Amidating reaction

As with polyesters, the amidation reaction of acid chlorides may be carried out in solution because of the enhanced reactivity of acid chlorides compared with carboxylic acids. A technique known as interfacial polymerization has been employed for the formation of polyamides and other step-growth polymers, including polyesters, polyurethanes, and polycarbonates. In this method the polymerization is carried out at the interface between two immiscible solutions, one of which contains one of the dissolved reactants, while the second monomer is dissolved in the other. Figure 5.7 shows a polyamide film forming at the interface between an aqueous solution of a diamine layered on a solution of a diacid chloride in an organic solvent. In this form interfacial polymerization is part of the standard repertoire of chemical demonstrations. It is sometimes called the nylon rope trick because of the filament of nylon produced by withdrawing the collapsed film. 

The HCl by-product of the amidation reaction is neutralized by also dissolving an inorganic base in the aqueous layer in interfacial polymerization. The choice of the organic solvent plays a role in determining the properties of the polymer produced, probably because of differences in solvent goodness for the resulting polymer. Since this reaction is carried out at low temperatures, the complications associated with side reactions can be kept to a minimum. 

Amides. Reaction of acryhc acid with ammonia or primary or secondary amines forms amides. However, acrylamide (qv) is better prepared by... 

Subsequent chlorination of the amide takes place ia a two-phase reaction mixture (a dispersion of diamide ia hydrochloric acid) through which a chlorine stream is passed. The temperature of this step must be maintained below 10°C to retard the formation of the product resulting from the Hofmann degradation of amides. Reaction of the A/,A/-dichloroamide with diethylamine [109-89-7] ia the presence of base yields /n j -l,4-cyclohexane-bis-l,3-diethylurea (35), which is transformed to the urea hydrochloride and pyroly2ed to yield the diisocyanate (36). 

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 slow development of these materials is generally ascribed to the slow amidation reactions, the inability of many of the polymers to melt without decomposition and the tendency to colour during polymerisation. 

If a pH-rate curve does not exhibit an inflection, then very probably the substrate does not undergo an ionization in this pH range. The kinds of substrates that often lead to such simple curves are nonionizable compounds subject to hydrolysis, such as esters and amides. Reactions other than hydrolysis may be characterized by similar behavior if catalyzed by H or OH . The general rate equation is... 

Diuretic activity can be retained in the face of replacement of one of the sulfonamide groups by a carboxylic acid or amide. Reaction of the dichlorobenzoic acid, 174, with chlorsulfonic acid gives the sulfonyl chloride, 175 this is then converted to the amide (176). Reaction of that compound with furfuryl ine leads to nucleophilic aromatic displacement of the highly activated chlorine at the 2 position. There is thus obtained the very potent diuretic furosemide (177). ... 

Reaction with water to yield a carboxylic acid Reaction with an alcohol to yield an ester Reaction with ammonia or an amine to yield an amide Reaction with a hydride reducing agent to yield an aldehyde or an alcohol... 

Butylation of ethyl phenylacetate, /-butyl phenylacetate, and ethyl 2-phenylhexanoate has also been accomplished with M-butyl bromide and sodium hydride in refluxing monoglyme in 64%, 66%, and 56% yields, respectively.6 In contrast to the sodium amide reactions above, however, careful fractionation of the crude products was required to obtain pure products. 

R= H, alkyl or aryl group Figure 3.13 Amidation reaction scheme.10... 

American Society for Testing and Materials (ASTM), 242 Amic acid ammonium salt, polyimide cyclization via, 305 Amic acid formation, 301 Amidation reaction scheme, 151 Amide-amide interchange reaction, 158 Amide concentration, in polyamides, 139-141... 

Palladium complexes also catalyze the carbonylation of halides. Aryl (see 13-13), vinylic, benzylic, and allylic halides (especially iodides) can be converted to carboxylic esters with CO, an alcohol or alkoxide, and a palladium complex. Similar reactivity was reported with vinyl triflates. Use of an amine instead of the alcohol or alkoxide leads to an amide. Reaction with an amine, AJBN, CO, and a tetraalkyltin catalyst also leads to an amide. Similar reaction with an alcohol, under Xe irradiation, leads to the ester. Benzylic and allylic halides were converted to carboxylic acids electrocatalytically, with CO and a cobalt imine complex. Vinylic halides were similarly converted with CO and nickel cyanide, under phase-transfer conditions. ... 

Note also the stereochemistry. In some cases, two new stereogenic centers are formed. The hydroxyl group and any C(2) substituent on the enolate can be in a syn or anti relationship. For many aldol addition reactions, the stereochemical outcome of the reaction can be predicted and analyzed on the basis of the detailed mechanism of the reaction. Entry 1 is a mixed ketone-aldehyde aldol addition carried out by kinetic formation of the less-substituted ketone enolate. Entries 2 to 4 are similar reactions but with more highly substituted reactants. Entries 5 and 6 involve boron enolates, which are discussed in Section 2.1.2.2. Entry 7 shows the formation of a boron enolate of an amide reactions of this type are considered in Section 2.1.3. Entries 8 to 10 show titanium, tin, and zirconium enolates and are discussed in Section 2.1.2.3. 

An expeditious route to the cyclic sulfamide HIV-1 protease inhibitors of type 145 and 146 (tetrahydro-l,2,7-thiadiazepine 1,1-dioxide derivatives) from 141 and 142 hinges on palladium-catalysed amidation reactions. These reactions of 144 and 143 were microwave promoted and provided, after removal of the cyclic ketal protecting group, moderate to good yields of (145, 57%) and (146, 66%) for example with R = NHCOCH2-2-naphthyl <06T4671>. 

The lysergic acid to lysergic acid amide reaction has been designed to utilize minimal quantities of solvents in order to squeeze as much material as possible into ordinary laboratory glassware. 

What mainly differentiates /V-[ (acyloxy)methyl] derivatives of primary and secondary amides are the relative contributions of Reactions a-d as a function of pH, and, mainly the onset of the base-catalyzed Reactions c or d. Thus, the pathway for hydrolysis of derivatives of primary amides is pH-independent (Reaction b) at ca. pH 2-5, and is base-catalyzed (Reaction d) above pH 5, which explains the lability of primary amides at pH 7.4. In contrast, the base-catalyzed pathway for derivatives of secondary amides (Reaction c) is not important below pH 9-10, which is why these amides are relatively stable at pH 7.4 [218], This specific behavior, thus, eliminates 7V-[(acyloxy )methyl] derivatives as potential prodrugs for primary amides. 

Amidation reactions of organic halides, palladium-catalyzed, 26 330, 331 Amides... 

Amidation. Reactions leading to the formation of amides R-C-NH2. Examples include the dehydration (water removal) of the ammonium salts... 

Flg.1. In the amino acid sequence of KO-42 is encoded its fold and its function as it controls the formation of a hairpin helix-loop-helix motif that dimerizes to form a four-helix bundle. On the surface of the folded motif a reactive site is formed that catalyzes hydrolysis, transesterification and amidation reactions of reactive esters, whereas unfolded peptides are incapable of cooperative catalysis. In addition the values, and thus the reactivities, of the histidine residues are controlled by the fold. The pK of each His residue of KO-42 is shown in the figure and deviate by as much as 1.2 units from that of random coil peptides which is 6.4... 

Histone acetylation is a reversible amidation reaction involving defined e-amino groups of lysine residues (see Fig. 6) at the N-terminal tails of core histones. The highly dynamic equilibrium between the acetylated and non-acetylated states of lysine is maintained by two enzymatic groups, referred to as histone acetyltransferases (HATs) and histone deacetylases (HDACs). 

Scheme 42 Movassaghi et al. proposed catalytic cycle for amidation reaction...

Ortholithiated oxazoline 62 is best transmetallated to its magnesium analogue before reaction with aldehydes. As with the equivalent amide reaction, treatment with 4.5 M HCl then cyclizes the products to lactones (Scheme 31) °. ... 

Bonnaterre F, Bois-Choussy M, Zhu JP (2006) Rapid access to oxindoles by the combined use of an Ugi four-component reaction and a microwave-assisted intramolecular Buchwald-Hartwig amidation reaction. Org Lett 8 4351-4354... 

N-Alkyl isoindolo[2,l-fc][2,4]benzodiazepines 190 (R = alkyl. Scheme 38, Section 3.1.1.2) are synthesized by an intramolecular N-acyliminium ion-amide reaction (1997TL2985, 1998T1497). Isothiocyanates 23 undergo under basic conditions in DMF ring closure by an intramolecular substitution between N1 of the pyrrole ring and isothiocyanate group to afford benzo[/]pyrrolo[l,2-c] [l,3]diazepine-5-thiones 25 (Scheme 2, Section 2.1.1.1 (2005BMCL3220)). 

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