Amines reaction with carboxylic

There are actually three reactions called by the name Schmidt reaction, involving the addition of hydrazoic acid to carboxylic acids, aldehydes and ketones, and alcohols and alkenes. The most common is the reaction with carboxylic acids, illustrated above.Sulfuric acid is the most common catalyst, but Lewis acids have also been used. Good results are obtained for aliphatic R, especially for long chains. When R is aryl, the yields are variable, being best for sterically hindered compounds like mesi-toic acid. This method has the advantage over 18-13 and 18-14 that it is just one laboratory step from the acid to the amine, but conditions are more drastic. Under the acid conditions employed, the isocyanate is virtually never isolated. 

Molecules containing phosphate groups, such as the 5 phosphate of oligonucleotides, also may be conjugated to amine-containing molecules by using a carbodiimide-mediated reaction (Chapter 27, Section 2.1). The carbodiimide activates the phosphate to an intermediate phosphate ester similar to its reaction with carboxylates (Chapter 3, Section 1). In the presence of an amine, the ester reacts to form a stable phosphoramidate bond (Reaction 13). 

Underivatized PE in liposomal membranes contains an amine group that can participate in the carbodiimide reaction with carboxylate groups on proteins or other molecules (Dunnick et al.,... 

Preparation of amides Ammonia, 1° and 2° amines react with carboxylic acids to produce, respectively, 1°, 2° and 3° amides, through a nucleophilic acyl substitution reaction. The reaction of ammonia and a carhoxylic acid initially forms a carhoxylate anion and an ammonium cation. Normally the... 

Amines undergo reactions with carboxylic acids comparable to the formation of esters from alcohols. The product is known as an amide. 

Carboxy terminal amino acid or peptide thiols are prepared from various p-amino alcohols by conversion into a thioacetate (R2NHCHR1CH2SAc) via a tosylate followed by saponification.Several methods have been used to prepare N-terminal peptide thiols, the most common procedure is the coupling of (acetylsulfanyl)- or (benzoylsulfanyl)alkanoic acids or add chlorides with a-amino esters or peptide esters, followed by deprotection of the sulfanyl and carboxy groups. 8 16 Other synthetic methods include deprotection of (trit-ylsulfanyl)alkanoyl peptides, 1718 alkaline treatment of the thiolactones from protected a-sulfanyl acids, 19 and preparation of P-sulfanylamides (HSCH2CHR1NHCOR2, retro-thior-phan derivatives) from N-protected amino acids by reaction of P-amine disulfides with carboxylic acid derivatives, followed by reduction. 20,21 In many cases, the amino acid or peptide thiols are synthesized as the disulfides and reduced to the corresponding thiols by the addition of dithiothreitol prior to use. 

Reaction of (5-Amine Disulfides with Carboxylic Derivatives... 

Carboxylic acids react with aryl isocyanates, at elevated temperatures to yield anhydrides. The anhydrides subsequently evolve carbon dioxide to yield amines at elevated temperatures (70—72). The aromatic amines are further converted into amides by reaction with excess anhydride. Ortho diacids, such as phthalic acid [88-99-3], react with aryl isocyanates to yield the corresponding N-aryl phthalimides (73). Reactions with carboxylic acids are irreversible and commercially used to prepare polyamides and polyimides, two classes of high performance polymers for high temperature applications where chemical resistance is important. Base catalysis is recommended to reduce the formation of substituted urea by-products (74). 

In practice, the reaction with carboxylic acids, DCC and amines leads to amides without problems, while the addition of approximately 5 mol-% DMAP is crucial for the efficient formation of esters. 

Reaction with Carboxylic and Inorganic Acids. The reaction of carbodiimides with carboxylic acids has dual character because acyl ureas 484 or acid anhydrides 485 are formed. Often mixtures of both products are formed. The product formation depends on the nature of the reagents and the reaction conditions. With aromatic carboxyhc acids mainly N-acylureas are formed, and in the presence of tertiary amines the anhydride formation is inhibited." ... 

Cyanuric chloride has been used for the preparation of acyl chlorides, amides, and peptides. Conversion of cyanuric chloride into 2-chloro-4,6-dimethoxy-l,3,5-triazine (CDMT, 6) leads to a reagent that upon reaction with carboxylic acids produces the highly reactive 2-acyloxy-4,6-dimethoxy-l,3,5-triazines.P l The resulting active ester is a powerful acylating agent for alcohols and amines. The activation is performed in presence of a base, preferentially NMM, which leads to intermediate formation of 4-(4,6-dimethoxy-l,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM, 7)P l (Scheme 5). This addition product is readily prepared from the commercially available CDMT (6) and NMM in THF and can be stored as solid compound in the cold.P P l It offers the advantage that it can be used in a one-... 

In combinatorial chemistry, the development of multicomponent reactions leading to product formation is an attractive strategy because relatively complex molecules can be assembled with fewer steps and in shorter periods. For example, the Ugi multicomponent reaction involving the combination of an isocyanide, an aldehyde, an amine, and a carboxylic acid results in the synthesis of a-acyl amino amide derivatives [32]. The scope of this reaction has been explored in solid-phase synthesis and it allows the generation of a large number of compounds with relative ease. This reaction has been employed in the synthesis of a library of C-glycoside conjugated amino amides [33]. Scheme 14.14 shows that, on reaction with carboxylic acids 38, isocyanides 39, and Rink amide resin derivatized with different amino acids 40, the C-fucose aldehyde 37 results in the library synthesis of C-linked fucosyl amino acids 41 as potential mimics of sialyl Lewis. ... 

Acyloxypyridinium ions 230 are formed as intermediates from 228 by an S Ar reaction with carboxylate. In these ions, the acyloxy group is activated and transferable to suitable nucleophiles (in the example shown above to alcohols with ester formation, or to primary and secondary amines with amide formation). The potentiality of the l-methyl-2-pyridone 229 as a leaving group is essential in this addition 231. 

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