The Carbocation

Reactions of the 2-amino-4,5-substituted thiazole (52) in acetic acid with ethylene oxide has been reported to give the N-exocyclic disubstitution product (S3) (201) in a 40% yield (Scheme 38). The reactive species in this reaction is probably the carbocation generated in acetic acid by ethvlene oxide. 

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 interesting reactions where a free mercapto group is linked to the nitrogen atom of the thiazole (63), after the cleavage of a fused ring, is another illustration of the additive properties of the carbocation (Scheme 40). 

The transition state is closer m energy to the carbocation (tert butyl cation) so Its structure more closely resembles the carbocation than it resembles tert butyloxonium ion The transition state has considerable carbocation character meaning that a significant degree of positive charge has developed at carbon... 

Step 3 IS bimolecular because two species the carbocation and chloride ion react together Figure 4 10 shows a potential energy diagram for this step... 

The step is exothermic it leads from the carbocation intermediate to the isolated products of the reaction... 

As we have just seen the rate determining intermediate m the reaction of tert butyl alco hoi with hydrogen chloride is the carbocation (CH3)3C Convincing evidence from a variety of sources tells us that carbocations can exist but are relatively unstable When carbocations are involved m chemical reactions it is as reactive intermediates formed slowly m one step and consumed rapidly m the next one... 

One important experimental fact is that the rate of reaction of alcohols with hydro gen halides increases m the order methyl < primary < secondary < tertiary This reac tivity order parallels the carbocation stability order and is readily accommodated by the mechanism we have outlined... 

The rate determining step m the S l mechanism is dissociation of the alkyloxo mum ion to the carbocation... 

Step 3 IS new to us It is an acid-base reachon m which the carbocation acts as a Br0n sted acid transferrmg a proton to a Brpnsted base (water) This is the property of carbo cations that is of the most significance to elimination reactions Carbocations are strong acids they are the conjugate acids of alkenes and readily lose a proton to form alkenes Even weak bases such as water are sufficiently basic to abstract a proton from a carbocation... 

Write a structural formula for the carbocation intermediate formed in the dehydration of each of the alcohols in Problem 5 14 (Section 5 10) Using curved arrows show how each carbocation is deprotonated by water to give a mixture of alkenes... 

Step (2) Ethanol acts as a base to remove a proton from the carbocation to give the alkene products (Deprotonation step)... 

One possibility is the two step mechanism of Figure 5 12 m which the carbon-halogen bond breaks first to give a carbocation intermediate followed by depro tonation of the carbocation m a second step... 

There is a strong similarity between the mechanism shown m Eigure 5 12 and the one shown for alcohol dehydration m Eigure 5 6 The mam difference between the dehy dration of 2 methyl 2 butanol and the dehydrohalogenation of 2 bromo 2 methylbutane IS the source of the carbocation When the alcohol is the substrate it is the correspond mg alkyloxonmm ion that dissociates to form the carbocation The alkyl halide ionizes directly to the carbocation... 

Section 5 17 In the absence of a strong base alkyl halides eliminate by an El mech anism Rate determining ionization of the alkyl halide to a carbocation is followed by deprotonation of the carbocation... 

Let s compare the carbocation intermediates for addition of a hydrogen halide (HX) to an unsymmetrical alkene of the type RCH=CH2 (a) according to Markovnikov s rule and (b) opposite to Markovnikov s rule (a) Addition according to Markovnikov s rule... 

Give a structural formula for the carbocation intermediate that leads to the major product in each of the reactions of Problem 6 3... 

The notion that carbocation formation is rate determining follows from our previous experience and by observing how the reaction rate is affected by the shucture of the aUcene Table 6 2 gives some data showing that alkenes that yield relatively stable carbocations react faster than those that yield less stable carbocations Protonation of ethylene the least reactive aUcene m the table yields a primary carbocation protonation of 2 methylpropene the most reactive m the table yields a tertiary carbocation As we have seen on other occa sions the more stable the carbocation the faster is its rate of formation... 

The chief reason why ethylenebromonium ion m spite of its strained three membered ring IS more stable than 2 bromoethyl cation is that both carbons and bromine have octets of electrons whereas one carbon has only six electrons m the carbocation... 

The two dimers of (CH3)2C=CH2 are formed by the mechanism shown m Figure 6 16 In step 1 protonation of the double bond generates a small amount of tert butyl cation m equilibrium with the alkene The carbocation is an electrophile and attacks a second molecule of 2 methylpropene m step 2 forming a new carbon-carbon bond and generating a carbocation This new carbocation loses a proton m step 3 to form a mixture of 2 4 4 tnmethyl 1 pentene and 2 4 4 tnmethyl 2 pentene... 

Step 2 The carbocation acts as an electrophile toward the alkene A carbon-carbon bond is formed resulting in a new carbocation—one that has eight carbons... 

Step 2 The carbocation formed m step 1 reacts rapidly with a water molecule Water IS a nucleophile This step completes the nucleophilic substitution stage of the mechanism and yields an alkyloxonium ion... 

Clearly the steric crowding that influences reaction rates in 8 2 processes plays no role in Stvfl reactions The order of alkyl halide reactivity in 8 1 reactions is the same as the order of carbocation stability the more stable the carbocation the more reactive the alkyl halide... 

We have seen this situation before m the reaction of alcohols with hydrogen halides (8ection 4 11) m the acid catalyzed dehydration of alcohols (8ection 5 12) and m the conversion of alkyl halides to alkenes by the El mechanism (8ection 5 17) As m these other reactions an electronic effect specifically the stabilization of the carbocation intermediate by alkyl substituents is the decisive factor The more stable the carbo cation the faster it is formed... 

Partial but not complete loss of optical activity m S l reactions probably results from the carbocation not being completely free when it is attacked by the nucleophile Ionization of the alkyl halide gives a carbocation-hahde ion pair as depicted m Figure 8 8 The halide ion shields one side of the carbocation and the nucleophile captures the carbocation faster from the opposite side More product of inverted configuration is formed than product of retained configuration In spite of the observation that the products of S l reactions are only partially racemic the fact that these reactions are not stereospecific is more consistent with a carbocation intermediate than a concerted bimolecular mechanism... 

Why does the carbocation intermediate in the hydrolysis of 2 bromo 3 methylbutane rearrange by way of a hydride shift rather than a methyl shift ... 

When formulating a mechanism for the reaction of alkynes with hydrogen halides we could propose a process analogous to that of electrophilic addition to alkenes m which the first step is formation of a carbocation and is rate determining The second step according to such a mechanism would be nucleophilic capture of the carbocation by a halide ion... 

The first step protonation of the double bond of the enol is analogous to the pro tonation of the double bond of an alkene It takes place more readily however because the carbocation formed m this step is stabilized by resonance involving delocalization of a lone pair of oxygen... 

Step 2 The carbocation transfers a proton from oxygen to a water molecule yielding a ketone... 

Modeling to view the carbocation repre sented by resonance struc tures A and B How is the positive charge distributed among its carbons ... 

It must be emphasized that we are not dealing with an equilibrium between two isomeric carbocations There is only one carbocation Its structure is not adequately represented by either of the individual resonance forms but is a hybrid having qualities of both of them The carbocation has more of the character of A than B because resonance struc ture A IS more stable than B Water attacks faster at the tertiary carbon because it bears a greater share of the positive charge... 

The carbocation formed on ionization of 1 chloro 3 methyl 2 butene is the same allylic carbocation as the one formed on ionization of 3 chloro 3 methyl 1 butene and gives the same mixture of products... 

The carbocation that leads to the observed product is secondary and allylic the other is secondary but not allylic... 

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 carbocation is aromatic the hydrocarbon is not Although cycloheptatriene has six TT electrons m a conjugated system the ends of the triene system are separated by an sp hybridized carbon which prevents continuous tt electron delocalization... 

The first step is rate determining In it a carbocation forms when the pair of tt electrons of the alkene is used to form a bond with the electrophile Following its formation the carbocation undergoes rapid capture by some Lewis base present m the medium... 

The carbocation formed m this step is a cyclohexadienyl cation Other commonly used terms include arenium ion and a complex It is an allylic carbocation and is stabilized by electron delocalization which can be represented by resonance... 

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