Reactions of Amines—General Features

Only three elements in the second row of the periodic table have nonbonded electron pairs in neutral organic compounds nitrogen, oxygen, and fluorine. Because basicity and nucleophilicity decrease across the row, nitrogen is the most basic and most nucleophilic of these elements. 

Amines are stronger bases and nucleophiles than other neutral organic compounds. 

Amines react as bases with compounds that contain acidic protons. 

Amines react as nucleophiies with compounds that contain eiectrophiiic carbons. 

SampiG ProbiGm 25.2 What aldehyde or ketone and nitrogen cxjmponent are needed to synthesize N-ethylcyclohexylamine by a 

Because N-ethylcyclohexylamine has two different alkyl groups bonded to the N atom, either R group can come from the carbonyl component and there are two different ways to form a C — N bond by reductive amination. 

Because reductive amination adds one R group to a nitrogen atom, both routes to form the 2° amine begin with a 1° amine. 

ProbiGm 25.18 What starting materials are needed to prepare each compound using reductive amination Give all possible pairs of starting materials when more than one possibility exists. 

ProbiGm 25.19 (a) Explain why phentermine [PhCH2C(CH3)2NH2] can t be made by a reductive amination reaction. 

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The synthesis of nitro dyes is relatively simple, a feature which accounts to a certain extent for their low cost. The synthesis, illustrated in Scheme 6.5 for compounds 140 and 141, generally involves a nucleophilic substitution reaction between an aromatic amine and a chloronitroaromatic compound. The synthesis of C. I. Disperse Yellow 14 (140) involves the reaction of aniline with l-chloro-2,4-dinitroaniline while compound 141 is prepared by reacting aniline (2 mol) with compound 144 (1 mol). 

This type of duality of action is presumably present in other situations, such as the Fries rearrangement (78), the Friedel-Crafts reaction with acid chlorides (65) or acid anhydrides (21), and the catalytic chlorination of nitrobenzene (17). In these reactions it appears that the uncoordinated Lewis acid is the effective catalyst. The same situation is illustrated by recent work on aromatic amination (32, 33) and halogenation (57, 58, 71) and seems to be general feature of Lewis acid-catalyzed electrophilic reactions of aromatic compounds containing suitable donor groups. 

The mechanism of addition of amines to the epoxy ring considered above is part of the general problem of the mechanism of the reaction under study. The main feature of this mechanism is formation of different hetero- and autocomplexes of the starting substances and reaction products characterized by different reactivity5,13,14,33). These complexes may be formed both inter- and intramolecularly. The existence of these complexes has been proved and the thermodynamic parameters in complexing reactions have been determined 5.13,14,29,33-43)... 

A sequential use of two pericyclic reactions involving sulfur compounds is also implied in a general allylic amination of alkenes with Kresze s reagent, 7V,A -bis(methoxycarbonyl)suIfurdiimide (8). A [2,3] sigmatropy, following an ene reaction of the S-allyl sulfinamidine (9) intermediary formed, affords the diamino sulfane (10), easily converted to the carbamate (11) and then to the amine (12) or (13) [511]. The reactions are featured with 2-methyl-2-butene as the alkene to be functionalized. They are described in Organic Syntheses [512]. 

A possible mechanism which accounts for the general features of the reaction in aqueous solution is shown in Scheme 4.7. B represents any base, in addition to OH, present in the aqueous reaction mixture, C032 or an amine, for example and, because acetaldehyde is only very weakly acidic in aqueous solution (pKa = 16.7) [18], the proposed enolate carbanion intermediate can be present at only extremely low concentrations. 

The results show that the presence of bulky substituent on a polymer chain may effectively inhibit the termination proceeding by this mechanism. The results presented at this point may be summarized as follows chain transfer to polymer is a general feature of cationic ring-opening polymerization although for different systems the contribution of this reaction may vary only in some systems this process results in termination (These systems involve, e.g., cyclic amines (3- and 4-membered) and cyclic sulfides (3- and 4-membered) and the contribution of the reaction is reduced for substituted chains. 

Use of excess alkali metal in liquid ammonia or an amine (generally EtNH2 or ethylenediamine, EDA) is also a widespread procedure used to desulfurize sulEdes, dithioketals and sulfones. - - From the numerous works published, a number of interesting features emerge. Thus desulfurization of sulfides in liquid NH3-THF tolerates esters and ketones, while Li-EtNH2 cleaves the C—S bonds of unsaturated substrates without side reactions (Scheme 1). Sodium in liquid ammonia was found to be a better... 

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