Alkyl Ring Research Articles

Novel Copolymers of Styrene and Alkyl Ring‐Substituted Methyl 2‐Cyano‐3‐phenyl‐2‐propenoates

Electrophilic trisubstituted ethylene monomers, alkyl ring substituted methyl 2‐cyano‐3‐phenyl‐2‐propenoates, RC6H4CH˭C(CN)CO2CH3, where R is 2‐methyl, 3‐methyl, 4‐methyl, 4‐isopropyl, and 2,5‐dimethyl were synthesized by piperidine catalyzed Knoevenagel condensation of ring‐substituted benzaldehydes and methyl cyanoacetate, and characterized by CHN elemental analysis, IR, 1H and 13C NMR. Novel copolymers of the ethylenes and styrene were prepared at equimolar monomer feed composition by solution copolymerization in the presence of a radical initiator (AIBN) at 70°C. The composition of the copolymers was calculated from nitrogen analysis, and the structures were analyzed by IR, 1H and 13C NMR, GPC, DSC, and TGA. High Tg of the copolymers in comparison with that of polystyrene indicates a substantial decrease in chain mobility of the copolymer due to the high dipolar character of the trisubstituted ethylene monomer unit. The gravimetric analysis indicated that the copolymers decompose in the 260–400°C range.

Enantioselective Alkylative Ring Opening of Heterobicyclic Alkenes via Fesulphos Ligands

Enantioselective Alkylative Ring Opening of Heterobicyclic Alkenes via Fesulphos Ligands

Porphyrins with Exocyclic Rings. Part 21. Influence of Pyrrolic and Carbocyclic Ring Alkyl Substituents on the Synthesis of Porphyrins Bearing Six‐Membered Exocyclic Rings.

Abstract A series of 5-substituted 4,5,6,7-tetrahydroindoles were prepared by reacting 4-substituted cyclohexanones with phenylhydrazones derived from esters of acetoacetic acid under Knorr-type reaction conditions. Related 6,6-dimethyltetrahydroindoles were also prepared by reacting dimedone with oximes by the Knorr pyrrole syntheses, followed by selective reduction of the remaining ketone moiety with diborane. The substituted tetrahydroindoles were regioselectively oxidized with lead tetraacetate to give the related 7-acetoxy derivatives, and these reacted with 5-unsubstituted pyrrole esters to give pyrrolyltetrahydroindoles. In one case, a bromo substituent was used to protect the β-position of the pyrrole reactant. Cleavage of the benzyl ester protective groups with hydrogen over Pd/C, which also removes the bromo-protective group, gave four dipyrrole carboxylic acids. These were condensed with a dipyrrylmethane dialdehyde using the MacDonald ‘2+2’ condensation to give substituted porphyrins with six-membered exocyclic rings. These structures are useful for comparison to porphyrin samples found in organic-rich sediments such as oil shales and petroleum. The presence of methyl substituents on the six-membered ring for the tetrahydroindole precursors slightly decreases the yields for porphyrin synthesis, and this effect is enhanced when the system becomes more sterically crowded due to the presence of an ethyl group of the adjacent pyrrole ring. 5-Alkyl substituted tetrahydroindoles were also converted to tetrapropanoporphyrins via a cyclotetramerization procedure. The alkyl substituents again decreased the yields, although 5-alkyl substituents were found to have a far less deleterious effect than 6-alkyl groups. In addition to providing samples to help assign the vibrational spectra of geoporphyrin samples, these results demonstrate that highly substituted porphyrin systems can be prepared from tetrahydroindole derivatives.

Fesulphos-Palladium(II) Complexes as Well-Defined Catalysts for Enantioselective Ring Opening of Meso Heterobicyclic Alkenes with Organozinc Reagents

The air-stable and readily available cationic methyl palladium(II) complexes of planar chiral Fesulphos ligands [(Fesulphos)Pd(Me)(PhCN)]+ X- are highly efficient catalysts for the alkylative ring opening of oxa- and azabicyclic alkenes with dialkylzinc reagents, showing broad scope with regards to both the bicyclic substrate and the dialkylzinc reagent. Catalyst loading as low as 0.5 mol % is sufficient to achieve good yields and enantioselectivities ranging 94 --> 99% ee in most cases. {Fesulphos = (1-phosphino-2-sulfenylferrocene); X- = tetrakis[3,5-bis(trifluoromethyl)phenyl]borate or PF6(-)].} The origin of the high asymmetric induction has been rationalized by mechanistic studies combining computational calculations and X-ray structural analysis.

Porphyrins with exocyclic rings. Part 21: Influence of pyrrolic and carbocyclic ring alkyl substituents on the synthesis of porphyrins bearing six-membered exocyclic rings

A series of 5-substituted 4,5,6,7-tetrahydroindoles were prepared by reacting 4-substituted cyclohexanones with phenylhydrazones derived from esters of acetoacetic acid under Knorr-type reaction conditions. Related 6,6-dimethyltetrahydroindoles were also prepared by reacting dimedone with oximes by the Knorr pyrrole syntheses, followed by selective reduction of the remaining ketone moiety with diborane. The substituted tetrahydroindoles were regioselectively oxidized with lead tetraacetate to give the related 7-acetoxy derivatives, and these reacted with 5-unsubstituted pyrrole esters to give pyrrolyltetrahydroindoles. In one case, a bromo substituent was used to protect the β-position of the pyrrole reactant. Cleavage of the benzyl ester protective groups with hydrogen over Pd/C, which also removes the bromo-protective group, gave four dipyrrole carboxylic acids. These were condensed with a dipyrrylmethane dialdehyde using the MacDonald ‘2+2’ condensation to give substituted porphyrins with six-membered exocyclic rings. These structures are useful for comparison to porphyrin samples found in organic-rich sediments such as oil shales and petroleum. The presence of methyl substituents on the six-membered ring for the tetrahydroindole precursors slightly decreases the yields for porphyrin synthesis, and this effect is enhanced when the system becomes more sterically crowded due to the presence of an ethyl group of the adjacent pyrrole ring. 5-Alkyl substituted tetrahydroindoles were also converted to tetrapropanoporphyrins via a cyclotetramerization procedure. The alkyl substituents again decreased the yields, although 5-alkyl substituents were found to have a far less deleterious effect than 6-alkyl groups. In addition to providing samples to help assign the vibrational spectra of geoporphyrin samples, these results demonstrate that highly substituted porphyrin systems can be prepared from tetrahydroindole derivatives.

Conformational control of flexible molecular tweezers by intramolecular CH/π interaction

The synthesis of new flexible molecular tweezers based on 3,4,8,10,11,13-hexahydro-1 H,6 H-2,5,9,12-tetraoxa-benzo[1,2:4,5]dicyclooctene bearing two naphthalenes is presented. Intramolecular CH/π interaction between the alkyl ring and the two terminal naphthalenes controls the conformation to give a self-quenched cleft form.

Regioselective Formation of β‐Alkyl‐α‐phenyliridabenzenes via Unsymmetrical 3‐Vinylcyclopropenes: Probing Steric and Electronic Influences by Varying the Alkyl Ring Substituent

The synthesis of unsymmetrical (Z)-1-alkyl-3-(2-iodovinyl)-2-phenyl-1-cyclopropenes (R=Me (8 a), Et (8 b), iPr (8 c), and tBu (8 d)) and their reactions with Vaska's complex [Ir(CO)Cl(PPh3)2] and its trimethylphosphine analogue [Ir(CO)Cl(PMe3)2] were investigated. Iridabenzvalene (13/20), iridabenzene (14/21), and/or eta(5)-cyclopentadienyliridium complexes (15/22) were obtained in modest yields and were fully characterized by spectroscopic means. X-ray structural data was secured for iridabenzvalene 13 d and iridabenzenes 14 a,b,d. Whereas iridabenzenes 14 a-c were stable at 75 degrees C for 48 h, 14 d, which possesses a bulky tBu group, rearranged cleanly to cyclopentadienyliridium 15 d at 50 degrees C over 15 h and displayed first-order kinetics. The influence of the alkyl substituent on the mechanisms of iridacycle generation, isomerization, and iridabenzene regioselectivity is discussed.

Fuel decomposition and hydrocarbon growth processes for substituted cyclohexanes and for alkenes in nonpremixed flames

Cycloalkanes are major constituents of petroleum-based fuels. In the experiments reported here, centerline profiles of C3–C12 hydrocarbons were measured in coflowing methane/air flames whose fuel was separately doped with 2000 ppm each of nine substituted cyclohexanes, cycloheptane, eight isomers of heptene, and three isomers of octene. The decomposition rates of the dopants increased in the following order: cycloalkanes with saturated side-chains < cycloalkanes with unsaturated side-chains ≈ non-cyclic alkanes < alkenes. This order and the absolute magnitude of the decomposition rates could be reproduced with the assumption that unimolecular dissociation was the dominant decomposition process for all of the dopants. The observed hydrocarbon products indicated that the specific dissociation pathways were allylic C–C fission plus six-center elimination for the alkenes, and ring-opening isomerization to alkenes for the cycloalkanes. All of the cycloalkanes produced similar distributions of aromatic hydrocarbons, which shows that they formed aromatics by addition reactions between their aliphatic decomposition products, not by direct dehydrogenation of their alkyl rings. Consequently, methylcycloheptane and cycloheptane produced the same concentrations of aromatics as 1-heptene and 2-heptene, which are their immediate decomposition products. Dimethylcyclohexanes produced more benzene than methylcyclohexane, and cyclohexanes with unsaturated side-chains (vinylcyclohexane, ethynylcyclohexane, and ethylidenecyclohexane) produced even more. The benzene production from methylcyclohexane was comparable to that from the most branched heptane isomer (2,3,3-trimethylbutane), which indicates that the cycloalkane portion of practical fuels will have a proportionately greater effect on soot production than the non-cyclic alkane portion.

Cationic planar chiral palladium P,S complexes as highly efficient catalysts in the enantioselective ring opening of oxa- and azabicyclic alkenes.

Open plan: Cationic methylpalladium(II) complexes of planar chiral Fesulphos ligands (Fesulphos=1-phosphanyl-2-sulfenylferrocene) show excellent performance in the alkylative ring opening of oxa- and azabicyclic alkenes with dialkyl zinc reagents (see scheme, Cy=cyclohexyl, ArF=3,5-bis(trifluoromethyl)phenyl). Catalyst loadings as low as 0.5 mol % are normally sufficient to achieve high enantioselectivities (94–>99 % ee).

Scope of Palladium‐Catalyzed Alkylative Ring Opening.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Interaction of amiloride and one of its derivatives with Vpu from HIV-1: a molecular dynamics simulation

Vpu is an 81-residue membrane protein, with a single transmembrane segment that is encoded by HIV-1 and is involved in the enhancement of virion release via formation of an ion channel. Cyclohexamethylene amiloride (Hma) has been shown to inhibit ion channel activity. In the present 12-ns simulation study a putative binding site of Hma blockers in a pentameric model bundle built of parallel aligned helices of the first 32 residues of Vpu was found near Ser-23. Hma orientates along the channel axis with its alkyl ring pointing inside the pore, which leads to a blockage of the pore.

Scope of palladium-catalyzed alkylative ring opening.

We have explored the scope of the palladium-catalyzed nucleophilic ring opening methodology. New highly selective and highly active catalysts have been found for the ring opening of oxabenzonorbornadienes. Employing these catalysts, the addition of various alkyl nucleophiles to oxabenzonorbornadiene has been achieved. In addition, reaction of diethylzinc with [3.2.1] oxabicyclic alkenes has been accomplished to yield ring-opened products as well as functionalized alkene addition products.

MgI2‐Mediated Ring Expansions of Secondary Methylenecyclopropyl Amides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

1‐Phosphino‐2‐sulfenylferrocenes: Efficient Ligands in Enantioselective Palladium‐Catalyzed Allylic Substitutions and Ring Opening of 7‐Oxabenzonorbornadienes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

MgI(2)-mediated ring expansions of secondary methylenecyclopropyl amides.

Ring expansion of secondary methylenecyclopropyl amides in the presence of MgI2 was investigated. Various isomeric five-membered unsaturated lactams were obtained, depending on the character of the substituent Q. The amide group served as a nucleophile in ring closing as well as an activator for ring opening. In the presence of a variety of aryl aldimines or aldehydes, alkylative ring expansion occurred in a single step under mild and neutral conditions leading to gamma'-amino- or -hydroxy-alkylated pyrrol-2-ones. Also, it was shown that a 4-methylpyrrol-2-one could be transformed to a gamma-hydroxy-alkylated product by the use of a direct vinylogous aldol reaction.

Tricyclohexylphosphate—A Unique Member in the Neutral Organophosphate Family

Tricyclohexylphosphate (TcyHP) was synthesised and characterized. The extraction of U(VI) and Th(IV) by TcyHP in n‐dodecane was studied and compared with tributylphosphate (TBP). The feasibility of the separation of Th and U with TcyHP has been explored and reported. The solubility of TcyHP in water at room temperature has been measured. The stoichiometry of the TcyHP solvates with Th(NO3)4 and UO2(NO3)2 was evaluated. The enthalpy of extraction of U(VI) by TcyHP was measured. The results of column runs with TcyHP impregnated Amberlite XAD‐7 resin for studying the loading and elution behavior of uranium from nitric acid medium are also reported in this paper. Hexavalent actinides form third phase with neutral organophosphate extractants only at very high nitric acid concentrations and high metal loading. However the presence of the three closed ring alkyl moieties in TcyHP is seen to lead to certain unique features with regard to the third phase formation behavior. It has been observed, for instance, that U(VI) forms third phase with this extractant even with highly polar diluents like 1‐chlorooctane. Further, the tendency for third phase formation with U(VI) is even higher than in the case of Th(IV), in contrast to the trend observed so far with other extractants.

Substituent Effects in Molecular Electronic Relaxation Dynamics via Time-Resolved Photoelectron Spectroscopy: ππ* States in Benzenes

We study the applicability of femtosecond time-resolved photoelectron spectroscopy to the study of substituent effects in molecular electronic relaxation dynamics using a series of monosubstituted benzenes as model compounds. Three basic types of electronic substituents were used: CC (styrene), CO (benzaldehyde), and C⋮C (phenylacetylene). In addition, the effects of the rigidity and vibrational density of states of the substituent were investigated via both methyl (α-methylstyrene, acetophenone) and alkyl ring (indene) substitution. Femtosecond excitation to the second ππ* state leads, upon time-delayed ionization, to two distinct photoelectron bands having different decay constants. Variation of the ionization laser frequency had no effect on the photoelectron band shapes or lifetimes, indicating that autoionization from super-excited states played no discernible role. From assignment of the energy-resolved photoelectron spectra, a fast decaying component was attributed to electronic relaxation of the ...

Phthalates Suppress the Calcium Signaling of Nicotinic Acetylcholine Receptors in Bovine Adrenal Chromaffin Cells

Researchers have recently reported on the nongenomic action of estrogen via membrane receptors and ion channels, especially nicotinic acetylcholine receptors (nAChR). We studied the nongenomic effects of eight phthalates (an endocrine disrupter that expresses estrogen-like activity through estrogen receptors): di- n -ethyl (DEP), di- n -propyl (DPrP), di- n -butyl (DBP), benzyl- n -butyl (BBP), di- n -pentyl (DPP), di- n -hexyl (DHP), dicyclohexyl (DCHP), and di-(2-ethylhexyl) (DEHP). Specifically, we looked at their individual effects on cytosolic free calcium concentration rise induced by three nAChR agonists: carbachol, 1,1-dimethyl-4-phenyl-piperazinium iodide, and epibatidine. Results show that all of the tested phthalates suppressed nAChR-coupled Ca 2+ response. Strongest to weakest potencies were observed as DPP → BBP → DBP → DCHP → DHP → DPrP → DEHP → DEP. DPP, DBP, and BBP were 10 times more potent than estradiol. We suggest that phthalate potency was associated with its chemical structure, since (a) the most effective phthalates had dialkyl group carbon numbers of C4 or C5, with shorter or longer numbers resulting in decreased potency, and (b) the presence of an alkyl ring or phenoic structure resulted in increasing potency. Because of the similarity between this relationship and estrogen receptor-binding potency, we suggest that the inhibitory effect of phthalates on nAChR-coupled Ca 2+ response is an indication of their nongenomic estrogen-like activity.

Phthalates Suppress the Calcium Signaling of Nicotinic Acetylcholine Receptors in Bovine Adrenal Chromaffin Cells

Researchers have recently reported on the nongenomic action of estrogen via membrane receptors and ion channels, especially nicotinic acetylcholine receptors (nAChR). We studied the nongenomic effects of eight phthalates (an endocrine disrupter that expresses estrogen-like activity through estrogen receptors): di- n-ethyl (DEP), di- n-propyl (DPrP), di- n-butyl (DBP), benzyl- n-butyl (BBP), di- n-pentyl (DPP), di- n-hexyl (DHP), dicyclohexyl (DCHP), and di-(2-ethylhexyl) (DEHP). Specifically, we looked at their individual effects on cytosolic free calcium concentration rise induced by three nAChR agonists: carbachol, 1,1-dimethyl-4-phenyl-piperazinium iodide, and epibatidine. Results show that all of the tested phthalates suppressed nAChR-coupled Ca 2+ response. Strongest to weakest potencies were observed as DPP → BBP → DBP → DCHP → DHP → DPrP → DEHP → DEP. DPP, DBP, and BBP were 10 times more potent than estradiol. We suggest that phthalate potency was associated with its chemical structure, since (a) the most effective phthalates had dialkyl group carbon numbers of C4 or C5, with shorter or longer numbers resulting in decreased potency, and (b) the presence of an alkyl ring or phenoic structure resulted in increasing potency. Because of the similarity between this relationship and estrogen receptor-binding potency, we suggest that the inhibitory effect of phthalates on nAChR-coupled Ca 2+ response is an indication of their nongenomic estrogen-like activity.

Activity of bisphosphonates against Trypanosoma brucei rhodesiense.

We report the results of a comparative molecular field analysis (CoMFA) investigation of the growth inhibition of the bloodstream form of Trypanosoma brucei rhodesiense trypomastigotes by bisphosphonates. A quantitative three-dimensional structure-activity relationship CoMFA model for a set of 26 bisphosphonates having a range of activity spanning approximately 3 orders of magnitude (minimum IC(50) = 220 nM; maximum IC(50) = 102 microM) yielded an R(2) value of 0.87 with a cross-validated R(2) value of 0.79. The predictive utility of this approach was tested for three sets of three compounds: the average pIC(50) error was 0.23. For the nitrogen-containing bisphosphonates, in general, the activity was aromatic- >> aliphatic-containing side chains. The activity of aromatic species lacking an alkyl ring substitution decreased from ortho to meta to para substitution; halogen substitutions also reduced activity. For the aliphatic bisphosphonates, the IC(50) values decreased nearly monotonically with increasing chain length (down to IC(50) = 2.0 microM for the n-C(11) alkyl side chain species). We also show, using a "rescue" experiment, that the molecular target of the nitrogen-containing bisphosphonate, risedronate, in T. b. rhodesiense is the enzyme farnesyl pyrophosphate synthase. In addition, we report the LD(50) values of bisphosphonates in a mammalian cell general toxicity screen and present a comparison between the therapeutic indices and the IC(50) values in the T. b. rhodesiense growth inhibition assay. Several bisphosphonates were found to have large therapeutic indices (> or =200:1) as well as low IC(50) values, suggesting their further investigation as antiparasitic agents against T. b. rhodesiense.