Amides using

Hlkanolamides. The fatty acid alkanolamides are used widely ia shampoo formulations as viscosity and lather builders. They are formed by the condensation of a fatty acid with a primary or secondary alkanolamine. The early amides were compositions of 2 1 alkanolamine to fatty acid. Available technology allows the formation of amides with a 1 1 ratio of these additives. These amides are classified as superamide types. The typical amide used ia shampoo preparations usually contains the mono- or diethanolamine adduct, eg, lauric diethanolamide [120-40-1] (see Amides, fatty acid). 

Alkanolamides, a special subclass of substituted amides used as surfactants, are produced by three principal methods the reaction of fatty amides with formaldehyde, fatty acids with hydroxyalkylamines, and fatty esters with hydroxyalkylamines (37). A fatty amide and formalin can be heated in the presence of sodium hydroxide to yield 70—95% substituted alkanolamides (38,39). 

Following the procedure given above, cyclopropylidenecyclopentane is prepared in 85% yield from 34.4 g (0.09 mole) of the phosphonium salt, 3.83 g (0.097 mole) of sodium amide (used instead of phenyllithium), and 8.4 g (0.1 mole) of cyclopentanone in ether as solvent (350 ml). The product has bp 69-70770 mm. 

Molecules of interest that contain free amino groups can be coupled in aqueous solution to /S-poIy(L-malate) as amides using carbodiimides such as the water-soluble l-ethyl-3(3-dimethyIaminopropyl)carbodiimide hydrochloride (EDC) [2,12,20,21]. By this method, the molecules are attached randomly. A selective amide bond formation at the carboxylate terminus can be achieved... 

Problem 21.12 How could you prepare the following amides using an acid chloride and an amine or ammonia ... 

Protonation of an amide using strong acid occurs on oxygen rather than on nitrogen. Suggest a reason for this behavior, taking resonance into account. 

As an alternative, tin enolates are very useful in these additions. Usually they are prepared in situ from the amide using tin(II) trifluoromethanesulfonate and a base. They are subsequently reacted with an enone, catalyzed by a Lewis acid47-48 (see Table 3). With triinethylsilyl trifluoromethanesulfonate as a catalyst, in the presence of proline derived diamines anti-adducts are formed exclusively49 (see Section 1.5.2.4.3.1.). 

Although, the enzymatic reaction of esters with amines or ammonia have been well documented, the corresponding aminolysis with carboxylic acids are rarer, because of the tendency of the reactants to form unreactive salts. For this reason some different strategies have been used to avoid this problem. Normally, this reaction has been used for the preparation of amides of industrial interest, for instance, one of the most important amides used in the polymer industry like oleamide has been produced by enzymatic amidation of oleic acid with ammonia and CALB in different organic solvents [10]. 

Acid derivatives that can be converted to amides include thiol acids (RCOSH), thiol esters (RCOSR), ° acyloxyboranes [RCOB(OR )2]. silicic esters [(RCOO)4Si], 1,1,1-trihalo ketones (RCOCXa), a-keto nitriles, acyl azides, and non-enolizable ketones (see the Haller-Bauer reaction 12-31). A polymer-bound acyl derivative was converted to an amide using tributylvinyl tin, trifluoroacetic acid, AsPh3, and a palladium catalyst. The source of amine in this reaction was the polymer itself, which was an amide resin. 

Initiation presumably involves metal alkyls as the primary source of carbanions. These are immediately available from the Grignard reagents, organosodium compounds, or sodium amide used as catalysts when the alkali metal itself or its solution in liquid ammonia is used, addition to the monomer may precede actual initiation. ... 

Amidation-the Bodroux reaction Finally, amidahon of methyl ester 33 was required to complete the process. To accomplish this transformation, we turned to a reaction first reported in 1904 by Bodroux [12]. The reaction involves activation of an amine by conversion to the magnesium amide using a Grignard reagent. Subsequent reaction of the magnesium amide with the ester produces the carboxamide. 

Gao JL, Pavelites JJ, Habibollazadeh D (1996) Simulation of liquid amides using a polarizable intermolecular potential function. J Phys Chem 100(7) 2689-2697... 

Most PARPi are based upon nicotinamide (1), the by-product of the PARylation reaction, which itself is a micromolar PARPi. PARPi have been developed using three design approaches constraining the amide using an internal hydrogen bond, forming a lactam, and incorporation of the amide into a heterocycle [3,15]. 

Most recently, Bentz and co-workers established that the Pd-catalyzed a-arylation of esters and amides, using Reformatsky reagents and the corresponding aryl bromides, can be successfully performed under microwave conditions.417 The reported yields are somewhat lower than those reported by Hartwig 414 however, this approach does not require the use of Q-phos and can be considered as valuable alternative for a-arylation. 

A recent report [6] has discussed the effect of monomode microwave irradiation in the palladium-catalyzed phenylation of 5-iodouracil 4 with the nontoxic sodium tet-raphenylborate 5 as phenyl reagent (Scheme 8.3). The authors showed that the use of monomethylformamide (MMF) as solvent increases the yield of 6 (70%), because MMF has a high boiling point (180 °C) and is more polar (s = 182.5) than other amides used in microwave-activated reactions. 

TABLE 4-20. Asymmetric Oxidation of Lithium Enolates and Amides Using ( + )-147 as the Oxidant... 

BENZHYDRYLAMINE RESIN FOR SYNTHESIS OF PEPTIDE AMIDES USING BOC/BZL CHEMISTRY... 

FIGURE 5.18 Resins and linkers for synthesis of peptide amides using Fmoc/tBu chemistry. Chain assembly is effected after removal of the Fmoc group. Treatment with CF3C02H releases a peptide amide by cleavage at the NH-CH/CH2 bond. 

PE Thompson, HH Keah, PT Gomme, PG Stanton, MTW Hearn. Synthesis of peptide amides using Fmoc-based solid-phase procedures on 4-methylbenzhydrylamine resins. Int J Pept Prot Res 46, 174, 1995. 

Benzhydryl- (phenylbenzyl) and 4-methylbenzhydrylamine resins (see Section 5.18) are available for preparing primary amides, using Boc/Bzl chemistry. 4-Methylben-zhydrylamine, Rink amide, Sieber amide and dhnethoxytritylamine resins and the linkers PAL and XAL (see Section 5.20) are available for preparing primary amides, using Fmoc/tBu chemistry. Secondary amides can be synthesized by making use of AJ-alkyl-Sieber or ALalkyl-PAL linkers. 

Scheme 29 Regioselective N-a-methoxylation of amides using an electroauxiliary.

Much of the recent work on the use of anodic amide oxidation reactions has focused on the utility of these reactions for functionalizing amino acids and for synthesizing peptide mimetics [13]. For example, in work related to the cyclization strategy outlined in Scheme 3, the anodic amide oxidation reaction has been used to construct a pair of angiotensin-converting enzyme inhibitors [14]. The retrosynthetic analysis for this route is outlined in Scheme 4. In this work, the anodic oxidation reaction was used to functionalize either a proline or a pipercolic add derivative and then the resulting methoxylated amide used to construct the bicyclic core of the desired inhibitor. A similar approach has recently been utilized to construct 6,5-bicyclic lactam building blocks for... 

Conversion of ketones to amides using HN3 (hydrazoic acid). 

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