Spectrophotometric study of the charge transfer complexation of some porphyrin derivatives as electron donors with tetracyanoethylene

Charge transfer complexes (CTC) of 5,10,15,20-tetraphenylporphyrin (TPP), 5,10,15,20-tetra(4-tolyl)porphyrin (TTP), 5,10,15,20-tetra(4-methoxyphenyl)porphyrin (TMP), Zn-5,10,15,20-tetraphenylporphyrin (Zn-TPP), and Zn-5,10,15,20-tetra(4-tolyl)porphyrin (Zn-TTP) with tetracyanoethylene (TCNE) have been studied at various temperatures in CH(2)Cl(2) and CCl(4). The data are discussed in terms of equilibrium constant (K(CT)), molar extinction coefficient (varepsilon(CT)), thermodynamic standard reaction quantities (DeltaG degrees , DeltaH degrees and DeltaS degrees ), oscillator strength (f), and transition dipole moment (mu). The spectrum obtained for TPP/TCNE, TTP/TCNE, and TMP/TCNE systems shows two main absorption bands at 475 and 690nm, which are not due to the absorption of any of the reactants. These bands are characteristic of an intermolecular charge transfer involving the overlap of the lowest unoccupied molecular orbital (LUMO) of the acceptor with the highest occupied molecular orbital (HOMO) of the donor. The results reveal that the interaction between the donors and acceptor is due to pi-pi(*) transitions by the formation of radical ion pairs. The stoichiometry of the complexes was found to be 1:1 ratio by the Job and straight line methods between donors and acceptor with the maximum absorption bands at wavelengths of 475 and 690nm. The observed data show salvation effects on the spectral and thermodynamics properties of CTC. The ionization potential of the donors and the dissociation energy of the CTC were also determined and are found to be constant.     

Arylhydrazonals as the aldehyde component in Baylis-Hillman reactions

Arylhydrazonals were added to acrylonitrile or methyl vinyl ketone in the presence of DABCO or benzotriazole to yield the intermediate Baylis-Hillman adduct that cyclized under the reaction conditions with water elimination to yield dihydropyridazines. A pyridazine reacted with DMAD to yield a pyridine via a [4+2] Diels-Alder addition followed by retro Diels-Alder elimination of methylene aniline. Two pyridazines were condensed with DMFDMA to yield the corresponding enaminones that reacted with NH₂NH₂ to afford the pyrazolylpyridazines.     

3-Amino- and 3-acylamido-2-phosphonopyridines: synthesis by Pd-catalyzed P-C coupling, structure and conversion to pyrido[b]-anellated PC-N heterocycles

Palladium catalyzed cross-coupling of 3-amino- and 3-acylamido-2-bromopyridines 1a-f with triethyl phosphite allowed the synthesis of 3-amino- and 3-acylamido pyridine-2-phosphonic acid diethyl esters 2a-f, whereas nickel catalysts, although providing access to related anilido-2-phosphonates, proved inactive. Reduction of the aminophosphonate 2a with LiAlH₄ afforded 3-amino-2-phosphinopyridine (3a), which was cyclocondensed with dimethylformamide dimethyl acetal (DMFA) via phosphaalkene intermediates 4a to the novel pyrido[b]-anellated 1,3-azaphosphole 5a. Reaction of amidophosphonates 2b-f with LiAlH₄ did not result in the expected reductive cyclization, as shown by closely related anilido-2-phosphonates, but led to product mixtures containing N-secondary 3-amino-2-phosphinopyridines 3b-f as the main or major component. The conversion of 3b,d,e with DMFA to 5b,d,e provides first examples of N-substituted pyrido[b]-anellated azaphospholes. Structures were confirmed by multinuclear NMR and X-ray crystallography (for 2c, 3b).     

Reactions of 4-(2-aminothiazole-4-yl)-3-methyl-5-oxo-1-phenyl-2-pyrazoline. Synthesis of thiazolo[3,2- a ]pyrimidine and imidazo[2,1- b ]thiazole derivatives

4-(2-Aminothiazol-4-yl)-3-methyl-5-oxo-1-phenyl-2-pyrazoline was synthesized via the reaction of 4-bromoacetyl-3-methyl-5-oxo-1-phenyl-2-pyrazoline with thiourea [7] and was transformed to related fused heterocyclic systems. The antifungal and antibacterial studies revealed in some cases excellent biocidal properties.     

6-Amino-2-thio- and 6-Aminouracils as Precursors for the Synthesis of Antiviral and Antimicrobial Methylenebis(2-thiouracils), Tricyclic Pyrimidines,and 6-Alkylthiopurine-2-ones

Summary. Several derivatives of 5-arylmethylenebis(1-methyl-6-amino-2-thiouracils) and 5-aryldipyrimidopyridines were prepared by stirring of 6-amino-1-methyl-2-thiouracil and 6-amino-1-benzyluracil with different aromatic aldehydes in ethanol in the presence of HCl or refluxing with AcOH. On the other hand, 6-alkylthio-3,9-dimethylpurine-2-ones were synthesized by the alkylation of 3,9-dimethyl-6-thioxanthine which was prepared by treatment of 3,9-dimethylxanthine with P₂S₅. The structures of the novel compounds were characterized by spectroscopic methods. The effects of the novel compounds on both HAV and HSV type 1 were investigated. Also, some compounds showed inhibitory effects on Gram-positive and Gram-negative bacteria as well as yeast and fungi. On leave from Chemistry Department, Faculty of Science, Zagazig University, Zagazig, Egypt     

Synthesis and reactions of thiosemicarbazides,triazoles, and <Emphasis Type="Italic">Schiff</Emphasis> bases as antihypertensive α-blocking agents

Methyl 2-(thiazol-2-ylcarbamoyl)acetate was synthesized and used as starting material. It was treated with hydrazine hydrate to afford the hydrazide, which was reacted with nitromethane and formaldehyde to give the saturated nitropyrimidine. The hydrazide was reacted with phenyl isothiocyanate to afford the thiosemicarbazide, which was cyclized with ethyl bromoacetate, sodium hydroxide, or sulfuric acid to afford N-phenylthiazolidinone, N-phenyltriazole, and thiadiazolyl derivatives. The methyl 2-(thiazol-2-ylcarbamoyl)acetate was coupled with diazonium salts of aniline, 4-chloroaniline, 4-bromoaniline, or 4-aminobenzenesulfonamide to afford the carbamoyl acetates, which were reacted with 2-aminobenzimidazole, 1,2,4,5-tetrachlorophthalic anhydride, and hydrazine hydrate to afford the corresponding thiazolylmalonamide, tetrachloroisoindolylimide, and tri-azole derivatives. Schiff bases and imides are newly synthesized candidates obtained via simple condensation of the hydrazide with aldehydes, 2,3-pyridinedicarboxylic anhydride, or 1,8-naphthalenedicarboxylic anhydride. The pharmacological screening showed that many of these compounds have good antihypertensive α-blocking activity and low toxicity. Correspondence: Abd El-Galil E. Amr, National Research Center, Applied Organic Chemistry, Dokki, Cairo, Egypt.     

Anti-inflammatory activity of heterocyclic systems using abietic acid as starting material

A series of pyridines, pyrimidinone, oxazinones, and their derivatives were synthesized as anti-inflammatory agents using abietic acid (7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,4b,5,6,10,10a-decahydrophenanthrene-1-carboxylic acid) as the starting material. The arylidiene derivative was treated with cyanothioacetamide to give cyano pyridine-thione, which was reacted with ethyl chloroacetate to yield the corresponding cyano ester. The ester was hydrolysed to the sodium salt, which was reacted with acetic anhydride to afford 2-methyloxazinone, which was treated with ammonium acetate to afford 2-methylpyrimidinone followed by methylation with methyl iodide to yield 2,3-dimethyl- pyrimidinone. In addition, the oxazinone derivative was reacted with aniline or hydrazine hydrate to give 3-phenyl- or 3-aminopyrimidinones. The latter reacted with thiophene-2-carboxaldehyde or phenylisothiocyanate to afford Schiff’s bases or thiosemicarbazide derivatives. The pharmacological screening showed that many of these compounds have good anti-inflammatory activity comparable to Prednisolone^® as reference drug.     

A general and efficient method for the synthesis of benzo-(iso)quinoline derivatives

A new, short and efficient synthesis of substituted benzo-(iso)quinoline derivatives is reported. The methodology is based on a Suzuki or Negishi cross-coupling followed by a cyclization reaction induced by t-BuOK in DMF to form the central ring. This approach allowed the synthesis of all four benzo-(iso)quinoline isomers and the substitution of each ring of the benzo-(iso)quinoline core.     

Lectin-based electrophoretic analysis of the expression of the 35 kDa inter-alpha-trypsin inhibitor heavy chain H4 fragment in sera of patients with five different malignancies

A 35 kDa glycoprotein whose abundance was previously demonstrated to be enhanced in sera of patients with endometrial adenocarcinoma (n = 12), was isolated from pooled sera of three of the cancer patients using champedak galactose-binding lectin affinity chromatography in the present study. Subjecting it to 2-DE and MS/MS, the glycoprotein was identified as the O-glycosylated fragment of inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4). When compared to control sera (n = 17), expression of the 35 kDa ITIH4 cleavage fragment was demonstrated to be significantly enhanced in sera of patients with breast carcinoma (n = 10), epithelial ovarian carcinoma (n = 10), and germ cell ovarian carcinoma (n = 10) but not in patients with nasopharyngeal carcinoma (n = 13) and osteosarcoma (n = 7). The lectin-based electrophoretic bioanalytical method adopted in the present study may be used to assess the physiological relevance of ITIH4 fragmentation and its correlation with different malignancies, their stages and progression.     

Improved method to determine succinylacetone in dried blood spots for diagnosis of tyrosinemia type 1 using UPLC-MS/MS

We describe an improved diagnostic method for tyrosinemia type 1 based on quantifying succinylacetone in dried blood spots by ultra-performance liquid chromatography tandem mass spectrometry. Succinylacetone extracted from a single 3/16 inch disk of specimen collection paper containing a dried blood spot was derivatized with dansylhydrazine, separated on an Acquity UPLC BEH C(18) column (2.1 x 50 mm, 1.7 microm) and detected by electrospray ionization tandem mass spectrometry. Succinylacetone derivative eluted at 0.6 min with a complete run time of 1 min. Using a 13C4 labeled succinylacetone as an internal standard, the calibration plot was linear up to 100 micromol/L with a detection limit (S/N = 3) of 0.2 micromol/L. Intra-day (n = 13) and inter-day (n = 10) variations were better than 10%. The cutoff level of succinylacetone in dried blood spots from healthy infants obtained by the current method was 0.63 micromol/L (n = 151). In dried blood spots from patients with established tyrosinemia type 1 (n = 11), concentration of succinylacetone was 6.4-30.8 micromol/L.