Carbon as a nucleophile

Stability of the conjugated base arises from the electron delocalization that can be identified by using the resonance structure method. Acids in which the proton is removed from the carbon atom are called carbon acids and their conjugate base is called an enolate ion. 

The anions which would be generated by removing a proton from the carbon atoms which are not neighbors of the carbonyl group are unstable because their electron pair is localized. No resonance structures can be written in such cases (see the structure below). 

Since under basic conditions the aldehyde molecules partially dissociate, their mixture contains two molecular species, dissociated and undissociated. The dissociated molecule, the enolate ion can behave as nucleophile because of the electron pair on its carbon atom. This nucleophile can attack the carbonyl group of the undissociated aldehyde yielding a product with two functional groups, aldehyde and alcohol. Such compounds are named aldols and the corresponding reaction is called aldol condensation. 

After loosing a molecule of water, aldol is transformed into the corresponding unsaturated aldehyde. 

Starting with alkyl halides, we can prepare the appropriate Grignard reagents and in combination with different aldehydes or ketones, synthesize a series of compounds with branched hydrocarbon chains. 

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Carbon as a nucleophile nitriles, Grignard reagents, acetylides... 

Nucleophilic substitution reactions employing carbon as a nucleophile are important in synthetic chemistry in that they create a new C-C bond. A carbon nucleophile, of course, must be in the form of anionic carbon, or its equivalent. One of the simplest sources of anionic carbon is the cyanide anion. HCN is a weak acid (pATa 9.1) and forms a series of stable... 

Second, comparison of II and III suggests that the latter may be converted into the former if just the acetylene and aldehydo groups were to form a C-C bond while, at the same time, the aldehydic proton was transferred to the ben-zylic position. If compound III would attempt to do this by trapping the proton in question with the triple bond, the ensuing cyclization would demand the use of the carbonyl carbon as a nucleophile, something that is highly unlikely. 

Enamines are employed in the majority of cases as a means of activating the a-carbon as a nucleophile for reaction with an electrophilic carbon partner (Scheme 13). In the historical picture of the development of methods for a-alkylation of ketones and aldehydes, they represented a significant advance over... 

Pd-coordinated oxygen first attacks the carbonyl carbon as a nucleophile to form a Pd metallacycle, which readily eliminates X to afford an acylperoxopalladium species, the precursor of the Pd oxenoid. Epoxidation occurs via oxene transfer and the same route is operative for the observed sulfide to sulfoxide transformation. 

If we were to do this, the Grignard reagent would simply react as a base with the acidic hydrogen rather than reacting at the carbonyl or epoxide carbon as a nucleophile. If we were to treat 4-hydroxy-2-butanone with methylmagnesium bromide, for example, the reaction that would take place is... 

Other initiators based on alkali metals such as sec-butyllithium (s c-BuLi) as well as sodium and potassium naphthalene were also surveyed.Sodium and potassium naphthalene, when used as electron-transfer reagents for the initiation of styrene polymerization, react with neopentyl carbonate as a nucleophile. The investigation of oligomers obtained in the initial stages of the polymerization by means of GPC using a UV-detector revealed naphthalene to be incorporated into the growing chain. 

Figure 3-22 shows a nucleophilic aliphatic substitution with cyanide ion as a nucleophile, i his reaction is assumed to proceed according to the S f2 mechanism with an inversion in the stereochemistry at the carbon atom of the reaction center. We have to assign a stereochemical mechanistic factor to this reaction, and, clearly, it is desirable to assign a mechanistic factor of (-i-1) to a reaction with retention of configuration and (-1) to a reaction with inversion of configuration. Thus, we want to calculate the parity of the product, of 3 reaction from the parity of the... 

The cyclic carbamate (oxazoIidin-2-one) 313 is formed by the reaction of phenyl isocyanate (312) with vinyloxirane[I92]. Nitrogen serves as a nucleophile and attacks the carbon vicinal to the oxygen exclusively. The thermodynamically less stable Z-isomer 315 was obtained as a major product (10 I) by the reaction of 2-methoxy-l-naphthyI isocyanate (314) with a vinyloxir-... 

When we discussed elimination reactions in Chapter 5 we learned that a Lewis base can react with an alkyl halide to form an alkene In the present chapter you will find that the same kinds of reactants can also undergo a different reaction one m which the Lewis base acts as a nucleophile to substitute for the halo gen substituent on carbon... 

Cyanide ion ( C = N ) The negatively charged carbon atom of cyanide ion IS usually the site of its nucleophilic character Use of cyanide ion as a nucleophile permits the extension of a carbon chain by carbon-carbon bond formation The product is an alkyl cyanide or nitrile... 

Next an alkyl halide (the alkylating agent) is added to the solution of sodium acetylide Acetylide ion acts as a nucleophile displacing halide from carbon and forming a new carbon-carbon bond Substitution occurs by an 8 2 mechanism... 

If the Lewis base ( Y ) had acted as a nucleophile and bonded to carbon the prod uct would have been a nonaromatic cyclohexadiene derivative Addition and substitution products arise by alternative reaction paths of a cyclohexadienyl cation Substitution occurs preferentially because there is a substantial driving force favoring rearomatization Figure 12 1 is a potential energy diagram describing the general mechanism of electrophilic aromatic substitution For electrophilic aromatic substitution reactions to... 

H3P—CH2 where it can be seen that the electron distribution is highly polarized m the direction that makes carbon electron rich The carbon has much of the character of a car banion and can act as a nucleophile toward C=0... 

Gngnard reagent acts as a nucleophile toward carbon dioxide... 

Ring syntheses in which a bond is formed between the heteroatom and a carbon atom are conveniently considered according to whether the heteroatom functions as a nucleophile, an electrophile, a radical or other electron deficient species. 

The stabilization of chloromethoxycarbene (234) was intensively studied. It is formed from diazirine (233) in a first order reaction with fi/2 = 34h at 20 C. It reacts either as a nucleophile, adding to electron poor alkenes like acrylonitrile with cyclopropanation, or as an electrophile, giving diphenylcyclopropenone with the electron rich diphenylacetylene. In the absence of reaction partners (234) decomposes to carbon monoxide and methyl chloride (78TL1931, 1935). 

In general, the reaction between a phenol and an aldehyde is classified as an electrophilic aromatic substitution, though some researchers have classed it as a nucleophilic substitution (Sn2) on aldehyde [84]. These mechanisms are probably indistinguishable on the basis of kinetics, though the charge-dispersed sp carbon structure of phenate does not fit our normal concept of a good nucleophile. In phenol-formaldehyde resins, the observed hydroxymethylation kinetics are second-order, first-order in phenol and first-order in formaldehyde. 

FIGURE 8.11 When a Lewis base reacts with an alkyl halide, either substitution or elimination can occur. Substitution (Sn2) occurs when the Lewis base acts as a nucleophile and attacks carbon to displace bromide. Elimination (E2) occurs when the Lewis base abstracts a proton from the p carbon. The alkyl halide shown is isopropyl bromide, and elimination (E2) predominates over substitution with alkox-ide bases. 

When a Br nsted base functions catalytically by sharing an electron pair with a proton, it is acting as a general base catalyst, but when it shares the electron with an atom other than the proton it is (by definition) acting as a nucleophile. This other atom (electrophilic site) is usually carbon, but in organic chemistry it might also be, for example, phosphorus or silicon, whereas in inorganic chemistry it could be the central metal ion in a coordination complex. Here we consider nucleophilic reactions at unsaturated carbon, primarily at carbonyl carbon. Nucleophilic reactions of carboxylic acid derivatives have been well studied. These acyl transfer reactions can be represented by... 

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