Amides direct synthesis

Even though form amide was synthesized as early as 1863 by W. A. Hoffmann from ethyl formate [109-94-4] and ammonia, it only became accessible on a large scale, and thus iadustrially important, after development of high pressure production technology. In the 1990s, form amide is mainly manufactured either by direct synthesis from carbon monoxide and ammonia, or more importandy ia a two-stage process by reaction of methyl formate (from carbon monoxide and methanol) with ammonia. 

Tantalum Nitrides. Tantalum nitride [12033-62-4] TaN, is produced by direct synthesis of the elements at 1100°C. Very pure TaN has been produced by spontaneous reaction of lithium amide, L1NH2, and TaCl ( )- The compound is often added to cermets in 3—18 wt %. Ta N [12033-94-2] is used as a red pigment in plastics and paints (78). 

Carbonylation is one of the most important reactions leading to C-C bond formation. Direct synthesis of carbonyl compounds with CO gives rise to carboxylic acids and their derivatives, such as esters, amides, lactones, lactams etc. The process can be represented by the simple reactions of Scheme 5.1. 

The synthesis of lanthionines via dehydroalanines has been carried out using an (9,5-di-benzoylated Z-L-Cys-L-Ser-OMe. 31 Using (3-elimination under basic conditions in sodium methoxide and subsequent intramolecular Michael addition, the corresponding L-lanthio-nine derivative was formed. However, as a final step the cyclolanthionyl dipeptide would have to be cleaved at the amide bond to obtain lanthionine. The same authors reported the use of the O-tosylated serine dipeptide which was subjected to (3-elimination, forming the desired dehydroalanine derivative. However, this synthesis also yielded cyclic L-lanthionine dimers as a result of an intermolecular Michael addition. The amounts of cyclolanthionine and lanthionine dimer derivatives depended on the initial concentration of the dipeptides. In addition, the directed synthesis of cyclic lanthionine dimers, which were produced from N-benzyloxycarbonyl-W-trityllanthionine monomethyl ester, has been reported. 32 ... 

A reaction by Clough et al. comes close to the direct synthesis shown in Scheme 1 (89TL7469). Here amides (62) react in a radical mechanism to 4-methylene compounds (63) that with 03/PPh3 are converted to tetramic acids (64). (See Fig. 29.) Several authors, however, prepared esters of 4-amino-3-oxo-butanoic acid, which served as precursors for intramolecular cyclization to tetramic acids (82JHC883). Koehler and Gerlach in an initial stage of a synthesis of dysidine, contained in marine sponge... 

EXTENSIONS AND COMMENTARY N-Methyltryptamine (monomethyltryptamine, NMT) is an alkaloid that has been found in the bark, shoots and leaves of several species of Virola, Acacia and Mimosa. However, the major snuffs associated with these plant have been shown to also contain 5-MeO-DMT and are discussed there. NMT has been synthesized in a number of ways. One can react 3-(2-bromoethyl)indole with methylamine. NMT can be isolated as the benzoyl derivative from the methylation of tryptamine with methyl iodide followed by reaction with benzoyl chloride, with the hydrolysis of this amide with alcoholic KOH. It can also be synthesized from indole with oxalyl chloride, with the resulting glyoxyl chloride reacting with methylamine in ether to give indol-3-yl N-methylglyoxalylamide (mp 223-224 °C from IPA) which is obtained in a 68% yield, which is reduced to NMT to give the amine hydrochloride (mp 175-177 °C from ) in a 75% yield. The most simple and direct synthesis is the formamide reduction given above. 

In order for this strategy to be competitive with the convergent approach, we would have to first improve the synthesis of the triazole fragment and tlien find an alternative to the Masamune chemistry to get access to P-keto amides directly. 

The acetyl-substituted complexes, initially prepared by Jager36 by direct synthesis, have served as the basis for all of the work in this area. It has been shown that the acetyl group can be replaced by substitution, especially nitration, where reaction conditions are rather vigorous.39 The acetyl-substituted complexes are not only nucleophilic at carbon, a property exhibited in the above reaction, but they are also nucleophilic at oxygen, being vinylogous amides, and undergo... 

The direct synthesis of aryl- or alkyl nitriles from cyanide and organohalide precursors is revered in synthetic chemistry, as the nitriles represent a flexible functionality that can easily be converted into (for example) carboxylic acids, esters, amides, amidines, amines and various hetero cycles [67], such as thiazoles, oxazolidones, triazoles and tetrazoles [68]. The tetrazole group... 

The synthesis of amides directly from carboxylic acids is not easy because the reaction of an amine with a carboxylic acid is a typical acid-base reaction resulting in the formation of a salt (Following fig.). Some salts can be converted to an amide by heating strongly to expel water. 

Mechanism 20-3 Esterification Using Diazomethane 966 20-12 Condensation ofAcids with Amines Direct Synthesis of Amides 966 20-13 Reduction of Carboxylic Acids 967 20-14 Alkylation of Carboxylic Acids to Form Ketones 968 20-15 Synthesis and Use of Acid Chlorides 969... 

Condensation of Acids with Amines Direct Synthesis of Amides... 

Amides can be synthesized directly from carboxylic acids, using heat to drive off water and force the reaction to completion. The initial acid-base reaction of a carboxylic acid with an amine gives an ammonium carboxylate salt. The carboxylate ion is a poor electrophile, and the ammonium ion is not nucleophilic, so the reaction stops at this point. Heating this salt to well above 100 °C drives off steam and forms an amide. This direct synthesis is an important industrial process, and it often works well in the laboratory. 

Direct synthesis of atropisomeric benzamides and anilides from prochiral precursors has been reported using chiral-amide-mediated deprotonation of 2,6-dimethyl-substituted ben-zamide and anilide chromium complexes. A screening of amides revealed that (R,R) 3 was the most selective in the deprotonation of the benzylic methyl groups (Scheme 51)92 94. 

A direct synthesis of chiral resorcarene octamethyl ethers 25 starting with chiral monomers has been also reported.55 The condensation of ( )-2,4-dimethoxycin-namic acid amides of D-, and L-valine catalyzed by BFjEtjO leads to a mixture of the rccc-, rect- and rcff-isomeres, which can be separated by chromatography. 

Katritzky AR, Singh SK, Cai C, Bobrov S. Direct synthesis of esters and amides from unprotected hydroxyaromatic and -aliphatic carboxyhc acids. J. Org. Chem. 2006 71 3364-3374. 

The recommended procedure for the synthesis of peptide amides is to use a resin (e.g., MBHA) that yields amides directly upon cleavage with HE Ammonolysis can be used to give amides of peptides on Merrifield or HMBA resins. Anunonolysis can also probably be used with PAM resins. 

The direct synthesis of fully functionalized sugars possessing amino or hydroxyl functions at C-2 has also been studied. Thus, activation of glycals by thianthrene-5-oxide 287 and Tf20, followed by treatment with an amide nucleophile and a glycosyl acceptor, led directly to various 2-acylamido glycosides 288 [610,611] (Scheme 4.59). 

An interesting reaction discovered by Wakamatsu involves the cobalt-catalyzed carbonylation of aldehydes in the presence of primary amides to give A-acylamino acids in high yield (equation 26). By combining this reaction with known catalytic routes to aldehydes, for example isomerization of allyl alcohols or hydroformylation of alkenes, it is possible to achieve the direct synthesis of A-acylamino acids from precursors other than aldehydes. ... 

In conjunction with proton sponge, the activated phosphate 256 turned out to be an effective reagent in the direct synthesis of peptides and branched amides from carboxylic acids (equation 21). In this process, diamine 1 surpassed in its efficiency for such bases as triethylamine, V,iV-dimethylaniline, 2,6-lutidine and Hiinig bases225. 

Unlike intermolecular cyclopropanation reactions, the intramolecular version is stereo-specific with respect to the configuration of both, the C-C double bond and (due to steric constraints) the carbenoid center. This fact can be used for the directed synthesis of cis-1,2-disubstituted, all-ci. -l,2,3-trisubstituted or d. , ra . -l,2,3-trisubstituted cyclopropanes. For example, a-diazo esters (a-diazocarboxamides) with an unsaturated ester (amide) residue yield bicyclic lactones (lactams) stereospecifically which can be ring opened to give the monocyclic cyclopropanes mentioned with defined stereochemistry. Some possibilities are illustrated by the examples, 20 -+ 22 -> 23, and 24 25. ... 

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