Acid-catalyzed elimination

The use of a reagent bearing a basic center or the addition of a base to the reaction mixture was recognized as necessary to prevent the acid-catalyzed elimination of the elements of water from the intermediates. Since the publication of this work, a number of similar intermediates have been isolated from thioamides and a-halogeno carbonyl compounds (608, 609, 619, 739, 754, 801), and as a result of kinetic studies, the exact mechanism of this reaction has been well established (739, 821). 

The dehydration of -hydroxy ketones is a closely related reaction. In the case of 5,6-disubstituted 3-ketones, the 6-substituent usually remains in the less stable configuration. With acid catalyzed elimination, prolonged treatment or high concentration may cause epimerization ... 

The acid catalyzed elimination of acylated amines has recently been described and is said to resemble the acid dehydration of alcohols in character ... 

The final variation of the Feist-Benary furan synthesis encompasses reactions of 1,3-dicarbonyls with 1,2-dibromoethyl acetate (52). For example, treatment of ethyl acetoacetate (9) with sodium hydride followed by addition of 52 at 50°C yields dihydrofuran 53. The product can be easily converted into the corresponding 2-methyl-3-furoate upon acid catalyzed elimination of the acetate, thus providing another strategy for the synthesis of 2,3-disubstituted furans. 

Bischler-Napieralski reaction conditions can be attributed, again, to the destabilizing ability of the trifluoromethyl group to the cationic transition state of the acid catalyzed elimination. Formation of compound 29 was ultimately accomplished by base catalyzed methanol elimination-conditions conditions that are quite unusual for isoquinoline formation. 

Instead of reducing the ketone function, a lithium organic reagent, e.g. phenyllithium, can be added followed by an acid-catalyzed elimination of water to give product 3.85 This procedure allows the introduction of various substituents. By this method 3-[2-(dimethylamino)ethoxy]-... 

Thus, in contrast to benzothiepins, dibenzo compounds can be synthesized by direct acid-catalyzed elimination of water from hydroxy derivatives, or of amines from amino derivatives, at elevated temperatures due to their thermal stability. As in the case of benzothiepins, dibenzo derivatives can also be prepared by base-catalyzed elimination from the corresponding halo derivatives however, the yields are somewhat lower compared to the acid-catalyzed reactions. As a special case, an aziridine derivative was deaminated by palladium-catalyzed hydrogenation to afford the corresponding dibenzothiepin.69... 

In 1992/1994, Grubbs et al. [29] and MacDiarmid et al. [30] described an improved precursor route to high molecular weight, structurally regular PPP 1, by transition metal-catalyzed polymerization, of the cyclohexa-1,3-diene derivative 14 to a stereoregular precursor polymer 16. The final step of the reaction sequence is the thermal, acid-catalyzed elimination of acetic acid, to convert 16 into PPP 1. They obtained unsupported PPP films of a definite structure, which were, however, badly contaminated with large amounts of polyphosphoric acid. 

A PPV derivative which is twofold phenylsubstituted at the vinylene unit, poly(l,4-phenylene-l,2-diphenylvinylene DP-PPV), (71b) (see also the discussion of dehydrochlorination of unsymmetrically substituted para-xylylene dichlorides in Section 3.1) was first synthesized by Smets et al., using acid-catalyzed elimination of nitrogen from l,4-bis(diazobenzyl)benzene 83 [106]. The yellow products obtained are fully soluble in common organic solvents (toluene, chloroform, ethylene chloride, DMF, THF). 

Clearly, the list can be enlarged by introducing additional steps, whereas the steps leading to the reactive species at the beginning (such as the acid-catalyzed elimination of water from an alcohol to form a carbocation) are not counted. 

Petrillo reports that the reaction of l,4-diaryl-2,3-dinitrobutadienes 42 with representative primary amines leads to //-alkyl-3-alkylamino-2,5-diaryl-4-nitropyrrolidines 43 presumably via a disfavored 5-endo-trig ring closure <00EJOC903>. Acid catalyzed elimination of the amine led to the corresponding trans-2,5-diaryl-3-nitro-3-pyrrolines 44 which could be dehydrogenated to the corresponding pyrroles 45. 

Furans.2 Enol ethers, p-dicarbonyl compounds, and Mn(III) acetate (2 equiv.) react in acetic acid (25°) to form l-aIkoxy-l,2-dihydrofurans, which form furans readily on acid-catalyzed elimination of ROH. 

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... 

Past methods used to synthesize 7-pyrones consist of the acylation of methoxy-butyne9 or 4-methoxy-3-buten-2-one10 followed by acid-catalyzed hydrolysis and cyclization. Addition of ketenes to siloxydienes followed by acid-catalyzed elimination has also been employed.11 The present method is superior to these procedures because of the greater diversity of substituted 7-pyrones that can be constructed, and because of the fact that the previous methods demand the use of strong base and low temperatures that make them less suited for scale up. 

The facile acid-catalyzed elimination of the elements of water from the carbinols derived from 2-methylindole and 1,3-dicarbonyl compounds, such as ethyl acetoacetate or pentane-2,4-dione, yields the 3-vinylindole derivatives (122) (B-70MI30500). Pyrroles tend to form 2 1 adducts with 1,3-diketones. For example, cyclohexane-1,3-dione produces the bispyrrolyl derivatives (121) (B-77MI30502). 

The second stage of acetal and ketal formation, the acid-catalyzed elimination of the hydroxyl group as a water molecule and addition of a second alcohol molecule to the resulting carbocation (Equations 8.37 and 8.38), is most conveniently investigated in the reverse direction starting from the acetal or ketal.88 As Structures 12 and 13 indicate, it is conceivable that either of two bonds could be broken in the hydrolysis. One method of settling the ambiguity is to hydrolyze... 

Addition of hydrogen sulfide and thiols is qualitatively similar to reaction with alcohols in that there are two stages, formation of hemithioacetal (or hemithio-ketal) followed by acid-catalyzed elimination of the hydroxy group and substitution of a second —SR (Equations 8.47 and 8.48). The transformation has been studied less extensively than hydration and acetal formation, and relatively little information on mechanism is available. The initial addition appears to be specific base-catalyzed, an observation that implies that RS is the species that adds. The situation is thus similar to cyanide addition. General acid catalysis has, however, been found at pH 1 to 2 for addition of weakly acidic alkyl thiols, and the reaction rate as a function of pH has a minimum and rises both on the... 

The process begins with complete ring closure to compound 13b, since acid-catalyzed elimination of water to the dihydropyridone shills the equilibrium between compounds 13a and 13b. 

Dehydrations produce olehns from alcohols by the acid-catalyzed elimination of a water molecule from between two carbons. Acid-catalyzed dehydrations often give mixtures of products because the intermediate carbocation is prone to cationic rearrangements to more stable carbocations prior to formation of the olefin product. Moreover, even when the intermediate carbocation is not subject to skeletal rearrangement, as in file case of tertiary alcohols, mixtures of regioisomers are often produced during file loss of a proton from file carbocation. As a consequence, the acid-catalyzed dehydration of alcohols is generally not a viable synthetic method. 

Acid-catalyzed elimination of RH has again proven a valuable tool, applied most extensively to Tp Pt(H)2Me (152). Thus, protonation of 152 with [H(OEt2)2]BArf4 affords the anticipated solvento complex... 

In the conversion that gave its name to this reaction, the acid-catalyzed elimination of water from pinacol give s r-butyl methyl ketone. 

Scheme 7 Acid-catalyzed elimination used to dehydrate [1-hydroxy ketones.

Ammonium ions have also been used as templates for creating pockets capable of stabilizing positively charged transition states. For example, antibodies raised against hapten 77 accelerate the dehydration of P-hydroxy ketone 75 to give enone 76. The ammonium group in 77 served as a surrogate for the protonated alcohol formed in the acid-catalyzed elimination reaction, and evidence obtained with... 

Figure 9.32 adds the information of how enol ethers are normally produced, i.e., enol ethers with no conjugation between the C=C- and the neighboring C=0 double bond 0,0-Acetals are subjected to an acid-catalyzed elimination of one equivalent of alcohol, via an El mechanism, that is, via an oxocarbenium ion intermediate that is deprotonated to give the respective enol ether (i.e., the product presented in the first line of Figure 9.32) or dienol ether (the product shown in the second line of Figure 9.32). Among other things, enol ethers are required for the Mukaiyama aldol addition (example Figure 12.23).

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