A spectrophotometric method was used to determine the rate law in buffered aqueous iodine-iodide solutions. Three iodinating agents other than iodine were considered: direct attack by hypoiodous acid, acid catalyzed attack by hypoiodous acid, and the iodinium ion. The first two were discarded because of the observed dependence of the rate on the buffer concentration and the observed independence of the rate on the hydrogen ion concentration. The postulated mechanism is in agreement with the mechanisms for aniline and pyrazole. The rate determining step is the removal of the proton from the intermediate by the buffer. However, it was found that iodine was the major iodinating species and that the iodinium ion had a much smaller effect. A qualitative discussion of the reactivities of pyrazole, J-methylpyrazole., and l-methylpyrazole was made. An attempt was made to show possible reasons for the observed results. / M.S.

Pyrazolopyrimidines are a general class of compounds which exhibit Aj adenosine receptor affmity. A number of pyrazolo(3,4-d)pyrimidine analogues of isoguanosine and i-methylisoguanosine has been synthesised. All compounds were tested forAi adenosine receptor affinity using a (311) R-PIA competitive binding assay. The N-i and N-5 positions were substituted with a number of different ailcyl and aryi groups. 3-Chiorophenyl substitution of the N-i position and butyl substitution of the N-5 position greatly enhanced the overall adenosine receptor affinity. Substitution by a methyl group at the N-7 position fixed the C-4 position in the imino tautomeric form. This resulted in a marked reduction in activity. The substitution of the N-2 position with a phenyl group produced an analogue with a similar structure to i,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine (PACPX). A 2-phenyl substituent was favourable for interaction with the adenosine receptor. A number of pyrazolo(3,4-d)pyrirnidine analogues of 4,6-bis-a-carbamoylethylthio-i-phenylthiopyrazolo(3,4-d)pyrinhidine (DJB-KK) has also been synthesised and tested for Aj adenosine receptor affinity. 4,6-Bis-alkylthio-1-phenylpyrazolo(3,4-d)pyrimidines with a-carbamoylethyl and u-carbamoylpropyi groups were compared. The additional methyiene of the a-carbamoylpropyl group produced increased adenosine receptor affinity. 6-a-Carbamoylethylthio-4-mercapto-1-phenylpyrazolo(3,4-d)pyrimidine and 4-cc-carbamoylethylthio- i-phenylpyrazolo(3,4-dlpyrimidine were compared. Substitution of the C-6 position maintained activity, while substitution of the C-4 reduced activity.

The goal of this project is to synthesize and purify a library of novel 4-alkyl-3,5-diamino-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazoles. These molecules are similar to other fiproles, which have been shown by Sammelson et al. to have pesticidal activities at the GABA receptor.' Fiproles are analogues of Fipronil, a very important pesticide. Replacing the cyano group normally located at the 3-position of the pyrazole ring with an amino group will change the binding potency of the phenylpyrazoles. Changes in binding produced by the changes introduced in molecular structure can create more information about the GABA receptor.Synthesis of our target compounds starts with production of monosubstituted malononitriles. Conventionally a two-step process, our research developed a new, efficient one-step process using borohydride as the only reagent. We utilized this method in the synthesis of desired monosubstituted malononitriles. These were converted to unsymmetrical disubstituted malononitriles, and to our target fiprole compounds, through a 4-alkyl-3,5-diaminopyrazole intermediate. / Department of Chemistry

Thesis (Ph.D.)--McMaster University (Canada), 1992. / Source: Dissertation Abstracts International, Volume: 54-08, Section: B, page: 4161. Adviser: John Warkentin.

A series of mononuclear complexes of general formula [M(η5-C5Me5)Cl3-n(pzH)n](n-1)+ (n = 1,2) has been prepared as a result of an investigation of the reactivity of pyrazole with rhodium and iridium cyclopentadienyl and pentamethyl-cyclopentadienyl precursors. These complexes are discussed in terms of the dynamic processes that are exhibited in the 1H NMR experiment and in terms of their use as precursors to dimeric species. Dinuclear complexes of formula [M(η5-C5R5)Cl(μ-pz)]2 containing pyrazolyl bridges have been prepared from the mononuclear compounds and from the chloro-bridged dimers of formula [M(η5-C5R5)Cl2]2 by treatment with triethylamine, but not from the dipyrazole iridium cation [Ir(η5-C5Me5)Cl(pzH)2]+ 26 which has been found to be unreactive to this type of symmetrical dimer formation: the low reactivity is attributed to a relative non-lability of the pyrazole groups. The dimeric complexes have been shown to undergo a core conformational change upon chemical reduction or halide abstraction. The chair conformation of the pyrazolyl bridged complex [Rh(η5-C5ME5)Cl(μ-pz)]2 38 has been proven crystallographically. Chloride abstraction from 38 yields the binuclear product [(Rh(η5-C5ME5)(μ-pz))2(μ-Cl)]BF4 46 which is bridged by two pyrazolyl and one chloride ligand and has been structurally characterized by X-ray diffraction to contain a boat conformation for the pyrazolyl framework. Reduction of either 38 or the C5H5 analogue 40 results in the metal-metal bonded dinuclear complexes [Rh(η5-C5ME5)(μ-pz)]2 48 and 49. The C5H5 complex 49 has been crystallographically determined to possess the boat conformation. The reactivity of the metal-metal bonded products has been investigated: one and two fragment addition is discussed and a number of oxidative addition products have been structurally characterized. The mononuclear dipyrazole iridium cation 26 which contains non-labile pyrazole groups is utilized to prepare mixed-metal and mixed-oxidation state dimers with the formula [Ir(η5-C5Me5)Cl(μ-pz)MLn]. The synthesis and potential for further investigation of these complexes is discussed. / Graduate

M.Sc. (Chemistry) / Compounds 2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl diphenlyphosphinite (L1), 2-(3,5-di-tert-butyl-1H-pyrazol-1-yl)ethyl diphenlyphosphinite (L2), 2-(3,5-diphenyl-1H-pyrazol-1-yl)ethyl diphenylphosphinite (L3), 2-(3,5-di-tert-butyl-1H-pyrazol-1-yl)ethyl diethylphosphite (L4), 2-(3,5-di-tert-butyl-1H-pyrazol-1-yl)ethyl diethylphosphite (L5) and 2-(3,5-diphenyl-1H-pyrazol-1-yl)ethyl diethylphosphite (L6) were synthesized and characterized by 1H NMR, 31P{1H} NMR and 13C{1H} NMR spectroscopy. Reactions of L1–L6 with [Ru(p-cymene)Cl2]2 in 2:1 ratio formed six neutral complexes, [Ru(p-cymene)Cl2(L1)] (1), [Ru(p-cymene)Cl2(L2)] (2), [Ru(p-cymene)Cl2(L3)] (3), [Ru(p-cymene)Cl2(L4)] (4), [Ru(p-cymene)Cl2(L5)] (5) and [Ru(p-cymene)Cl2(L6)] (6). The neutral complexes 1–6 were converted to salts of the general formula [Ru(p-cymene)ClL]X and [NaRu(p-cymene)Cl2L]X {X = BArF- or BPh4-} (1a,1b, 2a, 2b, 3a, 4a, 4b, 5a, 5b, and 6a) by reaction of complexes 1–6 with NaBArF (BArF = 3,5-CF3(C6H3) and/or NaBPh4 in 1:1 ratio. Neutral and ruthenium complexes and their salts were characterized by a combination of 1H, 31P{1H} and 13C{1H} NMR spectroscopy, mass spectrometry, elemental analysis and in selected cases by single crystal X-ray crystallography.

M.Sc. / Six pyrazole and pyrazolyl compounds, 3,5-dimethylpyrazole (L1), 3,5-diphenylpyrazole (L2), 3,5-di-tert-butylpyrazole (L3), bis(3,5-dimethylpyrazol-1-yl)methane (L4), bis(3,5-diphenylpyrazol-1-yl)methane (L5) and bis(1,2-bis{(3,5-dimethylpyrazol-1-yl)methyl}benzene (L6), were reacted with Zn(II) and Cu(II) benzoates to form pyrazole and pyrazolyl metal benzoates. The complexes are [Zn(C6H5COO)2(L1)2] (1), [Zn(3,5-NO2-C6H3COO)2(L1)2] (2), [Zn(4-OH-C6H4COO)2(L1)2] (3), [Zn(2-Cl-C6H4COO)2(L1)2] (4), [Zn(C6H5COO)2(L2)2] (5), [Zn(3,5-NO2-C6H3COO)2(L2)2] (6), [Zn(4-OH-C6H4COO)2(L2)2] (7), [Zn(2-Cl-C6H4COO)2(L2)2] (8), [Zn(3,5-NO2-C6H3COO)2L4] (9), [Zn(4-OH-C6H4COO)2L6] (10), [Zn2(C6H5COO)4L6]n (11), [Zn(3,5-NO2-C6H3COO)2L6] (12), [Zn(2-Cl-C6H4COO)2L6] (13), [Cu(C6H5COO)2(L1)2] (14), [Cu(3,5-NO2-C6H3COO)2(L1)2] (15), [Cu(4-OH-C6H4COO)2(L1)2] (16), [Cu(2-Cl-C6H4COO)2(L1)2] (17), [Cu(C6H5COO)2(C6H5COOH)]2 (18), [Cu(2-Cl-C6H4COO)2(L3)2] (19), [Cu(C6H5COO)2L4] (20), [Cu(2-Cl-C6H4COO)2L4] (21), [Cu(C6H5COO)2DMSO]2 (22), [Cu(C6H5COO)2L6]2 (23), [Cu(2-Cl-C6H4COO)2L6]2n (24), [Cu(4-OH-C6H4COO)2L6]2(25) and [Cu(3,5-NO2-C6H3COO)2L6]n (26). The molecular structures of the Zn(II) and Cu(II) complexes 6, 9, 11, 14, 17-19, 22-26 were determined by X-ray diffraction studies that revealed four types of geometries adopted by these complexes: (i) 4-coordinate tetrahedral (6, 9, 14), (ii) 6-coordinate octahedral (17), (iii) paddle wheel (18, 19, 22, 23, 25) and (iv) polymeric structures (11, 24, 26). Catalysis studies performed with selected complexes (1-4, 9-17, 23-26) revealed that they initiate the ring opening polymerization (ROP) of ε-caprolactone (ε-CL) and D,L-lactide at elevated temperatures, and under solvent-free conditions and in toluene respectively. Polycaprolactone (PCL) and poly(D,L-lactide) (PLA) produced were of moderate molecular weights (858-4 757 Da for PCL and 602-3 185 Da for PLA) and polydispersity indices (1.36-2.16 for PCL and 1.42-2.35 for PLA). End group of the iv polymers, determined by MALDI-TOF MS, were benzoates, hydroxyl, methoxy groups and cyclic. From the 13C{1H} NMR spectra of polymers synthesized, the stereochemistry of PLA was predominantly isotactic.

M.Sc. (Chemistry) / The main aim of this study was to use pyrazolyl-based bi-and tri-dentate ligands in the synthesis of several p-cymene-ruthenium complexes. These ruthenium complexes and their corresponding ligands were subsequently tested for their anticancer and antimalarial activities...

A versatile method for the reduction of 2-pyrazolines was developed in this research. In every reduction attempt, aluminum trihydride successfully reduced the carbonnitrogen double bond. Since carbon-carbon double bonds were stable to aluminum trihydride, the preparation of 3-vinyl1-pyrazolines by a new synthetic route became possible. Using this method, 3,3-dimethyl-5-(1-isobutenyl)-1-pyrazoline was prepared. This compound was thermalytically decomposed, and the products of the decomposition were determined.In the course of this research, a one-step method for the preparation of cyclopropanes in high yield from 2pyrazolines was uncovered, but not fully developed. A new route to alpha-gamma-diamino compounds was also accomplished with the use of aluminum trihydride.Ball State UniversityMuncie, IN 47306

The synthesis and characterization of the 1-pyrazolines produced from the addition of diazomethane to maleic anhydride, citraconic anhydride, isoprene, norbornene, and norbornadiene was carried out. This was followed by the thermal decomposition of the synthesised 1-pyrazolines. The thermal decomposition of the 1-pyrazolines proceded by the loss of nitrogen to yield both the expected cyclopropanes and olefins, as well as cyclic reversion products in the case of the mono- and disubstituted norbornadiene adducts.Ball State UniversityMuncie, IN 47306