Amides removal

The mechanism for basic hydrolysis begins with attack by hydroxide on the electrophilic carbon of the cyano group. Protonation gives the unstable enol tautomer of an amide. Removal of a proton from oxygen and reprotonation on nitrogen gives the amide. Further hydrolysis of the amide to the carboxylate salt involves the same base-promoted mechanism as that already discussed. 

Pleuss, N, Kunz, H, A-Glycosyl amides removal of the anomeric protecting group and conversion into glycosyl donors, Angew. Chem. Int. Ed., 42, 3174-3176, 2003. 

The diacid corresponding to 114 is callosobruchic acid (115), and forms part of the copulation release pheromone of the azuki bean weevil, Callosobruchus chinensis Both chiral isomers have been synthesized by Mori et al. from methyl geranate epoxide (123). After scission of the epoxide group, the iodide 124 was made conventionally, then the chiral group was introduced using the Evans (R)- or (5)-prolinol propionamide enolate anion (125) (made with lithium diethylamide in tetrahydrofuran on the amide). Removal of the proline group... 

According to Wittig,97 the base (sodium alkoxide, phenyllithium, or sod-amide) removes a proton from the -carbon atom, yielding the unstable ylide in which the benzyl group then migrates from nitrogen to carbon. 

Problem 8.20. A representation for a pathway for the conversion of the phenyl diethylphosphate to aminobenzene (aniline, C6H5NH2) is provided in Scheme 8.36. It has been proposed that the strong base (potassium amide) removes a proton ortho to the phosphate linkage of the aromatic bond and that benzyne is formed. Benzyne then reacts with the ammonia solvent to produce the product. An alternative process might involve, for example, direct displacement of the diethylphosphate anion. Write out at least these two suggested processes and propose what you might do to determine which is occurring (if either). 

Carboxylic acids from carboxylic acid amides Removal of photo-sensitive carboxyl-protective groups... 

Karady, S., J. S. Amato, L. M. Weinstock, and M. Sletzinger The Chemistry of Cephamycins. VI. Cleavage of the 7-Amido Group. Tetrahedron Letters 1978, 407. Applegate, H. E., C. M. Cimarusti, and W. A. Slusarchyk Deacylation of Amides Removal of the Acyl Side-chain from Cephamycin Derivatives. J. C. S. Chem. Commun. 1980, 293. 

Sodium and potassium hydroxides. The use of these efficient reagents is generally confined to the drying of amines (soda lime, barium oxide and quicklime may also be employed) potassium hydroxide is somewhat superior to the sodium compound. Much of the water may be first removed by shaking with a concentrated solution of the alkali hydroxide. They react with many organic compounds (e.g., acids, phenols, esters and amides) in the presence of water, and are also soluble in certain organic liquids so that their use as desiccants is very limited... 

The by-products are both gaseous and the excess of thiouyl chloride (b.p. 78°) may be readily removed by distillation. Interaction of the acid chloride with ammonia solution, aniline or p-toluidiiie yields the amide, anilide or p-toluidide respectively ... 

Hate 1. To a suspension of 0.40 mol of lithium amide in 400 ml of liquid NH3 (see Chapter II, Exp. 11) was added 0.30 mol of HCECCH20-tert.-CitHg Subsequently 0.46 mol of CjHsBr was introduced in 30 min. After an additional 1 h the NH3 was removed by placing the flask in a water-bath at 40°C. Addition of water, extraction with diethyl ether and distillation gave C2H C=CCH20-tert.-C,H in more than 85% yield. 

To a vigorously stirred suspension of 4 mol of lithium amide (see II, Exp. II) in 2.5 1 of liquid ammonia were added in 25 min 2 mol of propargyl alcohol (commercially available, purified before use by distillation at 100-120 mm). The suspension became very thin. Subsequently, the dropping funnel was combined with a gas inlet tube reaching about 1 cm beneath the surface of the ammonia. The vent on the splashing tube was removed. Methyl iodide (2 mol) was added to the vigorous-... 

To a mixture of 65 ml of dry benzene and 0.10 mol of freshly distilled NN-di-ethylamino-l-propyne were added 3 drops of BFa.ether and 0.12 mol of dry propargyl alcohol was added to the reddish solution in 5 min. The temperature rose in 5-10 min to about 45°C, remained at this level for about 10 min and then began to drop. The mixture was warmed to 60°C, whereupon the exothermic reaction made the temperature rise in a few minutes to B5 c. This level was maintained by occasional cooling. After the exothermic reaction (3,3-sigmatropic rearrangement) had subsided, the mixture was heated for an additional 10 min at 80°C and the benzene was then removed in a water-pump vacuum. The red residue was practically pure acid amide... 

The purity of the peptide finally obtained depends critically on the yield of each cycle. It must be extraordinarily good to produce even moderately pure products (K. Ltibke, 1975). If the average yield of amide formadon in the synthesis of an undecapeptide (n = 10) is. for example, 98< to, the product will contain already about 20% of different impurities which may be difficult to remove. 

APA may be either obtained directly from special Penicillium strains or by hydrolysis of penicillin Q with the aid of amidase enzymes. A major problem in the synthesis of different amides from 6-APA is the acid- and base-sensitivity of its -lactam ring which is usually very unstable outside of the pH range from 3 to 6. One synthesis of ampidllin applies the condensation of 6-APA with a mixed anhydride of N-protected phenylglydne. Catalytic hydrogenation removes the N-protecting group. Yields are low (2 30%) (without scheme). 

Phenyl-3-oxopropanoic acid (25 mmol) and EtjN (87.5 mmol) were dissolved in THF (150 ml) and cooled to —40°C. Ethyl chloroformate (27.5 mmol) was added dropwise to this solution and then the reaction mixture was stirred for 30 min at —20°C. Di-n-hexylamine (27.5 mmol) was added to the suspension and it was stirred at room temperature for an additional hour. The reaction mixture was diluted with water (100 ml) and extracted with ether (400 ml). The extract was washed with aq. 5% HCl (100 ml) and brine (2 X 100 ml) and dried over NajSO. The crude amide was obtained by removal of the solvent in vacuo and phenylhydrazine (25 mmol) was added. The mixture was heated to 100°C for 30 min. The residue was held in vacuo to remove the water formed and then powdered ZnCl2 (125 mmol) was added. The mixture was heated at 170"C with manual stirring for 5 min. The cooled residue was dissolved in acetone (100 ml) and diluted with ether (500 ml). Water (100 ml) was added. The organic layer was separated and washed successively with 5% aq. HCl (100 ml) and brine (2 x 100 ml) and dried over NajSO. The solvent was removed in vacuo, and the residue was recrystallized from EtOAc-hexane. The yield was 79%. 

Acetylene and terminal alkynes are more acidic than other hydrocarbons They have s of approximately 26 compared with about 45 for alkenes and about 60 for alkanes Sodium amide is a strong enough base to remove a proton from acetylene or a terminal alkyne but sodium hydroxide is not... 

A significant fraction of the body s cholesterol is used to form bile acids Oxidation m the liver removes a portion of the CsHi7 side chain and additional hydroxyl groups are intro duced at various positions on the steroid nucleus Cholic acid is the most abundant of the bile acids In the form of certain amide derivatives called bile salts, of which sodium tau rocholate is one example bile acids act as emulsifying agents to aid the digestion of fats... 

Treat the sodium salt of diethyl acetamidomalonate with isopropyl bromide Remove the amide and ester functions by hydrolysis in aqueous acid then heat to cause (CH3)2CHC(C02H)2... 

The product of this reaction can be removed as an azeotrope (84.1% amide, 15.9% acetic acid) which boils at 170.8—170.9°C. Acid present in the azeotrope can be removed by the addition of soHd caustic soda [1310-73-2] followed by distillation (2). The reaction can also take place in a solution having a DMAC-acetic acid ratio higher than the azeotropic composition, so that an azeotrope does not form. For this purpose, dimethylamine is added in excess of the stoichiometric proportion (3). If a substantial excess of dimethylamine reacts with acetic acid under conditions of elevated temperature and pressure, a reduced amount of azeotrope is formed. Optimum temperatures are between 250—325°C, and pressures in excess of 6200 kPa (900 psi) are requited (4). DMAC can also be made by the reaction of acetic anhydride [108-24-7] and dimethylamine ... 

Amidation. Heating of the diammonium salt or reaction of the dimethyl ester with concentrated ammonium hydroxide gives adipamide [628-94-4] mp 228°C, which is relatively insoluble in cold water. Substituted amides are readily formed when amines are used. The most industrially significant reaction of adipic acid is its reaction with diamines, specifically 1,6-hexanediamine. A water-soluble polymeric salt is formed initially upon mixing solutions of the two materials then hea ting with removal of water produces the polyamide, nylon-6,6. This reaction has been studied extensively, and the hterature contains hundreds of references to it and to polyamide product properties (31). 

---