Carbon nitrogen nucleophile attack

Introduction Photochemical Reactions Electrophilic Attack at Carbon Electrophilic Attack at Nitrogen Nucleophilic Attack at Carbon Radical Attack at Carbon... 

Nitrogen Nucleophile Attacking sp2 or sp3 Carbon Five-Membered Ring Formation... 

The most common method to decrease the reactivity of an unshared pair of electrons on an atom is to attach a carbonyl group to that atom. Therefore, the amine is first reacted with acetyl chloride to form an amide. (This reaction and its mechanism are described in detail in Section 19.6. To help you remember the reaction for now, note that the nitrogen nucleophile attacks the carbonyl carbon electrophile, displacing the chloride leaving group.)... 

The Lewis acid mechanism of catalysis is shown in Figure 6.2.8. In this mechanism, the tin compound functions as a classic Lewis acid, coordinating to the isocyanate either through the carbonyl oxygen or nitrogen in the initial step to polarize the carbonyl. This increases the electrophilicity of the isocyanate carbon toward nucleophilic attack by alcohol. It has been shown by cryoscopy that there is a strong association of isocyanate with di-n-butyltin dicarboxylates. ... 

Coordination of nitrile to metal directly through the nitrogen or through some other proximal atom activates the carbon toward nucleophilic attack by water and other nucleophiles. The products are commonly amides. The metal-mediated reactions of dicyanodiamide (19) have been further investigated in the presence of nickel or copper salts (19) reacts with alcohols to yield (20). 

As a consequence of the alternative distribution of an even number (2n) TT electrons on an odd number (2n - 1) carbon atoms, centers of the methine chain susceptible to nucleophilic attack are effectively the even carbons atoms starting from nitrogen, as it has been proven experimentally (103), particularly with a ketomethyiene giving a neutrocyanine compound (53, 67). 

Electron release from nitrogen stabilizes the carbonyl group of amides and decreases the rate at which nucleophiles attack the carbonyl carbon... 

Ring-atomic centers can undergo attack by electrophiles, easily at the ring nitrogen and less easily at ring carbons. Nucleophilic attack is also possible at ring carbons or hydrogens. 

Virtually all of the organo derivatives of CA are produced by reactions characteristic of a cycHc imide, wherein isocyanurate nitrogen (frequendy as the anion) nucleophilically attacks a positively polarized carbon of the second reactant. Cyanuric acid and ethylene oxide react neady quantitatively at 100°C to form tris(2-hydroxyethyl)isocyanurate [839-90-7] (THEIC) (48—52). Substitution of propylene oxide yields the hydroxypropyl analogue (48,49). At elevated temperatures (- 200° C). CA and alkylene oxides react in inert solvent to give A/-hydroxyalkyloxazohdones in approximately 70% yield (53). Alternatively, THEIC can be prepared by reaction of CA and 2-chloroethanol in aqueous caustic (52). THEIC can react further via its hydroxyl fiinctionahty to form esters, ethers, urethanes, phosphites, etc (54). Reaction of CA with epichlorohydrin in alkaline dioxane solution gives... 

Nucleophilic Attack at Hydrogen Attached to Ring Carbon or Ring Nitrogen... 

Very little is known about nucleophilic attack on an unsubstituted carbon atom of pyrazoles and their aromatic derivatives (pyrazolones, pyrazolium ions). The SwAr reaction of halogenopyrazoles will be discussed in Section 4.04.2.3.7. Sulfur nucleophiles do not attack the ring carbon atoms of pyrazolium salts but instead the substituent carbon linked to nitrogen with concomitant dequaternization (Section 4.04.2.3.lO(ii)). The ring opening of pyrazolium salts by hydroxide ion occurs only if carbon C-3 is unsubstituted the exact mechanism is unknown and perhaps involves an initial attack of OH on C-3. 

The nucleophilic attack of nitrogen bases leads to a variety of products as the result of addition or addition-elimination reactions The regioselectivity resembles that of attack by alcohols and alkoxides an intermediate carbanion is believed to be involved In the absence of protic reagents, the fluorocarbanion generated by the addition of sodium azide to polyfluonnated olefins can be captured by carbon dioxide or esters of fluonnated acids [J 2, 3] (equation I)... 

When written in this way it is clear what is happening. The mechanisms of these reactions are probably similar, despite the different p values. The distinction is that in Reaction 10 the substituent X is on the substrate, its usual location but in Reaction 15 the substituent changes have been made on the reagent. Thus, electron-withdrawing substituents on the benzoyl chloride render the carbonyl carbon more positive and more susceptible to nucleophilic attack, whereas electron-donating substituents on the aniline increase the electron density on nitrogen, also facilitating nucleophilic attack. The mechanism may be an addition-elimination via a tetrahedral intermediate ... 

FIGURE 16.27 A mechanism for the aspartic proteases. In the first step, two concerted proton transfers facilitate nucleophilic attack of water on the substrate carbonyl carbon. In the third step, one aspartate residue (Asp" " in pepsin) accepts a proton from one of the hydroxyl groups of the amine dihydrate, and the other aspartate (Asp" ) donates a proton to the nitrogen of the departing amine. 

Nucleophilic attack at a carbon atom, followed by a mesomeric shift to make a nitrogen atom quaternary, has been known for many years. The best example is the formation of 1,3,3-trisubstituted 3 -indole salts by the action of alkyl halides on 1,3-disubstituted indoles. 

In the reactions of nucleophilic addition to diacetylene, monoalkylhydrazines behave in two ways (71AKZ743). In an anhydrous medium at 40-50°C, the reaction with methyl- and ethylhydrazines proceeds in such a way that a more nucleophilic disubstituted nitrogen atom attacks the terminal carbon atom of diacetylene to form l-alkyl-3-methylpyrazoles (17), the content of isomeric 1-alkyl-5-methylpyrazoles being 15% according to GLC (71AKZ743 73DIS 77AKZ332). 

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