Amides, general

The mass spectra of underivatized amides generally show molecular ions. 

Some of the colleagues with whom I discussed my intention to write on this topic expressed polite scepticism. There is good historical reason for this. Several previous writers had amid general admiration used frontier orbital theories to rationalise such processes as concerted trans-addition, square four-carbon arrays in olefin metathesis, chelation of a metal by two strained carbon-carbon a-bonds, and trigonal bipyramidal Fe(II) alkyls. Belief in these is less widespread than it was five or ten years ago, and... 

Test-tube Preparation of MTPA Esters and Amides General Procedure15c ... 

The behavior of various alkyloxaairanee at elevated temperatures under pyrolysis conditions has also been, studied. Under these conditions amides generally are obtained in good yield. These reactions are carried out in the gas phase at 200-300° and are a direct consequence of the relatively weak oxygen-nitrogen bond. Whether unpairing of the electrons of this bond occurs is uncertain but the reaction may best be described as a concerted rearrangement as indicated below ... 

Resin-bound amides generally need to be activated to make them susceptible to saponification under acceptably mild reaction conditions [114] (Table 3.5). Particularly elegant are those linkers that allow this activation to be realized as the final synthetic step before cleavage (safety-catch linkers [115-117]). The activation of some amide-based safety-catch linkers is outlined in Figure 3.9. 

The intermolecular N-acylation of amides generally requires treatment of the latter with strong acylating agents, such as ketenes, acyl halides, or anhydrides, in the presence of a base. Few examples of such N-acylations have been reported (Entries 1-3, Table 13.20 see also saftey-catch linkers, Section 3.1.2.3). 

A strong carbonyl absorption is evident in the spectra of all amides, although the frequency of absorption varies somewhat with the structure of the amide. Thus primary amides generally absorb near 1680 cm 1, whereas secondary and tertiary amides absorb at slightly lower frequencies. The N—H stretching frequencies of amides are closely similar to those of amines and show shifts of 100 cm-1 to 200 cm 1 to lower frequencies as the result of hydrogen bonding. Primary amides have two N—H bands of medium intensity near 3500 cm 1 and 3400 cm 1, whereas secondary amides, to a first approximation, have only one N—H band near 3440 cm 1. However, a closer look reveals that the number, position, and intensity of the N—H bands of mono-substituted amides depend on the conformation of the amide, which can be either cis or trans ... 

Amides generally are formed from acid chlorides, acid azides, acid anhydrides, and esters. It is not practical to prepare them directly from an amine and a carboxylic acid without strong heating or unless the reaction is coupled to a second reaction that activates the acid (see Exercise 15-25). Notice that esters of phenols are more reactive toward amines than esters of alcohols because phenols are stronger acids than alcohols. 

Amides. Primary amides exhibit behaviour similar to the corresponding acid and methyl esters substituted amides resemble the higher alkyl esters. There is a common tendency to form M + 1 ions by ion-molecule reactions. Primary amides generally give a strong peak at m/z 44 ... 

Halolactamization.3 Unsaturated amides generally form lactones when cyclized by Br2 or I2. However the unsaturated N-tosyl amide I, when treated with Br2 in the presence of N a HC03, forms the bromo N-tosyl /J-lactam 2 (67%yield). Dehalogenation of 2 is best effected with Bu3SnH. 

In general, amides are much less hydrolytically reactive than esters. Typical hydrolysis half-lives under conditions common to aquatic environments range from hundreds to thousands of years. Hydrolysis of amides generally requires acid or base for the reactions to achieve measurable rates. 

Preparation of 6-[(2-aminomethyl)phenyl]-2-(2-pyridin-2-ylethyl)amide (General Deprotection Procedure)... 

Preparation of 3-(2-aminomethylphenyl)thiophene-2-carboxylic acid (3-methyl-butyl)-amide (General Procedure)... 

The reagent reacts with organic halides or acid chlorides to give acid amides, generally in good yield. Alkyl iodides and t-butyl bromide do not undergo dimethylcarbamoyla-tion. However, Arl and alkenyl halides (RCH=CHX) react readily. 

N -Protected Amino Acid 2,4-Dmb- or Tmb Amide General Procednre ... 

As indicated in equation (54) 7-lactones may be generated from 7-hydroxy acids, esters or amides, generally under acid catalysis. For esters and amides also base catalysis is appropriate. The rate of cycli-zation varies with the degree of substitution along the carbon chain. Bulky substituents, particularly if they have to be arranged cis to each other during ring formation, retard the reaction. For example (161)... 

Amides can in most cases be readily synthesized from activated derivatives of carboxylic acids and amines. They are fairly stable and often need harsh conditions for their removal. On the one hand this prompted a search for advanced methods for their selective cleavage on the other, however, amides generally are used for the protection of chemically stable compounds, e.g. in nucleotide chemistry. In more recent developments, acceleration of the deprotection reaction by intramolecular attack and the advantageous properties of amido hydrolases have been exploited. 

There is no guarantee that a given group of molecules nor any derivatives of them will provide conglomerates but there are some well known cases, thus with a-amino acids, certain known derivatives, such as the A-acetyl amides, generally crystallise as conglomerates. We shall give some examples to show how the method works. 

Carboxylic anhydrides are more powerful than the free acids as acylating agents and convert ammonia and primary and secondary amines into amides, generally smoothly and in very good yield. The equation... 

Esters and amides. General methods for the derivatization of carboxylic acids... 

This stabilization is lost in the transition state leading to the formation of the tetrahedral intermediate. The result is that the hydrolysis of amides generally requires base or acid catalysis, both of which can compete at neutral pH. The basic hydrolysis of amides occurs through a BAc2-type mechanism (Bender and Thomas, 1961). 

An unsubstituted amide An A/-substituted amide General formulas for amides An Af,N-disubstituted amide... 

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