol, dimethyl sulphoxide, dimethylformamide and pyridine, at room and liquid nitrogen temperatures. The molecular orbital coefficients were estimated assuming an axial symmetry. The parameter χ proportional to the hyperfine constants shows a variation with the solvent for all these complexes. The χ values in solution are lower than the corresponding average χ values reported in the solid state for each complex. The solvent effect and the influence of 4s character in the ground state are discussed. The χ values, either calculated or reported, for a number of copper complexes for [4O], [3O, N], [2O, 2N], [O, 3N] and [4N] environments around copper(II) are presented.     

Some reactions of 2-(4-substitutedphenyl)-2-(N-methyl-N-4-substitutedbenzamido) acetic acids

In situ generated 2,4-diaryl substituted münchnones from 2-(4-substitutedphenyl)-2-(N-methyl-N-4-substitutedbenzamido)acetic acids react with acetic anhydride in the presence of 2-nitromethylene thiazolidine, which is most likely acting as a base, and unexpectedly undergo a Dakin–West type reaction and a concurrent autoxidation reaction leading to the formation of (E)-1-(N,4-dimethylbenzamido)-1-(4-fluorophenyl)prop-1-en-2-yl acetate, 4-substitutedphenyl-N-methyl-N-(4-substitutedbenzoyl) benzamides and p-substituted benzoic acids. In addition, a novel and efficient access to N-acyl urea derivatives is described by the reaction between 2-(4-substitutedphenyl)-2-(N-methyl-N-4-substitutedbenzamido)acetic acids and cyclohexyl, isopropyl carbodiimides in the presence of a base. The structures of all new products were identified on the basis of NMR and IR spectra, along with X-ray diffraction data and HRMS measurements.     

Synthesis of isonipecotinoyl analogues of aminopterin and folic acid

The preparation of isonipecotinoyl analogues of aminopterin and methotrexate is described. Condensation of diethyl N-isonipecotinoyl-L-glutamate 4 with 2-amino-5-bromomethyl-3-cyanopyrazine 5 afforded diethyl N-(N-[(2-amino-3-cyanopyrazin-5-yl)methyl]isonipecotinoyl)-L-glutamate 6 . Cyclisation of 6 with guanidine followed by blocking group hydrolysis afforded N-([N-(2,4-diaminopteridin-6-yl)methyl]isonipecotinoyl)-L-glutamic acid 8 . Coupling of N-(2-amino-4(3H)ioxopteridin-6-yl]methyl)isonipecotinic acid 11 with diethyl L-glutamate gave diethyl N-[(N-[2-amino-4(3H)-oxopteridin-6-yl]methyl)isonipecotinoyl]-L-glutamate 12 . Blocking group hydrolysis afforded N-[(N-[2-amino-4(3H)-oxopteridin-6-yl]methyl)isonipecotinoyl]-L-glutamic acid 13 .     

Synthesis of 4-substituted 1,4-benzodiazepine-3,5-diones

Synthetic routes leading to the preparation of 4-substituted 1,4-benzodiazepine-3,5-diones are described. Thus, 2-carbobenzoxyaminobenzoic acid was converted to its p-nitrobenzyl ester (I) and the decarbobenzoxylated product (II) gave, with ethyl α-bromoacetate, N-(2-carboxy p-nitrobenzylate)phenylglycine ethyl ester (III). The latter was hydrogenolyzed to N-(2-car-boxy)phenylglycine ethyl ester (IV), which was coupled with benzylamine to give N-(2-carboxy-benzylamido)phenylglycine ethyl ester (VIa). Saponification of VIa afforded N-(2-carboxy-benzylamido)phenylglycine (VIIa) which was cyclized with DCCI to produce 4-benzyl-2H-1,4-benzodiazepine-3,5(lH,4H)dione (VIIIa). Alternatively, 2-nitro-N-phenylbenzamide (Xb) was reduced to 2-amino-N-phenylbenzamide (XIb) which was converted to N-(2-carboxanih'do)-phenylglycine ethyl ester (VIb). The latter was converted to 4-phenyl-2H-1,4-benzodiazepine-3,5(1H,4H)dione (VIIIb) in an analogous fashion described for VIIIa.     

Studies on the syntheses of azole derivatives. Part IX. Formation of 2,4-disubstituted δ2 -1,3,4-oxadiazolin-5-one and 4-substituted 1,2,4-triazolidin-3,5-dione derivatives by thermal reaetion of N-aryl-N-benzylearbamoyl azides

The structure of the novel produets, 2,4-ltis-(N-benzy1-4-nitroanilino)-Δ²-1,3,4-oxadiazolin-5-one (VII), 2-benzy1-1-(N-benzy1-4-chloroanilino)-4-(4-chlorophenyl)-1,2,4-triazolidin-3,5-dione (XIVa), and 2-benzy1-1-(N-benzylanilino)-4-pheny1-1,2,4-triazolidin-3,5-dione (XIVb), obtained upon thermal reaction of N-bcnzyl-N-(4-nitrophenyl)carbamoyl azide (la), N-benzyl-N-(4-chloro-phenyl)carbamoyl azide (Ib) and N-benzyl-N-phcnylcarbamoyl azide (le), respectively, were determined.     

Syntheses and polymerizations of some vinyl monomers containing nitro- or fluorophthalimides

4-Nitro-N-vinylphthalimide ( 4 ) was synthesized by two different procedures. Compound 4 was not polymerizable or copolymerizable by AIBN. Poly(N-vinylphthalimide) ( 17 ) was prepared and partially nitrated at 10–25°C. N,N′-(1,2-Ethanediyl)bis(4-nitrophthalimide) ( 15 ) and N,N′-(1,3-propanediyl)bis(4-nitrophthalimide) ( 16 ) were prepared by the condensation of the corresponding diamine with phthalic anhydride followed by nitration of the condensation products. 4-Nitrophthalic anhydride was prepared by the hydrolysis of 15 . Four styrene-substituted phthalimide monomers were synthesized. These include N-(4-vinylphenyl)phthalimide ( 25a ), N-(4-vinylphenyl)-3-fluorophthalimide ( 25b ), N-(4-vinylphenyl)-3-nitrophthalimide ( 25c ), and N-(4-vinylphenyl)-4-nitrophthalimide ( 25d ). Monomers 25a and 25b were polymerized by freeradical initiator (AIBN), whereas monomers 25c and 25d were not polymerizable or copolymerizable by AIBN due to a strong inhibitive effect exerted by the nitrophthalimide group. Monomers 25c and 25d were cationically polymerized (BF₃·OEt₂). Monomer 25b and styrene were copolymerized and their reactivity ratios were r₁ = 1.7 and r₂ = 0.55, respectively. The prepared polymers are useful as backbone polymers for grafting living anionic polymers.     

Reaction of N‐(phenyl and methyl)‐C‐arylnitrones with DMAD in ionic liquid: Efficient synthesis of Δ4‐isoxazolines

Facile synthesis of N‐(methyl and phenyl)‐Δ⁴‐isoxazolines via the reaction of (Z)‐N‐(methyl and phenyl)‐C‐arylnitrones with dimethyl acethylenedicarboxylate, DMAD, in ionic liquid is described. (Z)‐N‐methyl‐C‐arylnitrones afforded the high yield of N‐methyl‐Δ⁴‐isoxazolines 4a , 4b , 4c , 4d , 4e in ionic liquid, [bmim]BF₄, at room temperature. However, the reaction of (Z)‐N‐phenyl‐C‐arylnitrones with DMAD afforded the mixtures of cis and trans isomers of related N‐phenyl‐Δ⁴‐isoxazolines ( 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j , 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h , 6i , 6j ) under these conditions. J. Heterocyclic Chem., (2012).     

Synthesis and Structure of N,N-Dimethyldithiocarbamates of Tetraphenylantimony and Tetra-p-tolylantimony

Tetraphenylantimony N,N-dimethyldithiocarbamate (I) and tetra-p-tolylantimony N,N-dimethyldithiocarbamate (II) were synthesized via the reaction of tetraarylantimony chloride Ar₄SbCl (Ar = C₆H₅ or C₆H₄Me-4) with sodium N,N-dimethyldithiocarbamate in water. According to the X-ray diffraction data, the tetraarylantimony N,N-dimethyldithiocarbamate molecules have a distorted octahedral configuration. The Sb–S bond lengths are equal to 2.7158(5) Å, 2.7440(5) Å and 2.761(2) Å, 2.8002(2) Å for I and II, respectively.     

Convergent Versus Divergent Three-Step Synthesis of the First (4-Aminophenoxy)alkanoic Acid–Based Tripodal Melamines

Starting from N-(4-hydroxyphenyl)acetamide (Paracetamol, convergent approach) or from cyanuric chloride in reaction with 4-aminophenol (divergent approach), two synthetic routes toward novel tripodal N-substituted melamines as s-triazine derivatives of (4-aminophenoxy)acetic acid or of 4-(4-aminophenoxy)butyric acid are comparatively defined. The key steps consist of Williamson etherification of N-masked forms of 4-aminophenol and acidic hydrolysis of the N- and/or O-protected (4-aminophenoxy)alkanoic segments.     

Novel dialkylaminoalkyl- and dialkylaminoalcoxi-benzophenones as photoinitiators of polymerization. I. Photochemical characteristics and radical efficiencies

The behavior of the nonconjugated aminated benzophenones—4-[2′-N,N-(diethylamino)ethoxy]benzophenone (E4), 2-[2′-N,N-(diethylamino)ethoxy]-4-methoxybenzophenone (E2), and 4-N,N-dimethylaminomethylbenzophenone (DM)—as photoinitiators of MMA polymerization has been studied and the results compared with those obtained with the conjugated aminobenzophenone 4-N,N-dimethylamino-4′-isopropyl-benzophenone (CU—MI). Photoreduction behavior of these compounds in various solvents in the presence and absence of MMA has been also examined. The order of the polymerization reaction with respect to monomer and initiator concentrations has been investigated; values of initiation quantum yield (Φ_i), K_p/K^1/2_t and efficiencies of the different radicals have also been determined. Similar polymerization rates (R_p) of methyl methacrylate (MMA) were found when E4 and CU-MI were used as photoinitiators under the same range of absorbed irradiation intensity. This fact results from a compensation between the higher rate of E4 radical production (n-π* transition type) and the greater reactivity of the radicals generated from CU-MI.