Acid-catalyzed additions

Acid catalyzed addition of alcohols to alkenes is sometimes used Indeed before Its use as a gasoline additive was curtailed billions of pounds of tert butyl methyl ether (MTBE) was prepared by the reaction... 

Methyl glycosides of 2 deoxy sugars have been prepared by the acid catalyzed addition of methanol to unsaturated sugars known as glycals... 

There are a few economical routes that can be employed for production of the largest-volume phosphines as specialty chemicals. The preparation of alkyl phosphines, where R > C2H, employs the addition of lower phosphines across an olefinic double bond. The reaction may be either acid-, base-, or radical-catalyzed. The acid-catalyzed addition probably proceeds through the generation of a carbonium ion intermediate which is attacked by the unshared... 

The presence of free radicals can invert this rule, to form anti-Markovnikov products. Free-radical addition in this fashion produces a radical on the central carbon, C-2, which is more stable than the allyl radical. This carbon can then experience further addition. For example, acid-catalyzed addition of... 

Citral readily forms acetals by acid-catalyzed addition of alcohols or by the use of trialkoxyorthoformates. Citral dimethyl acetal [7549-37-3] is stable under alkaline conditions, whereas citral is not. Neryl and geranyl nitriles can be made by oximation of citral and dehydration of the intermediate oxime. For instance, geranonitrile [31983-27-4] is made as follows ... 

Azirines react with alcohols in the presence of alkoxides to give alkoxyaziridines (67JA4456). Further treatment with alcohol and alkoxide results in the formation of amino ketone acetals. Alkoxyaziridines are not isolated in general from the acid-catalyzed addition of methanol to azirines. Azirines are also known to react with amines (66JOC1423). Frequently the initially produced adducts undergo subsequent transformations. 

The acid-catalyzed additions of bromide and chloride ion to thiiranes occurs readily, with halide preferentially but not exclusively attacking the most substituted carbon atom of the thiirane. The reaction of 1-substituted thiiranes with acetyl chloride shows a slight preference for halide attack at the less substituted carbon atom (80MI50601). For further discussion of electrophilic catalysis of halide ion attack see Section 5.06.3.3.2. The reaction of halogens with thiiranes involves electrophilic attack on sulfur (Section 5.06.3.3.6) followed by nucleophilic attack of halide ion on carbon. 

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. 

The formation of alcohols by acid-catalyzed addition of water to alkenes is a fundamental organic reaction. At the most rudimentary mechanistic level, it can be viewed as involving a carbocation intermediate. The alkene is protonated, and the carbocation is then captured by water. 

A mercurinium ion has both similarities and differences as compared with the intermediates that have been described for other electrophilic additions. The proton that initiates acid-catalyzed addition processes is a hard acid and has no imshared electrons. It can form either a carbocation or a hydrogen-bridged cation. Either species is electron-deficient and highly reactive. 

Symmetrical labile ethers such as cycloalkenyl ethers (15) or mixed acetals (16) can also be prepared from the 3-hydroxyl group by acid-catalyzed exchange etherification or by acid-catalyzed addition to cyclohexanone methyl enol ether. 

Acid-Catalyzed Additions across Double Bonds... 

The Lewis acid-catalyzed addition of silyl kelene acetals occurred m high yield, and when the ketene acetal bore a substituent, the reactions occurred with modest diastereofacial selectivity [d] (equation 7) (Table 3)... 

Figure 5-23. RIP diagram for the general acid-catalyzed addition of anilines to dicyanamide.

The acid-catalyzed addition of an aldehyde—often formaldehyde 1—to a carbon-carbon double bond can lead to formation of a variety of products. Depending on substrate structure and reaction conditions, a 1,3-diol 3, allylic alcohol 4 or a 1,3-dioxane 5 may be formed. This so-called Prins reaction often leads to a mixture of products. 

Isopropyl acrylate is produced by an acid catalyzed addition reaction of acrylic acid to propylene. The reaction occurs in the liquid phase at about100°C ... 

A Alkenes can be converted into alcohols by acid-catalyzed addition of water. Assuming that Vlarkovnikov s rule is valid, predict the major alcohol product from each of the following alkenes. 

Most of the biochemical reactions that take place in the body, as well as many organic reactions in the laboratory, yield products with chirality centers. Fo example, acid-catalyzed addition of H2O to 1-butene in the laboratory yield 2-butanol, a chiral alcohol. What is the stereochemistry of this chiral product If a single enantiomer is formed, is it R or 5 If a mixture of enantiomers i formed, how much of each In fact, the 2-butanol produced is a racemic mix ture of R and S enantiomers. Let s see why. 

Acid-catalyzed addition of methanol to 1,4-dimethyl 7-ethyl pyridazino[4,5-d]azepine-1,4,7-tri-carboxylate (3) gives 4 in low yield.112... 

For example, using (/ )-5-trimethylsilyl-2-cyclohexenone as the chiral Michael acceptor, optically active m // .v-3.5-disubstituied cyclohexanones 1 are obtained via a Lewis acid catalyzed addition of silylenol ethers or ketene acetals. 

Triple bonds can be monohydroborated to give vinylic boranes, which can be reduced with carboxylic acids to cis alkenes or oxidized and hydrolyzed to aldehydes or ketones. Terminal alkynes give aldehydes by this method, in contrast to the mercuric or acid-catalyzed addition of water discussed at 15-4. However, terminal alkynes give vinylic boranes (and hence aldehydes) only when treated with a hindered borane such as 47, 48, or catecholborane (p. 798)," or with BHBr2—SMe2. The reaction between terminal alkynes and BH3 produces 1,1-... 

An important cyclization procedure involves acid-catalyzed addition of diene-ketones such as 58, where one conjugated alkene adds to the other conjugated alkene to form cyclopentenones (59). This is called the Nazarov cyclization Cyclization can also give the nonconjugated five-membered ring. ... 

Hydration and Other Acid-Catalyzed Additions of Oxygen Nucleophiles... 

Acid-catalyzed additions to terminal alkynes follow the Markovnikov rule. 

Lewis acid-catalyzed additions can be carried out in the presence of other chiral ligands that induce enantioselectivity.156 Titanium TADDOL induces enantioselectivity in alkylzinc additions to aldehydes. A variety of aromatic, alkyl, and a, (3-unsaturated aldehydes give good results with primary alkylzinc reagents.157... 

Lewis acid-catalyzed hydrostannylation has been observed using ZrCl4. With terminal alkynes the Z-alkenylstannane is formed.142 These reactions are probably similar in mechanism to Lewis acid-catalyzed additions of silanes (see p. 811). 

As with the silanes, the most useful synthetic procedures involve electrophilic attack on alkenyl and allylic stannanes. The stannanes are considerably more reactive than the corresponding silanes because there is more anionic character on carbon in the C-Sn bond and it is a weaker bond.156 The most useful reactions in terms of syntheses involve the Lewis acid-catalyzed addition of allylic stannanes to aldehydes.157 The reaction occurs with allylic transposition. 

The acid-catalyzed addition of water to the double bond of an alkene is a method for the preparation of low molecular weight alcohols that has its greatest utility in large-scale industrial processes. 

In the context of preparing potential inhibitors of dihydrofolate reductase (DHFR), the group of Organ has developed a rapid microwave-assisted method for the preparation of biguanide libraries (Scheme 6.174) [330]. Initial optimization work was centered around the acid-catalyzed addition of amines to dicyandiamide. It was discovered that 150 °C was the optimum temperature for reaction rate and product recovery, as heating beyond this point led to decomposition. While the use of hydrochloric acid as catalyst led to varying yields of product, evaluation of trimethylsilyl chloride in acetonitrile as solvent led to improved results. As compared to the protic... 

Carbon monoxide rapidly inserts into the carbon—zirconium bond of alkyl- and alkenyl-zirconocene chlorides at low temperature with retention of configuration at carbon to give acylzirconocene chlorides 17 (Scheme 3.5). Acylzirconocene chlorides have found utility in synthesis, as described elsewhere in this volume [17]. Lewis acid catalyzed additions to enones, aldehydes, and imines, yielding a-keto allylic alcohols, a-hydroxy ketones, and a-amino ketones, respectively [18], and palladium-catalyzed addition to alkyl/aryl halides and a,[5-ynones [19] are examples. The acyl complex 18 formed by the insertion of carbon monoxide into dialkyl, alkylaryl, or diaryl zirconocenes may rearrange to a r 2-ketone complex 19 either thermally (particularly when R1 = R2 = Ph) or on addition of a Lewis acid [5,20,21]. The rearrangement proceeds through the less stable... 

A variety of other powerful electrophiles add to the allylzirconium species 91, as shown in Scheme 3.26. Such reactions include the Lewis acid catalyzed addition of aryl, alkyl, or alkenyl acetals, derived from aldehydes, but not from ketones, and the addition of imi-nium species that lack p-hydrogens [56,58]. 

Several other types of photochemical reactions involving unsaturated carbohydrates have been reported. One of these is38 photochemical, E -Z isomerization of the groups attached to a double bond (see Scheme 5). A second is the internal cycloaddition between two double bonds connected by a carbohydrate chain.39-41 Although the carbohydrate portion of the molecule is not directly involved in this cycloaddition, its presence induces optical activity in the cyclobutane derivatives produced photochemically. Finally, a group of acid-catalyzed addition-reactions has been observed for which the catalyst appears to arise from photochemical decomposition of a noncarbohydrate reactant.42-44... 

The fourth reaction is transformation of the aldehyde into an acetal. This proceeds by acid-catalyzed addition of an alcohol to the carbonyl, loss of H2O, and then addition of the acid O to the carbocation. Other perfectly correct sequences of steps could be written here. 

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