Acid-catalyzed formation

On the basis of the mechanism for the acid catalyzed formation of diethyl ether from ethanol in Figure 15 3 write a stepwise mechanism for the formation of oxane from 1 5 pentanediol (see the equation on page 637)... 

CF3COOH, 2.5% phenol, 30°, 2 h, 65% yield. Zervas and co-workers tried many conditions for the acid-catalyzed formation and removal of the 5-diphenyl methyl, 5-4,4 -dimethoxydiphenylmethyl, and 5-tripheny I methyl thioethers. The best conditions for the 5-diphenylmethyl thioether are shown above. Phenol or anisole act as cation scavengers. 

FIGURE 15.3 The mechanism of acid-catalyzed formation of diethyl ether from ethyl alcohol. 

Step from general acid-catalyzed formation of immonium ions to general base-catalyzed hydration of these ions to the amino alcohol [Eq. (6)]. 

Show all the steps in the acid-catalyzed formation of a cyclic acetal from ethylene glycol and an aldehyde or ketone. 

Acid-catalyzed formation of an enol is followed by deuteronalion of the enol double bond and dedeuteronation of oxygen. 

In a study of the acid-catalyzed formation of the hemiacetal, Grunwald has shown that the data best fit a mechanism in which the three steps shown here are actually all concerted that is, the reaction is simultaneously catalyzed by acid and base, with water acting as the base ... 

The THP group can be removed by dilute aqueous acid. The chemistry involved in both the introduction and deprotection stages is the reversible acid-catalyzed formation and hydrolysis of an acetal (see Part A, Section 7.1). 

As expected, some sequences also occur where a domino anionic/pericyclic process is followed by another bond-forming reaction. An example of this is an anionic/per-icyclic/anionic sequence such as the domino iminium ion formation/aza-Cope/ imino aldol (Mannich) process, which has often been used in organic synthesis, especially to construct the pyrrolidine framework. The group of Brummond [450] has recently used this approach to synthesize the core structure 2-885 of the immunosuppressant FR 901483 (2-886) [451] (Scheme 2.197). The process is most likely initiated by the acid-catalyzed formation of the iminium ion 2-882. There follows an aza-Cope rearrangement to produce 2-883, which cyclizes under formation of the aldehyde 2-884. As this compound is rather unstable, it was transformed into the stable acetal 2-885. The proposed intermediate 2-880 is quite unusual as it does not obey Bredf s rule. Recently, this approach was used successfully for a formal total synthesis of FR 901483 2-886 [452]. 

The scope of the acid-catalyzed formation of C-glycosyl compounds has been greatly expanded with the finding that enol ethers and ketene acetals can be used as the carbon source in electrophilic substitution reactions at the anomeric center.126 Treatment of 198 with the trimethylsilyl enol ether derived from cyclohexanone, in the presence of stannic chloride, led to 2-(2,3,5-tri-0-benzoyl-/J-D-ribofuranosyl)cyelohexanone (206), presumably by way of the inter-... 

In order to rationalize the complex reaction mixtures in these slurry reactions the authors suggested that irradiations of the oxygen CT complexes resulted in simultaneous formation of an epoxide and dioxetane36 (Fig. 34). The epoxide products were isolated only when pyridine was co-included in the zeolite during the reaction. Collapse of the 1,1-diarylethylene radical cation superoxide ion pair provides a reasonable explanation for the formation of the dioxetane, however, epoxide formation is more difficult to rationalize. However, we do point out that photochemical formation of oxygen atoms has previously been observed in other systems.141 All the other products were formed either thermally or photochemically from these two primary photoproducts (Fig. 34). The thermal (acid catalyzed) formation of 1,1-diphenylacetaldehyde from the epoxide during photooxygenation of 30 (Fig. 34) was independently verified by addition of an authentic sample of the epoxide to NaY. The formation of diphenylmethane in the reaction of 30 but not 31 is also consistent with the well-established facile (at 254 nm but not 366 or 420 nm) Norrish Type I... 

Scheme 5.15. Lewis acid-catalyzed formation of an a-amino ketone.

TABLE 4. The nitrogen, carbon-13 and carbon-14 kinetic isotope effects found for the acid-catalyzed formation of the disproportionation product, the ortho-semidine and the para-semidine at 0°C in 60% aqueous dioxane that was 0.5 M in perchloric acid and 0.5 M in lithium perchlorate... 

In a study of the Lewis-acid catalyzed formation of. 4 in the presence of... 

This method is called the Fischer esterification. It s a condensation reaction where the loss of a water molecule accompanies the joining of the alcohol portion to the acid portion. The acid gives up the OH and the alcohol gives up the H to make the water molecule. All steps in the mechanism are reversible (that is, it establishes an equilibrium), so removing the ester as soon as it forms is helpful. Removal of the ester is normally easy since esters typically have lower boiling points than alcohols and carboxylic acids. Figure 12-20 illustrates the mechanism for the acid-catalyzed formation of an ester by the reaction of an alcohol with a Ccirboxylic acid. 

This protective group is introduced by an acid-catalyzed addition of the alcohol to the vinyl ether moiety in dihydropyran. />-Toluenesulfonic acid or its pyridinium salt is used most frequently as the catalyst,3 although other catalysts are advantageous in special cases. The THP group can be removed by dilute aqueous acid. The chemistry involved in both the introduction and deprotection stages is the reversible acid-catalyzed formation and hydrolysis of an acetal (see Part A, Section 8.1). 

In the currently accepted mechanistic pathway outlined in Scheme 7, the key step in the Biginelli sequence involves the acid-catalyzed formation of an Wacyliminium ion intermediate of type 719 from the aldehyde and urea precursors <1997JOC7201, 2000ACR879, 20040R1>. Interception of the iminium ion 719 by the CH-acidic carbonyl component 715, presumably through its enol tautomer, produces an open-chain ureide 720, which subsequently cyclizes to hexahydropyrimidine 721. Acid-catalyzed elimination of water from 721 ultimately leads to the... 

When solid-phase peptide synthesis was initially being developed, the question of whether or not a separate neutralization step is necessary was considered. Since it was known from the work of others that the chloride ion promotes racemization during the coupling step in classical peptide synthesis, and since we were deprotecting the Boc group with HC1, it seemed advisable to neutralize the hydrochloride by treatment with TEA and to remove chloride by filtration and washing. This short, additional step was simple and convenient and became the standard protocol. Subsequently, we became aware of three other reasons why neutralization was desirable (1) to avoid weak acid catalysis of piperazine-2,5-dione formation, 49 (2) to avoid acid-catalyzed formation of pyroglutamic acid (5-oxopyr-rolidine-2-carboxylic acid), 50 and (3) to avoid amidine formation between DCC and pro-tonated peptide-resin. The latter does not occur with the free amine. 

Mechanisms for Formation and Hydrolysis of Finishes. The general mechanism for acid-catalyzed formation and hydrolysis of. ZV-methylol cellulose cross-links has been shown to pass through a carbonium ion intermediate as in equations 4 and 5 (41) ... 

The acid catalyzes formation of the dimethoxy compound from the initial ozonolysis products (see Note 6 of the diphenalde-hyde preparation, p. 42). Compound I forms only slowly in the absence of the hydrochloric acid. 

In retrospect, the postulated mechanism for amic acid back reaction to anhydride and amine as the main pathway to explain hydrolytic instability of the poly(amic acid) system may have prompted the search for more stable systems in the form of derivatized polyfamic acids). Realizing that if proton transfer in the internal acid catalyzed formation of the intermediate illustrated in Scheme 9 (reaction 1) can be prevented, then the potential for the amic acid back reaction might be eliminated [51]. This, of course, can be accomplished in... 

SAMPLE SOLUTION (a) The reaction given is the acid-catalyzed esterification of methanol by benzoic anhydride. The tetrahedral intermediate is formed by addition of a molecule of methanol to one of the carbonyl groups of the anhydride. This reaction is analogous to the acid-catalyzed formation of a hemiacetal by reaction of methanol with an aldehyde or ketone. 

Wohl4 was the first to refer to the formation of higher saccharides by the action of acids on monosaccharides as reversion. This process, the acid-catalyzed formation of glycosidic bonds between sugar residues, constitutes the most rudimentary form of condensation polymerization. Reversion of oligosaccharides has also been observed. 0 The relationships between the hydrolysis of polysaccharides and the reversion of mono- and oligo-saccha-rides is illustrated for amylose in Fig. 1. 

Exercise 17-32 The immonium ion formed on C-alkylation of an enamine is easily hydrolyzed to a ketone. Write the steps involved and show how this reaction differs from the acid-catalyzed formation of enamines discussed in Section 16-4C. 

The O-protonated quinone methide corresponds to the p-hydroxybenzyl cation 24. Richard measured the rate constant ku for acid-catalyzed formation of this cation from p-hydroxybenzyl alcohol by monitoring formation of a thiol-trapped product by HPLC.157 Combining this rate constant with h2o yields pAR = -9.6 for the cation from the usual relationship KR = k]]2()/ku. This equilibrium constant may be combined with the pAa for the protonated quinone methide and an estimated pAa 9.9 for p-hydroxybenzyl alcohol to give pAR = 2.3 for the p O -substituted alcohol based on the cycle of Scheme 21. 

Acid-catalyzed formation of NO+ (or H2N02 +) followed by oxidation of substrates (Equations 8.98-8.100). 

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