Carbocations forming reactions

As the understanding of the ionic intermediates has progressed, advantage has been taken of the fact that bromination, like SN1 heterolysis, is a carbocation-forming reaction. Kinetic data on this addition have therefore been used to examine in detail how the basic concepts of physical organic chemistry work as regards transition-state shifts with reactivity (Ruasse et al, 1984). Bromination lends itself particularly well to the quantitative application of the BEMA HAPOTHLE (acronym for Bell, Marcus, Hammond, Polanyi, Thornton and Leffler Jencks, 1985). In particular, it has been possible to evaluate the transition-state dependence on the solvent and substituents. The major disadvantage that bromination shares with many... 

The ct" " substituent constant scale was developed based upon the solvolysis of substituted cumyl chlorides, where cumyl cations are formed in the rate-determining ionization. For the carbocation-forming reaction of Eq. 20, there is a good correlation of log versus the sum of the constants for the substituents directly on the carbon. Such a correlation clearly does not exist for the reaction where the... 

Long-lived cyclopropylcarbinyl cation chemistry, including spiro cations and dications, has been reviewed,7 and some of the more interesting newer carbocations, such as (1), are the subject of a short survey.8 The use of secondary deuterium isotope effects in the study of carbocation-forming reactions has been revisited,9 and the... 

Another way in which the electron-donating ability of cyclopropyl is manifested is in the influence of this group on the sensitivity of reaction centers to the effect of other substituents. This is conveniently examined in carbocation forming reactions by the values which measure the dependence of the reaction to the electron-donating ability of aryl substituents as expressed by their Brown-Hammett values by the relation log k/kii = p (7 as shown in Table 9 ... 

Treating 5.5 g of 2-amino-4,5-dimethylthiazole HCl with 0.66 g of solid sodium hydroxide 15 min at 220°C yields 53% of 4.4. 5.5 -tetramethyT 2,2 -dithiazolylamine, whose structure w as proved by identification with the produa obtained from the reaction between dithiobiuret and 3-bromo-2-butanone (467). This result is comparable to the reaction between 2-aminopyridine and its hydrochloride to yield bis(pyridyl-2)amine (468). Gronowitz applied this reaction to 2-aminothiazole, refluxing it with its hydrochloride 4 hr in benzene and obtained the dimeric 2-aminothiazole (236). He proposed a mechanism (Scheme 143) that involves the addition of a proton to the 5-position of the ring to give 234. The carbocation formed then reacts on the 5-position of a second... 

The carbocations formed as intermediates when allylic halides undergo Stvfl reactions have their positive charge shared by the two end carbons of the allylic system and may be attacked by nucleophiles at either site Products may be formed with the same pattern of bonds as the starting allylic halide or with allylic rearrangement... 

The tertiary carbocation formed m this step can react according to any of the various reaction pathways available to carbocations One of these is loss of a proton to give a double bond... 

The rates of hydration of alkenes increase dramatically with increasing alkyl substitution (see table at left). This is usually attributed to the relative stabilities of carbocations formed as intermediates in the initial (and rate-hmiting) step of the reaction, e.g., for hydration of propene. 

Problem 5.7 Reaction of HBr with 2-methylpropene yields 2-bromo-2-methvlpropane. What is the structure of the carbocation formed during the reaction Show the mechanism of the reaction. 

According to the Hammond postulate (Section 6.10), any factor that stabilizes a high-energy intermediate also stabilizes the transition state leading to that inlermediate. Since the rate-limiting step in an S l reaction is the spontaneous, unimolecLilar dissociation of the substrate to yield a carbocation, the reaction is favored whenever a stabilized carbocation intermediate is formed. The more stable the carbocation intermediate, the faster the S l reaction. 

When the addition is initiated by attack of the jr-electrons in an unsaturated bond on an electrophile to form a carbocation the reaction is an electrophilic addition, a very common class of reactions for alkenes. The reaction is governed by Markovnikov s rule, which states that in addition of HX to a substituted alkene, the H will form a bond to the carbon of the alkene carrying the greater number of hydrogen atoms. 

Carbocations form during the course of a reaction but are usually consumed rapidly. Describe the bonding and geometry of the carbocation (CH3)3 C ... 

There are, however, serious problems that must be overcome in the application of this reaction to synthesis. The product is a new carbocation that can react further. Repetitive addition to alkene molecules leads to polymerization. Indeed, this is the mechanism of acid-catalyzed polymerization of alkenes. There is also the possibility of rearrangement. A key requirement for adapting the reaction of carbocations with alkenes to the synthesis of small molecules is control of the reactivity of the newly formed carbocation intermediate. Synthetically useful carbocation-alkene reactions require a suitable termination step. We have already encountered one successful strategy in the reaction of alkenyl and allylic silanes and stannanes with electrophilic carbon (see Chapter 9). In those reactions, the silyl or stannyl substituent is eliminated and a stable alkene is formed. The increased reactivity of the silyl- and stannyl-substituted alkenes is also favorable to the synthetic utility of carbocation-alkene reactions because the reactants are more nucleophilic than the product alkenes. 

For a long time, it was considered that the formation of a bromonium ion from olefin and bromine is irreversible, i.e. the product-forming step, a cation-anion reaction, is very fast compared with the preceding ionization step. There was no means of checking this assumption since the usual methods—kinetic effects of salts with common and non-common ions—used in reversible carbocation-forming heterolysis (Raber et al., 1974) could not be applied in bromination, where the presence of bromide ions leads to a reacting species, the electrophilic tribromide ion. Unusual bromide ion effects in the bromination of tri-t-butylethylene (Dubois and Loizos, 1972) and a-acetoxycholestene (Calvet et al, 1983) have been interpreted in terms of return, but cannot be considered as conclusive. 

Addition of hydroxide occurs as a rapid follow-up reaction. Even if the alkyl halide was chiral before the carbocation formed, racemization occurs about the central carbon atom because the hydroxide can bond to the planar central carbon from either side (see Figure 8.17(b)). Statistically, equal numbers of each racemate are formed, so the angle through which the plane polarized light rotated during reaction will, therefore, decrease toward 0°, when reaction is complete. 

Pyrrolo[l,2-c][l,3]oxazin-l-one 248 has been obtained by reaction of allylsilanes with a pyrrolidine-lV-acyliminium ion 247 (Scheme 32), formed by addition of a Lewis acid on compound 244. The /3-silyl carbocation formed by the reaction with allylsilane 246 reacted with the oxygen of the N-15OC group followed by the loss of 2-methylpropene. The reaction was not very stereoselective when trimethylsilane was used, whereas with larger group on the silicon the selectivity was increased <1997J(P1)2163>. 

Not only is the leaving group important, but if the reaction has SnI character, the stability of the positive charge left behind is also important. In the examples above, a primary carbocation is difficult to form and therefore the reaction of busulfan with glutathione would likely be a SN2-type reaction, whereas the nitrenium ion and carbocation formed from N -acetylaminofluorene and safrole, respectively, are relatively stable and likely to be Sn 1 -type reactions. 

Thus the carbanion owe their importance in the synthesis of great variety of bond-forming reactions. Unlike carbocations most carbanions do not undergo rearrangements but in many cases react in substitution and addition reactions in high yields. Changing the cation and solvent can greatly affect the reaction. 

Although the geometric relationship suggested by Shiner and by Sunko and their co-workers clearly demonstrates that hyperconjugation is the major contributor to the secondary /3-deuterium KIE in carbocation reactions, Williams (1985) has suggested that there is a significant inductive component to these KIEs. Williams used ab initio MO methods to calculate the geometries of the substrates and the isopropyl carbocation formed in a gas-phase heterolysis (30) of series of isopropyl derivatives at the RHF/4-31G level. 

Finally, as is the case for the secondary a-deuterium KIEs, the /3-deuterium KIE is assumed to vary in magnitude from near unity for a reactant-like transition state to a maximal value for a transition state resembling the carbocation formed in an SN1 reaction. The experimentally determined KIE may, therefore, be used as a measure of transition state structure provided that the maximum value of the KIE, i.e. the EIE for the formation of the carbocation, is known. 

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