Formyl Chloride Research Articles

"Marriage" of Inorganic to Organic Chemistry as Motivation for a Theoretical Study of Chloroform Hydrolysis Mechanisms.

Incorporation of chlorides in coordination complexes, prepared by reactions in CHCl3, stimulated MP2 and DFT studies of its complete hydrolysis mechanisms. In excellent agreement with previous experimental results, the most important mechanism for CHCl3 basic hydrolysis at room temperature is the radical one producing :CCl2. The latter inserts into the H-O bond of H2O yielding dichloromethanol (1). The hydrolysis mechanism of α-H-lacking PhCCl3 to the corresponding dichloro(phenyl)methanol (3) was also studied. 1 decomposes by H2O to formyl chloride (2) and HCl. 2, following a variety of pathways, leads to known CHCl3 hydrolysis products, such as CO (4) and formic acid (6), via the intermediates chloromethanediol (5), s-cis, s-trans-dihydroxycarbene (ct-7), and s-trans, s-trans-dihydroxycarbene (tt-7). Interestingly, both ct-7 and tt-7 intermediates have recently been implicated in the reduction of CO2 with H2 to 6. The conversion of CO to HCOOH was studied. Most of the reactions studied are asynchronous concerted processes, the radical mechanism being a multistep one. The synthetic utility of this mechanism is briefly mentioned. To avoid chloride ions when performing reactions in CHCl3, we should use the solvent at room temperature even in the presence of water. This has been verified further by coordination chemistry reactions in progress.

Synthesis of pyrazole and 1,3,4-oxadiazole derivatives of pharmaceutical potential

Heterocyclic compounds are important molecules that serve as scaffolds or linkers for the core structure of numerous drug substances. In particular, pyrazole and 1,3,4-oxadiazole are compounds of great interest due to their comprehensive biological activities and interesting structural features. Here, we described an efficient and economical synthetic route leading to N-phenyl substituted pyrazole and 1,3,4-oxadiazole derivatives. Retrosynthetic disconnective analysis showed that the N-phenyl substituted pyrazole can be obtained from chalcone, accessible from the respective aldehyde, and acetophenone. The disubstituted 1,3,4-oxadiazole can be constructed from the respective aldehyde, which originates from pyrrole-containing compound, and formyl chloride. Based on our retrosynthetic analysis, N-phenyl substituted pyrazole was obtained by cyclization of the respective chalcone with phenylhydrazine to give pyrazoline which was in turn converted into pyrazole by oxidative aromatization. Potassium carbonate and a catalytic amount of molecular iodine were used to oxidatively cyclize semicarbazones into 1,3,4-oxadiazoles in a transition metal-free process. Novel pyrazole and 1,3,4-oxadiazoles with potential biological activity are investigated as antituberculosis, anticonvulsant, antidiabetic, anticancer, and tyrosinase inhibitory agents.

Effect of substitution on thermal decomposition of formaldehyde: A theoretical study

Unimolecular decomposition of organic compounds is strongly influenced by substituted functional group. The present work focusses to explore the energetics and kinetics of unimolecular decomposition of formaldehyde and chloro- substituted formaldehydes. Dissociation of molecular systems are observed to compete between molecular elimination reaction and bond dissociation reaction. It is observed that degradation of formaldehyde and formyl chloride ruled by 3-centered concerted mechanism produced H2 and HCl fragments respectively. On the other hand, Cl2 elimination reaction is generated via formation of isohalon structure. Despite of presence of isohalon intermediate, molecular elimination in phosgene required higher energy as compared to formyl chloride. Ease of molecular elimination in case of formyl chloride is attributed to favourable electrostatic interaction between hydrogen and chlorine atom, which assist in lower activation barrier. Further, the kinetic analysis suggested the applied temperature and pressure play a key role in formation of dominant elimination channel during decomposition reaction.

Modulation of n → π* Interaction in the Complexes of p-Substituted Pyridines with Aldehydes: A Theoretical Study.

n → π* interaction is analogous to the hydrogen bond in terms of the delocalization of the electron density between the two orbitals. Studies on the intermolecular complexes stabilized by the n → π* interaction are scarce in the literature. Herein, we have studied intermolecular N···C═O n → π* interactions in the complexes of p-substituted pyridines (p-R-Py) with formaldehyde (HCHO), formyl chloride (HCOCl), and acetaldehyde (CH3CHO) using quantum chemistry calculations. We have shown that the strength of the n → π* interaction can be modulated by varying the electronic substituents at the donor and acceptor sites in the complexes. Variation of the substituents at the para position of the pyridine ring from the electron-withdrawing groups (EWGs) to the electron-donating groups (EDGs) results in a systematic increase in the strength of the n → π* interaction. The strength of this interaction is also modulated by tuning the electron density toward the carbonyl bond by substituting the hydrogen atom of HCHO with the methyl and chloro groups. The modulation of this interaction due to the electronic substitutions at the n → π* donor and acceptor sites in the complexes is monitored by probing the relevant geometrical parameters, binding energies, C═O frequency redshift, NBO energies, and electron density for this interaction derived from QTAIM and NCI index analyses. Energy decomposition analysis reveals that the electrostatic interaction dominates the binding energies of these complexes, while the charge transfer interaction, which is representative of the n → π* interaction, also has a significant contribution to these.

Study on Synthesis and Performance of Methyl Diphenyl Urea Stabilizer

Diphenylamine (DPA), formyl chloride, and sodium hydride (NaH) as raw materials synthesize methyldiphenylurea stabilizer by alkylation reaction. The physical and chemical properties of methyldiphenylurea were characterized by nuclear magnetic resonance hydrogen spectrum (1HNMR), X-ray energy spectrum (EDS), Fourier transforms infrared spectroscopy (FT-IR) and differential thermal analysis (DTA). Thermal Decomposition Experiment of Nitrate Propellant Containing Stabilizer by Thermogravimetric Analysis (TGA), exploring the Effect of Different Stabilizers. The molecular surface electrostatic potential energy of methyl diphenyl urea, triphenylamine ( TPA ), dimethyl diphenyl urea (C2), and glycerol trinitrate were calculated by Materials Studio software. The interaction between the stabilizer and glycerol trinitrate molecule was studied. The results showed that the weight loss rate of methyl diphenyl urea was less than 0.1 % within 30 days, and the chemical stability was good. And its negative electrostatic potential energy is larger than that of C2 and TPA, its intermolecular binding ability with glycerol trinitrate is stronger, and its inhibition of nitrate decomposition stability is the best.

Atmospheric degradation of chloroacetoacetates by Cl atoms: Reactivity, products and mechanism in coastal and industrialized areas

Kinetic studies of the reaction of Cl atoms with ethyl 2-chloroacetoacetate, CH3C(O)CHClC(O)OCH2CH3, (k1) and methyl 2-chloroacetoacetate, CH3C(O)CHClC(O)OCH3, (k2) have been developed for the first time using SPME/GC-FID and in situ FTIR spectroscopy at (298 ± 2) K and 1000 mbar in glass atmospheric chambers. Relative rate coefficients obtained by Fourier Transform Infrared Spectroscopy (FTIR) using different reference compounds, were the following (in cm3.molecule−1.s−1): kE2CAA-FTIR= (2.41 ± 0.57) × 10−10 and kM2CAA-FTIR= (2.16 ± 0.85) × 10−10. Similar and reproducible values were obtained using Gas Chromatography equipped with Flame Ionization Detection coupled with Solid Phase Micro Extraction (SPME), kE2CAA-GC-FID = (2.54 ± 0.81) × 10−10 and kM2CAA-GC-FID = (2.34 ± 0.87) × 10−10 all values in units of cm3.molecule−1.s−1. In addition, product studies were performed in similar conditions to the kinetic experiments to identify the reaction products and postulate their tropospheric degradation mechanisms. The reaction of Cl atoms with saturated esters initiates via H-atom abstraction from the alkyl groups of the molecule. Formyl chloride, chloroacetone, and acetyl chloride were positively identified as reaction products by FTIR. On the other hand, acetyl chloride, 1,1,1-trichloropropan-2-one, 1,1-dichloropropan-2-one, 1-chloropropan-2-one, ethyl chloroformate, and methyl chloroformate were identified by the GC-MS technique. Structure–Activity Relationship (SAR), calculations were also performed to estimate the more favorable reactions pathways in agreement with the products observed. The atmospheric implications of these reactions were assessed by the estimation of the residence times of the chloroesters studied as following: τCl-E2CAA = 1.47 days, and τCl-M2CAA = 1.57 days. Additionally, the possible impact of the emission of chloro acetoacetates in rain acidification was evaluated from the moderate Acidification Potentials (AP), 0.19, and 0.21 obtained for E2CAA and M2CAA, respectively.

Reaction mechanism and kinetics of H and Cl atom abstraction in Dichloromethane with OH radical

Dichloromethane or methylene chloride (DCM, CH2Cl2) is a hazardous toxic pollutant that enters the stratosphere via reaction with OH radicals. The present study examines DCM's complete reaction mechanism with OH radicals via H and Cl atom abstraction using density functional theory (DFT) methods such as B3LYP, M06-2X level of theory with 6–311++G(d,p) and 6–311++G(3df,2p) basis sets. In addition to DFT results, ab initio and composite methods such as MP2, CCSD(T), G3B3, and CBS-QB3 level of theory are utilized to validate the results. The subsequent secondary reaction mechanism of peroxy radicals with HO2 and NO radicals was studied in both singlet and triplet states. H-atom abstraction is the most favorable with a small relative energy barrier of 2.70 kcal/mol. The rate constant calculated by canonical variational transition state theory with the small curvature tunneling method (CVT/SCT) at 298 K is 9.50 × 10-13 cm3 molecule-1 s−1, which agrees well with previous experimental studies, and the atmospheric lifetime of the reaction is 12.18 days at 298 K. Possible new intermediates and products, such as dichloromethyl peroxide, dichloromethyl nitrate, and formyl chloride, have been identified.

Novel Carbene Hydroxymethylene Derivatives: Gibbs free energy, NBO, AIM, and Hammett approaches via DFT and MP2 methods

Density functional theory (DFT) and the Møller-Plesset expansion (MP2) calculations were benchmarked to characterize the structure of novel derivatives of carbene hydroxymethylene. In this regard, eleven numbers of primary aldehydes including formaldehyde, acetaldehyde, formyl chloride, 2-chloroacetaldehyde, formyl fluoride, 2-fluoroacetaldehyde, formic acid, propionaldehyde, glyoxal, methyl formate, and formyl bromide (1H-11Br) were scrutinized, at the B3LYP/6-311++G(3d,3p) level of theory. Thereafter, the process of keto-enol tautomerism via a [1,2]-H-shift of 1H-11Br was monitored to reach their corresponding enol forms (1P-11P). For all species (except for one structure), the TS involves a triangle structure of C-O-H and yields cis or trans isomers of a singlet ground-state (S) carbene that contrasts the multiplicity of ordinary carbenes. The bond dissociation energy (BDE) calculations were carried out for the homolytic cleavage of C−H bonds of 1H-11Br. The AIM, as a promising analysis that definitely reveals the nature of the bond, was conducted to characterize the eigenvalues at the bond critical points (BCPs). In addition, the relation between the Hammett equation and thermodynamic parameters was obtained. Our investigation suggests new stable S derivatives of carbene hydroxymethylene that can be isolated.

Heterologous expression of bacterial cytochrome P450 from Microbacterium keratanolyticum ZY and its application in dichloromethane dechlorination

Dichloromethane (DCM) is a volatile halogenated hydrocarbon with teratogenic, mutagenic and carcinogenic effects. Biodegradation is generally regarded as an effective and economical approach of pollutant disposal. In this study, a novel strain was isolated and its cytochrome P450 was heterologously expressed for DCM degradation. The isolate, Microbacterium keratanolyticum ZY, was characterized as a Gram-positive, rod-shaped and flagella-existed bacterium without spores (GenBank No. SUB8814364; CCTCC M 2019953). After successive whole-genome sequencing, assembly and annotation, eight identified functional genes (encoding cytochrome P450, monooxygenase, dehalogenase and hydrolase) were successfully cloned and expressed in Escherichia coli BL21 (DE3). The recombinant strain expressing cytochrome P450 presented the highest degradation efficiency (90.6%). Moreover, the specific activity of the recombinant cytochrome P450 was more than 1.2 times that of the recombinant dehalogenase (from Methylobacterium rhodesianum H13) under their optimum conditions. The kinetics of DCM degradation by recombinant cytochrome P450 was well fitted with the Haldane model and the value of maximum specific degradation rate was determined to be 0.7 s−1. The DCM degradation might occur through successive hydroxylation, dehydrohalogenation, dechlorination and oxidation to generate gem-halohydrin, formyl chloride, formaldehyde and formic acid. The study helps to comprehensively understand the DCM dechlorination process under the actions of bacterial functional enzymes (cytochrome P450 and dehalogenase).

Atmospheric fate of formyl chloride and mechanisms of the gas-phase reactions with OH radicals and Cl atoms

Formyl chloride (HCOCl) is a major product in the atmospheric degradation of several chlorinated hydrocarbons, but its atmospheric fate is not well known. Here, the kinetics of HCOCl with OH radicals and Cl atoms were studied over the temperature range of 180 to 400 K using Canonical Variational Transition state theory including Small Curvature Tunneling correction (CVT/SCT). The obtained temperature-dependent rate coefficients for the reactions of HCOCl with OH and Cl are (1.86 ± 0.7) × 10−11 exp[(−1217 ± 19)/T] cm3molecule−1s−1 and (9.87 ± 0.6) × 10−12 exp[(−747 ± 33)/T] cm3molecule−1s−1, respectively. Reaction mechanisms and thermodynamic parameters for the title reactions were studied, and the atmospheric lifetime of HCOCl was determined.

OH-initiated degradation of methyl 2-chloroacetoacetate and ethyl 2-chloroacetoacetate: Kinetics, products and mechanisms at 298 K and atmospheric pressure

Rate coefficients for the gas-phase reactions of OH radicals with CH3C(O)CHClC(O)OCH3 (k1) and CH3C(O)CHClC(O)OCH2CH3 (k2) were measured using the relative technique with different reference compounds. The experiments were performed at (298 ± 2) K and 750 Torr of nitrogen or synthetic air by in situ FTIR spectroscopy and GC-FID chromatography. The following rate coefficients (in units of cm3molecule−1 s−1) were obtained: k1FTIR= (2.70 ± 0.51) × 10−11; k1GC-FID= (2.30 ± 0.71) × 10−11 and k2FTIR= (3.37 ± 0.62) × 10−11; k2GC-FID= (3.26 ± 0.85) × 10−11. This work reports the first kinetic study for the reactions of OH radicals with the mentioned chloroacetoacetates. Additionally, product studies are reported in similar conditions of the kinetic experiments. Acetic acid, acetaldehyde, formyl chloride, and methyl 2-chloro-2-oxoacetate were positively identified and quantified as degradation products. According to the identified products, atmospheric chemical mechanisms were proposed. The environmental implications of these reactions were assessed by the tropospheric lifetimes calculations of the title chloroesters. Significant average ozone production of 4.16 ppm for CH3C(O)CHClC(O)OCH3 and 5.98 ppm for CH3C(O)CHClC(O)OCH2CH3, respectively were calculated.

Coulomb explosion imaging for gas-phase molecular structure determination: An ab initio trajectory simulation study.

Coulomb explosion velocity-map imaging is a new and potentially universal probe for gas-phase chemical dynamics studies, capable of yielding direct information on (time-evolving) molecular structure. The approach relies on a detailed understanding of the mapping between the initial atomic positions within the molecular structure of interest and the final velocities of the fragments formed via Coulomb explosion. Comprehensive on-the-fly ab initio trajectory studies of the Coulomb explosion dynamics are presented for two prototypical small molecules, formyl chloride and cis-1,2-dichloroethene, in order to explore conditions under which reliable structural information can be extracted from fragment velocity-map images. It is shown that for low parent ion charge states, the mapping from initial atomic positions to final fragment velocities is complex and very sensitive to the parent ion charge state as well as many other experimental and simulation parameters. For high-charge states, however, the mapping is much more straightforward and dominated by Coulombic interactions (moderated, if appropriate, by the requirements of overall spin conservation). This study proposes minimum requirements for the high-charge regime, highlights the need to work in this regime in order to obtain robust structural information from fragment velocity-map images, and suggests how quantitative structural information may be extracted from experimental data.

Highly-excited state properties of cumulenone chlorides in the vacuum-ultraviolet.

Recent observations of chloromethane in interstellar environments suggest that other organohalogens, which are known to be critically important in Earth's atmosphere, may also be of significance beyond our own terrestrial veil. This raises the question of how such molecules behave under extreme conditions such as when exposed to vacuum ultraviolet (VUV) radiation. VUV photons promote molecules to highly excited states that fragment in non-statistical patterns controlled by the initial femtosecond dynamics. A detailed understanding of VUV-driven photochemistry in complex organic molecules that consist of more than one functional group is a particularly challenging task. This quantum chemical analysis reports the electronic states and ionization potentials up to the VUV range (6-11 eV) of the chlorine-substituted cumulenone series molecules. The valence and Rydberg properties of lone-pair terminated, π-conjugated systems are explored for their potential resonance with lone pairs from elsewhere in the system. The carbon chain elongation within the family ClHCnO, where n = 1-4, influences the electronic excitations, associated wavefunctions, and ionization potentials of the molecules. The predicted geometries and ionization potentials are in good agreement with the available experimental photoelectron spectra for formyl chloride and chloroketene, n = 1-2. Furthermore, comparison between the regular cumulenone species and the corresponding chlorinated derivatives exhibit similar behaviors especially for n = 3, where the allene backbone in propadienone chloride is severely bent. Most notably for the excited states is that the Rydberg character becomes more dominant as the energy increases, with some retaining valence characters.

A comprehensive quantum chemical study on the mechanism and kinetics of atmospheric reactions of 3-chloro-2-methyl-1-propene with OH radical

The detailed reaction mechanism of 3-chloro-2-methyl-1-propene (3CMP) with OH radical was investigated by employing highly accurate electronic structure calculations and kinetic modelling. Due to the unsaturated structure of 3CMP, it is highly reactive in the troposphere with OH radical. The fate of the so-formed alkyl radical intermediates and intermediate adducts in the favourable pathways is determined by its reaction with other atmospheric oxidants, such as HO2, NO and NO2 radicals. The rate constants computed within the temperature range of 200–1000 K for the favourable hydrogen atom abstraction and OH radical addition reactions are in reasonable agreement with the available experimental values. The oxidation of 3CMP results in the formation of stable chlorinated products, such as chloroacetone and formyl chloride, which are identified experimentally. These products may be transported to the stratosphere which will affect the ozone layer.

Atmospheric sink of styrene, α-methylstyrene, trans-β-methylstyrene and indene: Rate constants and mechanisms of Cl atom-initiated degradation

The kinetics and products of the oxidation of four aromatic compounds, i.e. styrene, α-methylstyrene, trans-β-methylstyrene and indene, with Cl atoms were determined at atmospheric pressure and room temperature. Kinetic experiments were carried out in a 400 L Teflon reaction chamber using GC-FID for the analysis of reactants and products were determined using a 56 L quartz-glass reactor coupled to FTIR spectrophotometer. The rate constants at 298 K, using different reference compounds, were (in units of cm3 molecule−1 s−1): kstyrene = (1.29 ± 0.52)×10−10, kα-methylstyrene = (1.55 ± 0.27)×10−10, ktrans-β-methylstyrene = (1.09 ± 0.23)×10−10 and kindene = (1.01 ± 0.30)×10−10. Observations with FTIR suggest that the main reaction is the addition of the Cl to the aliphatic chain of the aromatic molecules. We found benzaldehyde, benzoyl chloride, formaldehyde and formyl chloride from styrene; acetophenone, formaldehyde and formyl chloride from α-methylstyrene; and benzaldehyde, formaldehyde and acetyl chloride from trans-β-methylstyrene as the main oxidation products. DFT theoretical calculations were performed in order to shed light on the identification of the reaction products. To the best of our knowledge, this work represents the first determination of the rate coefficients and products for the reaction of the Cl atoms with these compounds, except for the rate constant of styrene which has been studied previously. The loss processes of the title compounds in the atmosphere are mostly controlled by reactions with OH radicals during the day and with NO3 at night, but in coastal areas and some polluted environments, Cl reactions became comparable with OH and NO3 radicals, with lifetimes of 2.2 h for styrene, 1.8 h for AMS, 2.5 h for TBMS and 2.8 h for indene.

Fate of Chloromethanes in the Atmospheric Environment: Implications for Human Health, Ozone Formation and Depletion, and Global Warming Impacts.

Among the halogenated hydrocarbons, chloromethanes (i.e., methyl chloride, CH3Cl; methylene chloride, CH2Cl2; chloroform, CHCl3; and carbon tetrachloride, CCl4) play a vital role due to their extensive uses as solvents and chemical intermediates. This article aims to review their main chemical/physical properties and commercial/industrial uses, as well as the environment and health hazards posed by them and their toxic decomposition products. The environmental properties (including atmospheric lifetime, radiative efficiency, ozone depletion potential, global warming potential, photochemical ozone creation potential, and surface mixing ratio) of these chlorinated methanes are also reviewed. In addition, this paper further discusses their atmospheric fates and human health implications because they are apt to reside in the lower atmosphere when released into the environment. According to the atmospheric degradation mechanism, their toxic degradation products in the troposphere include hydrogen chloride (HCl), carbon monoxide (CO), chlorine (Cl2), formyl chloride (HCOCl), carbonyl chloride (COCl2), and hydrogen peroxide (H2O2). Among them, COCl2 (also called phosgene) is a powerful irritating gas, which is easily hydrolyzed or thermally decomposed to form hydrogen chloride.

Reactions of Three Lactones with Cl, OD, and O3: Atmospheric Impact and Trends in Furan Reactivity

Lactones, cyclic esters of hydroxycarboxylic acids, are interesting biofuel candidates as they can be made from cellulosic biomass and have favorable physical and chemical properties for distribution and use. The reactions of γ-valerolactone (GVL), γ-crotonolactone (2(5H)-F), and α-methyl-γ-crotonolactone (3M-2(5H)-F) with Cl, OD, and O3 were investigated in a static chamber at 700 Torr and 298 ± 2 K. The relative rate method was used to determine kGVL+Cl = (4.56 ± 0.51) × 10-11, kGVL+OD = (2.94 ± 0.41) × 10-11, k2(5H)-F+Cl = (2.94 ± 0.41) × 10-11, k2(5H)-F+OD = (4.06 ± 0.073) × 10-12, k3M-2(5H)-F+Cl = (16.1 ± 1.8) × 10-11, and k3M-2(5H)-F+OD = (12.6 ± 0.52) × 10-12, all rate coefficients in units of cm3 molecule-1 s-1. An absolute rate method was used to determine k2(5H)-F+O3 = (6.73 ± 0.18) × 10-20 and k3M-2(5H)-F+O3 = (5.42 ± 1.23) × 10-19 in units of cm3 molecule-1 s-1. Products were identified for reactions of the lactones with Cl. In the presence of O2 the products are formic acid (HCOOH), formyl chloride (CHClO), and phosgene (CCl2O), and also maleic anhydride (C2H2(CO)2O) for 2(5H)-F. In addition both reactions produced a number of unidentified products that likely belong to molecules with the ring-structure intact. A review of literature data for reactions of other furans show that the reactivity of the lactones are generally lower compared to that of corresponding compounds without the carbonyl group.

Kinetic Determination of the Gas-Phase Decarbonylation of Butyraldehyde in the Presence of HCl Catalyst

The gas-phase kinetics and mechanism of the homogeneous elimination of CO from butyraldehyde in the presence of HCl has been experimentally studied. The reaction is homogeneous and follows the second-order kinetics with the following rate expression: log k1 (s−1 L mol−1) = (13.27 ± 0.36) – (173.2 ± 4.4) kJ mol−1(2.303RT)−1. Experimental data suggested a concerted four-membered cyclic transition state type of mechanism. The first and rate-determining step occurs through a four-membered cyclic transition state to produce propane and formyl chloride. The formyl chloride intermediate rapidly decomposes to CO and HCl gases.

Novel biologically active series of N-acetylglucosamine derivatives for the suppressive activities on GAG release

(d)-Glucosamine and other nutritional supplements have emerged as safe alternative therapies for osteoarthritis, a chronic and degenerative articular joint disease. N-acetyl-(d)-glucosamine, a compound that can be modified at the N position, is considered to improve the oral bioavailability of (d)-glucosamine and has been proven to possess greater in vitro chondroprotective activity compared with the parent agent. In this study, to further utilize these properties, we focus on the modification of the N position with a benzenesulfonyl and different isoxazole formyl groups. Among these compounds, the 3-(2-chlorobenzene)-5-methyl-isoxazole formyl chloride and p-methoxybenzenesulfonyl chloride modifying structures proved to be the most active of the series and efficiently processed the chondrocytes in vitro. These novel N-position substitution compounds may represent promising leads for osteoarthritis drug development.

Mechanistic Studies of the Solvolyses of Carbamoyl Chlorides and Related Reactions.

Carbamoyl chlorides are important intermediates, both in the research laboratory and in industrial scale syntheses. The most studied and used are the disubstituted derivatives, incorporating either aryl or alkyl groups (Ar2NCOCl or R2NCOCl). Sometimes, the groups are tied back to give a ring and piperidino- and morpholino-derivatives are commonly encountered. Some studies have been made with two different groups attached. Solvolyses tend to occur at the carbonyl carbon, with replacement of the chloride ion. Studies of both rate and products are reviewed and the solvolysis reactions are usually SN1, although addition of an amine leads to a superimposable bimolecular component. Many of the studies under solvolytic conditions include the application of the extended Grunwald–Winstein equation. The monosubstituted derivatives (ArNHCOCl or RNHCOCl) are less studied. They are readily prepared by the addition of HCl to an isocyanate. In acetonitrile, they decompose to set up and reach equilibrium with the isocyanate (ArNCO or RNCO) and HCl. Considering that the structurally related formyl chloride (HOCOCl) is highly unstable (with formation of HCl + CO2), the unsubstituted carbamoyl chloride (H2NCOCl) is remarkably stable. Recommended synthetic procedures require it to survive reaction temperatures in the 300–400 °C range. There has been very little study of its reactions.