Amides, from acid derivatives basicity

Ketenimines are usually prepared from carboxyHc acid derivatives such as amides and imino chlorides via elimination and from nitriles via alkylation with alkyl haHdes under strong basic conditions (21,64). 

The application of antibiotics as chiral selectors has resulted in the successful resolution of almost all types of neutral, acidic, and basic racemic molecule. These antibiotics have been used for the enantiomeric resolution of amino acids, their derivatives, peptides, alcohols, and other pharmaceuticals. The selectivities of the most commonly used antibiotic-based (vancomycin, teicoplanin, and ristocetin A) CSPs varied from one racemate to another and are given in Table 1. Vancomycin was used for the chiral resolution of amino acids, amines, amides, imides, cyclic amines, amino alcohols, hydantoins, barbiturates, oxazolidinones, acids, profens, and other pharmaceuticals. Teicoplanin was found to be excellent chiral selector for the enantiomeric resolution of amino acids, amino alcohols, imides, peptides, hydantoins, a-hydroxy and halo acids, and oxazolidinones, whereas ristocetin A is capable of chiral resolution of amino acids, imides, amino... 

All acid derivatives hydrolyze to give carboxylic acids. In most cases, hydrolysis occurs under either acidic or basic conditions. The reactivity of acid derivatives toward hydrolysis varies from highly reactive acyl halides to relatively unreactive amides. 

The synthesised amidic polyols have an hydroxyl number between 350-500 mg KOH/g and viscosities between 7000-25000 mPa-s at 25 °C, the lowest viscosity being in the polyols derived from the bis (diethanolamide) of phthalic acid. The pH of amidic polyols is slightly basic, in the range of 8-9.5. 

Since the discovery of the synthesis of 1,3,5-triazine-2,4-diamines from biguanide and its derivatives,328-329 a large variety of carboxylic acid derivatives, e.g. acid chlorides,332 342,346 lactones,333 amides,334,335 imides,336,337 ortho esters,338 amidines,338 esters334, 339- 343 and acid anhydrides,332,344,345 have been used as starting materials in the preparation of these triazines (Table 8).330,331 The preferred procedure is the reaction of biguanides 1 with esters 2 in alcoholic solution, sometimes in the presence of a basic catalyst. The reaction mechanism is thought to be as indicated.341... 

Based on lysine as before, single chain derivatives (18) and bicatenar compounds (19) have been prepared by a strategy the inverse of that described earlier [46]. The products (18 and 19) are obtained with higher overall yields than 17. As before, no protection or deprotection steps are needed in this case [46,47]. The synthesis consists of a reaction between two moduU prepared beforehand, one representing the polar head group in the final product and the other the junction modulus. The preparation of this intermediate starts from aldoses or acids derived Irom them that are coupled with lysine in its basic form (Scheme 15). The yields for this step are quantitative. A subsequent amidation reaction with a hydrogenated or perfluorinated fatty acid (Scheme 16) leads to the monosubstituted compounds (18). Esterification of the free acid function of lysine (Scheme 17) yields in a final step the bicatenar structures (19). 

In this chapter, we first introduce the system of naming carboxylic acids and then list some of their physical and spectroscopic characteristics. We then examine their acidity and basicity, two properties that are strongly influenced by the interaction between the electron-withdrawing carbonyl group and the hydroxy function. Methods for the preparation of the carboxy group are considered next, followed by a survey of its reactivity. Reactions of carboxylic acids will feature a new two-step substitution pathway, addition-elimination, for the replacement of the hydroxy group by other nucleophiles, such as halide, alkoxide, and amide. The chemistry of the carboxylic acid derivatives, which result from these transformations, is the subject of Chapter 20. 

The electrophilic reactivity of the carbonyl carbon in carboxylic acid derivatives is weakened by good electron-donating substituents. This effect, measurable by IR spectroscopy, is responsible not only for the decrease in the reactivity with nucleophiles and acid, but also for the increased basicity along the series acyl habdes-anhydrides-esters-amides. Electron donation by resonance from the nitrogen in amides is so pronounced that there is hindered rotation about the amide bond on the NMR time scale. 

In base the tetrahedral intermediate is formed m a manner analogous to that pro posed for ester saponification Steps 1 and 2 m Figure 20 8 show the formation of the tetrahedral intermediate m the basic hydrolysis of amides In step 3 the basic ammo group of the tetrahedral intermediate abstracts a proton from water and m step 4 the derived ammonium ion dissociates Conversion of the carboxylic acid to its corresponding carboxylate anion m step 5 completes the process and renders the overall reaction irreversible... 

Pentafluoroaniline. Pentafluoroaniline [771 -60-8] i2is been prepared from amination of hexafluoroben2ene with sodium amide inbquid ammonia or with ammonium hydroxide in ethanol (or water) at 167—180°C for 12—18 h. It is weakly basic (p = 0.28) and dissolves only in concentrated acids. Liquid crystals have been prepared from Schiff bases derived from pentafluoroaniline (230). 

Sulfonamides (R2NSO2R ) are prepared from an amine and sulfonyl chloride in the presence of pyridine or aqueous base. The sulfonamide is one of the most stable nitrogen protective groups. Arylsulfonamides are stable to alkaline hydrolysis, and to catalytic reduction they are cleaved by Na/NH3, Na/butanol, sodium naphthalenide, or sodium anthracenide, and by refluxing in acid (48% HBr/cat. phenol). Sulfonamides of less basic amines such as pyrroles and indoles are much easier to cleave than are those of the more basic alkyl amines. In fact, sulfonamides of the less basic amines (pyrroles, indoles, and imidazoles) can be cleaved by basic hydrolysis, which is almost impossible for the alkyl amines. Because of the inherent differences between the aromatic — NH group and simple aliphatic amines, the protection of these compounds (pyrroles, indoles, and imidazoles) will be described in a separate section. One appealing proj>erty of sulfonamides is that the derivatives are more crystalline than amides or carbamates. 

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