Amines reaction with acids

Chemical Properties The formation of salts with acids is the most characteristic reaction of amines. Since the amines are soluble in organic solvents and the salts are usually not soluble, acidic products can be conveniendy separated by the reaction with an amine, the unshared electron pair on the amine nitrogen acting as proton acceptor. Amines are good nucleophiles reactions of amines at the nitrogen atom have as a first step the formation of a bond with the unshared electron pair of nitrogen, eg, reactions with acid anhydrides, haUdes, and esters, with carbon dioxide or carbon disulfide, and with isocyanic or isothiocyanic acid derivatives. 

Primary cycloaUphatic amines react with phosgene to form isocyanates. Reaction of isocyanates with primary and secondary amines forms ureas. Dehydration of ureas or dehydrosulfuri2ation of thioureas results in carhodiimides. The nucleophilicity that deterrnines rapid amine reactivity with acid chlorides and isocyanates also promotes epoxide ring opening to form hydroxyalkyl- and dihydroxyalkylaniines. Michael addition to acrylonitrile yields stable cyanoethylcycloalkylarnines. 

Acylation. Aromatic amines react with acids, acid chlorides, anhydrides, and esters to form amides. In general, acid chlorides give the best yield of the pure product. The reaction with acetic, propionic, butanoic, or benzoic acid can be catalyzed with phosphoms oxychloride or trichloride. 

The most important group of derivatives for the amino function (Fig. 7-4) is the carbamate group, which can be formed by reactions with acids, acid chlorides or acid anhydrides. A series of chlorides as 2-chloroisovalerylchloride [1], chrysanthe-moylchloride [2] and especially chloride compounds of terpene derivatives (cam-phanic acid chloride [3], camphor-10-sulfonyl chloride [4]) are used. The a-methoxy-a-trifluoromethylphenylacetic acid or the corresponding acid chloride introduced by Mosher in the 1970s are very useful reagents for the derivatization of amines and alcohols [5]. 

This reaction type has been intensely studied °. The application of highly polar solvents, catalysis with tertiary amines" or with acids mesomeric stabilization of intermediate carbenium ions " (allylic and benzylic systems propargylic systems" ) as well as derivatives of sulfinic acids with increasing acidity - usually indicate an ionic pathway (intra- and/or inter-molecular) ... 

Acid chlorides are very reactive, and they readily react with ammonia, primary amines, or secondary amines to form an amide. Figure 12-26 illustrates the reaction of an acid chloride with ammonia. Replacing one or two of the hydrogen atoms of ammonia with an organic group will result in an N-substituted amide. Tertiary amines react with acid chlorides to form a carboxylic acid and an ammonium salt. 

Many such activated acyl derivatives have been developed, and the field has been reviewed [7-9]. The most commonly used irreversible acyl donors are various types of vinyl esters. During the acylation of the enzyme, vinyl alcohols are liberated, which rapidly tautomerize to non-nucleophilic carbonyl compounds (Scheme 4.5). The acyl-enzyme then reacts with the racemic nucleophile (e.g., an alcohol or amine). Many vinyl esters and isopropenyl acetate are commercially available, and others can be made from vinyl and isopropenyl acetate by Lewis acid- or palladium-catalyzed reactions with acids [10-12] or from transition metal-catalyzed additions to acetylenes [13-15]. If ethoxyacetylene is used in such reactions, R1 in the resulting acyl donor will be OEt (Scheme 4.5), and hence the end product from the acyl donor leaving group will be the innocuous ethyl acetate [16]. Other frequently used acylation agents that act as more or less irreversible acyl donors are the easily prepared 2,2,2-trifluoro- and 2,2,2-trichloro-ethyl esters [17-23]. Less frequently used are oxime esters and cyanomethyl ester [7]. S-ethyl thioesters such as the thiooctanoate has also been used, and here the ethanethiol formed is allowed to evaporate to displace the equilibrium [24, 25]. Some anhydrides can also serve as irreversible acyl donors. 

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. 

Figure 45 Amine reaction with tartaric acid.

The reaction sequence - including subsequent reaction with water which leads to amines - is named the Curtius Reaction. This reaction is similar to the Schmidt Reaction with acids, differing in that the acyl azide in the present case is prepared from the acyl halide and an azide salt. 

Powerful reductant supplied as hydrocarbon solution.2 Violent reaction with acids, air, alcohols, amines, and water.3... 

Another interesting modification of glass surfaces was introduced by Beier and Hoheisel.23 They synthesized a flexible, dendritic linker system that enables covalent immobilization of oligonucleotides and PNAs with high loading capacity in a controlled manner. This method facilitates the modulation of surface properties such as hydrophobicity and charge. The synthesis of the linker system involves two consecutive reactions an acylation of surface-bound amine groups with acid chloride (4-nitrophenyl-chloroformate or acryloylchloride) and subsequent reaction with an amine. A bis-amine results in a linker system, while a polyamine produces a dendritic structure (Fig. 14.3). Because polyamines possess primary and secondary amine... 

Amines react as nucleophiles or bases, since the nitrogen atom has a readily available lone pair of electrons that can participate in bonding (Following fig.). Because of this the amines react with acids to form water soluble salts. This permits the easy separation of amines from other compounds. A crude reaction mixture can be extracted with dilute hydrochloric acid such that any amines present are protonated and dissolve into the aqueous phase as water-soluble salts. The free amine can be recovered by... 

Primary and secondary amines react with acid halides to form amides. This reaction is a nucleophilic acyl substitution the replacement of a leaving group on a carbonyl carbon by a nucleophile. We will study nucleophilic acyl substitution in detail in Chapters 20 and 21. In this case, the amine replaces chloride ion. 

In addition to the synthesis of /1-dicarbonyl compounds3,25, the acylation of enamines also gives access to a wide variety of acyclic, carbocyclic and heterocyclic systems. The course of the reaction is often critically dependent upon the type of enamine used, on the substituents present in the two reagents, and on the experimental conditions, such as temperature, solvent, presence of added tertiary amine, etc. In contrast to alkylation, A-acylation is readily reversible. Since enamines are stronger bases than the C-acylated enamines, half an equivalent of the enamine is lost by salt formation in their reaction with acid chlorides. This can be avoided by addition of a tertiary amine179, but this in... 

Other experimental reproductive effects. A skin and severe eye irritant. A narcotic. Human mutation data reported. A common air contaminant. Highly flammable liquid. NCxmres of 30-60% of the vapor in air ignite above 100°. It can react violently with acid anhydrides, alcohols, ketones, phenols, NH3, HCN, H2S, halogens, P, isocyanates, strong alkalies, and amines. Reactions with cobalt chloride, mercury(II) chlorate, or mercury(II) perchlorate form violendy in the presence of traces of metals or acids. Reaction with oxygen may lead to detonation. When heated to decomposition it emits acrid smoke and fumes. 

In addition to the formation of silyl enol ethers, isomerization of epoxides to allylic alcohols is another highly typical transformation performed by combination of a silicon Lewis acid with a tertiary amine. Reaction with la was examined, and its scope and limitation reported, by Noyori [61]. Epoxide 44 can be successfully converted into the corresponding allyl silyl ether 45 (Sch. 34). 

Reactions of Aromatic Amines.—(i) With acids. The first prominent reaction of aromatic amines is the one already given, viz., with acids they form salts. These salts are soluble crystalline compounds, which, like the ammonium salts, are easily decomposed with strong alkalies yielding the free base. The reactions with aniline are as... 

We ve already studied the two most general reactions of amines—alkylation and acylation. As we saw earlier in this chapter, primary, secondare and tertiary amines can be alkylated by reaction with a primary alkyl halide. Alkylations of primary and secondary amines are difficult to conind and often give mixtures of products, but tertiary amines are cleanly allqd-ated to give quaternary ammonium salts. Primary and secondary (bat not tertiary) amines can also be acylated by reaction with acid chlorides or add anhydrides to yield amides (Sections 21.4 and 21.5). 

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