22, - tertiary rearrangement

The affected region covers a larger part of the protein, reflecting the size of the peptide and the tertiary rearrangements known from the X-ray structure. 

Why do carbocations rearrange The answer is straightforward once we recall that tertiary carbocations are more stable than secondary carbocations (Section 4.10). Thus, rearrangement of a secondary to a tertiary carbocation is energetically favorable. As shown in Mechanism 5.2, the carbocation that is formed first in the dehydration of 3,3-dimethyl-2-butanol is secondary the rearranged carbocation is tertiary. Rearrangement occurs, and almost all of the alkene products come from the tertiary carbocation. 

The reaction of the alkene shown with aqueous acid leads to an anomalous product. Contrary to what you have learned about cationic rearrangements, secondary-to-secondary and tertiary-to-tertiary rearrangements are possible under some circumstances. With this in mind, predict the structure of the product using a mechanism to do so. 

ROH Elimination Acid Alkenes Easiest when the alcohol is tertiary. Rearrangement may compete. 

This involves the formation of a carbenium ion which is best described as a hybrid of the two structures shown. This then rearranges by migration of a bond, and in so doing forms a more stable tertiary carbenium ion. Elimination of a proton yields camphene. 

Apart from the thoroughly studied aqueous Diels-Alder reaction, a limited number of other transformations have been reported to benefit considerably from the use of water. These include the aldol condensation , the benzoin condensation , the Baylis-Hillman reaction (tertiary-amine catalysed coupling of aldehydes with acrylic acid derivatives) and pericyclic reactions like the 1,3-dipolar cycloaddition and the Qaisen rearrangement (see below). These reactions have one thing in common a negative volume of activation. This observation has tempted many authors to propose hydrophobic effects as primary cause of ftie observed rate enhancements. 

Note 1. At higher temperatures the tertiary chloride undergoes a rearrangement, catalysed by CuCl, giving H2C=C(C1)CH=CH2. In these cases the refractive index of the crude product is much higher. 

Allylic nitro compounds form rr-allylpalladium complexes by displacement of the nitro group and react with nucleophiles, and allylation with the tertiary nitro compound 202 takes place at the more substituted side without rearrangement to give 203[8,9,128]. 

Why do carbocations rearrange The answer is straightforward once we recall that tertiary carbocations are more stable than secondary carbocations (Section 4 10) Thus rearrangement of a secondary to a tertiary carbocation is energetically favorable As... 

FIGURE 5 7 The first formed carbocation from 3 3 dimethyl 2 butanol is secondary and rearranges to a more stable tertiary carbocation by a methyl migration The major portion of the alkene products is formed by way of the tertiary carbocation... 

Dehydration of alcohols (Sections 5 9-5 13) Dehydra tion requires an acid catalyst the order of reactivity of alcohols IS tertiary > secondary > primary Elimi nation is regioselective and proceeds in the direction that produces the most highly substituted double bond When stereoisomeric alkenes are possible the more stable one is formed in greater amounts An El (elimination unimolecular) mechanism via a carbo cation intermediate is followed with secondary and tertiary alcohols Primary alcohols react by an E2 (elimination bimolecular) mechanism Sometimes elimination is accompanied by rearrangement... 

Addition begins m the usual way by protonation of the double bond to give m this case a secondary carbocation This carbocation can be captured by chloride to give 2 chloro 3 methylbutane (40%) or it can rearrange by way of a hydride shift to give a tertiary carbocation The tertiary carbocation reacts with chloride ion to give 2 chloro 2 methylbutane (60%)... 

Additional evidence for carbocation intermediates in certain nucleophilic substitutions comes from observing rearrangements of the kind normally associated with such species For example hydrolysis of the secondary alkyl bromide 2 bromo 3 methylbutane yields the rearranged tertiary alcohol 2 methyl 2 butanol as the only substitution product... 

Unbranched primary alcohols and tertiary alcohols tend to react with hydrogen halides without rearrangement The alkyloxonmm ions from primary alcohols react rap idly with bromide ion for example m an Sn2 process Tertiary alcohols give tertiary alkyl halides because tertiary carbocations are stable and show little tendency to rearrange... 

The reactions of alcohols with hydrogen halides to give alkyl halides (Chapter 4) are nucleophilic substitution reactions of alkyloxonium ions m which water is the leaving group Primary alcohols react by an 8 2 like displacement of water from the alkyloxonium ion by halide Sec ondary and tertiary alcohols give alkyloxonium ions which form carbo cations m an S l like process Rearrangements are possible with secondary alcohols and substitution takes place with predominant but not complete inversion of configuration... 

The preparation and properties of these tertiary aminimides, as weU as suggested uses as adhesives (qv), antistatic agents (qv), photographic products, surface coatings, and pharmaceuticals, have been reviewed (76). Thermolysis of aminimides causes N—N bond mpture foUowed by a Curtius rearrangement of the transient nitrene (17) intermediate to the corresponding isocyanate ... 

If aromatic aldehydes or ketones are used, the tertiary phosphine product sometimes rearranges to a mixed phosphine oxide. 

The rate of rearrangement increases as the basicity of the parent tertiary amine decreases (14). Strong support for a free-radical mechanism has been demonstrated (15,16). 

Chemical Properties. Reactions of quaternaries can be categorized iato three types (169) Hoffman eliminations, displacements, and rearrangements. Thermal decomposition of a quaternary ammonium hydroxide to an alkene, tertiary amine, and water is known as the Hoffman elimination (eq. la) (170). This reaction has not been used extensively to prepare olefins. Some cycHc olefins, however, are best prepared this way (171). Exhaustive methylation, followed by elimination, is known as the Hoffman degradation and is important ia the stmctural determination of unknown amines, especially for alkaloids (qv) (172). 

Sulfation by sulfamic acid has been used ia the preparation of detergents from dodecyl, oleyl, and other higher alcohols. It is also used ia sulfating phenols and phenol—ethylene oxide condensation products. Secondary alcohols react ia the presence of an amide catalyst, eg, acetamide or urea (24). Pyridine has also been used. Tertiary alcohols do not react. Reactions with phenols yield phenyl ammonium sulfates. These reactions iaclude those of naphthols, cresol, anisole, anethole, pyrocatechol, and hydroquinone. Ammonium aryl sulfates are formed as iatermediates and sulfonates are formed by subsequent rearrangement (25,26). 

Esters derived from the primary alcohols are the most stable and those derived from the tertiary alcohols are the least stable. The decomposition temperature is lower in polar solvents, eg, dimethyl sulfoxide (DMSO), with decomposition occurring at 20°C for esters derived from the tertiary alcohols (38). Esters of benzyl xanthic acid yield stilbenes on heating, and those from neopentyl alcohols thermally rearrange to the corresponding dithiol esters (39,40). The dialkyl xanthate esters catalytically rearrange to the dithiol esters with conventional Lewis acids or trifluoroacetic acid (41,42). The esters are also catalytically rearranged to the dithiolesters by pyridine Ai-oxide catalysts (43) ... 

Carbonylation, or the Koch reaction, can be represented by the same equation as for hydrocarboxylation. The catalyst is H2SO4. A mixture of C-19 dicarboxyhc acids results due to extensive isomerization of the double bond. Methyl-branched isomers are formed by rearrangement of the intermediate carbonium ions. Reaction of oleic acid with carbon monoxide at 4.6 MPa (45 atm) using 97% sulfuric acid gives an 83% yield of the C-19 dicarboxyhc acid (82). Further optimization of the reaction has been reported along with physical data of the various C-19 dibasic acids produced. The mixture of C-19 acids was found to contain approximately 25% secondary carboxyl and 75% tertiary carboxyl groups. As expected, the tertiary carboxyl was found to be very difficult to esterify (80,83). 

The preparation of neopentyl alcohol from diisobutylene herein described represents an example of acid-catalyzed addition of hydrogen peroxide to a branched olefin, followed by an acid-catalyzed rearrangement of the tertiary hydroperoxide formed. In addition to neopentyl alcohol, there are formed acetone and also small amounts of methanol and methyl neopentyl ketone by an alternative rearrangement of the hydroperoxide. 

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