Kinetic isotope effect bromination

The distribution of a-bromoketones formed in the reaction of acetylcyclopentane with bromine was studied as a function of deuterium substitution. On the basis of the data given below, calculate the primaiy kinetic isotope effect for enolization of... 

Bromination has been shown not to exhibit a primary kinetic isotope effect in the case of benzene, bromobenzene, toluene, or methoxybenzene. There are several examples of substrates which do show significant isotope effects, including substituted anisoles, JV,iV-dimethylanilines, and 1,3,5-trialkylbenzenes. The observation of isotope effects in highly substituted systems seems to be the result of steric factors that can operate in two ways. There may be resistance to the bromine taking up a position coplanar with adjacent substituents in the aromatization step. This would favor return of the ff-complex to reactants. In addition, the steric bulk of several substituents may hinder solvent or other base from assisting in the proton removal. Either factor would allow deprotonation to become rate-controlling. 

Christen and Zollinger303 have made an extensive study of kinetic isotope effects in bromination of the disodium salt of 2-naphthol-6,8-disulphonic acid with hypobromous acid and with bromine in aqueous buffers at 20 °C. Both bro-minating agents give the same rate (within 20 %) and the reactions are first-order... 

A kinetic isotope effect, kH/kD = 1.4, has been observed in the bromination of 3-bromo-l,2,4,5-tetramethylbenzene and its 6-deuterated isomer by bromine in nitromethane at 30 °C, and this has been attributed to steric hindrance to the electrophile causing kLx to become significant relative to k 2 (see p. 8)268. A more extensive subsequent investigation304 of the isotope effects obtained for reaction in acetic acid and in nitromethane (in parentheses) revealed the following values mesitylene, 1.1 pentamethylbenzene 1.2 3-methoxy-1,2,4,5-tetramethyl-benzene 1.5 5-t-butyl-1,2,3-trimethylbenzene 1.6 (2.7) 3-bromo-1,2,4,5-tetra-methylbenzene 1.4 and for 1,3,5-tri-f-butylbenzene in acetic acid-dioxan, with silver ion catalyst, kH/kD = 3.6. All of these isotope effects are obtained with hindered compounds, and the larger the steric hindrance, the greater the isotope... 

The bromination of phenol in acetic acid, containing lithium bromide and perchlorate at a constant total concentration of 0.2 M, gave kinetic isotope effects... 

The use of secondary deuterium kinetic isotope effects in mechanistic studies of olefin bromination... 

Apart from a few studies (ref. 7), the use of deuterium kinetic isotope effects (kie s) appears to have had limited use in mechanistic studies of electrophilic bromination of olefins. Secondary alpha D-kie s have been reported for two cases, trans-stilbene fi and p-substituted a-d-styrenes 2, these giving relatively small inverse kie s of... 

Kinetic isotope effects have not been observed for chlorination, and only rarely for bromination, i.e. the reactions normally follow pathway [2a] like nitration. In iodination, which only takes place with iodine itself on activated species, kinetic isotope effects are the rule. This presumably arises because the reaction is readily reversible (unlike other halogenations), loss of I occurring more often from the a complex (14) than loss of H, i.e. k, > k2 ... 

The electrophile E+ attacks the unhindered side of the still unsubstituted second aromatic ring. A proton (deuteron) is transferred from this ring to the second, originally substituted ring, from which it leaves the molecule. Thus, the electrophile enters, and the proton (deuteron) leaves the [2.2]paracyclophane system by the least hindered paths. Some migration of deuterium could be detected in the bromination of 4-methyl[2.2]paracyclophane (79). The proposed mechanism is supported by the kinetic isotope effects ( h/ d) found for bromination of p-protio and p-deuterio-4-methyl[2.2]paracyclophanes in various solvents these isotope effects demonstrate that proton loss from the a complex is the slowest step. 

The deuterium kinetic isotope effect (DKIE) for the electrophilic bromination of ethylene-/z4 and ethylene- 4 in methanol and dichloroethane at 25 °C has been... 

The oxidation of a-hydroxy acids by benzyltrimethylammonium tribromide (BTMAB) to the corresponding carbonyl compounds shows a substantial solvent isotope effect, A (H20)/A (D20) = 3.57, but no KIE for a-deuteromandelic acid.133 The oxidation of glucose by hypobromous acid is first order in glucose and the acid.134 [l,l-2H2]Ethanol shows a substantial kinetic isotope effect when oxidized by hexamethylenetetramine-bromine (HABR) in acetic acid to aldehyde.135 Kinetics of the oxidation of aliphatic aldehydes by hexamethylenetetramine-bromine have been studied by the same group.136 Dioxoane dibromide oxidizes y-tocopherol to 5-bromomethyl-y-tocopherylquinone, which spontaneously cyclizes to 5-formyl-y-tocopherol.137... 

The kinetics and the products of bromination of several substituted stilbenes with Bu4N+Br3 have been investigated in aprotic solvents at different temperatures and concentrations. Stilbenes bearing electron-withdrawing or moderately electron-donating substituents gave stereospecifically the anti addition products the reaction followed a second-order rate law and inverse kinetic isotope effect Ap/Ap = 0.85 ( 0.05) was... 

An unusually large inverse secondary deuterium kinetic isotope effect (1.53-2.75, depending on the reaction conditions) has been reported for bromination of the sterically congested olefin 74. This behaviour can be rationalized by decreased steric hindrance due, in particular, to the ewrfo-placement of the deuterium atoms relative to the double bond135. 

The oxidation of a-hydroxy acids by hexamethylenetetramine-bromine (HABR) is first order with respect to each of the hydroxy acids and HABR. The oxidation of o -deuteriomandelic acid exhibited a kinetic isotope effect of kn/ko = 5.91 at 298 K. The rates of oxidation of the substituted mandelic acids show excellent correlation with Brown s er+ values with negative reaction constants. A mechanism involving transfer of a hydride ion from the acid to the oxidant has been postulated.128... 

Figure 7 2H and 13C kinetic isotope effects for bromination of 1-pentene 17. 

The reverse kinetic isotope effect (82Br reacts faster than 77Br ) of about 0.5-5% would imply that the covalent bond between aromatic ring carbon and bromine is practically formed in the transition state of the bromodestannylation reaction. 

Isotope effect and relative rate studies also suggest an early TS for benzylic chlorination and bromination. The benzylic position is only moderately activated toward uncomplexed chlorine atoms. Relative to ethane, toluene reactivity is increased only by a factor of 3.3. The kinetic isotope effect observed for bromination and chlorination of toluene suggest little rehybridization at the TS. 

Predict whether chlorination or bromination would have a greater deuterium kinetic isotope effect. 

A. Differentiation between S 2- and S -Mechanisms Kinetic isotope effects had a fundamental importance, however, for the elucidation of the substitution proper. Melander (1950) showed that a series of benzene derivatives containing tritium were nitrated and brominated at the same rate as the corresponding ordinary protium compound. This is the most important and elegant experimental support for the Sjj2- or two-stage mechanism (reactions 1-2, the... 

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