Oxygen carbon nucleophiles

Reactions with Carbon and Oxygen Nucleophiles, and Other Reactions... 

Addition of Carbon, Oxygen, Nitrogen, and Sulfur Nucleophiles... 

A long standing method for the preparation of ethers is the Williamson ether synthesis Nucleophilic substitution of an alkyl halide by an alkoxide gives the carbon-oxygen bond of an ether... 

The experimental observations combine with the principles of nucleophilic substi tution to give the picture of epoxide ring opening shown m Figure 16 5 The nucleophile attacks the less crowded carbon from the side opposite the carbon-oxygen bond Bond... 

Step 2 Nucleophilic attack by water on carbon of the oxonium ion The carbon-oxygen bond of the ring is broken in this step and the ring opens... 

FIGURE 18 7 Nucleophilic addition to a p unsaturated aldehydes and ketones may take place either in a 1 2 or 1 4 manner Direct addition (1 2) occurs faster than conjugate addition (1 4) but gives a less stable product The product of 1 4 addition retains the carbon-oxygen double bond which is in general stronger than a carbon-carbon double bond... 

The carbon-nitrogen triple bond of nitriles is much less reactive toward nucleophilic addition than is the carbon-oxygen double bond of aldehydes and ketones Strongly basic nucleophiles such as Gngnard reagents however do react with nitriles in a reaction that IS of synthetic value... 

The susceptibihty of dialkyl peroxides to acids and bases depends on peroxide stmcture and the type and strength of the acid or base. In dilute aqueous sulfuric acid (<50%) di-Z fZ-butyl peroxide is resistant to reaction whereas in concentrated sulfuric acid this peroxide gradually forms polyisobutylene. In 50 wt % methanolic sulfuric acid, Z fZ-butyl methyl ether is produced in high yield (66). In acidic environments, unsymmetrical acychc alkyl aralkyl peroxides undergo carbon—oxygen fission, forming acychc alkyl hydroperoxides and aralkyl carbonium ions. The latter react with nucleophiles,... 

Oxygen nucleophiles usually attack a ring carbon atom rather than the sulfur atom of a thiirane, and those cases in which desulfurization is observed on treatment of a thiirane with oxygen bases probably involve the extrusion of sulfur by mechanisms other than a nucleophilic attack on sulfur, e.g. thermal. Desulfurization of thiirane intermediate (43)... 

S-Substituted thiiranium ions react with water and alcohols to give trans ring opening (Scheme 72). A report that oxygen nucleophiles attack sulfur as well as carbon has been shown to be incorrect (79ACR282). The intermediate thiiranium ion (57) in the presence of lithium perchlorate readily yields the carbenium ion which undergoes a transannular hydride... 

Ethylene oxide is a very reactive substance. It reacts rapidly and exothermically with anionic nucleophiles to yield 2-substituted derivatives of ethanol by cleaving the carbon-oxygen bond of the ring ... 

These Br nsted-type plots often seem to be scatter diagrams until the points are collated into groups related by specific structural features. Thus, p-nitrophenyl acetate gives four separate, but parallel, lines for reactions with pyridines, anilines, imidazoles, and oxygen nucleophiles.Figure 7-4 shows such a plot for the reaction of trans-cmmm c anhydride with primary and secondary aliphatic amines to give substituted cinnamamides.All of the primary amines without substituents on the a carbon (R-CHi-NHi) fall on a line of slope 0.62 cyclopentylamine also lies on this line. If this line is characteristic of normal behavior, most of the deviations become qualitatively explicable. The line drawn through the secondary amines (slope 1.98) connects amines with the structure R-CHi-NH-CHi-R. The different steric requirements in the acylation reaction and in the model process... 

Enolates can act either as carbon or as oxygen nucleophiles. The product depends on the electrophile e.g. 

The most common reaction of aldehydes and ketones is the nucleophilic addition reaction, in which a nucleophile, Nu , adds to the electrophilic carbon of the carbonyl group. Since the nucleophile uses an electron pair to form a new bond to carbon, two electrons from the carbon-oxygen double bond must move toward the electronegative oxygen atom to give an alkoxide anion. The carbonyl carbon rehybridizes from sp2 to sp3 during the reaction, and the alkoxide ion product therefore has tetrahedral geometry. 

When a carbonyl group is bonded to a substituent group that can potentially depart as a Lewis base, addition of a nucleophile to the carbonyl carbon leads to elimination and the regeneration of a carbon-oxygen double bond. Esters undergo hydrolysis with alkali hydroxides to form alkali metal salts of carboxylic acids and alcohols. Amides undergo hydrolysis with mineral acids to form carboxylic acids and amine salts. Carbamates undergo alkaline hydrolysis to form amines, carbon dioxide, and alcohols. 

All the mechanisms so far discussed take place at a saturated carbon atom. Nucleophilic substitution is also important at trigonal carbons, especially when the carbon is double bonded to an oxygen, a sulfur, or a nitrogen. Nucleophilic substitution at vinylic carbons is considered in the next section at aromatic carbons in Chapter 13. 

Protonation of the enolate ion is chiefly at the oxygen, which is more negative than the carbon, but this produces the enol, which tautomerizes. So, although the net result of the reaction is addition to a carbon-carbon double bond, the mechanism is 1,4 nucleophilic addition to the C=C—C=0 (or similar) system and is thus very similar to the mechanism of addition to carbon-oxygen double and similar bonds (see Chapter 16). When Z is CN or a C=0 group, it is also possible for Y to attack at this carbon, and this reaction sometimes competes. When it happens, it is called 1,2 addition. 1,4 Addition to these substrates is also known as conjugate addition. The Y ion almost never attacks at the 3 position, since the resulting carbanion would have no resonance stabilization " ... 

The carbonyl group also possesses electrophilic properties at the carbon atom. nucleophilic properties at the oxygen atom. Nucleophilic attack of the carbonyl gn is favored if this is attached to an aromatic ring (inductive effect) and there is als methoxy or phenolic OH group present in the 4-position. Changing a neutral react medium by proton addition has the same effect. 

The cleavage of carbon-oxygen bonds in ethers or esters by nucleophilic substitution is frequently a useful synthetic transformation. 

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