Acid-Catalyzed Isomerizations

Acid-catalyzed isomerization reactions of alkanes as well as alkylation and condensation reactions are initiated by protolytic ionization. Available evidence indicates nonlinear but not necessarily triangular... 

Spherical, pentagonal dodecahedrane is the thermodynamically most stable CjoHjo-polycycloalkane. It is the so-called CjjHjo stabilomer . It should therefore be available by thermod5mamically controlled, e.g. acid-catalyzed, isomerization of less stable C24H20-isomers. Experiments along this line, e.g. treatment of the basketene photo-dimer with Lewis... 

Acid catalyzed dehydration of 2 2 dimethyl 1 hexanol gave a number of isomeric alkenes including 2 methyl 2 heptene as shown in the following formula... 

Although 2 methylpropene undergoes acid catalyzed hydration m dilute sulfuric acid to form tert butyl alcohol (Section 6 10) a different reaction occurs m more concentrated solutions of sulfuric acid Rather than form the expected alkyl hydrogen sulfate (see Sec tion 6 9) 2 methylpropene is converted to a mixture of two isomeric C Hig alkenes... 

Acid catalyzed hydration (Section 9 12) Water adds to the triple bond of alkynes to yield ketones by way of an unstable enol intermediate The enol arises by Markovnikov hydration of the alkyne Enol formation is followed by rapid isomerization of the enol to a ketone... 

Addition of phenylmagnesium bromide to 4 tert butylcyclohexanone gives two isomeric ter tiary alcohols as products Both alcohols yield the same alkene when subjected to acid catalyzed dehydration Suggest reasonable structures for these two alcohols... 

The enzyme catalyzed reactions that lead to geraniol and farnesol (as their pyrophosphate esters) are mechanistically related to the acid catalyzed dimerization of alkenes discussed m Section 6 21 The reaction of an allylic pyrophosphate or a carbo cation with a source of rr electrons is a recurring theme m terpene biosynthesis and is invoked to explain the origin of more complicated structural types Consider for exam pie the formation of cyclic monoterpenes Neryl pyrophosphate formed by an enzyme catalyzed isomerization of the E double bond m geranyl pyrophosphate has the proper geometry to form a six membered ring via intramolecular attack of the double bond on the allylic pyrophosphate unit... 

Fum ric Acid. Eumaric acid [110-17-8] C H O, is unique in its low solubiUty in cold water and slow rate of solution, making it ideal for use in chilled biscuit leavening systems and for dry pudding mixes and beverage powders. It is also used for gelatin desserts, pie filling, fmit juices, and wine. Eumaric acid is produced by the acid-catalyzed isomerization of maleic acid (8,9) (see Maleic anhydride, maleic acid, and fumaric acid). 

Maleic anhydride and the two diacid isomers were first prepared in the 1830s (1) but commercial manufacture did not begin until a century later. In 1933 the National Aniline and Chemical Co., Inc., installed a process for maleic anhydride based on benzene oxidation using a vanadium oxide catalyst (2). Maleic acid was available commercially ia 1928 and fumaric acid production began in 1932 by acid-catalyzed isomerization of maleic acid. 

Uses ndReactions. a-Pinene (8) is useful for synthesizing a wide variety of terpenoids. Hydration to pine oil, acid-catalyzed isomerization to camphene, thermal isomerization to ocimene and aHoocimene, and polymerization to terpene resins are some of its direct uses. Manufacture of linalool, nerol, and geraniol has become an economically important use of a-pinene. 

Work at Rhc ne-Poulenc has involved a different approach to retinal and is based on the paHadium-cataly2ed rearrangement of the mixed carbonate (41) to the aHenyl enal (42). Isomerization of the aHene (42) to the polyene (43) completes the constmction of the carbon framework. Acid-catalyzed isomerization yields retinal (5). A decided advantage of this route is that no by-products such as triphenylphosphine oxide or sodium phenylsulfinate are formed. However, significant yield improvements would be necessary for this process to compete with the current commercial syntheses (25—27) (Fig. 9). 

Increasingly, biochemical transformations are used to modify renewable resources into useful materials (see Microbial transformations). Fermentation (qv) to ethanol is the oldest of such conversions. Another example is the ceU-free enzyme catalyzed isomerization of glucose to fmctose for use as sweeteners (qv). The enzymatic hydrolysis of cellulose is a biochemical competitor for the acid catalyzed reaction. 

Clay-catalyzed dimerization of unsaturated fatty acids appears to be a carbonium ion reaction, based on the observed double bond isomerization, acid catalysis, chain branching, and hydrogen transfer (8,9,11). 

Pyrazine 1,4-dioxides are available by the direct self-condensation of 1,2-hydroxyaminooximes (70JOC2790). 1,2-Nitrooximes are obtained by the isomerization of alkene initrogen trioxide adducts, which are reduced with palladium on charcoal to the hydroxyaminooximes which undergo acid-catalyzed auto-condensation to the pyrazine 1,4-dioxides (Scheme 19). 

The stereochemistry of pyrazolines and pyrazolidines has already been discussed (Section 4.04.1.4.3). Optically active A - and A -pyrazolines have seldom been described (77JA2740, 79CJC360), but cis-trans isomeric pairs are common. The C-4 acid-catalyzed epimerization involves the mechanism shown in Scheme 38 (70TL3099), but in spite of some inconclusive arguments the C-5 epimerization has never been established with certainty. 

The intervention of mesoionic intermediates is suggested by the facile transformation of steroidal dienones, and by a number of acid-catalyzed nonphotolytic reactions which either parallel the photoisomerizations or correlate photoproducts from reactions in protic and aprotic solvents. The isomerization (175) -> (176) -l- (177) has also beeen achieved in the dark by acetic and formic acid catalysis and clearly involves the conjugate acid of the proposed mesoionic intermediate (199) in the dark reaction. Further,... 

As a method for the preparation of alkenes, a weakness in the acid-catalyzed dehydration of alcohols is that the initially formed alkene (or mixture of alkenes) sometimes isomerizes under the conditions of its formation. Write a stepwise mechanism showing how 2-methyl-1-butene might isomerize to 2-methyl-2-butene in the presence of sulfuric acid. 

The p-methoxybenzylidene ketal can be prepared by DDQ oxidation of a p-methoxybenzyl group that has a neighboring hydroxyl. This methodology has been used to advantage in a number of syntheses. " In one case, to prevent an unwanted acid-catalyzed acetal isomerization, it was necessary to recrystallize the DDQ and use molecular sieves. The following examples serve to illustrate the reaction " ... 

Many carbamates have been used as protective groups. They are arranged in this chapter in order of increasing complexity of structure. The most useful compounds (not necessarily the simplest structures) are /-butyl (BOC), readily cleaved by acidic hydrolysis benzyl (Cbz or Z), cleaved by catalytic hydrogenol-ysis 2,4-dichlorobenzyl, stable to the acid-catalyzed hydrolysis of benzyl and /-butyl carbamates 2-(biphenylyl)isopropyl, cleaved more easily than /-butyl carbamate by dilute acetic acid 9-fluorenylmethyl, cleaved by /3-elimination with base isonicotinyl, cleaved by reduction with zinc in acetic acid 1-adamantyl, readily cleaved by trifluoroacetic acid and allyl, readily cleaved by Pd-catalyzed isomerization. 

This was confirmed by taking a sample of 9-acetylanthracene and allowing it to isomerize in the ionic liquid. This gave a mixture of anthracene, 1,5-diacetylan-thracene and 1,8-diacetylanthracene. It should be noted that a proton source was needed for this reaction to occur, implying an acid-catalyzed mechanism (Scheme 5.1-65) [95]. 

Isomerization is a small-volume but important refinery process. Like alkylation, it is acid catalyzed and intended to produce highly-branched hydrocarbon mixtures. The low octane C5/C6 fraction obtained from natural gasoline or from a light naphtha fraction may be isomerized to a high octane product. 

Nonconjugated jS.y-unsaturated ketones, such as 3-cvclohe enone. are in an acid-catalyzed equilibrium with their conjugated a-,/3-unsaturated isomers. Propose a mechanism for this isomerization. 

Curran s synthesis of ( )-A9(l2)-capnellene [( )-2] is detailed in Schemes 30 and 31. This synthesis commences with the preparation of racemic bicyclic vinyl lactone 147 from ( )-norbomenone [( )-145] by a well-known route.61 Thus, Baeyer-Villiger oxidation of (+)-145 provides unsaturated bicyclic lactone 146, a compound that can be converted to the isomeric fused bicyclic lactone 147 by acid-catalyzed rearrangement. Reaction of 147 with methylmagne-sium bromide/CuBr SMe2 in THF at -20 °C takes the desired course and affords unsaturated carboxylic acid 148 in nearly quantitative yield. Iodolactonization of 148 to 149, followed by base-induced elimination, then provides the methyl-substituted bicyclic vinyl lactone 150 as a single regioisomer in 66% overall yield from 147. 

In contrast, the diphenyl derivative 44 (R1 = R2 = Ph) fails to ring expand, whereas the methyl derivative 44 (R1 = Me R2 = H) yields the a.xo-methylene compound 45 (63 %), which undergoes quantitative acid-catalyzed isomerization to 10-methyl-5/7-dibenz[6,/]azepine (46) in refluxing toluene. The mechanistic implications of these reactions have been discussed. 

These observations were explained in terms of an SE reaction between the 2-butenyl-(tributyl)stannane and tin(IV) chloride, which competes with Lewis acid catalyzed carbonyl attack. The 1 -methyl-2-propenyltin trichloride so formed reacts with the aldehyde to give linear products, or isomerizes to give the more stable ( )- and (Z)-2-butenyltin trichlorides which then react74. Similar results were obtained with titanium(lV) chloride, except that the anti-ad-duct was the major product from the butenyltitanium intermediate74. 

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