Isopropyl Chloroformate Research Articles

Theoretical study on the mechanism of the gas-phase elimination kinetics of alkyl chloroformates

ABSTRACTThe theoretical calculations on the mechanism of the homogeneous and unimolecular gas-phase elimination kinetics of alkyl chloroformates– ethyl chloroformate (ECF), isopropyl chloroformate (ICF), and sec-butyl chloroformate (SCF) – have been carried out by using CBS-QB3 level of theory and density functional theory (DFT) functionals CAM-B3LYP, M06, MPW1PW91, and PBE1PBE with the basis sets 6-311++G(d,p) and 6-311++G(2d,2p). The chlorofomate compounds with alkyl ester Cβ–H bond undergo thermal decomposition producing the corresponding olefin, HCl and CO2. These homogeneous eliminations are proposed to undergo two different types of mechanisms: a concerted process, or via the formation of an unstable intermediate chloroformic acid (ClCOOH), which rapidly decomposes to HCl and CO2 gas. Since both elimination mechanisms may occur through a six-membered cyclic transition state structure, it is difficult to elucidate experimentally which is the most reasonable reaction mechanism. Theoretical calculations show that the stepwise mechanism with the formation of the unstable intermediate chloroformic acid from ECF, ICF, and SCF is favoured over one-step elimination. Reasonable agreements were found between theoretical and experimental values at the CAM-B3LYP/6-311++G(d,p) level.

Determination of bisphenol A in foods as 2,2-bis-(4-(isopropoxycarbonyloxy)phenyl)propane by gas chromatography/mass spectrometry

A procedure has been developed for the determination of bisphenol A (BPA) in foods by gas chromatography/mass spectrometry as 2,2-bis-(4-(isopropoxycarbonyloxy)phenyl)propane formed in the reaction with isopropyl chloroformate. Optimal conditions have been found for BPA derivatization, providing its quantitative conversion into diether derivative in aqueous media. The concentration of BPA has been determined in some samples of canned foods and beverages (from 2.15 to 42.91 ng/g). The detection limit is 0.05–0.1 ng/g.

A bioanalytical method to determine the cell wall composition of Mycobacterium tuberculosis grown in vivo

Mycobacterium tuberculosis bacilli exhibit cell wall alterations during in vivo growth. Development of ultrasensitive analytical techniques with high specificities is required to analyze the cell wall of M. tuberculosis isolated from experimental animals because of the low amounts of bacteria available and contamination by host tissue. Here we present a novel methodology to analyze all three major components (mycolic acids, arabinogalactan, and peptidoglycan) of the mycobacterial cell wall from mycobacteria isolated from animal tissue. In this procedure, the cell wall carbohydrates are analyzed by gas chromatography tandem mass spectrometry (GC/MS/MS) of alditol acetates, the peptidoglycan by GC/MS (mass spectrometry) analysis of the unique amino acid diaminopimelic acid (after derivatization with isopropyl chloroformate), and the mycolic acids by liquid chromatography (LC)/MS (negative ion) without derivatization. The procedure was designed so that all three analyses could be performed starting with a single sample given the difficulty of preparing multiple aliquots in known ratios. Linkage analysis, including an enantiomeric specific procedure, of the arabinogalactan polymer is also presented. These procedures will enable the determination of the cell wall alterations known to occur in the important nongrowing “dormant” M. tuberculosis present during disease. With some adaptations, the methodology is also applicable to the analysis of small amounts of in vivo grown bacteria of other species.

Correlation of the Rates of Solvolysis of t-Butyl Fluoroformate Using the Extended Grunwald-Winstein Equation

The specific rates of solvolysis of t-butyl fluoroformate (1) have been measured at 40.0 o C in 21 pure and binary solvents. These give a satisfactory correlation over the full range of solvents when the extended Grunwald-Winstein equation, with incorporation of the solvent nucleophilicity and the solvent ionizing power, is applied. The actual values are very similar to those obtained in earlier studies of the solvolyses of isopropyl chloroformate and ethyl chlorothioformate in the more ionizing and least nucleophilic solvents, which are believed to proceed by an ionization pathway. The small negative values for the entropies of activation are consistent with the ionization nature of the proposed rate-determining step. These observations are also compared with those previously reported for the corresponding primary and secondary alkyl haloformate esters.

Analysis of the nucleophilic solvation effects in isopropyl chlorothioformate solvolysis.

Correlation of the solvent effects through application of the extended Grunwald-Winstein equation to the solvolysis of isopropyl chlorothioformate results in a sensitivity value of 0.38 towards changes in solvent nucleophilicity (l) and a sensitivity value of 0.72 towards changes in solvent ionizing power (m). This tangible l value coupled with the negative entropies of activation observed indicates a favorable predisposition towards a modest rear-side nucleophilic solvation of a developing carbocation. Only in 100% ethanol was the bimolecular pathway dominant. These observations are very different from those obtained for the solvolysis of isopropyl chloroformate, where dual reaction channels were proposed, with the addition-elimination reaction favored in the more nucleophilic solvents and a unimolecular fragmentation-ionization mechanism favored in the highly ionizing solvents.

ChemInform Abstract: Friedel-Crafts Alkylation of Alkenes: Ethylaluminum Sesquichloride Induced Alkylations with Alkyl Chloroformates.

The formal addition of propane to nonactivated double bonds can be achieved with isopropyl chloroformate (2) in the presence of Et(3)Al(2)Cl(3). Thus, a 1:1 mixture of 10-isopropyloctadecanoic acid (3) and the 9-regioisomer is formed from oleic acid (1). The reaction may also be carried out with 1-alkenes by the addition of triethylsilane as a hydride donor.

Clinical assay of four thiol amino acid redox couples by LC–MS/MS: Utility in thalassemia

The total concentrations of four sulfur amino acid (SAA) metabolite redox couples (reduced and oxidized forms of homocysteine, cysteine, glutathione, and cysteinylglycine) in human blood are assayed with a simple and sensitive method by liquid chromatography–electrospray positive ionization–tandem mass spectrometry. To prevent ex vivo thiol oxidation, iodoacetamide (IAM) is used immediately following the blood draw. To selectively enrich for S-carboxyamidomethylated SAA, and other cationic amino acids metabolites, proprietary strong cation-exchange solid phase extraction tips are used. Analytes are further derivatized with isopropylchloroformate (IPCF) to esterify the amino and the carboxylic groups. Double derivatization with IAM and IPCF improves the reverse phase liquid chromatography separation of SAA metabolites. The use of detection mode of multiple-reaction monitoring (MRM) allows sensitive and specific simultaneous detection of SAA. The internal standards used to account for the matrix effects of human plasma and erythrocytes were plant glutathione analogue, homoglutathione, and stable isotopes of cystine and homocystine. The method was validated for its linearity, accuracy, and precision. Excellent linearity of detection ( r 2 > 0.98) was observed over relevant ranges for plasma and erythrocyte samples, and the limits of detection were established to be between 5 and 20 nM. Relative standard deviations were <9% for within-day variations and <15% for between-day variations. The method was used to assess thiol redox states in plasma and erythrocytes isolated from healthy subjects and thalassemia patients.

Grunwald-Winstein Analysis - Isopropyl Chloroformate Solvolysis Revisited

Specific rates of solvolysis at 25 °C for isopropyl chloroformate (1) in 24 solvents of widely varying nucleophilicity and ionizing power, plus literature values for studies in water and formic acid, are reported. Previously published solvolytic rate constants at 40.0 °C are supplemented with two additional values in the highly ionizing fluoroalcohols. These rates are now are analyzed using the one and two-term Grunwald-Winstein Equations. In the more ionizing solvents including ten fluoroalcohols negligible sensitivities towards changes in solvent nucleophilicity (l) and very low sensitivities towards changes in solvent ionizing power (m) values are obtained, evocative to those previously observed for 1-adamantyl and 2-adamantyl chloroformates 2 and 3. These observations are rationalized in terms of a dominant solvolysis-decomposition with loss of the CO2 molecule. In nine of the more nucleophilic pure alchohols and aqueous solutions an association-dissociation mechanism is believed to be operative. Deficiencies in the acid production indicate 2-33% isopropyl chloride formation, with the higher values in less nucleophilic solvents.

Preparation of activated esters of N-alkoxycarbonylamino and other acids by a modification of the mixed anhydride procedure.

Generation of a mixed anhydride using ethyl or isopropyl chloroformate and N-methylmorpholine in dichloromethane at room temperature, followed by addition of excess ring-substituted phenol or N-substituted hydroxylamine and a catalytic amount of tertiary amine, provides an efficient synthesis of activated esters.

Solvolysis-decomposition of 2-adamantyl chloroformate: evidence for two reaction pathways.

Reaction of 2-adamantyl chloroformate under a variety of solvolytic conditions leads to 2-adamantyl chloride accompanied by solvolysis products, some with and some without retention of the CO(2) unit. For example, in 100% ethanol, only 4.8% 2-adamantyl chloride is formed with the mixed carbonate (88%) being the dominant product, and in 100% 2,2,2-trifluoroethanol, the products are both formed with loss of CO(2), 59% of the chloride and 41% of the ether. With exclusion of the specific rates in 100% and 90% ethanol and methanol, a good Grunwald-Winstein plot against Y(Cl) values (solvent ionizing power) is obtained, with a slope of 0.47 +/- 0.03. The results are compared with those reported earlier for 1-adamantyl chloroformate and isopropyl chloroformate and mechanistic conclusions are drawn.

Regioselective Cationic 1,2- and 1,4-Additions Forming Carbon−Carbon Bonds to Methyl Santalbate, a Conjugated Enyne

Lewis acid-induced carbocationic addition reactions to methyl santalbate [methyl (E)-octadec-11-en-9-ynoate] [(E)-1] give products by regioselective formation of a new carbon−carbon bond at C-9 of the molecule chain. The allenic fatty acid derivatives methyl 12-chloro-9-(1-oxoheptyl)-9,10-octadecadienoate (2) and methyl 9-isopropyl-9,10-octadecadienoate (3) were obtained by Friedel−Crafts acylation of 1 with heptanoyl chloride and alkylation of 1 with isopropyl chloroformate, respectively. While the reaction between 1 and formaldehyde induced by Me2AlCl or Et3Al2Cl3 gives a mixture of the conjugated chlorodienes 5a and 5b, the corresponding reaction carried out in the presence of AlCl3 affords the α,β-unsaturated ketone 6.

Friedel–Crafts Alkylation of Alkenes: Ethylaluminum Sesquichloride Induced Alkylations with Alkyl Chloroformates

The formal addition of propane to nonactivated double bonds can be achieved with isopropyl chloroformate (2) in the presence of Et3Al2Cl3. Thus, a 1:1 mixture of 10-isopropyloctadecanoic acid (3) and the 9-regioisomer is formed from oleic acid (1). The reaction may also be carried out with 1-alkenes by the addition of triethylsilane as a hydride donor.

Friedel-Crafts Alkylation of Alkenes: Ethylaluminum Sesquichloride Induced Alkylations with Alkyl Chloroformates

The formal addition of propane to nonactivated double bonds can be achieved with isopropyl chloroformate (2) in the presence of Et(3)Al(2)Cl(3). Thus, a 1:1 mixture of 10-isopropyloctadecanoic acid (3) and the 9-regioisomer is formed from oleic acid (1). The reaction may also be carried out with 1-alkenes by the addition of triethylsilane as a hydride donor.

Furopyridines. XX. Wittig‐horner reaction of a phosphonate of reissert analogues of furo[3,2‐c]‐, ‐[2,3‐c]‐ and ‐[3,2‐b]pyridines

AbstractFuro[3,2‐c]‐(1a), ‐[2,3‐c]‐ (1b) and ‐[3,2‐b]pyridine (1c) were reacted with isopropyl chloroformate and trimethyl phosphite to give dimethyl 5‐isopropoxycarbonyl‐4,5‐dihydrofuro[3,2‐c]pyridine‐4‐phosphonate (2a), dimethyl 6‐isopropoxycarbonyl‐6,7‐dihydrofuro[2,3‐c]pyridine‐7‐phosphonate (2b) and dimethyl 4‐isopropoxycarbonyl‐4,7‐dihydrofuro[3,2‐b]pyridine‐7‐phosphonate (2c) as unstable syrups. Reaction of 2b and 2c with n‐butyllithium and then with benzaldehyde, p‐methoxybenzaldehyde, p‐cyanobenzalde‐hyde or propionaldehyde afforded the normal Wittig reaction products 5b‐H, 5b‐OMe, 5b‐CN, 5b‐Et, 5c‐H, 5c‐H, 5c‐OMe and 5c‐CN, except for 2b with propionaldehyde. While, the same reactions of compound 2a and the reaction of 2b with propionaldehyde afforded the unexpected products, 5‐isopropoxycar‐bonylfuro[3,2‐c]pyridinio‐4‐aryl‐(or ethyl)methoxides 3a‐H, 3a‐OMe, 3a‐CN and 3a‐Et, 4‐(1′‐aryl(or ethyl)‐1′‐hydroxymethyl)furo[3,2‐c]pyridines 4a‐H, 4a‐OMe, 4a‐CN and 4a‐Et accompanying formation of the normal products. Treatment of the normal Wittig reaction products with lithium diisopropylamide and then with acetone gave the derivatives alkylated at the 2‐or the benzylic positions.

Orientation of the isopropyl grouping in isopropyl chloroformate and isopropyl cyanoformate

The vapour phase infrared contours of the carbonyl stretching of five differently deuterated derivatives of isopropyl chloroformate, and of three differently deuterated derivatives of isopropyl cyanoformate have been investigated. Simulations using rigid asymmetric top calculations of the observed contours indicate that the COCH dihedral angle is close to 20° in both the chloroformate and the cyanoformate ester.

ChemInform Abstract: Isopropyl Chloroformate as a Superior Reagent for Mixed Anhydride Generation and Couplings in Peptide Synthesis.

ChemInformVolume 19, Issue 44 Natural Products ChemInform Abstract: Isopropyl Chloroformate as a Superior Reagent for Mixed Anhydride Generation and Couplings in Peptide Synthesis. N. L. BENOITON, N. L. BENOITON Dep. Biochem., Univ. Ottawa, Ottawa, Ont. K1N 6N5, Can.Search for more papers by this authorY. LEE, Y. LEE Dep. Biochem., Univ. Ottawa, Ottawa, Ont. K1N 6N5, Can.Search for more papers by this authorF. M. F. CHEN, F. M. F. CHEN Dep. Biochem., Univ. Ottawa, Ottawa, Ont. K1N 6N5, Can.Search for more papers by this author N. L. BENOITON, N. L. BENOITON Dep. Biochem., Univ. Ottawa, Ottawa, Ont. K1N 6N5, Can.Search for more papers by this authorY. LEE, Y. LEE Dep. Biochem., Univ. Ottawa, Ottawa, Ont. K1N 6N5, Can.Search for more papers by this authorF. M. F. CHEN, F. M. F. CHEN Dep. Biochem., Univ. Ottawa, Ottawa, Ont. K1N 6N5, Can.Search for more papers by this author First published: November 1, 1988 https://doi.org/10.1002/chin.198844318AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume19, Issue44November 1, 1988 RelatedInformation

Isopropyl chloroformate as a superior reagent for mixed anhydride generation and couplings in peptide synthesis

Mixed anhydrides of N‐tert.‐butoxycarbonyl‐, N‐benzyloxycarbonyl‐ and N‐9‐fluorenylmethoxycarbonylamino acids were prepared using isopropyl chloroformate, and purified by edulcoration. They were more stable than the corresponding anhydrides obtained using ethyl and isobutyl chloroformates. Aminolysis of the anhydrides by an amino acid ester proceeded efficiently, the amount of urethane generated by reaction at the carbonate moiety being the same as that generated from the other anhydrides. Racemization attending the coupling of N‐benzyloxycarbonylglycylamino acids by the mixed anhydride method using isopropyl chloroformate was one third to one quarter of that observed for the same couplings using ethyl and isobutyl chloroformate.

Gas-phase pyrolysis of isopropyl chloroformate

Homogeneous, molecular elimination of propene from isopropyl chloroformate takes place at 229-277�C with rate ke = 1013.94exp(-174000/8.314T) s-1 Rate comparisons indicate that a polar transition state is involved.

Wittig-horner reaction of a phosphonate of reissert analogue a new method for introduction of alkyl groups into isoquinoline

Dimethyl 2-isopropoxycarbonyl-1, 2-dihydroisoquinoline-1-phosphonate ( 1 ) was prepared from isoquinoline, isopropyl chloroformate, and trimethyl phosphite. Wittig-Horner reaction of 1 with various aldehydes afforded the corresponding exo-methylene compounds, which were converted to 1-substituted isoquinolines with hydrogen chloride.

Kinetics of the hydrolysis of acyl chlorides in pure water

The activation parameters ΔH≠, ΔS≠, and ΔCP≠ for the hydrolyses of a series of alkyl chloroformates and dimethylcarbamyl chloride in water have been determined. The results indicate that, with increasing electron donation to the chlorocarbonyl group, the mechanism changes from bimolecular to unimolecular (SN1) displacement at this position. For isopropyl chloroformate, some concurrent alkyl–oxygen bond fission is also indicated. The bimolecular mechanism involves reversible addition of water to the carbonyl group followed by ionization of the carbon–chlorine bond.