Involving a proton shift

A particularly interesting example is the fusion of cyclohexanone (20) with biguanide at 140°, which is reported to yield the spirane 2-cyclo-hexylguanamine (CXLII) by cyclisation of the intermediate (CXLI) involving a proton shift ... 

Due to the properties of the cx-hydrogen and carbonyl ketones and aldehydes exist at room temperature as enol tautomers. Tautomerization involves a proton shift, in this case from the a-carbon position to the carbonyl oxygen position. Both tautomers exist at room temperature, but the ketone or aldehyde tautomer is usually favored. Tautomerization is a reaction at equilibrium, not a resonance. (Remember, in resonance structures atoms don move and neither resonance structure actually exists.)... 

D is correct Tautomerization involves a proton shift where the double bond of the carbonyl shifts to the carbonyl/a-carbon bond when the carbonyl oxygen is protonated. You should memorize tautomer formatio and structure. 

Formation of the hydroperoxide 74 is suggested by the authors to involve a proton shift to the zwitterion deriving from the initial addition of singlet oxygen [70c]. This sequence has been successfully used to prepare a,a -bipyrroles, precursors of bioactive natural products in the prodigiosin family and ring A analogs (Sch. 42] [70a],... 

Depending on solvent, temperature, and the nature of the groups Ri and R2, the equilibrium may lie to either side. Thus it has been found that in pure acetone at 25°C, there is about 2.5 X 10 per cent of eiiol. In contrast, pure acetyl acetone, CII3COCH2COCH3, exists as 80 per cent enol, but it is only 15 per cent enol in water solution. The transformation of ketones to enols involves a proton shift, and as we might expect, the rate is susceptible to catalysis by acids and bases. 

In contrast, the S,C-ylide (139a) prepared from tetrachlorothiophene and diazomalonic ester under rhodium acetate catalysis undergoes cycloaddition with acenaphthylene much more slowly however, after heating at 80 °C for 7 h, the reaction leads to the aromatized fluoranthene (226) in 97% yield. The formation of (226) involves a proton shift and loss of chlorine the exact mechanism and the location of the chlorine atoms are not clear <86JCS(Pl)233>. 

Under acidic conditions, the first step involves protonation of the imine nitrogen followed by tautomerization to form an ene-hydrazine intermediate (7). After the tautomerization, a [3,3]-sigmatropic rearrangement occurs, which provides intermediate 8. Rearomatization then occurs via a proton shift to form the imine 9 which cyclizes to form the 5-membered ring 10. Finally, loss of ammonia from 11 generates the indole nucleus in 12. 

Some such pathway is necessary to account for the migration of oxygen that is found. It may involve a protonated epoxide, a 1,2-diol, or simply a 1,2 shift of an OH group. 

The mechanism747 of the Cannizzaro reaction74 involves a hydride shift (an example of mechanism type 2, p. 1160). First OH adds to the C=0 to give 50, which may lose a proton in the basic solution to give the diion 51. 

In hydroxylic solvents an alternative pathway is followed that involves ring-opening accompanied by a proton shift to yield a... 

Amination of 5-bromo-l,6-naphthyridine (113) gives as tele product 2-amino-l,6-naphthyridine (51 ),24 but in addition to the intermediacy of anionic cr-adduct (114) (as proved by H-NMR spectroscopy), its formation involves anionic cr-adduct 115, which is formed by a proton shift from 114. The number of atoms between positions 2 and 5 is five, thus this reaction is referred to as an odd tele substitution. Both types of tele substitution involve Addition of the nucleophile as the initial step and Elimination of the leaving group as the last step. However, in the even tele substitution the elimination can be described to take place from a neutral dihydro species, while in the odd tele substitution the elimination must occur from an anionic intermediate. In the naphthyridines several examples of even and odd tele substitutions are found, and in the following sections the results of studies concerned with tele amination are presented. 

In a recent pubhcation the nitrile (EWG = CN) variant [ 126] of this chemistry was performed in water by applying N,N-diethylaminopropylated sihca gel as heterogeneous catalyst [ 128]. Another variant of this reaction sequence, leading to chiral sulfinylated enones, has been developed by Llera [ 129] employing the enantiomerically pure geminal bis(sulfoxide) 208 (Scheme 54). This bis(sulfoxide) was prepared from (-)-p-toluenesulfinic acid menthyl ester [100], as described by Kunieda [130]. Later this procedure was improved to increase the yield from 35 to 91% [13,131]. Treatment of 208 with enolizable aldehydes or ketones, in the presence of piperidine as a base and thiophile, initiated a reaction cascade involving a condensation step (to 210), a proton shift to allylic sulfoxide 211, and a [2,3]-0-shift followed by a piperidine-mediated desulfuration delivering the alcohols 212 as isomeric mixtures. Oxidation of the latter compounds (one of the R = H) led to enantiomerically pure E-y-oxo vinyl sulfoxides 213. 

Termination involving intramolecular proton shift or intermolecular proton transfer, both followed by elimination of a molecule of water has been reported for the high temperature cationic polymerization of lactams a) intramolecular ... 

In accordance with the generally accepted mechanism ofthe MBH reaction, the aza MBH reaction involves, formally, a sequence of Michael addition, Mannich type reaction, and (3 elimination. A commonly accepted mechanism is depicted in Scheme 13.2. A reversible conjugate addition of the nucleophilic catalyst to the Michael acceptor generates an enolate, which can intercept the acylimine to afford the second zvdtterionic intermediate. A proton shift from the a carbon atom to the P amide followed by P elimination then affords the aza M BH adduct with concurrent regeneration of the catalyst [5]. 

With the normal substrate the next step would involve a hydride shift to the methylene of the folate and a proton abstraction from C-5, leading to thymidylic acid. Here, however, removal of an F from C-5 is impossible. The result is an irreversible blockade of the enzyme by a ternary covalent complex (Fig. 4-13). The synthesis of thymidylic acid (Fig. 

The decarboxylation, which appears to occur without migration of the double bond, actually involves two migrations, of which the second is the reverse of the first. It would then be expected that an, / -unsaturated acid that is unable to rearrange to the / ,y-unsaturated isomer by a proton shift would be difficult to decarboxylate, and in fact terf-butylacrylic acid (4,4-di-methyl-2-pentenoic acid) remains unchanged when heated for 2 hours at 200° because it does not contain allylic hydrogen 35... 

To sum up, the addition of an unsaturated system X=Y=Z to Hector s base may be represented31,33 by the reaction sequence of Scheme 3, in which the final step involves merely a proton shift, and a rotation about a C—N bond. In the case of the isothiocyanate esters, factors as yet unknown terminate the reaction at the simple addition stage 25, but permit it to continue to 26 in the case of cyanamides and carbon disulfide. The dimethylated Hector s base does not form adducts with any of these reagents.31... 

Compared to the expression for the gas phase equilibrium (eq 3), the increment of +665 kJ/mol leads to a protonic shift in the the hydridic-protonic preference. However, for monoatomic ions, like those involved in reactions of the hydrides of the copper triade, the simplifications, which led to eq 6, are no longer valid. The protonic shift as a consequence of solvation is nevertheless prominent, as can be seen from the values in Table 2. AuH thus behaves as an acid, AgH is expected to be a borderline case, and CuH is a hydride. 

Step 2 is the isomerization of glucose to fructose. This reaction involves the conversion of the aldohexose into the 2-ketohexose. Retro-aldol reaction of the aldohexose leads to a C4 and C2 sugar, whereas the ketohexose leads to the two trioses, dihydroxyacetone (DHA) and glyceraldehyde (GLY). As the pathway to LA involves the trioses, selective glucose isomerization is essential, its conversion being limited by equilibrium in the operational temperature window. The isomerization of aldo- to ketoses can proceed via an acid-catalyzed hydride shift, a base-catalyzed mechanism with a proton shift (and intermediate enol), or via a concerted 1,2-hydride shift in neutral media [96, 97]. The latter isomerization mechanism occurs at mild temperatures (100°C) in the presence of Lewis acid catalysts, first... 

Clearly, no hydride transfer is involved, only proton shifts via the formation of a covalent intermediate at position 4a. Hamilton argues that biological oxidoreduction (dehydration) reactions rarely, if at all, involve hydride ions because protons are not shielded by electrons and thus travel much faster and more efficiently in biological media (279). 

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