Isothiocyanates carboxylic acid amide

Carboxylic acid amides from carboxylic acids and isothiocyanates or thioureas... 

The phosphinic isocyanates (116) and isothiocyanates (117) react with oxygen, nitrogen, and phosphorus nucleophiles by attack at carbon rather than phosphorus. Phenyl phosphonodichloridate has been recommended as a useful reagent for the activation (presumably by mixed anhydride formation) of carboxylic acids for conversion to amides and hydrazides. ... 

Fluorinated alkylisocyanates and isothiocyanates add alcohols, mercaptans, and amines to yield stable 1 1 adducts [76]. When the reaction is performed with carboxylic acids, the anhydrides first formed decompose to give A -fluoroalky-lated amides [77]... 

Review. New synthetic reactions based on the onium salts of aza-arenes have been reviewed (75 references). The reactions discussed involve activation of carboxylic acids or alcohols with 2-haIopyridinium, benzoxazolium, benzothiazolium, and pyridinium salts to afford 2-acyloxy or 2-alkoxy intermediates, which can be transformed into esters, amides, thiol esters, (macrocyclic) lactones, acid fluorides, olefins, allenes, carbodiimides, isocyanates, isothiocyanates, and nitriles under appropriate conditions. 

Figure 10 Schematic representation of the most common reactions for labeling an amine (a) reaction with isothiocyanate to give a thiourea (b) reaction with a Succinimidil ester to give an amide (c) reaction with a sulfonyl chloride to give a sulfonamide (d) reaction with an aldehyde to give an imine (Schiff s base) and (e) reaction with a carbodiimide-activated carboxylic acid to give an amide.

Labelling with the isothiocyanate ligands has been effected by reaction with protein amine groups to form thiourea bonds. The coupled antibodies could be stored for months. The use of the cyclic dianhydride (CA-DTPA), 17 , has some disadvantage since one ligand carboxylate metal binding site is occupied in an acid amide bond to form a protein-linked diethylenetriaminetetraacetic acid (DTTA). 

A conceptual alternative way to the activation of the carboxylic acid function is the reaction of carboxylic acids with amino groups activated as isocyanates - and isothiocyanates (equation 16). Preparation of these derivatives is racemization free. The reaction proceeds via mixed acid anhydrides in aromatic hydrocarbon solvents at elevated temperatures, and decarboxylation leads to the V-substituted amide. Pyridine as solvent enhances the conversion rate but increases also the amount of the urea side product via disproportionation. Application to peptide chemistry is limited, because peptide ester fragments tend to form hydantoins. ... 

The classical Ugi four-component reaction (U-4CR) originally described by Ugi et al. [1] consists in the reaction of a primary amine, a carbonyl compound (aldehyde or ketone), an isocyanide, and a carboxylic acid to afford a-acylamino amides 36 (Scheme 7.14) [31, 32], Rapidly, other components or adducts were found to give the Ugi-4CR—that is, ammonia, hydroxylamine, or hydrazine as amine component or thiosulfates [33], thiocarboxylic acids [34], isothiocyanic acids [35], hydrazoic acid [36], or carbonic acid monoesters... 

Functionalized terpyridines can be created to contain a variety of binding and catalytic functional groups (15). Bromomethyl derivatives can be reacted with the sodium salts of alcohols to form ethers, or reacted with the sodium salts of amines to form substituted amines. Each sodium salt was formed by reaction with sodium hydride. Gabriel synthesis leads to the creation of an aminomethyl derivative, which can be converted into amide with acyl chlorides, ureas with isocyanates, or thioureas with isothiocyanates. Terpyridine-5-carboxylic acid is converted to the acyl chloride with thionyl chloride and can be coupled with a variety of amines to form amide derivatives. 

N-Substituted amides can be prepared by direct attack of isocyanates on aromatic rings.The R group may be alkyl or aryl, but if the latter, dimers and trimers are also obtained. Isothiocyanates similarly give thioamides. The reaction has been carried out intramolecularly both with aralkyl isothiocyanates and acyl isothiocyanates.In the latter case, the product is easily hydrolyzable to a dicarboxylic acid this is a way of putting a carboxyl group on a ring ortho to one already there (34 is... 

A series of solid-state reactions has been explored by Kaupp et al., in which gaseous amines were reacted with aldehydes to give imines. Analogous reactions with solid anhydrides, imides, lactones or carbonates, and isothiocyanates were used to give, respectively, diamides or amidic carboxylic salts or imides, diamides, carbamic acids, and thioureas [24]. In general the yields were found to be quantitative. Ammonia and other gaseous amines, in particular methyl-amine, have also been shown to aminolyse thermoplastic polycarbonates [25]. 

Step 1 of the Edman degradation is the addition of the NH2 group of the N-ter-minal amino acid to the C=N double bond of phenyl isothiocyanate. Step 2 (B —> C) is an intramolecular SN reaction of an S nucleophile on the carboxyl carbon of a pro-tonated amide. It follows the substitution mechanism shown in Figure 6.5. The substitution product C is a heterocyclic derivative of the N-terminal amino acid. The simultaneously formed second reaction product, the oligopeptide D, which has been shortened by one amino acid, is ejected as the leaving group. 

---