Kinetics chlorination

Dodd MC, C-H Huang (2004) Transformation of the antibacterial agent sulfamethoxazole in reactions with chlorine kinetics, mechanisms, and pathways. Environ Sci Technol 38 5607-5615. 

Zhang Q, SO Pehkonen (1999) Oxidation of diazinon by aqueous chlorine kinetics, mechanisms, and product studies. J Agric Eood Ghent Al 1760-1766. 

Westaway KC, T Koerner, Y-R Fang, J Rudzinski, P Paneth (1998) A new method of determining chlorine kinetic isotope effects. A a/ Chem 70 3548-3552. 

For heavy atom isotope effects tunneling is relatively unimportant and the TST model suffices. As an example the dehalogenation of 1,2-dichloroethane (DCE) to 2-chloroethanol catalyzed by haloalkane dehalogenase DhlA is discussed below. This example has been chosen because the chlorine kinetic isotope effect for this reaction has been computed using three different schemes, and this system is among the most thoroughly studied examples of heavy atom isotope effects in enzymatic reactions. 

The haloalkane dehalogenase DhlA mechanism takes place in two consecutive Sn2 steps. In the first, the carboxylate moiety of the aspartate Aspl24, acting as a nucleophile on the carbon atom of DCE, displaces chloride anion which leads to formation of the enzyme-substrate intermediate (Equation 11.86). That intermediate is hydrolyzed by water in the subsequent step. The experimentally determined chlorine kinetic isotope effect for 1-chlorobutane, the slow substrate, is k(35Cl)/k(37Cl) = 1.0066 0.0004 and should correspond to the intrinsic isotope effect for the dehalogenation step. While the reported experimental value for DCE hydrolysis is smaller, it becomes practically the same when corrected for the intramolecular chlorine kinetic isotope effect (a consequence of the two identical chlorine labels in DCE). 

Another approach to modeling the chlorine kinetic isotope effect of this reaction has been carried out using a true QM/MM scheme. 

O Neil JR (1986) Theoretical and experimental aspects of isotopic fractionation. Rev Mineral 16 1-40 Oi T (2000) Calculations of reduced partition function ratios of monomeric and dimeric boric acids and borates by the ab initio molecular orbital theory. J Nuclear Sci Tech 37 166-172 Oi T, Nomura M, Musashi M, Ossaka T, Okamoto M, Kakihana H (1989) Boron isotopic composition of some boron minerals. Geochim Cosmochim Acta 53 3189-3195 Oi T, Yanase S (2001) Calculations of reduced partition function ratios of hydrated monoborate anion by the ab initio molecular orbital theory. J Nuclear Sci Tech 38 429-432 Paneth P (2003) Chlorine kinetic isotope effects on enzymatic dehalogenations. Accounts Chem Res 36 120-126... 

Lewandowicz A, Rudzinski J, Tronstad L, Widersten M, Ryberg P, Matsson O, Paneth P (2001) Chlorine Kinetic Isotope Effects on the Haloalkane Dehalogenase Reaction. J Am Chem Soc 123 4550... 

Paneth P (2003) Chlorine Kinetic Isotope Effects on Enzymatic Dehalogenations. Acc Chem Res 36 120... 

The mcd chlorination kinetics for V-CIPO (C. inaequalis) also fit a substrate inhibited bi-bi Ping-Pong mechanism. The kinetic constant for chloride, Kmc is reported to be 0.25 mMat pH 4.5 [3], The kinetic constant for dihydrogen peroxide, KmU2° varies as a function of pH 0.5 mM at pH 3.2 to 0.01 mM at pH 5 [59], As with V-BrPO (A. nodosum), chloride is both a substrate for and... 

The chlorination reaction rate can be limited either by chemical kinetics or ethylene mass transfer, depending on ethylene partial pressure, agitation, catalyst composition, and temperature. If the ethylene partial pressure, and/or agitation rate are low, the transfer rate of ethylene to the catalyst solution will be too small to satisfy the kinetic capabilities of the catalyst, and the system will be mass-transfer limited. As either or both ethylene partial pressure and agitation are increased, the mass transfer rate will increase, and eventually ethylene can be supplied to the system at a rate equal to, or in excess of, the kinetic rate capabilities, and the reaction system will be limited kinetically from this point. The mass transfer and kinetic-limiting regimes have been delineated, and simultaneous feed operations were normally made under conditions where chlorination kinetics—not ethylene mass transfer—was controlling. 

The chlorine kinetic isotope effect in nucleophilic displacement at saturated carbon in para-substituted benzyl chlorides, with thiolate and analogous oxygen nucleophiles, has been examined . The reactions proceed via a concerted transition state. 

Chang J P, Arnold J C, Zau G C H, Shin H-S and Sawin H H 1997 Kinetic study of low energy ion-enhanced plasma etching of polysilicon with atomic/molecular chlorine J. Vac. Sc/. Technol. A 15 1853-63... 

We have seen ( 6.2.3) hat there is a close relationship between the rates of electrophilic substitutions and the stabilities of tr-complexes, and facts already quoted above suggest that no such relationship exists between those rates and the stabilities of the 7r-complexes of the kind discussed here. These two contrasting situations are further illustrated by the data given in table 6.2. As noted earlier, the parallelism of rate data for substitutions with stability data for o"-complexes is not limited to chlorination ( 6.2.4). Clearly, rr-complexes have no general mechanistic or kinetic significance in electrophilic substitutions. 

Kinetic data are available for the nitration of a series of p-alkylphenyl trimethylammonium ions over a range of acidities in sulphuric acid. - The following table shows how p-methyl and p-tert-h xty augment the reactivity of the position ortho to them. Comparison with table 9.1 shows how very much more powerfully both the methyl and the tert-butyl group assist substitution into these strongly deactivated cations than they do at the o-positions in toluene and ferf-butylbenzene. Analysis of these results, and comparison with those for chlorination and bromination, shows that even in these highly deactivated cations, as in the nitration of alkylbenzenes ( 9.1.1), the alkyl groups still release electrons in the inductive order. In view of the comparisons just... 

When unsubstituted, C-5 reacts with electrophilic reagents. Thus phosphorus pentachloride chlorinates the ring (36, 235). A hydroxy group in the 2-position activates the ring towards this reaction. 4-Methylthiazole does not react with bromine in chloroform (201, 236), whereas under the same conditions the 2-hydroxy analog reacts (55. 237-239. 557). Activation of C-5 works also for sulfonation (201. 236), nitration (201. 236. 237), Friede 1-Crafts reactions (201, 236, 237, 240-242), and acylation (243). However, iodination fails (201. 236). and the Gatterman or Reimer-Tieman reactions yield only small amounts of 4-methyl-5-carboxy-A-4-thiazoline-2-one. Recent kinetic investigations show that 2-thiazolones are nitrated via a free base mechanism. A 2-oxo substituent increases the rate of nitration at the 5-position by a factor of 9 log... 

The lack of dependence on ionic strength in the first reaction indicates that it occurs between neutral species. Mono- or dichloramine react much slower than ammonia because of their lower basicities. The reaction is faster with CI2 because it is a stronger electrophile than with HOCl The degree of chlorination increases with decreasing pH and increasing HOCINH mol ratio. Since chlorination rates exceed hydrolysis rates, initial product distribution is deterrnined by formation kinetics. The chloramines hydrolyze very slowly and only to a slight extent and are an example of CAC. 

Some nitrate is also formed, thus the HOCl/NH stoichiometry is greater than theoretical, ie, - 1.7. This reaction, commonly called breakpoint chlorination, involves intermediate formation of unstable dichloramine and has been modeled kinetically (28). Hypobromous acid also oxidizes ammonia via the breakpoint reaction (29). The reaction is virtually quantitative in the presence of excess HOBr. In the case of chlorine, Htde or no decomposition of NH occurs until essentially complete conversion to monochloramine. In contrast, oxidation of NH commences immediately with HOBr because equihbrium concentrations of NH2Br and NHBr2 are formed initially. As a result, the typical hump in the breakpoint curve is much lower than in the case of chlorine. 

The intermediate HCIO2 is rapidly oxidized to chloric acid. Some chlorine dioxide may also be formed. Kinetic studies have shown that decomposition to O2 and chloric acid increase with concentration, temperature (88), and exposure to light (89—92), and are pH dependent (93). Decomposition to O2 is also accelerated by catalysts, and decomposition to chlorate is favored by the presence of other electrolytes, eg, sodium chloride (94—96). 

Aqueous chlorine oxidizes numerous inorganic substrates. However, since HOCl and C10 coexist over a wide pH range, kinetic studies are necessary to estabHsh their respective roles both species are seldom active in the same reaction (97). The oxidation of CN is an important reaction in the treatment of waste-water and proceeds by the intermediate CICN (98). 

The kinetics of formation and hydrolysis of /-C H OCl have been investigated (262). The chemistry of alkyl hypochlorites, /-C H OCl in particular, has been extensively explored (247). /-Butyl hypochlorite reacts with a variety of olefins via a photoinduced radical chain process to give good yields of aUyflc chlorides (263). Steroid alcohols can be oxidized and chlorinated with /-C H OCl to give good yields of ketosteroids and chlorosteroids (264) (see Steroids). /-Butyl hypochlorite is a more satisfactory reagent than HOCl for /V-chlorination of amines (265). Sulfides are oxidized in excellent yields to sulfoxides without concomitant formation of sulfones (266). 2-Amino-1, 4-quinones are rapidly chlorinated at room temperature chlorination occurs specifically at the position adjacent to the amino group (267). Anhydropenicillin is converted almost quantitatively to its 6-methoxy derivative by /-C H OCl in methanol (268). Reaction of unsaturated hydroperoxides with /-C H OCl provides monocyclic and bicycHc chloroalkyl 1,2-dioxolanes. 

The stoichiometric relationship between chlorine dioxide added and color removed during bleaching is nonlinear, but it is independent of temperature, pH, and pulp concentration under conditions normally used. Models used to explain the kinetics and stoichiometry show a strong dependence on chromophore concentration that probably results from differences in the reaction rates of the various chromophores present in the pulps (80). 

Equation 22 gives the maximum theoretical obtainable chlorine dioxide from the disproportionation of HCIO,. Experimentally, differences in the stoichiometry have been reported. This is because the chloride formed in equation 21 can catalyze the reaction to form more chlorine dioxide as in equation 22. Proposed mechanisms for these reactions and the kinetics under various conditions have been described (16,108). 

Nucleophilic Substitution. The kinetics of the bimolecular nucleophilic substitution of the chlorine atoms in 1,2-dichloroethane with NaOH, NaOCgH, (CH2)3N, pyridine, and CH COONa in aqueous solutions at 100—120°C has been studied (24). The reaction of sodium cyanide with... 

Liquid-phase chlorination of butadiene in hydroxyhc or other polar solvents can be quite compHcated in kinetics and lead to extensive formation of by-products that involve the solvent. In nonpolar solvents the reaction can be either free radical or polar in nature (20). The free-radical process results in excessive losses to tetrachlorobutanes if near-stoichiometric ratios of reactants ate used or polymer if excess of butadiene is used. The "ionic" reaction, if a small amount of air is used to inhibit free radicals, can be quite slow in a highly purified system but is accelerated by small traces of practically any polar impurity. Pyridine, dipolar aptotic solvents, and oil-soluble ammonium chlorides have been used to improve the reaction (21). As a commercial process, the use of a solvent requites that the products must be separated from solvent as well as from each other and the excess butadiene which is used, but high yields of the desired products can be obtained without formation of polymer at higher butadiene to chlorine ratio. 

Noncatalytic ring chlorination of toluene in a variety of solvents has been reported. Isomer distributions vary from approximately 60% ortho in hydroxyhc solvents, eg, acetic acid, to 60% para in solvents, eg, nitromethane, acetonittile, and ethylene dichloride (49,50). Reaction rates are relatively slow and these systems are particularly appropriate for kinetic studies. 

The reactivity of halogens in pyridazine N- oxides towards nucleophilic substitution is in the order 5 > 3 > 6 > 4. This is supported by kinetic studies of the reaction between the corresponding chloropyridazine 1-oxides and piperidine. In general, the chlorine atoms in pyridazine A-oxides undergo replacement with alkoxy, aryloxy, piperidino, hydrazino, azido, hydroxylamino, mercapto, alkylmercapto, methylsulfonyl and other groups. 

Substituted 2-haloaziridines are also known to undergo a number of reactions without ring opening. For example, displacement of chlorine in (264) with various nucleophilic reagents has been found to occur with overall inversion of stereochemistry about the aziridine ring (65JA4538). The displacements followed first order kinetics and faster rates were noted for (264 R = Me) than for (264 R = H). The observed inversion was ascribed to either ion pairing and/or stereoselectivity. 

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