Directivity amide

Amide interchange reactions of the type represented by reaction 3 in Table 5.4 are known to occur more slowly than direct amidation nevertheless, reactions between high and low molecular weight polyamides result in a polymer of intermediate molecular weight. The polymer is initially a block copolymer of the two starting materials, but randomization is eventually produced. 

Direct Amidation. The direct reaction of amino acids to form Type AB polyamides (eq. 1) and diacids and diamines to form type AABB polyamides (eq. 2) ate two of the most commonly used methods to produce polyamides. The... 

Direct amidation is generally carried out ia the melt, although it can be done ia an iaert solvent starting from the dry salt (46). Because most aUphatic polyamides melt ia the range of 200—300°C and aromatic-containing polyamides at even higher temperatures, the reactants and products must be thermally stable to be polymerized via this method. 

Although there are several reports in the literature on boron-mediated amide formations, the boron reagents had to be used in stoichiometric amounts.1-4-5-6-7-8-9 Recently, Yamamoto et al. presented the first truly catalytic method allowing for a direct amide formation from free carboxylic acids and amines as the reaction partners.10-1112 Best results were obtained by using phenylboronic acids bearing electron withdrawing substituents in the meta- and/or para-positions such as 3,4,5-trifluorophenylboronic acid or 3,5-bis(trifluoromethyl)boronic acid as the catalysts. 

Direct amidation can be carried out if an aromatic compound is heated with a hydroxamic acid in polyphosphoric acid, though the scope is essentially limited to phenolic ethers. 

Direct amide formation in aqueous solution between carboxylic acids and amines can occur and the rates are first order in the anion of the acid and the basic form of the amine (Eq. 9.12).23 The second-order rate constant is independent of the acidity of the medium. The condensation reaction of glycine to form di- and triglycine occurs in aqueous solution... 

In many of the direct amide oxidations illustrated above, the reactions were used to functionalize amino acid derivatives. Because of the reactions effectiveness in this area, anodic electrochemistry has proven to be an outstanding tool for building constrained peptidomimetics [78-81]. In this work, a series of constrained peptide analogs were designed by replacing spatially close hydrogens in a proposed... 

Amination of ketene has been studied by ab initio methods.Reactions of ammonia, its dimer, and its (mono)hydrate with ketene have been calculated and compared with earlier smdies of ammonia (at lower levels of theory), of water, and of water dimer. In general, the results favour initial addition of ammonia to the C=0 bond (giving the enol amide), as against addition to the C=C bond (which gives the amide directly). Amide formation is compared with the corresponding hydration reaction where enol acid and acid are the alternative immediate products. Most of the reactions, i.e. both additions and tautomerizations, are suggested to involve cyclic six-membered transition states. 

The synthesis of polyamides follows a different route from that of polyesters. Although several different polymerization reactions are possible, polyamides are usually produced either by direct amidation of a diacid with a diamine or the self-amidation of an amino acid. The polymerization of amino acids is not as useful because of a greater tendency toward cycliza-tion (Sec. 2-5b). Ring-opening polymerization of lactams is also employed to synthesize polyamides (Chap. 7). Poly(hexamethylene adipamde) [IUPAC poly(iminohexanedioylimi-nohexane-l,6-diyl) or poly(iminoadipoyliminohexane-l,6-diyl)], also referred to as nylon 6/6, is synthesized from hexamethylene diamine and adipic acid [Zimmerman, 1988 Zimmerman and Kohan, 2001]. A stoichiometric balance of amine and carboxyl groups is readily obtained by the preliminary formation of a 1 1 ammonium salt (XU ) in aqueous solution at a concentration of 50%. The salt is often referred to as a nylon salt. Stoichiometric... 

Yamamoto reported the first boron reagent-based catalytic method that allows direct amide formahon from a free carboxylic acid and amine as the reaction partners [21]. Aryl boronic acid derivahves bearing electron-withdrawing subshtu-ents in the meta and/or para posihons were found to be the catalyst of choice for these kinds of transformations. Tang s work [22] featured the use of a cheap, readily available, non-toxic, and eco-friendly boric acid, B(OH)i, as a highly effective catalyst that proved to be superior to other known catalysts involved in the amidation process. 

Scheme 14 Route to Cyclic Depsipeptides via Direct Amide CyclizationI1141...

Recognition of these drawbacks prompted the Ley group to design a new polymer-supported reagent 9 for direct amide thionation149. Preparation of this immobilised... 

Hydrolysis of the homologous esters has been reported but the direct amidation of these esters failed.131 133,261 The 3-acetamide derivative was prepared from the corresponding hydrazide with the aid of Raney nickel.131,133... 

Cyclic amido-A3-iodane prepared from 85 in one step can be used as a direct amidating reagent toward polycyclic alkanes under radical conditions [Eq. (83)] [155]. 

This compound, as well as the symmetric 37, was used in a series of microwave-heated aminocarbonylations and direct amide N-arylations, producing 12 compounds (six unsymmetric and six symmetric) with a two- or three-atom spacer between the aromatic moieties (Scheme 20) [80]. The best unsymmetric inhibitor had a Ki of 140 nM (43) and the best symmetric inhibitor 20 nM (44). 

A gas-phase derivatization procedure was employed for direct amidization of oxidized SWCNTs with simple aliphatic amines. In some cases a minor amount... 

Scheme VI/24. Synthesis of cyclic depsipeptides via direct amide cyclization [92]. a) HCI, toluene, 100°.

A new efficient method for the direct amidation of /-lysergic acid was used to prepare a variety of lysergamides. A pharmacological evaluation of these compounds, their di- and tetrahydro derivatives, and derivatives bearing substituents in the indole portion of the molecule showed that, in general, only 9,10-dihydrolysergamides of primary amines possess activity comparable to the potent emetic activity of the components of dihydroergotoxine. 

Throughout this research we have made constant use of columns coated with cholesteric phases (54-55). Thus, for example, asymmetric induction in amide alkylations as well as asymmetric reductions of carbonyl were conveniently judged either on the product directly (amides) or on any of several derivatives of the product (alcohols) with cholesteryl cinnamate as a GLC stationary phase. 

BF3 Et20 is effective in the direct amidation of carboxylic acids to form carboxamides (Eq. 88) [144]. The reaction is accelerated by bases and by the azeotropic removal of water. 

Direct amidation can be carried out if an aromatic compound is heated with a hydroxamic acid (34) in polyphosphoric acid, but the scope is essentially limited to phenolic ethers.The reaction of an aromatic compound with aniline, BU4NF and KMn04 led to the diarylamine. The formation of hydroindole derivatives was accomplished by reaction of a A-carbamoyl phenylethylamine derivative with phenyliodine (III) diacetate, followed by Bu4NF. Direct amidation via ipso substitution by nitrogen was accomplished when a A -methoxy arylethylamide (35) was... 

The most important method used in the preparation of polyamides is direct amidation, usually through the intermediate formation of a salt of the diamine and dicarboxylic acid, but without it in the case of aminoacids or for pairs of monomers that do not readily form a salt. Esters can react with diamines to form polyamides with liberation of alcohol or phenol. Diamines can be reacted with diamides yielding polyamides and freeing ammonia. Polyamides have been prepared by acidolysis of acyl derivatives of diamines (compare Section 5.4 for acidolysis in polyester preparation). Bis-anhydrides react with diamines to form polyamides and, if reacted further, polyimides. The low-temperature reaction of acid chlorides with diamines has been used, interfacially or as a solution technique, to prepare certain polyamides (compare Section 5.7 for related reactions in polyester synthesis). 

In certain other cases, where the diamine and dicarboxylic acid do not readily form a salt, as in the case of 4,4 -methylenedianiline and sebacic acid, direct amidation is used to prepare the polymer [80]. 

The mechanism of the direct amidation reaction between diamines and dicarboxylic acids is not clear, though it certainly proceeds through a tetrahedral intermediate. It is not known whether the amide-formation step involves the substituted ammonium salt or whether small equilibrium amounts of free acid and free amine that are always present interact. The latter would seem more likely. 

Attempts to prepare polyamides by direct amidation can fail for various reasons. Thus, lactams are readily formed from 7- or 5-amino acids. For example... 

Direct amidation at room temperature is sometimes possible. For instance, peptides have been synthesized directly from amines and acids at room temperature using dehydrating agents such as dicyclohexyl-carbodiimide [82]. IV,Ar, -carbonyldiimidazole, viz. 

---