Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “IMINES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1986

Reactions of N-acetyl-p-benzoquinone imine with reduced glutathione, acetaminophen, and NADPH.

Synthetic N-acetyl-p-benzoquinone imine reacted with reduced glutathione (GSH), [14C]acetaminophen, and NADPH. It reacted rapidly with GSH to yield acetaminophen (33%) and 3-(glutathion-S-yl)acetaminophen (67%), and with acetaminophen or NADPH to yield acetaminophen polymers. The data suggested that N-acetyl-p-benzoquinone imine was reduced by GSH to form acetaminophen but primarily reacted with GSH to form 3-(glutathion-S-yl)acetaminophen. The evidence further suggested that N-acetyl-p-benzoquinone imine comproportionated with [14C]acetaminophen to yield a mixture of radioactive and nonradioactive N-acetyl-p-benzosemiquinone imine which subsequently formed acetaminophen polymers by a radical coupling reaction. [14C]Acetaminophen was incorporated into the acetaminophen polymers. The amount of 14C incorporation was dependent on the initial concentration of [14C]acetaminophen and N-acetyl-p-benzoquinone imine. An increase in the ratio of [14C]acetaminophen to N-acetyl-p-benzoquinone imine resulted in an increase in [14C] acetaminophen incorporation into the acetaminophen polymers. NADPH reduced N-acetyl-p-benzoquinone imine to acetaminophen and acetaminophen polymers were formed. When [14C]N-acetyl-p-benzoquinone imine was incubated without acetaminophen, only minor amounts of acetaminophen polymerization were observed.

Acetaminophen↗
PubMed2000

Catalytic enantioselective aza-Diels-alder reactions of imines--an approach to optically active nonproteinogenic alpha-amino acids

A catalytic enantioselective aza-Diels-Alder reaction of imines has been developed. The reaction of N-tosyl alpha-imino ester with different dienes including activated, non-activated, cyclic, and acyclic dienes has been investigated in the presence of various chiral Lewis acids. A series of phosphino-oxazoline ligands have been synthesized and evaluated for the reaction. It was found that the combination of phosphino-oxazoline ligands with copper(I) salts gives the best results for the activated dienes, while BINAP-copper(I) complexes are good catalysts for all the dienes studied. In the case of activated acyclic dienes the aza-Diels-Alder products can be obtained in higher than 80% isolated yield and 96% ee, while for the unactivated cyclic dienes the exo diastereomer is formed as the major product in up to 95 % ee. For an activated cyclic conjugated diene, 2-trimethylsilyloxy-1,3-cyclohexadiene, the reaction proceeds as a Mannich-type addition reaction giving optically active gamma-oxo alpha-amino acid derivatives in good yields and up to 96% ee. The reaction of an unactivated acyclic diene, 2,3-dimethyl-1,3-butadiene, with the N-tosyl alpha-imino ester gives both the aza-Diels-Alder and aza-ene products, in a ratio of 9:1 favoring the aza-Diels-Alder product. Furthermore, a series of different imines have been synthesized and investigated as possible substrates for the present catalytic enantioselective aza-Diels-Alder reaction in order to obtain mechanistic insight. All imines studied gave moderate to high ee. Particularly, the reaction of the N-phenyl and N-p-methoxyphenyl substituted glyoxylate imines with Danishefsky's diene proceeded well affording the corresponding aza-Diels-Alder product in high yield with up to 91% ee at room temperature. The present catalytic enantioselective reaction of imines provided an effective route to optically active nonproteinogenic alpha-amino acids. The products of the catalytic enantioselective aza-Diels-Alder reaction of the cyclic dienes can be used for the preparation of key compounds such as natural products and compounds of pharmaceutical interest. The absolute configurations of five products have been solved by X-ray structural analysis, and it is found that the absolute configuration of the aza-Diels-Alder adduct is dependent on the substituent on the imine nitrogen atom. It turned out that the N-tosyl glyoxylate imine and N-p-methoxyphenyl glyoxylate imine give the aza-Diels-Alder adduct with opposite absolute configuration using the same enantiomer of the catalyst. On the basis of the results the mechanistic aspects for the reactions are discussed.

Journal Article↗
PubMed1986

Mutagenicity of N-substituted phenanthrene 9,10-imines in Salmonella typhimurium and Chinese hamster V79 cells.

We previously showed that some (nonsubstituted) aziridines derived from polycyclic aromatic hydrocarbons (arene imines) elicit various mutagenic and genotoxic effects in bacteria and mammalian cells and that these arene imines are active at much lower concentrations than the corresponding epoxide analogues. In the present study, N-substituted derivatives of phenanthrene 9,10-imine were investigated. All 10 derivatives studied showed direct mutagenicity in Salmonella typhimurium TA100. Some of the compounds additionally exhibited weak effects in the strains TA98 and TA1537. Most N-substituted derivatives were weaker mutagens than unsubstituted phenanthrene 9,10-imine but stronger mutagens than phenanthrene 9,10-oxide. Bulky substituents reduced the mutagenicity more than did small substituents. In addition, the derivatives with electron-withdrawing substituents (with the exception of N-chlorophenanthrene 9,10-imine) were weaker mutagens than those with electron-donating substituents. Phenanthrene 9,10-imine and five N-substituted derivatives were investigated to determine whether they induce gene mutations at the hgprt locus in V79 cells. Four compounds, including the parent aziridine, were positive in the V79 test. The other two compounds were negative. The mutagenic potencies in the V79 cell system did not correlate well with those obtained with the Salmonella system. Overall, the study shows that in addition to unsubstituted arene imines, N-substituted derivatives are mutagenic. This finding is of interest, as metabolic pathways leading from aromatic compounds to N-substituted arene imines are conceivable.

Animals↗
PubMed1987

Mechanisms of acetaminophen oxidation to N-acetyl-P-benzoquinone imine by horseradish peroxidase and cytochrome P-450.

Horseradish peroxidase rapidly catalyzed the H2O2-dependent polymerization of acetaminophen. Acetaminophen polymerization was decreased and formation of GSSG and minor amounts of GSH-acetaminophen conjugates were detected in reaction mixtures containing GSH. These data suggest that horseradish peroxidase catalyzed the 1-electron oxidation of acetaminophen and that GSH decreased polymerization by reducing the product, N-acetyl-p-benzosemiquinone imine, back to acetaminophen. Analyses of reaction mixtures that did not contain GSH showed N-acetyl-p-benzoquinone imine formation shortly after initiation of reactions. When GSH was added to similar reaction mixtures at various times, 3-(glutathion-S-yl)-acetaminophen was formed. The formation and disappearance of this product were very similar to N-acetyl-p-benzoquinone imine formation and were consistent with the disproportionation of 2 mol of N-acetyl-p-benzosemiquinone imine to 1 mol of N-acetyl-p-benzoquinone imine and 1 mol of acetaminophen followed by the rapid reaction of N-acetyl-p-benzoquinone imine with GSH to form 3-(glutathion-S-yl)acetaminophen. When acetaminophen was incubated with NADPH, oxygen and hepatic microsomes from phenobarbital-pretreated rats, 1.2 nmol 3-(glutathion-S-yl)acetaminophen/nmol cytochrome P-450/10 min was formed. Formation of polymers was not observed indicating that N-acetyl-p-benzoquinone imine was formed via an overall 2-electron oxidation rather than a disproportionation reaction. However, when cumene hydroperoxide was replaced by NADPH in microsomal incubations, polymerization was observed suggesting that cytochrome P-450 might also catalyze the 1-electron oxidation of acetaminophen.

Acetaminophen↗
PubMed1980

Studies on the mechanism of toxicity of acetaminophen. Synthesis and reactions of N-acetyl-2,6-dimethyl- and N-acetyl-3,5-dimethyl-p-benzoquinone imines.

N-Acetyl-2,6-dimethyl-p-benzoquinone imine and N-acetyl-3,5-dimethyl-p-benzoquinone imine were prepared from 2,6-dimethylacetaminophen and 3,5-dimethylacetaminophen by oxidation with lead tetraacetate. Reaction of N-acetyl-2,6-dimethyl-p-benzoquinone imine with hydrochloric acid gave 3'-chloro-2',6'-dimethyl-4'-hydroxyacetanilide, whereas ethanethiol, aniline, and ethanol gave tetrahedral adducts resulting from addition to the imine carbon. Water gave 2,6-dimethyl-p-benzoquinone. With N-acetyl-3,5-dimethyl-p-benzoquinone imine, water and aniline gave substitution on the imine carbon, yielding 2,6-dimethyl-p-benzoquinone and 3,5-dimethyl-N-phenyl-p-benzoquinone imine, respectively. Ethanethiol gave 3'.5'-dimethyl-2'-(ethylthio)-4'-hydroxyacetanilide. The toxicity of 2,6-dimethylacetaminophen and 3,5-dimethylacetaminophen was examined histologically in mice and rats. 3,5-Dimethylacetaminophen was slightly more nephrotoxic but showed a similar hepatotoxicity to acetaminophen. 2,6-Dimethylacetaminophen, like N-methylacetaminophen, showed very little tissue damage.

Acetaminophen↗
PubMed2002

Intracellular processing of poly(ethylene imine)/ribozyme complexes can be observed in living cells by using confocal laser scanning microscopy and inhibitor experiments.

PURPOSE: Critical steps in the subcellular processing of poly(ethylene imine)/nucleic acid complexes, especially endosomal/lysosomal escape, were visualized by using living cell confocal laser scanning microscopy (CSLM) to obtain an insight into their mechanism. METHODS: Living cell confocal microscopy was used to examine the intracellular fate of poly(ethylene imine)/ribozyme and poly(L-lysine)/ribozyme complexes over time, in the presence of and without bafilomycin Al, a selective inhibitor of endosomal/lysosomal acidification. The compartment of complex accumulation was identified by confocal microscopy with a fluorescent acidotropic dye. To confirm microscopic data, luciferase reporter gene expression was determined under similar experimental conditions. RESULTS: Poly(ethylene imine)/ribozyme complexes accumulate in acidic vesicles, most probably lysosomes. Release of complexes occurs in a sudden event, very likely due to bursting of these organelles. After release, poly(ethylene imine) and ribozyme spread throughout the cell, during which slight differences in distribution between cytosol and nucleus are visible. No lysosomal escape was observed with poly(L-lysine)/ribozyme complexes or when poly(ethylene imine)/ ribozyme complexes were applied together with bafilomycin A1. Poly(ethylene imine)/plasmid complexes exhibited a high luciferase expression, which was reduced approximately 200-fold when lysosomal acidification was suppressed with bafilomycin A1. CONCLUSIONS: Our data provide, for the first time, direct experimental evidence for the escape of poly(ethylene imine)/nucleic acid complexes from the endosomal/lysosomal compartment. CLSM, in conjunction with living cell microscopy, is a promising tool for studying the subcellular fate of polyplexes in nucleic acid/gene delivery.

Animals↗
PubMed1985

Arene imines, a new class of exceptionally potent mutagens in bacterial and mammalian cells.

K-region aziridines of polycyclic aromatic hydrocarbons reverted Salmonella typhimurium his- (TA100, TA98) and Escherichia coli trp- strains (WP2 uvrA), without requiring activation by mammalian enzymes. The number of revertants induced per nmol in S. typhimurium TA 100, the most responsive strain, variea from 6 to 10,000 for the seven monoaziridines and the two bisaziridines tested. Interestingly, the mutagenic potencies (y) of the monoaziridines were closely related (r = 0.984) with those of the corresponding epoxide analogues (x) by the equation y = 19.6 X0.97, i.e., the aziridines were about 20-fold stronger mutagens than were the epoxides. One of the aziridines, benzo(a)pyrene (BP)-4,5-imine, was investigated in several additional mutagenicity test systems: toxicity in DNA repair-deficient (rec-) and -proficient (rec+) Bacillus subtilis strains; induction of 6-thioguanine resistance in V79 Chinese hamster cells; and induction of sister chromatid exchanges in cultured human fibroblasts. In all systems, BP-4,5-imine was much more active than the epoxide analogue, BP-4,5-oxide. The difference in activity was particularly large in the two test systems with mammalian target cells in which several hundredfold higher concentrations of the epoxide had to be used in order to elicit equipotent effects. Even r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydro-BP, which is one of the most potent mutagens known for V79 cells, was less active in the mammalian cells than was BP-4,5-imine. One reason that arene imines are such potent mutagens may be that they are poorly detoxified. Addition of highly purified microsomal epoxide hydrolase, which strongly reduced the mutagenicity of BP-4,5-oxide and benz(a)anthracene-5,6-oxide in S. typhimurium, had no effect on the mutagenicity of the corresponding aziridines. Furthermore, while benz(a)anthracene-5,6-oxide was inactivated by highly purified cytosolic epoxide hydrolase, benz(a)anthracene-5,6-imine was not inactivated. It is noteworthy that the arene imines are isomeric with and structurally closely related to aromatic amines. Some aziridines derived from nonaromatic structures (ethylene imines) have been reported as metabolites of xenobiotics; others are used as chemotherapeutics. At present, however, the results are mainly of theoretical interest in that a new type of arene derivatives with exceptionally potent, probably ultimate, mutagenicity was discovered and may be exploited for the study of mechanisms of chemical carcinogenesis.

Animals↗
PubMed2003

Theoretical study concerning the reactivity of imine derivatives of polycyclic aromatic hydrocarbons.

The opening reaction of N-protonated polycyclic aromatic hydrocarbon imines has been computed by means of ab initio, density functional, and semiempirical methods of calculation. Imines are predicted to be more stable than the corresponding O-protonated derivatives, epoxides and diol epoxides. On the other hand, the activated N-methanesulfonylbenzene imine presented more favorable DeltaE( not equal ) and DeltaE(r) for ring opening due to the effect of hydrogen-bond interactions. Anti and syn trans-diol benzene imines did not show a different behavior from the unsubstituted imine. According to these calculations, bay-region, fjord-region, and bay-region methyl-substituted compounds opened more easily among the imine derivatives, following the same reactivity pattern as the oxygen analogs. The exothermicity of the opening process correlated with the charge delocalization in the resulting carbocation.

Carcinogens↗
PubMedDate not supplied

A novel ternary ligand system for 99mTc-labeling of hydrazino nicotinamide-modified biologically active molecules using imine-N-containing heterocycles as coligands.

A hydrazinonicotinamide-functionalized cyclic platelet glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonist [HYNICtide, cyclo(D-Val-NMeArg-Gly-Asp-Mamb(5-(6-(6-hydrazinonicotina mido)hexanamide)))] was labeled with 99mTc using tricine and a series of imine-N-containing heterocycles as coligands. The imine-N-containing heterocycles include N-omega-Acetylhistamine (HIS-AC), N-(2-hydroxyethyl)isonicotinamide (ISONIC-HE), isonicotinic acid (ISONIC), isonicotinoyl-L-aspartic acid dimethyl ester (ISONIC-L-Asp-OMe2), 4-methyl-5-thiazoleethanol (MTE), nicotinic acid (NIC), 3-nitro-1,2,4-triazole (NTZ), 4-pyridylacetic acid (PA), 4-pyridineethanesulfonic acid (PES), and 3-pyridinesulfonic acid (PSA). The synthesis of these new ternary ligand [99mTc]HYNICtide complexes can be performed in one or two steps in high yield and high specific activity (>/=10 000 Ci/mmol HYNICtide). For example, the reaction of HYNICtide, [99mTc]pertechnetate, nicotinic acid, stannous chloride, and tricine at pH approximately 5 and 100 degreesC for 20 min results in the complex [99mTc(HYNICtide)(tricine)(NIC)] in >/=90% yield as determined by radio-HPLC. It was found that ternary ligand technetium complexes, [99mTc(HYNICtide)(tricine)(L)] (L = ISONIC, ISONIC-L-Asp-OMe2, ISONIC-HE, MTE, PA, PES, and PSA) are formed as equal mixtures of two isomeric forms. Complex [99mTc(HYNICtide)(tricine)(L)] (L = HIS-AC and NTZ) showed more than two well-resolved radiometric peaks at the retention times of interest, suggesting that they may have more than two forms in solution due to different bonding modalities of HIS-AC and NTZ. By a chirality experiment, it was found that the presence of two radiometric peaks is a result of the resolution of the two diastereomers which are formed by the combination of the chiral HYNICtide and the chiral technetium chelate. The formation of two diastereomers was also observed when a chiral imine-N-containing coligand was used for the radiolabeling of HYNIC-BA. The new ternary ligand [99mTc]HYNICtide complexes were found to be stable for up to 6 h in the reaction mixture. The high solution stability is attributed to their kinetic inertness. The composition of these complexes was determined to be 1:1:1:1 for Tc:HYNICtide:L:tricine (L = imine-N-containing heterocycles) through a series of mixed ligand experiments on the tracer (99mTc) level. The lipophilicity of the ternary ligand [99mTc]HYNICtide complexes can be systematically varied by the choice of polyaminocarboxylate and imine-N-containing coligands. Using the combination of tricine and an imine-N-containing coligand, HYNIC-derivatized peptides or other small molecules can be labeled with 99mTc in high specific activity and high stability for potential use as radiopharmaceuticals.

Chromatography, High Pressure Liquid↗
PubMed1985

Formation of 4-aminophenoxyl free radical from the acetaminophen metabolite N-acetyl-p-benzoquinone imine.

N-Acetyl-p-benzoquinone imine, a hepatic metabolite of acetaminophen, and its analogue, N-acetyl-3,5-dimethyl-p-benzoquinone imine, were metabolized by rat liver microsomes and NADPH to their corresponding 4-aminophenoxyl free radicals. ESR spectra were recorded and unambiguously identified. As indicated by the purple color and confirmed by UV and mass spectroscopy, indophenols were formed as final products. The 4-aminophenoxyl free radical formation could be suppressed by the deacetylase inhibitors, sodium fluoride and paraoxon. Microsomal incubations of N-acetyl-2,6-dimethyl-p-benzoquinone imine and NADPH do not result in a detectable radical concentration; in addition, no indophenol was found. Substitution of NADPH-cytochrome P-450 reductase for rat liver microsomes eliminates the deacetylase activity and results in direct reduction of N-acetyl-3,5-dimethyl-p-benzoquinone imine to the N-acetyl-2,6-dimethyl-4-aminophenoxyl free radical. Neither the incubation of N-acetyl-p-benzoquinone imine nor that of N-acetyl-2,6-dimethyl-p-benzoquinone imine with NADPH-cytochrome P-450 reductase yielded a detectable concentration of the corresponding phenoxyl free radical. When starting material that had been exposed to the atmosphere was used, a previously reported free radical with a splitting constant of approximately 2 G was formed. This spectrum is identical with that of the 2,6-dimethyl-p-benzosemiquinone free radical, implying hydrolysis of the starting material. Neither the N-acetyl-4-aminophenoxyl nor the N-acetyl-2,6-dimethyl-4-aminophenoxyl radical reduces oxygen to form superoxide or react with oxygen in any other detectable way.

Animals↗
PubMed2000

Catalytic Asymmetric Hetero-Diels-Alder Reactions of Carbonyl Compounds and Imines.

Asymmetric catalysis is a challenge for chemists: How can we design catalysts to achieve the goal of forming optically active compounds? This review provides the reader with an overview of the development of catalytic asymmetric hetero-Diels-Alder reactions of carbonyl compounds and imines. Since its discovery, the Diels-Alder reaction has undergone intensive development and is of fundamental importance for synthetic, physical, and theoretical chemists. The Diels-Alder reaction has been through different stages of development, and at the beginning of the 21st century catalytic Diels-Alder reactions are one of the main areas of focus. The preparation of numerous compounds of importance for our society is based on cycloaddition reactions to carbonyl compounds and imines. There are several parallels between the reactions of carbonyl compounds and those of imines, which, however, begin to vanish on entering the field of catalytic reactions. Why? From a mechanistic point of view some similarities can be drawn, but the synthetic development of catalytic enantioselective hetero-Diels-Alder reactions of imines are several years behind those of the carbonyl compounds. For hetero-Diels-Alder reactions of carbonyl compounds there a number of different chiral catalysts, and great progress has been achieved in developing enantioselective reactions for unactivated and activated carbonyl compounds. In contrast the development of catalytic enantioselective hetero-Diels-Alder reactions of imines is in its infancy and only few catalytic reactions have been published. This review will focus on the most important developments, and discuss the synthetic and mechanistic aspects of enantioselective hetero-Diels-Alder reactions of carbonyl compounds catalyzed by chiral Lewis acids. For the hetero-Diels-Alder reactions of imines, the diastereoselective reactions of optically substrates catalyzed by Lewis acids will be presented first, followed by the catalytic enantioselective reactions.

Journal Article↗
PubMed2002

Living polymerization of ethylene catalyzed by titanium complexes having fluorine-containing phenoxy-imine chelate ligands.

Seven titanium complexes bearing fluorine-containing phenoxy-imine chelate ligands, TiCl(2)[eta(2)-1-[C(H)=NR]-2-O-3-(t)Bu-C(6)H(3)](2) [R = 2,3,4,5,6-pentafluorophenyl (1), R = 2,4,6-trifluorophenyl (2), R = 2,6-difluorophenyl (3), R = 2-fluorophenyl (4), R = 3,4,5-trifluorophenyl (5), R = 3,5-difluorophenyl (6), R = 4-fluorophenyl (7)], were synthesized from the lithium salt of the requisite ligand and TiCl(4) in good yields (22%-76%). X-ray analysis revealed that the complexes 1 and 3 adopt a distorted octahedral structure in which the two phenoxy oxygens are situated in the trans-position while the two imine nitrogens and the two chlorine atoms are located cis to one another, the same spatial disposition as that for the corresponding nonfluorinated complex. Although the Ti-O, Ti-N, and Ti-Cl bond distances for complexes 1 and 3 are very similar to those for the nonfluorinated complex, the bond angles between the ligands (e.g., O-Ti-O, N-Ti-N, and Cl-Ti-Cl) and the Ti-N-C-C torsion angles involving the phenyl on the imine nitrogen are different from those for the nonfluorinated complex, as a result of the introduction of fluorine atoms. Complex 1/methylalumoxane (MAO) catalyst system promoted living ethylene polymerization to produce high molecular weight polyethylenes (M(n) > 400 000) with extremely narrow polydispersities (M(w)/M(n) < 1.20). Very high activities (TOF > 20 000 min(-1) atm(-1)) were observed that are comparable to those of Cp(2)ZrCl(2)/MAO at high polymerization temperatures (25, 50 degrees C). Complexes 2-4, which have a fluorine atom adjacent to the imine nitrogen, behaved as living ethylene polymerization catalysts at 50 degrees C, whereas complexes 5-7, possessing no fluorine adjacent to the imine nitrogen, produced polyethylenes having M(w)/M(n) values of ca. 2 with beta-hydrogen transfer as the main termination pathway. These results together with DFT calculations suggested that the presence of a fluorine atom adjacent to the imine nitrogen is a requirement for the high-temperature living polymerization, and the fluorine of the active species for ethylene polymerization interacts with a beta-hydrogen of a polymer chain, resulting in the prevention of beta-hydrogen transfer. This catalyst system was used for the synthesis of a number of unique block copolymers such as polyethylene-b-poly(ethylene-co-propylene) diblock copolymer and polyethylene-b-poly(ethylene-co-propylene)-b-syndiotactic polypropylene triblock copolymer from ethylene and propylene.

Journal Article↗
PubMed2006

Stereoselective alkylation of alpha,beta-unsaturated imines via C-H bond activation.

The stereoselective alkylation of alpha,beta-unsaturated imines via C-H activation followed by imine hydrolysis produces tri- and tetrasubstituted alpha,beta-unsaturated aldehydes. In the presence of a rhodium catalyst, alpha,beta-unsaturated N-benzyl imines derived from methacrolein, crotonaldehyde, and tiglic aldehyde undergo directed C-H activation at the beta-position and react with terminal alkenes and alkynes to form the tri- and tetrasubstituted alpha,beta-unsaturated imines with very high stereoselectivity. Hydrolysis to provide alpha,beta-unsaturated aldehydes can be performed under carefully controlled conditions that maintain the stereochemistry of the beta-alkylated imine products. Alternatively, for beta-alkylation products of the N-benzyl imine of methacrolein, hydrolysis can be performed under conditions that provide complete isomerization to the E isomer.

Alkylation↗
PubMed2000

Zirconium-mediated metathesis of imines: a study of the scope, longevity, and mechanism of a complicated catalytic system.

By kinetically stabilizing imidozirconocene complexes through the use of a sterically demanding ligand, or by generating a more thermodynamically stable resting state with addition of diphenylacetylene, we have developed transition metal-catalyzed imine metathesis reactions that are mechanistically analogous to olefin metathesis reactions catalyzed by metal carbene complexes. When 5 mol % of Cp*Cp(THF)Zr=N(t)Bu is used as the catalyst precursor in the metathesis reaction between PhCH=NPh and p-TolCH=N-p-Tol, a 1:1:1:1 equilibrium mixture with the two mixed imines p-TolCH=NPh and PhCH=N-p-Tol is generated in C(6)D(6) at 105 degrees C. The catalyst was still active after 20 days with an estimated 847 turnovers (t(1/2) 170 m; TON = 1.77 h(-1)). When the azametallacyclobutene Cp(2)Zr(N(Tol)C(Ph)=C(Ph)) is used as the catalyst precursor under similar reaction conditions, a total of 410 turnovers are obtained after 4 days (t(1/2) 170 m; TON = 4.3 h(-1)). An extensive kinetic and equilibrium analysis of the metallacyclobutene-catalyzed metathesis of PhCH=N-p-Tol and p-F-C(6)H(4)CH=N-p-F-C(6)H(4) was carried out by monitoring the concentrations of imines and observable metal-containing intermediates over time. Numerical integration methods were used to fit these data to a detailed mechanism involving coordinatively unsaturated (16-electron) imido complexes as critical intermediates. Examination of the scope of reaction between different organic imines revealed characteristic selectivity that appears to be unique to the zirconium-mediated system. Several zirconocene complexes that could generate the catalytically active "CpCp'Zr=NAr" (Cp' = Cp or Cp*) species in situ were found to be effective agents in the metathetical exchange between different N-aryl imines. N-Alkyl aldimines were found to be completely unreactive toward metathesis with N-aryl aldimines, and metathesis reactions involving the two N-alkyl imines TolCH=NPr and PhCH=NMe gave slow or erratic results, depending on the catalyst used. Metathesis was observed between N-aryl ketimines and N-aryl aldimines, but for N-aryl ketimine substrates, the catalyst resting state consists of zirconocene enamido complexes, generated by the formal C-H activation of the alpha position of the ketimine substrates.

Journal Article↗
PubMed2004

Proton as the simplest of all catalysts for [2 + 2] cycloadditions: DFT study of acid-catalyzed imine metathesis.

The mechanism of imine metathesis was studied as a prototype reaction for the impact that heteroatom substitution has on thermally forbidden [2 + 2] addition reactions using high-level density functional theory in combination with a continuum solvation model. The intuitively expected high activation barriers were confirmed for N-alkyl- and N-aryl-substituted imine reactants with transition state free energies of 78.8 and 68.5 kcal/mol, respectively, in benzene. The computed reaction energy profiles were analyzed to discover possible strategies for lowering the transition state energy. Protonation of the imine nitrogen was proposed as a possible catalytic route and was explicitly modeled. The computed reaction energy profile shows that protonation of one of the imine reactants has an enormous effect on the overall rate of metathesis and lowers the activation barrier by as much as 37.3 and 30.6 kcal/mol for the N-alkyl and N-aryl reactants, respectively. These results suggest that acid-catalyzed imine metathesis should be amenable at elevated temperatures. Furthermore, the protonation of both reactants of the metathesis reaction is predicted to be not productive owing to electrostatic repulsion of the reactants, thus suggesting that there should be an optimum pH for the catalytic turnover. A detailed analysis of the catalytic mechanism is presented, and the primary driving force for the catalysis is identified. Upon protonation of the imine nitrogen, the key [2 + 2]-addition step becomes asynchronous and one of the two intermolecular N-C bonds is formed before traversing the transition state, resulting in a substantial net decrease of the overall energy requirement. The general applicability of this intuitively understandable mechanism for designing structural features for lowering the energy of transition state structures is explored.

Journal Article↗
PubMed2006

Synthesis of heteroaryl imines: theoretical and experimental approach to the determination of the configuration of C=N double bond.

The reaction between an iminophosphorane with furan-2-carbaldehyde, thiophene-2-carbaldehyde, furan-3-carbaldehyde, and thiophene-3-carbaldehyde at 60 degrees C gives the corresponding trans imines in 53-84% yields, while the same reaction at 100 degrees C gives a mixture of the corresponding trans and cis imines. Whether the iminophosphorane reacted with 5-nitrofuran-2-carbaldehyde or 5-nitrothiophene-2-carbaldehyde only the trans imines were obtained in 85-89% yields. The irradiation of the imines obtained from thiophene-2-carbaldehyde and thiophene-3-carbaldehyde gave the corresponding photocyclization products. Cis/trans stereochemistry of the imines can be assigned simulating the UV-vis spectra. In the case of the imine from furan-2-carbaldehyde the computed spectra are characterized by an intense absorption at 361 and 357 nm respectively for the trans-1 and trans-2 structures. No other absorptions of comparable intensity have been predicted: the agreement with the experimental spectrum can be considered good. Furthermore, the experimental weak peaks at 280 and 270 nm can be associated to the computed transitions at 278 and 260 nm for the trans-1 isomer. Several minima of the energy surface can be assigned to the cis isomer, and they all present a very similar energy. The structures of the cis-1 and cis-2 isomers present quite coincident computed electronic spectra. In both cases, the computed spectrum shows two principal features. For the cis-1 structure, the first characteristic absorption is located at 414 nm and the second one at 284 nm. For the cis-2 structure, the first feature is located at 412 nm and the second one at 286 nm. The second transition is computed somewhat more intense. The experimental spectrum could be the consequence of similar populations of the planar cis structure (cis-3) and nonplanar cis structures (cis-1, cis-2, and their enantiomers).

Journal Article↗
PubMed2002

Ruthenium-catalyzed transfer hydrogenation of imines by propan-2-ol in benzene.

Transfer hydrogenation of a variety of different imines to the corresponding amines by propan-2-ol in benzene catalyzed by [Ru2(CO)4(mu-H)(C4Ph4COHOCC4Ph4)] (1) has been studied. The reaction is highly efficient with turnover frequencies of over 800 per hour, and the product amines were obtained in excellent yields. A remarkable concentration dependence of propan-2-ol was observed when the reaction was run in benzene as cosolvent. An optimum was obtained at 24 equivalents of propan-2-ol to imine, and further increase of the propan-2-ol led to a dramatic decrease in rate. Also the use of polar cosolvents with 24 equivalents of propan-2-ol gave a low rate. It was found that ketimines react faster than aldimines and that electron-donating substituents on the imine increase the rate of the catalytic transfer hydrogenation. Electron-withdrawing substituents decreased the rate. An isomerization was observed with imines having an alpha-hydrogen at the N-alkyl substituent, which is in accordance with a mechanism involving a ruthenium-amine intermediate. It was demonstrated that the ruthenium-amine complex from alpha-methylbenzylamine, corresponding to the postulated intermediate, can replace 1 as catalyst in the transfer hydrogenation of imines. A primary deuterium isotope effect of kCH/CD = 2.7 +/- 0.25 was observed when 2-deuterio-propan-2-ol was used in place of propan-2-ol in the transfer hydrogenation of N-phenyl-(1-phenylethylidene)amine.

2-Propanol↗
PubMed2006

Conjecture: imines as unidirectional photodriven molecular motors-motional and constitutional dynamic devices.

Compounds containing the C==N group, such as imines and their derivatives, may undergo syn-anti isomerization by two different routes: 1) photochemically, by out-of-plane rotation around the carbon-nitrogen double bond through a "perpendicular" form, and 2) thermally, by in-plane nitrogen inversion through a "linear" transition state. When the two interconversions occur in sequence, a full, closed process is accomplished, restoring the initial state of the system along two different steps. In a chiral imine-type compound, for example, with an asymmetric center next to the C==N function, photoinduced rotation may be expected to occur in one sense in preference to the opposite one. Thus, photoisomerization followed by thermal isomerization in a chiral imine compound generates unidirectional molecular motion. Generally, imine-type compounds represent unidirectional molecular photomotors converting light energy into mechanical motion. As they are also able to undergo exchange of the carbonyl and amine partners, they present constitutional dynamics. Thus, imine-type compounds are double dynamic, motional, and constitutional devices.

Imines↗