Amides, group

With RAMSES, the conjugation between the C=0 rr-system and the lone pair of the nitrogen atom in the amide group is taken into account (see Figure 2-51b). 

The catalyst is inactive for the hydrogenation of the (isolated) benzene nucleus and so may bo used for the hydrogenation of aromatic compounds containing aldehyde, keto, carbalkoxy or amide groups to the corresponding alcohols, amines, etc., e.g., ethyl benzoate to benzyl alcohol methyl p-toluate to p-methylbenzyl alcohol ethyl cinnamate to 3 phenyl 1-propanol. 

The phenolic hydroxyl group of tyrosine, the imidazole moiety of histidine, and the amide groups of asparagine and glutamine are often not protected in peptide synthesis, since it is usually unnecessary. The protection of the hydroxyl group in serine and threonine (O-acetylation or O-benzylation) is not needed in the azide condensation procedure but may become important when other activation methods are used. 

Synthesis by high-dilution techniques requires slow admixture of reagents ( 8-24 hrs) or very large volumes of solvents 100 1/mmol). Fast reactions can also be carried out in suitable flow cells (J.L. Dye, 1973). High dilution conditions have been used in the dilactam formation from l,8-diamino-3,6-dioxaoctane and 3,6-dioxaoctanedioyl dichloride in benzene. The amide groups were reduced with lithium aluminum hydride, and a second cyclization with the same dichloride was then carried out. The new bicyclic compound was reduced with diborane. This ligand envelops metal ions completely and is therefore called a cryptand (B. Dietrich, 1969). 

In the synthesis of commercial sulfur-heterocycles two interesting reactions are used (i) diphenylamines may be connected by a sulfur bridge in the orfho-positions (ii) the amino grouping of sulfonamides undergoes condensation reactions with neighboring imino- and amide groups. 

An intramolecular version offers useful synthetic methods for heterocycles. The total syntheses of a- and 7-lycoranes (373 and 374) have been carried out by applying the intramolecular aminochlorination of the carbamate of 5-(2-aminoethyl)-l,3-cyclohexadiene (372) as a key reaction[312,313]. Interestingly, the 4,6- and 5,7-diene amides 375 and 377 undergo the intramolecular amina-tion twice via x-allylpalladium to form alkaloid skeletons ofpyrrolizidine (376) and indolizidine (378), showing that amide group is reactive[314]. 

Another variation of the Madelung synthesis involves use of an O-alkyl or O-silyl imidate as the C2 electrophile. The mechanistic advantage of this modification stems from avoiding competing N-deprotonation, which presumably reduces the electrophilicity of the amide group under the classical conditions. Examples of this approach to date appear to have been limited to reactants with a EW substituent at the o-alkyl group[15,16]. 

In this section we turn to a consideration of the experimental side of condensation kinetics. The kind of ab links which have been most extensively studied are ester and amide groups, although numerous additional systems could also be cited. In many of these the carbonyl group is present and is believed to play an important role in stabilizing the actual chemical transition state involved in the reactions. The situation can be represented by the following schematic reaction ... 

Hydrolyzed Polyacrylamide. HPAM (6) can be prepared by a free-radical process ia which acrylamide is copolymerized with incremental amounts of acryUc acid or through homopolymerization of acrylamide followed by hydrolysis of some of the amide groups to carboxylate units. 

Acrylamide, C H NO, is an interesting difiinctional monomer containing a reactive electron-deficient double bond and an amide group, and it undergoes reactions typical of those two functionalities. It exhibits both weak acidic and basic properties. The electron withdrawing carboxamide group activates the double bond, which consequendy reacts readily with nucleophilic reagents, eg, by addition. 

The reaction with sodium sulfite or bisulfite (5,11) to yield sodium-P-sulfopropionamide [19298-89-6] (C3H7N04S-Na) is very useful since it can be used as a scavenger for acrylamide monomer. The reaction proceeds very rapidly even at room temperature, and the product has low toxicity. Reactions with phosphines and phosphine oxides have been studied (12), and the products are potentially useful because of thek fire retardant properties. Reactions with sulfide and dithiocarbamates proceed readily but have no appHcations (5). However, the reaction with mercaptide ions has been used for analytical purposes (13)). Water reacts with the amide group (5) to form hydrolysis products, and other hydroxy compounds, such as alcohols and phenols, react readily to form ether compounds. Primary aUphatic alcohols are the most reactive and the reactions are compHcated by partial hydrolysis of the amide groups by any water present. 

The amide group is readily hydrolyzed to acrylic acid, and this reaction is kinetically faster in base than in acid solutions (5,32,33). However, hydrolysis of N-alkyl derivatives proceeds at slower rates. The presence of an electron-with-drawing group on nitrogen not only facilitates hydrolysis but also affects the polymerization behavior of these derivatives (34,35). With concentrated sulfuric acid, acrylamide forms acrylamide sulfate salt, the intermediate of the former sulfuric acid process for producing acrylamide commercially. Further reaction of the salt with alcohols produces acrylate esters (5). In strongly alkaline anhydrous solutions a potassium salt can be formed by reaction with potassium / /-butoxide in tert-huty alcohol at room temperature (36). 

The preparation of polyacrylamides and postpolymeri2ation reactions on polyacrylamides are usually conducted ia water. Reactions on the amide groups of polyacrylamides are often more compHcated than reactions of simple amides because of neighboring group effects. Reaction rates, for example, can differ considerably. 

Polyacrylamide, whether charged or not, can be detected by reactions of the amide group (67,68) however, a number of substances can interfere with the determination. If the molecular weight is high enough, flocculation of a standard slurry of clay or other substrate is a sensitive method for detecting low levels of polyacrylamide (69). Once polymers are adsorbed on a surface, many of these methods caimot be used. One exception is the use of a labeled polymer. 

New heat-resistant polymers containing -iiitrophenyl-substituted quinoxaline units and imide rings as well as flexible amide groups have been synthesi2ed by polycondensation reaction of a dianainoquinoxaline derivative with diacid dichlorides (80). These polymers are easily soluble in polar aprotic solvents with inherent viscosities in the range of 0.3—0.9 dL/g in NMP at 20°C. AH polymers begin to decompose above 370°C. 

The necessary molecular rigidity of polybenzamide undoubtedly results from the hindered bond rotation within the planar amide group. 

Acrylamide copolymers designed to reduce undesired amide group hydrolysis, increase thermal stability, and improve solubility in saline media have been studied for EOR appHcations (121—128). These polymers stiH tend to be shear sensitive. Most copolymers evaluated for EOR have been random copolymers. However, block copolymers of acrylamide and AMPS also have utiHty (129). 

It is generally accepted that transamidation is not a concerted reaction, but occurs through the attack of a free end on the amide group via aminolysis (eg, eq. 4) or acidolysis (eg, eq. 3) (65). Besides those ends always present, new ends are formed by degradation processes, especially hydrolysis (eq. 5), through which the amide groups are in dynamic equiUbrium with the acid and amine ends. 

Chemical Properties. The chemical reactivity of nylon is a function of the amide groups and the amine and carboxyl ends. The aHphatic segment of the chain is relatively stable. 

Copolymers. There are two forms of copolymers, block and random. A nylon block copolymer can be made by combining two or more homopolymers in the melt, by reaction of a preformed polymer with diacid or diamine monomer by reaction of a complex molecule, eg, a bisoxazolone, with a diamine to produce a wide range of multiple amide sequences along the chain and by reaction of a diisocyanate and a dicarboxybc acid (193). In all routes, the composition of the melt is a function of temperature and more so of time. Two homopolyamides in a moisture-equiUbrated molten state undergo amide interchange where amine ends react with the amide groups. 

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