Amines with acid anhydrides

The classes of compounds which are conveniently considered together as derivatives of carboxylic acids include the carboxylic acid anhydrides, acyl chlorides, esters, and amides. In the case of simple aliphatic and aromatic acids, synthetic transformations among these derivatives are usually a straightforward matter involving such fundamental reactions as ester saponification, formation of acyl chlorides, and the reactions of amines with acid anhydrides or acyl chlorides ... 

Amides can be prepared by the reaction of ammonia, primary amines or secondary amines with acid anhydrides, esters or acyl chloride. 

Acylation is one of the most popular derivatization reactions for primary and secondary amines (Figure 11.1). The reagents listed in Table 11.5 easily react with amino groups under mild reaction conditions. In the reactions of amines with acid anhydrides and acyl chlorides, it is usually necessary to remove excess reagent and byproduct acid because these compounds damage the GC column. 

The reverse reaction is an intramolecular acidolysis of amide group by the o-carboxyhc acid to reform anhydride and amine. This unique feature is the result of an ortho neighboring effect. In contrast, the acylation of an amine with ben2oic anhydride is an irreversible reaction under the same reaction conditions. The poly(amic acid) stmcture (8) can be considered as a class of polyamides. Aromatic polyamides that lack ortho carboxylic groups are very... 

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. 

Both amines and acid anhydrides are extensively used cross-linking agents. The resins may also be modified by reacting with other polymers containing hydroxyl or mercaptan groupings, e.g. 

Compared with standard diglycidyl ether resins, the liquid cyclic aliphatic resins are paler in colour and have a much lower viscosity. Whereas in general the cyclic aliphatic resins react more slowly with amines, there is less difference with acid anhydrides. Table 26.7 provides data illustrating this point. 

The epoxidised polybutadiene resins available to date are more viscous than the diglycidyl ethers except where volatile diluents are employed. They are less reactive with amines but have a similar reactivity with acid anhydride hardeners. Cured resins have heat distortion temperatures substantially higher than the conventional amine-cured diglycidyl ether resins. A casting made from an epoxidised polybutadiene hardened with maleic anhydride and cured for two hours at 50°C plus three hours at 155°C plus 24 hours at 200°C gave a heat... 

As with the other non-glycidyl ether resins the absence of the ether oxygen near to the epoxide group results in low reactivity with amine hardemers whereas activity with acid anhydride proceeds at reasonable rates. 

Figure 7-4. Br nsted-type plot for reaction of aliphatic amines with cinnamic anhydride at 25°C in acetonitrile "" the pK values are for the conjugate acids in water. Open circles primary amines closed circles secondary amines.

By contrast with tertiary amines used in catalytic quantities, primary and secondary amines or acid anhydrides may be used to bring about the cure of epoxy resins by reaction in stoichiometric proportions. A typical amine curing agent used at this level is diaminodiphenylmethane (DDM), which reacts with an individual epoxy-group in the way shown in Reaction 4.17. 

It must further be mentioned that the acylation of alcohols, phenols, and amines with acid chlorides (and also anhydrides) is now frequently carried out in pyridine solution instead of according to the older Schotten-Baumann method (action of acid chloride in aqueous-alkaline suspension). The hydrogen chloride is fixed by the pyridine. 

By far the most common method for preparation of amides is the reaction of ammonia or a primary or secondary amine with one of the reactive reagents described in Section 3.4.1. When acyl halides are used, some provision for neutralizing the hydrogen halide is necessary, because it will otherwise react with the reagent amine to form the corresponding salt. Acid anhydrides give rapid acylation of most amines and are convenient if available. The Schotten-Bauman conditions, which involve shaking an amine with excess anhydride or acyl chloride and an alkaline aqueous solution, provide a very satisfactory method for preparation of simple amides. 

Reaction of 4-nitro-l-benzoyl chloride with benzocyclobutene 1 provided the benzoylated product 15 [36]. The nitro group of 15 was reduced with hydrogen in the presence of palladium on charcoal to afford he amine product 16 [44]. Reaction of the amine with maleic anhydride provided the amic acid which was converted to the maleimide 17 by cyclodehydration with acetic anhydride and sodium acetate at 95 °C [45-47], This monomer and its homo-polymer will be discussed in greater detail in a later section. 

Reactivity. Flammable polymerizes violently in the presence of trace amounts of metals or acids can react violently with acid anhydrides, alcohols, ketones, phenols, ammonia, hydrocyanic acid, hydrogen sulfide, halogens, phosphorus, isocyanates, strong alkalis and amines (American Conference of Governmental Industrial Hygienists, 1991)... 

Amides of trifluoromethanesulfonic acid (triflamides) can be prepared by the reaction of the corresponding amines with triflic anhydride The most applicable in organic synthesis are iV-phenyltriflamides, which can be used as mild and selective Inflating reagents [110, lll ... 

The dynamic mechanical properties of the cured resin are very similar to those of resins cured with amines or acid anhydrides (Fig. II)44. ... 

The phthalimlde group is typically introduced by reaction of a primary amine with phthalic anhydride in chloroform at 70 °C for 4 h (85-93% yield)1 or phthaloyl chloride in the presence of triethylamine [Scheme 8.10].20 2-Ch oro-carbonylbenzoic acid methyl ester in the presence of base [Scheme 8.11JT21-22 or N-ethoxycarbonylphthalimide23 have also been used with the latter reagent being especially useful for the -protection of a-amino acids [Scheme 8 12] m. 24... 

Primary and secondary amines can be acylated readily by treatment with acid anhydrides and heat. Acetic anhydride, propionic anhydride, and trifluo-... 

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. 

The acylation of alcohols, thiols, and amines with acetic anhydride, or directly with acetic acid, can be accomplished with the aid of catalytic (2.5 mol %) Cu(OTf)2 [40]. Copper(I) and (II) chloride has been used for the acylation of a variety of a,/8-unsaturated acid chlorides (Sch. 17). Copper powder is usually added to prevent polymerization. The A -silylsulfonamide 65 was directly acylated without first deprotection to afford 66 in high... 

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