Amides, from acid derivatives anhydrides

Acid chlorides are often used in these syntheses because they are the most electrophilic of all acid derivatives and because they can be made from the acids themselves with PCI5 or SOCI2. The other important acid derivatives can all be made from acid chlorides or from any compound above them in the chart of reactivity. So you can make amides from acid chlorides, anhydrides or esters but it is very difficult to make any other derivatives from amides. All derivatives except amides can easily be made from the acids themselves. 

Since amides are the least reactive of the carboxylic acid derivatives (shown on the chart above), we can therefore make amides from any carboxylic acid derivatives that are higher on the chart. In other words, we can make amides from acid halides, from anhydrides, or from esters. 

Acid derivatives are made directly from acids or by conversion from other acid derivatives depending on their stabihty. The most important are esters (RCOiEt), amides (RCO2NR2), anhydrides (RCOO COR) and add clilorides (RCOCI). Arrange these in an order of stabilily, the most reactive at the top of the list, the most stable at the bottom. 

The carbonyl group of an amide is stabilized to a greater extent than that of an acyl chlo ride acid anhydride or ester amides are formed rapidly and m high yield from each of these carboxylic acid derivatives... 

Amidation. Reaction of maleic anhydride or its isomeric acids with ammonia [7664-41-7] (qv), primary amines (qv), and secondary amines produces mono- or diamides. The monoamide derivative from the reaction of ammonia and maleic anhydride is called maleamic acid [557-24-4] (8). Another monoamide derivative formed from the reaction of aniline [62-53-3] and maleic anhydride is maleanilic acid [555-59-9] (9). 

The acylation of enamines derived from cyclic ketones, which can lead to the acyl ketone or ring expansion (692-694), was studied by NMR and mass spectroscopic analysis of the products (695,696). In a comparative study of the rates of diphenylketene addition to olefins, a pronounced activation was observed in enamines (697). Enamine N- and C-acylation products were obtained from reactions of Schiff s bases (698), vinylogous urethanes (699), cyanamides (699), amides (670,700), and 2-benzylidene-3-methylbenzothiazoline (672) with acid chlorides, anhydrides, and dithio-esters (699). 

Besides the technical method starting from naphthalene, phthalic acid and its substituted derivatives can be prepared by oxidation of o-xylene to phthalic acid with potassium permanganate. This compound can be subsequently transformed via an anhydride, imide, and amide to a derivative of phthalonitrile, which is the more convenient starting material for several coordination compounds. The synthesis of the ferf-butyl-substituted dicarbonitrile, which is a very common starting material for highly soluble phthalocyanines, is shown below.97,105... 

Carboxylic acids and their derivatives like esters, amides, anhydrides, and acyl halides are formally synthesized from olefins, carbon monoxide, and compounds represented by Nu-H such as H2O, ROH, RNH2, RCOOH (Equations (4) and (5)). Alkynes also react under similar conditions to afford the corresponding unsaturated carboxylic acid derivatives. These reactions have been named hydrocarboxylation, hydroalkoxycarbonylation, and hydroaminocarbonylation. 

Amides are the least reactive of the carboxylic acid derivatives, and undergo acid or base hydrolysis to produce the parent carboxylic acids, and reduction to appropriate amines (see Section 4.3.10). They can also be dehydrated to nitriles, most commonly with boiling acetic anhydride, (AcO)20, sulphonyl chloride (SOCI2) or phosphoms oxychloride (POCI3) (see Section 4.3.18). Amines (with one less carbon) are prepared from amides by the treatment of halides (Br2 or CI2) in aqueous NaOH or KOH. This reaction is known as Hofmann rearrangement (see Section 4.3.10). 

In addition to the procedures listed in Table 3.38, further reactions have been used to generate halides upon cleavage. In Section 3.5.2, iodolactonization is presented as a method for the preparation of iodomethyl lactones from resin-bound pentenoic or hexenoic acid derivatives. Closely related to the iodolactonization is the iodine-mediated formation of 2-(iodomethyl)tetrahydrofurans from resin-bound isoxazoli-dines (Entry 9, Table 3.38 for the mechanism, see Figure 15.5). Nitriles can also be prepared by cleavage and simultaneous dehydration of amides RCONH2 from the Rink or Sieber linkers with TFA anhydride (Entry 10, Table 3.38). 

The esterification of support-bound carboxylic acids has not been investigated as thoroughly as the esterification of support-bound alcohols. Resin-bound activated acid derivatives that are well suited to the preparation of esters include O-acylisoureas (formed from acids and carbodiimides), acyl halides [23,226-228], and mixed anhydrides (Table 13.15). A-Acylurea formation does not compete with esterifications as efficiently as it does with the formation of amides from support-bound acids. Esters can also be prepared from carboxylic acids on insoluble supports by acid-catalyzed esterification [152,229]. Alternatively, support-bound carboxylic acids can be esteri-fied by O-alkylation, either with primary or secondary aliphatic alcohols under Mitsu-nobu conditions or with reactive alkyl halides or sulfonates (Table 13.15). 

Triflic anhydride is a useful reagent for the preparation of covalent triflate esters from alcohols, ketones, and other organic substrates [66] In many cases, very reactive Inflates can be generated in situ and subjected to subsequent transformation without isolation [94, 95, 96, 97] Typical examples are cyclization of amides into dihydroisoquinolines (equation 45) and synthesis of N-hydroxy-a-amino acid derivatives (equation 46) via the intermediate covalent triflates... 

Synthesis of Amides Amides are the least reactive acid derivatives, and they can be made from any of the others. In the laboratory, amides are commonly synthesized by the reaction of an acid chloride (or anhydride) with an amine. The most common industrial synthesis involves heating an acid with an amine (at high temperatures, in the absence of oxygen) to drive off water and promote condensation. This simple industrial technique rarely works well in the laboratory, but it may succeed with the use of a coupling reagent (Section 24-11). Esters react with amines and ammonia to give amides, and the partial hydrolysis of nitriles also gives amides. 

Cleavage of an ester by ammonia (or an amine) to give an amide and an alcohol, (p. 1003) (carboxylic acid anhydride) An activated acid derivative formed from two acid molecules with loss of a molecule of water. A mixed anhydride is an anhydride derived from two different acid molecules, (p. 986)... 

Amides and Imides, Orgonlc. An organic amide is a compt contg the monovalent -CO.NH, radical (eg, acetamide CHj.CO.NH], oxamide HjN.CO.CO.NH], benzamide C(H, CONH], etc). An organic imide is a compd of the general formula R NH in which R is an acyl radical such as CH,CO—. Another type of imide is a compd derived from acid anhydrides in which one oxygen is reolaced... 

A different approach toward preparation of phosphinous and phosphonous iodides uses the reaction of iodoalkanes with either PI3 or PI5. This reaction is specific for iodoalkanes and phosphorus iodides and is not applicable to other halides. From the resultant highly reactive phosphinous and phosphonous iodides, the full range of the parent acid derivatives may be prepared (esters, other acid halides, anhydrides, amides). We will not be concerned here with these preparations of derivatives of the parent acids, topics that are considered in other reports. ... 

Chapter 22 focuses on carbonyl compounds that contain an acyl group bonded to an electronegative atom. These include the carboxylic acids, as well as carboxylic acid derivatives that can be prepared from them acid chlorides, anhydrides, esters, and amides. 

Carboxylic acid derivatives (Section 20.1) Compounds having the general structure RCOZ, which can be synthesized from carboxylic acids. Common carboxylic acid derivatives include acid chlorides, anhydrides, esters, and amides. 

Among the most important reactions of carboxylic acids are those that convert the carboxyl group into an acid derivative by a nucleophilic acyl substitution. Acid chlorides, anhydrides, esters, and amides can all be prepared from carboxylic acids (Figure 21.4). 

The six common groups derived from carboxylic acids are, in decreasing priority after carboxylic acids salts, anhydrides, esters, acyl halides, amides, and nitriles. 

The reaction of N-arylsulfonylsuinmides with a range of trivalent phosphorus compounds gave near quantitative yields of the phosphinimides and the sulfide. I Addition of protic solvents led to reduction products, which contain, besides the original sulfides, an alkyl-exchanged sulfide in which the alkyl group derived from the alcohol. 126.127 other derivatives, (acid anhydride, amide, ester or thioester) were formed in the presence of carboxylic acid derivatives. 128,129 xhese reactions were favoured by the dipolar nature of the intermediately formed sulfurane. 127... 

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