Amides, from acid derivatives

No Additional Examples SECTION 77 Amides from Acid Derivatives... 

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. 

Amides are acid derivatives that result from a combination of an acid with ammonia or an amine. Proteins have the structure of long-chain, complex amides. 

The border line for solubility in water ranges from three to five carbons for the esters to five or six carbons for the amides. The acid derivatives are soluble in the usual organic solvents. 

SECTION 77 AMIDES FROM ACIDS AND ACID DERIVATIVES... 

Carboxylic acid amides from ethylene derivatives G G GH G GON <... 

Carboxylic acid amides from ethylene derivatives... 

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. 

The high reactivity of chlorides is utilized for the preparation of carboxylic acid derivatives by first converting the acids to chlorides and then allowing them to react with amines or alcohols to give suitable derivatives. For the identification of acid chlorides, reactions described on p. 254 are employed. A simple method of preparation of amides from acid chlorides is illustrated by the preparation of stearoylamide. Other useful amines are aniline or p-toluidine the reaction of amines with chlorides is usually carried out by heating the components in an inert solvent (benzene). 

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. 

In synthetic target molecules esters, lactones, amides, and lactams are the most common carboxylic acid derivatives. In order to synthesize them from carboxylic acids one has generally to produce an activated acid derivative, and an enormous variety of activating reagents is known, mostly developed for peptide syntheses (M. Bodanszky, 1976). In actual syntheses of complex esters and amides, however, only a small selection of these remedies is used, and we shall mention only generally applicable methods. The classic means of activating carboxyl groups arc the acyl azide method of Curtius and the acyl chloride method of Emil Fischer. 

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... 

Ketenimines are usually prepared from carboxyHc acid derivatives such as amides and imino chlorides via elimination and from nitriles via alkylation with alkyl haHdes under strong basic conditions (21,64). 

Selected physical properties of various methacrylate esters, amides, and derivatives are given in Tables 1—4. Tables 3 and 4 describe more commercially available methacrylic acid derivatives. A2eotrope data for MMA are shown in Table 5 (8). The solubiUty of MMA in water at 25°C is 1.5%. Water solubiUty of longer alkyl methacrylates ranges from slight to insoluble. Some functionalized esters such as 2-dimethylaniinoethyl methacrylate are miscible and/or hydrolyze. The solubiUty of 2-hydroxypropyl methacrylate in water at 25°C is 13%. Vapor—Hquid equiUbrium (VLE) data have been pubHshed on methanol, methyl methacrylate, and methacrylic acid pairs (9), as have solubiUty data for this ternary system (10). VLE data are also available for methyl methacrylate, methacrylic acid, methyl a-hydroxyisobutyrate, methanol, and water, which are the critical components obtained in the commercially important acetone cyanohydrin route to methyl methacrylate (11). 

Introduction of the cobalt atom into the corrin ring is preceeded by conversion of hydrogenobyrinic acid to the diamide (34). The resultant cobalt(II) complex (35) is reduced to the cobalt(I) complex (36) prior to adenosylation to adenosylcobyrinic acid i7,i -diamide (37). Four of the six remaining carboxyhc acids are converted to primary amides (adenosylcobyric acid) (38) and the other amidated with (R)-l-amino-2-propanol to provide adenosylcobinamide (39). Completion of the nucleotide loop involves conversion to the monophosphate followed by reaction with guanosyl triphosphate to give diphosphate (40). Reaction with a-ribazole 5 -phosphate, derived biosyntheticaHy in several steps from riboflavin, and dephosphorylation completes the synthesis. 

Tetrahydroharman, m.p. 179-80°, has been prepared by a number of workers by a modification of this reaction, viz., by the interaction of tryptamine (3-)5-aminoethylindole) with acetaldehyde or paraldehyde and Hahn et al. have obtained a series of derivatives of tetrahydronorharman by the use of other aldehydes and a-ketonic acids under biological conditions of pH and temperature, while Asahina and Osada, by the action of aromatic acid chlorides on the same amine, have prepared a series of amides from which the corresponding substituted dihydronorharmans have been made by effecting ring closure with phosphorus pentoxide in xylene solution. 

FIGURE 20.1 Structure, reactivity, and carbonyl-group stabilization in carboxylic acid derivatives. Acyl chlorides are the most reactive, amides the least reactive. Acyl chlorides have the least stabilized carbonyl group, amides the most. Conversion of one class of compounds to another is feasible only in the direction that leads to a more stabilized carbonyl group that is, from more reactive to less reactive. 

Substances of this type have hitherto received little attention. One of the reasons appears to be the limited possibilities of preparation. The only known method of preparation, described by Woolley et ai./ proceeds from the derivatives of 4-aminoimidazole-5-carboxylic acid. The amide of this acid (142) is treated with nitrous acid to yield 4-hydroxyimidazo [4,5-d]-i -triazine (2-azahypoxanthine) (143), the amidine (144) yielding the 4-amino derivative (2-azaadenine) (145) under the same conditions. 2-Azahypoxanthine was probably obtained in the same way earlier but was not identified. ... 

Most of the inhibitors in use are organic nitrogen compounds and these have been classified by Bregman as (a) aliphatic fatty acid derivatives, b) imidazolines, (c) quaternaries, (d) rosin derivatives (complex amine mixtures based on abietic acid) all of these will tend to have long-chain hydrocarbons, e.g. CigH, as part of the structure, (e) petroleum sulphonic acid salts of long-chain diamines (preferred to the diamines), (/) other salts of diamines and (g) fatty amides of aliphatic diamines. Actual compounds in use in classes (a) to d) include oleic and naphthenic acid salts of n-tallowpropylenediamine diamines RNH(CH2) NH2 in which R is a carbon chain of 8-22 atoms and x = 2-10 and reaction products of diamines with acids from the partial oxidation of liquid hydrocarbons. Attention has also been drawn to polyethoxylated compounds in which the water solubility can be controlled by the amount of ethylene oxide added to the molecule. 

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... 

Photodriven reactions of Fischer carbenes with alcohols produces esters, the expected product from nucleophilic addition to ketenes. Hydroxycarbene complexes, generated in situ by protonation of the corresponding ate complex, produced a-hydroxyesters in modest yield (Table 15) [103]. Ketals,presumably formed by thermal decomposition of the carbenes, were major by-products. The discovery that amides were readily converted to aminocarbene complexes [104] resulted in an efficient approach to a-amino acids by photodriven reaction of these aminocarbenes with alcohols (Table 16) [105,106]. a-Alkylation of the (methyl)(dibenzylamino)carbene complex followed by photolysis produced a range of racemic alanine derivatives (Eq. 26). With chiral oxazolidine carbene complexes optically active amino acid derivatives were available (Eq. 27). Since both enantiomers of the optically active chromium aminocarbene are equally available, both the natural S and unnatural R amino acid derivatives are equally... 

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