Isocyanates reaction with carboxylic acids

TETRINE ACID (60-00-4) CioH.sNjOg A weak organic (carboxylic) acid. Reaction with dithiocarbamates, isocyanates, mercaptans, nitrides, nitrites, sulfides, forms flammable and/or toxic gases + heat. Incompatible with acids, azo compounds, epoxides and other polymerizable compounds oxidizers, sulfuric acid, reducing agents bases, ammonia, aliphatic amines alkanolamines, alkylene oxides cyanide salts and cyanide solutions (forms... 

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). 

There are several types of chiral derivatizing reagents commonly used depending on the functional group involved. For amines, the formation of an amide from reaction with an acyl halide [147,148], chloroformate reaction to form a carbamate [149], and reaction with isocyanate to form the corresponding urea are common reactions [150]. Carboxyl groups can be effectively esterified with chiral alcohols [151-153]. Isocynates have been used as reagents for enantiomer separation of amino acids, iV-methylamino acids, and 3-hydroxy acids [154]. In addition to the above-mentioned reactions, many others have been used in the formation of derivatives for use on a variety of packed and capillary columns. For a more comprehensive list, refer to References 155-159. 

It has also been reported that 4-substituted-5,5-dimethyloxazoIidin-2-ones can be prepared as illustrated in eq 3. Initially, stereoselective condensation of an N-acyloxazolidinone enolate with acetone affords a functionalized acyl fragment, which is then hydrolyzed to the carboxylic acid. Reaction of the hydroxy acid with DPPA at elevated temperatures yields the target via formation of the acyl azide, Curtius rearrangement and trapping of the isocyanate intermediate by the hydroxyl group (eq 3). 

The A -acylation and A -sulfonylation of benzisoselenazol-3(2//)-one with carboxylic acid chlorides or sulfonyl chlorides is an efficient method for the synthesis of 2-acyl and 2-sulfonylbenzisoselenazol-3(2//)-ones 48 and 49 <1997SC283>. A reaction with formalin resulted in A -hydroxymethylbenzisoselenazol-3(2//)-one 50, while reaction with isocyanates yielded the 2-carbamoylbenzisoselenazol-3(2//)-ones 51 (Scheme 13) <2005UP3>. 

The Lessen reaction of peptide carboxylic acids has teen investigated in order to determine the carboxy terminal amino acid residue of peptides." The procedure first involves the formation of 0-pivaloylhydroxamic acids (187) by condensation of peptide carboxylic acids (184) with 0-pivaloylhy-droxylamine (185) using a water soluble carbodimide, l-ethyl-3-(3-dimethylaminopropyl)carbodiimide (186). The Lossen rearrangement of (187) occurs at pH 8.5 and 50 C to give a mixture of isocyanates (188) and their reaction products, which, on acidic hydrolysis, afford the aldehydes (189), ammonia and amino acids, as shown in Scheme 30." Identification of aldehydes determines the C-terminal amino acids of the original peptides. 

Similarly, reaction of carboxylic acid halides with sodium azide led to the formation of the respective acyl azides, which are stable. " By contrast, reaction of carboxylic acid chlorides with sodium azide in toluene at 70-100 °C transpires via a Curtins rearrangement to generate isocyanates. The details of these transformations are outlined in eqs 41-43. 

Alcohols too are chemically very resistant but they react with alkali metals, alkaline-earth metals, and aluminum to form salts. Under certain conditions alcohols can be converted into carboxylic acids by powerful oxidizing agents. They are, however, stable toward atmospheric oxygen. On account of their reaction with isocyanates to form urethanes, solvents containing hydroxyl groups (e.g., alcohols, glycols, and glycol ethers) must not be used as solvents for polyurethane paints [14.101], [14.102]. 

Subst. carboxylic acid amides from isocyanates Reactions with alanes... 

Imines act as blocked amines because they hydrolyze to yield free amines, which react with an isocyanate. Ketimines also react directly with isocyanates to yield a variety of products, depending on the particular reactants and conditions. Aldimines react analogously with isocyanates to yield unsaturated substituted ureas. Since aldimines are more stable to hydrolysis than ketimines, the fraction undergoing direct reaction with isocyanate in the presence of water is greater than that with ketimines. Carboxylic acids react relatively slowly to form amides and CO2. Hindered carboxylic acid groups, such as in 2,2-dimethylolpropionic acid (3-hydroxy-2-(hydroxymethyl)-2-methylpropanoic acid) [4767-03-7], react very slowly. 

Organoaluminum compounds also undergo insertion reaction with isocyanates. For example, aluminum trialkyls react with alkyl and aryl isocyanates to give carboxylic acid amides after hydrolysis . Alkyl aluminum chlorides react similarly . Aluminium trichloride also forms insertion products with isocyanates Diethylaluminum ethyl thiolate or dimethylamide react with equimolar amounts of alkyl or aryl isocyanates to give the expected insertion products 274. ... 

The ketocarbene 4 that is generated by loss of Na from the a-diazo ketone, and that has an electron-sextet, rearranges to the more stable ketene 2 by a nucleophilic 1,2-shift of substituent R. The ketene thus formed corresponds to the isocyanate product of the related Curtius reaction. The ketene can further react with nucleophilic agents, that add to the C=0-double bond. For example by reaction with water a carboxylic acid 3 is formed, while from reaction with an alcohol R -OH an ester 5 is obtained directly. The reaction with ammonia or an amine R -NHa leads to formation of a carboxylic amide 6 or 7 ... 

Reaction of Isocyanates with Water and Carboxylic Acids... 

Scheme 4.13 Reaction of isocyanates with water and carboxylic acids.

Isocyanates react with carboxylic acids to form amides, ureas, anhydrides, and carbon dioxide, depending on reaction conditions and the structure of the starting materials (Scheme 4.13). Aliphatic isocyanates more readily give amides. Aromatic isocyanates tend to react with carboxylic acids to first generate anhydrides and ureas, which at elevated temperatures (ca. 160°C) may further react to give amides. In practice, the isocyanate reaction with carboxylic acid is rarely utilized deliberately but can be an unwanted side reaction resulting from residual C02H functionality in polyester polyols. 

Salts of aliphatic or aromatic carboxylic acids can be converted to the corresponding nitriles by heating with BrCN or CICN. Despite appearances, this is not a substitution reaction. When R COO was used, the label appeared in the nitrile, not in the C02, and optical activity in R was retained. The acyl isocyanate... 

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. 

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