George Mathai

A biopolymer mediated efficient synthesis of cyclic carbonates from epoxides and carbon dioxide

A promising application of carboxymethyl cellulose (CMC), which is a congener of the cellulose family, as a supporting material for a variety of imidazolium based ionic liquid catalysts in the chemical fixation of CO2 has been studied here. The ionic liquids immobilized on the carboxymethyl cellulose (CMIL) showed high catalytic activity and selectivity in the cycloaddition of carbon dioxide with propylene oxide (PO) resulting in propylene carbonate (PC) under mild and solvent free conditions. A new pathway was proposed based on the density functional theory (DFT) calculations performed at the B3LYP/6-31G (d,p) level, where the carboxyl and hydroxyl moieties on the CMC were found to act synergistically with the halide ions to eventuate in the cycloaddition reaction. The carboxyl group entities on the carboxymethyl cellulose support supposedly stabilize the product complex via strong hydrogen bonds, thereby promoting the reaction. The catalyst system also displayed good reusability.

Microwave-assisted synthesis of cyclic carbonates by a formic acid/KI catalytic system

An environment-friendly synthesis of cyclic carbonates from CO2 and epoxides with a HCOOH/KI catalytic system was performed in a microwave reactor. Various epoxide substrates were subjected to microwave irradiated cycloaddition using a HCOOH/KI catalyst. The effects of reaction parameters like catalyst composition, microwave power, CO2 pressure, and reaction time have been investigated. The synergistic influence of the COOH/KI catalyst in the reaction has been compared with that of an OH/KI system and was theoretically simulated using density functional theory.

A computational study of the mechanistic insights into base catalysed synthesis of cyclic carbonates from CO2: bicarbonate anion as an active species

The standalone catalytic potential of common organic bases such as imidazole, pyridine and dimethylaminopyridine (DMAP) for the solvent-free cycloaddition of CO2 with epoxides yielding five-membered cyclic carbonates is reported here. Appreciable conversion of various epoxides with excellent selectivity towards the desired products was materialized in this metal/halide/hydrogen bond donors/solvent-free reaction. The presence of catalytic amounts of water was found significantly advantageous in this base catalyzed chemical fixation of CO2 and the conversion almost got doubled or tripled under the same reaction conditions. A definitive mechanism for the activation of base catalysis was also proposed with the aid of ab initio calculations performed at the B3LYP/6-31G(d,p) level. Besides, a bicarbonate anion mediated catalytic cycle was also proposed utilizing computational calculations. The possible intermediates and transition states as well as the related energy constraints of the base alone and base–water catalyzed reactions were deduced and the activation energy obtained was found higher for the former (∼30 kcal mol−1) than for the latter (∼12 kcal mol−1), which rationalizes the experimental observation of the higher activity of the latter.

Electrospray ionization tandem mass spectrometry of 3-phenyl-N-(3-(4-phenylpiperazin-1-yl)propyl)-1H-pyrazole-5-carboxamide derivatives: unusual fragmentation involving loss of 11 u.

Many pharmaceuticals are synthetic compounds, and a large number of them are heterocycles. Common examples are the widely used arylpyrazoles in medicinal and pesticide chemistry. Several of the pyrazole derivatives are known to exhibit a wide range of biological activities such as anti-hyperglycemic, analgesic, anti-inflammatory, anti-pyretic, anti-bacterial, hypoglycemic, sedative–hypnotic activity and anticoagulant activity. Recently, some arylpyrazoles were reported to have non-nucleoside HIV-1 reverse transcriptase inhibitory activity. They may prove to be clinically useful compounds and extensive studies have been devoted to arylpyrazole derivatives such as Celecoxib, a well-known COX-2 inhibitor. As a part of an ongoing synthetic research program towards the synthesis of novel and alternative non-steroidal antiinflammatory drugs, we have synthesized a new series of 3-phenyl-N-[3-(4-phenylpiperazin-1-yl)propyl]-1H-pyrazole-5carboxamide derivatives and evaluated their anti-inflammatory activity to inhibit carrageenan-induced paw edema in rats. An initial examination of the electrospray ionization (ESI) mass spectra of these compounds revealed an interesting and unusual apparently impossible fragmentation involving loss of 11 u. As there exist no reports in the literature on mass spectrometric studies of the title compounds and also because of the observed unusual fragmentation, we have undertaken a detailed study of these compounds using ESI tandemmass spectrometry (MS/MS) in combinationwith accuratemassmeasurements and density functional theory (DFT) calculations. ESI mass spectra of 3-phenyl-1H-pyrazole-5-carboxamide derivatives (Scheme 1) were recorded using a LCQ ion trap mass spectrometer (Thermo Finnigan, San Jose, CA, USA), equipped with an ESI source. The data acquisition was under the control of Xcalibur software (Thermo Finnigan). The typical source conditions were: spray voltage, 5 kV; capillary voltage, 15–20 V; heated capillary temperature, 200 C; tube lens offset voltage, 20 V; sheath gas (N2) pressure, 30 psi; and helium was used as damping gas. For the ion trap mass analyzer, the automatic gain control (AGC) settings were 2 10 counts for a full-scanmass spectrum and 2 10counts for a full product ion mass spectrum with a maximum ion injection time of 200 ms. In the full-scan MS and MS modes, the precursor ion of interest was first isolated by applying an appropriate waveform across the end-cap electrodes of the ion trap to resonantly eject all trapped ions, except those ions of the m/z ratio of interest. The isolated ions were then subjected to a supplementary ac signal to resonantly excite them and to induce the collision-activated dissociation (CAD) process. The collision energies used were 20–35 eV. The excitation time used was 30 ms and isolation width used was 1.0 Da.

Protonated N-benzyl- and N-(1-phenylethyl)tyrosine amides dissociate via ion/neutral complexes

RATIONALE The collisional-induced dissociations (CID) of the [M+H]+ ions of molecules having benzyl groups attached to N-atoms have been proposed to involve migration of the benzyl group through the intermediacy of ion/neutral complexes (INCs). We report the investigation of the mechanism of dissociation of protonated N-benzyl- and N-(1-phenylethyl)tyrosine amides by electrospray ionization (ESI) tandem mass spectrometry (MS/MS) and density functional theory (DFT) calculations. METHODS The amides were synthesized from the corresponding amino acids and amines. The ESI-MS/MS spectra were recorded using an Agilent QTOF 6540 mass spectrometer. The DFT calculations were performed by using Gaussian 09 software. The structures of the [M+H]+ ions, intermediates, products and transition states (TS) were optimized at the B3LYP/6-31G(d,p) level of theory. RESULTS CID of the [M+H]+ ions of N-benzyltyrosine amide yields two product ions due to rearrangements: (i) the [M+H-74]+ ion (m/z 197) due to benzyl migration to the hydroxyphenyl ring and (ii) the [M+H-45]+ ion (m/z 226) due to benzyl migration to the NH2 group. DFT calculations suggest that the rearrangements occur through an INC in which the benzyl cation is the cation partner. The [M+H]+ ion of N-(1-phenylethyl)tyrosine amide rearranges to an INC of the 1-phenylethyl cation. Subsequent elimination of styrene occurs by transfer of a proton from the 1-phenylethyl cation to the neutral partner. CONCLUSIONS The [M+H]+ ions of both N-benzyl (1) and N-(1-phenylethyl) (2) tyrosine amide rearrange into INCs. The dissociation of [M+H]+ ion of 1 yields the benzyl cation and [M+H-74]+ and [M+H-45]+ due to benzyl migration to the hydroxyphenyl ring and NH2 group, respectively. However, the formation of the [M+H-74]+ ion is not observed when the aromatic ring is deactivated. The [M+H]+ ion of 2 either dissociates to form the 1-phenylethyl cation or [M+H-styrene]+ . Copyright

McLafferty-type rearrangement of protonated N-[nicotinoyl]phenylethyl amines and consequent elimination of styrene

RATIONALE McLafferty rearrangements occur in radical cations of molecules containing a carbonyl group and a γ hydrogen atom but are not common in the [M+H](+) ions of carbonyl compounds. We propose to investigate the collision-induced dissociation (CID) of the [M+H](+) ions of nicotinoyl and picolinoyl amides of 1- and 2-phenylethylamines to explore the possibility of McLafferty-type rearrangement. METHODS The compounds for study were synthesized by the reaction of methyl nicotinate or methyl picolinate with 1- and 2-phenylethylamines. The CID mass spectra of electrospray ionization (ESI)-generated protonated molecules were obtained using a QSTAR XL quadrupole time-of-flight (QTOF) mass spectrometer, and density functional theory (DFT) calculations using the B3LYP method were employed to elucidate the fragmentation mechanisms. The total electronic and thermal energies of intermediate transition states (TSs) and product ions are reported relative to those of the [M+H](+) ions. RESULTS CID of the [M+H](+) ions of N-[nicotinoyl]-2-phenylethylamine (1) yielded product ions of m/z 105 (1-phenylethyl cation) and 123 ([M+H-styrene](+) cation). The competitive formation of the ions of m/z 123 and 105 is proposed to involve a McLafferty-type rearrangement. Similarly, the [M+H](+) ions of the isomeric compound 2 and the N-[picolinoyl] phenylethyl amines (3 and 4) dissociate to yield ions of m/z 123 and 105. CONCLUSIONS A molecule of styrene was eliminated from the ESI-generated [M+H](+) ions of N-[nicotinoyl]phenylethylamines and the isomeric N-[picolinoyl]phenylethylamines, through a mechanism involving a McLafferty-type 1,5-H shift. The transition state energy for the 1,5-H shift is less for the amides of 1-phenylethylamine than for the amides of 2-phenylethylamine. The process occurs as a charge remote process and the presence of the pyridine ring is essential for the process.