1- ethyl urea amino acid

In view of the rapid reaction of carbodiimides with water they are often used in dehydration reactions. Major examples are the intra- and intermolecular esterification reactions of carboxylic acids, and the formation of peptides from carboxylic acids and protected amino acids. Especially, dicyclohexylcarbodiimide (DCC) or diisopropylcar-bodiimide (DIPCD) are often used in carbodiimide mediated reactions because the corresponding urea byproducts are insoluble in most organic solvents and water, and therefore are readily removed by filtration. Also, water soluble carbodiimides, such as N-ethyl-N -(3-dimethylamino)propylcarbodiimide (EDC) or its hydrochloride (EDCCl, sometimes referred to as EDAC) are often used in these reactions. EDC reacts with carboxyl groups at pH of 4.0-6.0, but loses its reactivity at lower pH. Sometimes solid phase reactions are conducted using carbodiimide terminated linear or crosslinked polymers. 

Achiral lanthanide chelates can also be added to CSAs such as arylperfluoroalkyl-carbinols, the ethyl ester of 3,5-dinitrobenzoyl-L-leucine (25) , the 3,5-dinitrobenzoyl derivative of 1-phenylethylamine, Af-(l-(l-naphthyl)ethyl)trifluoroacetamide (26) and a series of l-(l-naphthyl)ethyl urea derivatives of amino acids (27) to enhance the enantiomeric discrimination. With sulfoxide or lactone substrates , the europium ion preferentially associates with the substrate in the bulk solution. Provided the enantiomers have different association constants with the CSA, the isomer that shows the weaker association with the CSA shows the larger lanthanide-induced shifts. Low concentrations of lanthanide relative to the substrate and CSA lead to enhancements of enantiomeric discrimination in the NMR spectrum. If the concentration of lanthanide is too high, binding of the substrate to the lanthanide strips the substrate from the chiral solvating agent and diminishes the chiral discrimination in the NMR spectrum. 

Ough, C.S., Crowell, E.A., and Mooney, L.A. (1988). Formation of ethyl carbamate precursors during grape juice (Chardonnay) fermentation. I. Addition of amino acids, urea, and ammonia effects of fortification on intracellular and extracellular precursors, Am. J. Enol. Vitic., 39(3), 243-249. 

The application of additives was investigated in order to suppress or diminish side reactions (A-acyl urea formation and racemization). Al-Hydroxysuccinimide (HOSu), 1-hydroxybenzotriazole (HoBt), and ethyl l-hydroxy-lH-l,2,3-triazole-4-carboxylate are potential additives in the DCC-based coupling synthesis. Solid-phase peptide synthesis (SPPS) is a variant of the linear (stepwise) coupling of amino acids in the C N direction using two major protection groups Boc/Bzl (iert-butoxycarbonyl/benzyl) and Fmoc/tBu (/9-fluorenylmethoxycarbonyl/ieri-butyl). The synthetic scheme for peptides on a polymer (Atherton and Sheppard, 1989 Fields, 1997) is illustrated in Figure 8.1. 

Free a-amino acid deficiencies in juice are often corrected by the addition of ammonium salts. The most widely used of these, diammonium phosphate or sulfate, are 27% NH4 and 73% P04 or S04 . The maximum level of diammonium phosphate (DAP) permitted by the United States BATF to correct nutritional deficiencies is 968 mg/L, whereas in OIV countries, the maximum allowable addition is 300 mg/L. In Australia, additions are limited by maximum phosphate levels in the wine. In this case, 400 mg/L inorganic phosphate/L is permitted (Henschke and Jiranek, 1993). Historically, urea has been used as a nitrogen supplement during fermentation. However, owing to its demonstrated involvement as a precursor in ethyl carbamate (urethane) formation, the nitrogen source has been eliminated as an approved fermentation adjunct in many countries. 

Ethyl carbamate in wine is formed (mostly at the end of fermentation) from urea. The intermediates of its degradation are probably cyanates and cyanic acid (HO-C=N), also known as hydrogen cyanate, which may isomerise to isocyanic acid (H-N=C=0). Iso-cyanic acid can also arise by protonation of the cyanate anion and nucleophilic addition of ethanol to isocyanic acid yields ethyl carbamate. Isocyanic acid also reacts with other nucleophilic reagents, such as water (with formation of ammonia and carbon dioxide), thiols and amino groups of proteins. By catalysis with ornithinecar-bamoyl transferase, citrulline is transformed into ornithine and carbamoyl phosphate, the ethanolysis of which yields ethyl carbamate (Figure 12.39). 

Under the mild reaction conditions (0°C), the second amino acid (carboxyl protected) will not react with DCC, but only with the anhydride-like intermediate. The DCU formed is insoluble in most organic solvents so that most often separation from the product merely involves filtrations. However, it occasionally may be difficult to remove the last trace of DCU by filtration. As such, the use of carbodiimides that are soluble in aqueous solvents may be necessary. One example is l-ethyl-3-(3-dimethylaminopropyl)-carbodi-imide hydrochloride. The urea by-product formed is also water soluble. 

Ethyl 2-ethylthio-4-chloro-5-pyrimidinecarboxylate (XXIIa), as well as the corresponding4-hydroxy-(XXIIb) and 4-amino-(XXIIIa) derivatives, possess-anti-cytogenic activity on Neurospora crassa [223, 224]. Compounds (XXIIIa, b and c) were found to inhibit the conversion of orotic acid to the uridine nucleotides [202]. Ethyl 2-methylthio-4-(halo-substituted anilino)-5-pyrimidinecarboxylates (XXIV), particularly the o-bromo- and the o-chloro- derivatives, substantially inhibit the growth of five experimental mouse tumours (Krebs-2 ascites carcinoma, Ehrlich carcinoma clone 2, leukaemia L-1210, carcinoma 755 and lymphocytic neoplasm P-288) [225]. Compounds of this type are usually prepared by the base catalysed condensation of ethoxymethylenemalonic esters or related derivatives with urea, thiourea, guanidine, or substituted amidine-type analogues [212, 225-237]. 

Potassium nitrate, Sulfuric acid, 1,3,5-Trifluorobenzene, Methylene chloride, Hexane, Tert-butylamine, Trifluoroacetic acid, 1,2-Dichloroethane, 3-Amino-1,2,4-traizole, Glacial acetic acid, Sodium nitrite, Urea, Ethyl acetate, Dimethylformamide, Diethyl ether, Sodium sulfate, Methanol Ethanolamine, Diethyl ether, Ethyl chlorocarbonate, Sodium hydroxide, Magnesium sulfate, Nitric acid, Anhydrous ammonia... 

Amide formation, from a carboxylic acid and urea, 37, 50 from 2-amino-5-nitroanisole and ethyl benzoylacetate, 37, 4 from aniline and ethyl benzoylacetate, 37, 3... 

A stirred solution of 0.0158 mole of ethyl-a-[(l-carboxyethyl)amino] benzenebutanoate hydrochloride in 200 ml of methylene chloride was treated successively with 1.60 g (0.0158 mole) of triethylamine, 0.0158 mole of 1-hydroxybenzotriazole, 0.0158 mole of l,2,3,4-tetrahydro-6,7-dimethoxy-3-isoquinolinecarboxylic acid and then with 0.0158 mole of dicyclohexylcarbodiimide in 10 ml of methylene dichloride. Dicyclohexylurea gradually separated. The mixture was allowed to stand at room temperature overnight. Hexane (300 ml) was added and the urea was filtered. The filtrate was washed with 250 ml of saturated sodium bicarbonate, dried over sodium sulfate and concentrated to remove solvent. The viscous residue was triturated with 50 ml of ether and filtered to remove insolubles. The filtrate was concentrated to give 2-[2-[[l-(ethoxycarbonyl)-3-phenylpropyl]amino]-l-oxopropyl]-l,2,3,4-tetrahydro-6,7-dimethoxy-3-isoquinolinecarboxylic acid. 

How an unsymmetrical urea can be prepared from a primary amine with a (diethyl-amino )propyl substituent (A) and ethyl isocyanate is illustrated using the example of compound C. This urea is the starting material for preparing a carbodiimide (see Figure 8.9), which activates carboxylic acids towards heteroatom nucleophiles. 

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