Amidates, basicity

Amides Basic (reflux) hydrolysis All amides yield ammonia or the corresponding amine detected by odor or by placing wet blue litmus paper on top of the condenser... 

Several decisive groups of facts concerning protein structure have been derived from the monomeric amides. Basically, these facts deal with the size, shape, and electronic make-up of the model compounds, particularly the amide grouping. X-ray diffraction and IR spectroscopy have been the most important tools in obtaining this information. 

In base, the nucleophilic hydroxide ion adds to the carbon-nitrogen triple bond (Fig. 18.46). Protonation on nitrogen and deprotonation from oxygen leads to the amidate anion, which is protonated to give an intermediate amide. Basic hydrolysis of the intermediate amide leads to the carboxylate salt. 

Aliphatic Hydroxy Acidic, neutral amides Basic Sulphur Aromatic Imino... 

Organic components can also be introduced in perfluorinated membranes, to increase the membrane selectivity. Polyvinylidene (PVDF) can effectively suppress the swelling of Nafion due to its high crystallite nature and further improve the selectivity [17]. By simple blending of PVDF with Nafion, the CE of the battery can be improved due to its higher ion selectivity, and the EE increases as well. The use of acid-base membranes such as SPEEK (sulphonated poly(ether ether ketone)), and PSf-ABIm (polysulphone-2-amide-benzimidazole) is another way to improve membrane selectivity via the interactions between sulphonated acid and amide basic groups [18,19]. 

Other experimental methods that have been applied to amide basicities are potentiometric titration (65,164,165) kinetic analysis of acid hydrolj is (100), rate retardation of acid catalyzed etherification of benzhydrol (280), and the Hammett indicator method using NMR (338) or Raman spectrometry (80) for measuring concentrations. 

As an example, experimental kinetic data on the hydrolysis of amides under basic conditions as well as under acid catalysis were correlated with quantitative data on charge distribution and the resonance effect [13]. Thus, the values on the free energy of activation, AG , for the acid catalyzed hydrolysis of amides could be modeled quite well by Eq. (5)... 

Acid amides have weakly amphoteric properties, and thus give salts such as CjHsCONHj.HCl with strong acids, and salts of the type C HsCONHNa with strong bases. These compounds have to be prepared at low temperatures to avoid hydrolysis, and are difficult to isolate. The mercury derivatives can, however, usually be readily prepared, because mercuric oxide is too feebly basic to cause hydrolysis of the amide, and the heavy mercuric derivatives crystallise well. 

The industrial process for preparing the reagent usually permits a little hydrolysis to occur, and the product may contain a little free calcium hydroxide or basic chloride. It cannot therefore be employed for drying acids or acidic liquids. Calcium chloride combines with alcohols, phenols, amines, amino-acids, amides, ketones, and some aldehydes and esters, and thus cannot be used with these classes of compounds. 

This group comprises substances of the tjrpe RCONHR and RCONR R", i.e., substituted amides of the aromatic series. They are all well-defined crystalline sohds, sparingly soluble in cold but, often, appreciably soluble hi hot water and moderately soluble in ether they are generally neutral or feebly basic in reaction. 

With the exception of the nuclear amination of 4-methylthiazole by sodium amide (341, 346) the main reactions of nucleophiles with thiazole and its simple alkyl or aryl derivatives involve the abstraction of a ring or substituent proton by a strongly basic nucleophile followed by the addition of an electrophile to the intermediate. Nucleophilic substitution of halogens is discussed in Chapter V. 

Water can also be a Brpnsted acid donating a proton to a base Sodium amide (NaNH2) for example is a source of the strongly basic amide ion which reacts with water to give ammonia... 

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... 

FIGURE 20 8 The mecha nism of amide hydrolysis in basic solution... 

We already discussed bolh Ihe acidic and basic hydrolysis of amides (see Seclion 20 17) All lhal remains to complete Ihe mechamslic piclure of nilrile hydrolysis is to examine Ihe conversion of Ihe nilnle to Ihe conespondmg amide... 

Acrylamide, C H NO, is an interesting difiinctional monomer containing a reactive electron-deficient double bond and an amide group, and it undergoes reactions typical of those two functionalities. It exhibits both weak acidic and basic properties. The electron withdrawing carboxamide group activates the double bond, which consequendy reacts readily with nucleophilic reagents, eg, by addition. 

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). 

Biosynthesis. Two closely related genes encode the three mammalian tachykinins. The preprotachykinin A gene encodes both substance P and substance K, while the preprotachykinin B gene encodes neuromedin K (45—47). The active sequences are flanked by the usual double-basic amino acid residues, and the carboxy-terrninal amino acid is a glycine residue which is decarboxylated to an amide. As with most neuropeptide precursors, intermediates in peptide processing can be detected, but their biological activities are not clear (ca 1994). 

The imide proton N-3—H is more acidic than N-1—H and hence this position is more reactive toward electrophiles in a basic medium. Thus hydantoins can be selectively monoalkylated at N-3 by treatment with alkyl haUdes in the presence of alkoxides (2,4). The mono-A/-substituted derivatives (5) can be alkylated at N-1 under harsher conditions, involving the use of sodium hydride in dimethylform amide (35) to yield derivatives (6). Preparation of N-1 monoalkylated derivatives requires previous protection of the imide nitrogen as an aminomethyl derivative (36). Hydantoins with an increased acidity at N-1—H, such as 5-arylmethylene derivatives, can be easily monoalkylated at N-3, but dialkylation is also possible under mild conditions. 

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). 

Goelenterate. Coelenterates Penilla reformis (sea pansy) -cradViequoreaforskalea (jelly fish) produce bioluminescence by similar processes (223). The basic luciferin stmcture is (49) (224) and excited amide (50) is the emitter. The stmctural relationship to Varela is evident. A stmctural analogue where R = CH is active ia bioluminescence. The quantum yield is about 4% (223), with at 509 nm (56). This reaction iavolves a charge transfer between green fluorescent proteia and the excited-state coelenterate oxylucifetin. 

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