Proton abstracting

Thompson points out that there is no evidence that adducts give other than acetates on thermolysis. The exocyclic methylene intermediate (iv) postulated by Robinson could arise by proton abstraction from a Wheland intermediate analogous to (vll) above, rather than from the adduct (in). Similarly its decomposition does not necessarily require the intermediacy of the adduct (v). The fact that i -methyl-4-nitromethylnaphthalene is the product even when the nitrating medium is nitric acid and nitromethane would then require no separate explanation. 

Thiazolium derivatives unsubstituted at the 2-position (35) are potentially interesting precursors of A-4-thiazoline-2-thiones and A-4-thiazoline-2-ones. Compound 35 in basic medium undergoes proton abstraction leading to the very active nucleophilic species 36a and 36b (Scheme 16) (43-46). Special interest has been focused upon the reactivity of 36a and 36b because they are considered as the reactive species of the thiamine action in some biochemical reaction, and as catalysts for several condensation reactions (47-50). 

Rearrangement to an open chain imine (165) provides an intermediate whose acidity toward lithiomethylthiazole (162) is rather pronounced. Proton abstraction by 162 gives the dilithio intermediate (166) and regenerates 2-methylthiazole for further reaction. During the final hydrolysis, 166 affords the dimer (167) that could be isolated by molecular distillation (433). A proof in favor of this mechanism is that when a large excess of butyllithium is added to (161) at -78°C and the solution is allowed to warm to room temperature, the deuterolysis affords only dideuterated thiazole (170), with no evidence of any dimeric product. Under these conditions almost complete dianion formation results (169), and the concentration of nonmetalated thiazole is nil. (Scheme 79). This dimerization bears some similitude with the formation of 2-methylthia-zolium anhydrobase dealt with in Chapter DC. Meyers could confirm the independence of the formation of the benzyl-type (172) and the aryl-type... 

Dihalocarbenes are formed when trihalomethanes are treated with a strong base such as potassium tert butoxide The trihalomethyl anion produced on proton abstraction dissociates to a dihalocarbene and a halide anion... 

Only the a hydrogens are replaced by deuterium m this reaction The key intermediate IS the enolate ion formed by proton abstraction from the a carbon atom of cyclopen tanone Transfer of deuterium from the solvent D2O to the enolate gives cyclopentanone containing a deuterium atom m place of one of the hydrogens at the a carbon... 

Each act of proton abstraction from the a carbon converts a chiral molecule to an achi ral enol or enolate ion The sp hybridized carbon that is the chirality center m the start mg ketone becomes sp hybridized m the enol or enolate Careful kinetic studies have established that the rate of loss of optical activity of sec butyl phenyl ketone is equal to Its rate of hydrogen-deuterium exchange its rate of brommation and its rate of lodma tion In each case the rate determining step is conversion of the starting ketone to the enol or enolate anion... 

An important feature of aldol addition is that carbon-carbon bond formation occurs between the a carbon atom of one aldehyde and the carbonyl group of another This is because carbanion (enolate) generation can involve proton abstraction only from the a carbon atom The overall transformation can be represented schematically as shown m Figure 18 5... 

All these facts—the observation of second order kinetics nucleophilic attack at the carbonyl group and the involvement of a tetrahedral intermediate—are accommodated by the reaction mechanism shown m Figure 20 5 Like the acid catalyzed mechanism it has two distinct stages namely formation of the tetrahedral intermediate and its subsequent dissociation All the steps are reversible except the last one The equilibrium constant for proton abstraction from the carboxylic acid by hydroxide is so large that step 4 is for all intents and purposes irreversible and this makes the overall reaction irreversible... 

Step 1 Proton abstraction from the a carbon atom of ethyl acetate to give the corresponding enolate... 

This reaction is an example of a Dieckmann cyclization The anion formed by proton abstraction at the carbon a to one carbonyl group attacks the other carbonyl to form a five membered ring... 

Ester enolates generated by proton abstraction with dialkylamide bases add to aldehydes and ketones to give (3 hydroxy esters... 

Protonated molecule. An ion formed by interaction of a molecule with a proton abstracted from an ion, as often occurs in chemical ionization according to the reaction ... 

The degree of duorination can be limited by the thermal stabiUty of the solvent or by its reaction with basic potassium duoride through proton abstraction. Such solvent-derived by-products can subsequentiy react with the starting material and/or main product. 

Experiments ( P nmr) using 0.8 and 2 equivalents of octyhnagnesium chloride with ethyl ben2enephosphinate indicate that the nucleophilic displacement occurs first, foHowed by proton abstraction (80). Interestingly, the order of the two steps is reversed when methyhnagnesium chloride is used (81). This reaction demonstrates the difference ia reactivity between the octyl and the methyl Grignard reagents. 

Introduction of a 3-bromosubstituent onto thiophene is accompHshed by initial tribromination, followed by reduction of the a-bromines by treatment with zinc/acetic acid, thereby utilizing only one of three bromines introduced. The so-called halogen dance sequence of reactions, whereby bromothiophenes are treated with base, causing proton abstraction and rearrangement of bromine to the produce the most-stable anion, has also been used to introduce a bromine atom at position 3. The formation of 3-bromotbiopbene [872-31-1] from this sequence of reactions (17) is an efficient use of bromine. Vapor-phase techniques have also been proposed to achieve this halogen migration (18), but with less specificity. Table 3 summarizes properties of some brominated thiophenes. 

Proton Abstraction. Although the exopolyhedral hydrogens of nido and arachno boranes are generally considered hydridic, the bridge hydrogens are acidic as first demonstrated by titration of and deuterium exchange (71). Some typical reactions are... 

B2qH240H] anion (75). Both B2QH24OH2 and [B2qH240H] are isoelectronic with the [B qH ] anion (77). The hydropolyborate ions formed by proton abstraction from decaborane are usehil intermediates for the preparation of metaHaboranes and heteroboranes. 

Inductive and resonance stabilization of carbanions derived by proton abstraction from alkyl substituents a to the ring nitrogen in pyrazines and quinoxalines confers a degree of stability on these species comparable with that observed with enolate anions. The resultant carbanions undergo typical condensation reactions with a variety of electrophilic reagents such as aldehydes, ketones, nitriles, diazonium salts, etc., which makes them of considerable preparative importance. 

The first proton to be removed from iV-methylpyrrole by w-butyllithium is from an a-position a second deprotonation occurs to give a mixture of 2,4- and 2,5-dilithiated derivatives. The formation of a 2,4-dilithio derivative is noteworthy since in the case of both furan and thiophene initial abstraction of a proton at C-2 is followed by proton abstraction from C-5 (77JCS(P1)887). iV-Methylindole, benzo[6]furan and benzo[6]thiophene are also deprotonated at C-2. Selenophene and benzo[6]selenophene and tellurophene and benzo[6]tellurophene similarly yield 2-lithio derivatives (77AHC(21)119). 

Isoxazoles are susceptible to attack by nucleophiles, the reactions involving displacement of a substituent, addition to the ring, or proton abstraction with subsequent ring-opening. Isoxazolium salts are even more susceptible to attack by a variety of nucleophiles, providing useful applications of the isoxazole nucleus in organic synthesis. Especially useful is the reductive cleavage of isoxazoles, which may be considered as masked 1,3-dicarbonyl compounds or enaminoketones. 

Unsubstituted 2,1-benzisoxazoles undergo C(3)-proton abstraction with base to give an intermediate iminoketene which can undergo further reaction with nucleophiles. However, alternative Michael addition pathways are possible and these have been discussed (81AHC(29)l,p.56). 

Nucleophilic attack on ring hydrogen (proton abstraction) (Section 5.05.3.5)... 

Nucleophilic Attack on Ring Hydrogen (Proton Abstraction)... 

Thiophenium fluorosulfonate, 1,2,3,4,5-tetramethy 1-ylide, 4, 724 Thiophenium salts aromaticity, 4, 724 proton abstraction, 4, 766 pyramidal inversion barrier, 4, 724 structure, 4, 715 synthesis, 4, 723-724 Thiophenium salts, 1-alkyl-solvolysis, 4, 766 UV spectra, 4, 766 Thiophenium salts, aryl-synthesis, 4, 726... 

In an attempt to metalate a MEM-protected phenol with BuLi, the methoxy group was eliminated, forming the vinyloxymethyl ether. This was attributed to intramolecular proton abstraction. ... 

These results are compatible with an evolutionary history in which the new enzyme activity of mandelate racemase has evolved from a preexisting enzyme that catalyzes the basic chemical reaction of proton abstraction and formation of an intermediate. Subsequent mutations have modified the... 

Figure 4.9 Mechanisms of the reactions catalyzed by the enzymes mandelate racemase (a) and muconate lactonizing enzyme (b). The two overall reactions are quite different a change of configuration of a carbon atom for mandelate racemase versus ring closure for the lactonizing enzyme. However, one crucial step (red) in the two reactions is the same addition of a proton (blue) to an intermediate of the substrate (red) from a lysine residue of the enzyme (E) or. In the reverse direction, formation of an intermediate by proton abstraction from the carbon atom adjacent to the carboxylate group.

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