Amides carboxylic

The ease of dehydration of pyridazine carboxamides, their hydrolysis, and Hofmann degradation to amines was outlined in CHEC-I 84CHEC-I(3B)1 . More recently, in the early 1990s, the Curtius rearrangement (Equation (19)) of the 4-carboxylic hydrazide of 6-(4-pyridyl)-3(2//)-pyridazinone to give an aza analogue of amrinone has been reported 90H(3i)2l63 . 

Heating a carboxylic acid with ammonia or urea gives a carboxamide. For example, heptanoic acid plus urea at 140-180°C gives heptanamide in 75% yield plus CO and H O [17], The highly reactive acid halides and anhydrides combine with ammonia or primary or secondary amines to give amides at ordinary temperatures. Esters will react slowly with ammonia at room temperature (Eq. 6.12) [18]. Higher-boiling amines may be used if the alcohol is removed continuously by distillation. 

Nitriles may be hydrated to amides by using acid or base catalysis and vigorous heating. This hydration may be accomplished under neutral anhydrous conditions using acetaldoxime and a rhodium catalyst, which leaves other functionality intact (Eq. 6.13) [19]. 

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The "zip-reaction (U. Kramer, 1978, 1979) leads to giant macrocycles. Potassium 3- ami-nopropyl)amide = KAPA ( superbase ) in 1,3-diaminopropane is used to deprotonate amines. The amide anions are highly nucleophilic and may, for example, be used to transam-idate carboxylic amides. If N- 39-atnino-4,8,12,16,20,24,28,32,36-nonaazanonatriacontyl)do-decanolactam is treated with KAPA, the amino groups may be deprotonated and react with the macrocyclic lactam. The most probable reaction is the intramolecular formation of the six-membered ring intermediate indicated below. This intermediate opens spontaneously to produce the azalactam with seventeen atoms in the cycle. This reaction is repeated nine times in the presence of excess KAPA, and the 53-membered macrocycle is formed in reasonable yield. 

The biochemical basis for the toxicity of mercury and mercury compounds results from its ability to form covalent bonds readily with sulfur. Prior to reaction with sulfur, however, the mercury must be metabolized to the divalent cation. When the sulfur is in the form of a sulfhydryl (— SH) group, divalent mercury replaces the hydrogen atom to form mercaptides, X—Hg— SR and Hg(SR)2, where X is an electronegative radical and R is protein (36). Sulfhydryl compounds are called mercaptans because of their ability to capture mercury. Even in low concentrations divalent mercury is capable of inactivating sulfhydryl enzymes and thus causes interference with cellular metaboHsm and function (31—34). Mercury also combines with other ligands of physiological importance such as phosphoryl, carboxyl, amide, and amine groups. It is unclear whether these latter interactions contribute to its toxicity (31,36). 

On curing, amino resins not only react with the nucleophilic sites (hydroxyl, carboxyl, amide) on the other film formers in the formulation, but also self-condense to some extent. Highly alkylated amino resins have less tendency to self-condense (33,34) and are therefore effective cross-linking agents, but may require the addition of a strong acid catalyst to obtain acceptable cure even at bake temperatures of 120—177°C. 

Carboxylic Amides. Carboxyhc amide nonionic surfactants are condensation products of fatty acids and hydroxyalkyl amines. 

A7-Acylhexafluoroacetone imines are prepared from hexafluoroacetone and carboxylic amides m the presence of p-toluenesulfonic acid (TsOH) [100] (equation 86)... 

FIGURE 18.35 Formation of THF from folic acid by the dihydrofolate reductase reaction. The R group on these folate molecules symbolizes the one to seven (or more) glutamate units that folates characteristically contain. All of these glutamates are bound in y-carboxyl amide linkages (as in the folic acid structure shown in the box A Deeper Look Folic Acid, Pterins, and Insect VFingis). The one-carbon units carried by THF are bound at N, or at or as a single carbon attached to both... 

Cyclization of A -aryl-2-(ethoxycarbonyl)-3-(2-pyridylamino)acrylamides 307 in AcOH, and in PPA, or in ethylene glycol afforded A-aryl-4-oxo-4//-pyrido[l,2-n]pyrimidine-3-carboxylic amide 308 (94KGS629, 95KFZ(5)39). 

Rearrangement of oximes to give TV-substituted carboxylic amides... 

The rearrangement of oximes 1 under the influence of acidic reagents to yield A -substituted carboxylic amides 2, is called the Beckmann rearrangement. The reaction is usually applied to ketoximes aldoximes often are less reactive. 

The cationic species 4 thus formed reacts with water to give the iminol 5, which tautomerizes to a more stable amide tautomer, the N-substituted carboxylic amide 2. Those steps correspond to the formation of amides by the Schmidt reaction. A side reaction can give rise to the formation of nitriles. 

For the Flofmann rearrangement reaction, a carboxylic amide 1 is treated with hypobromite in aqueous alkaline solution. Initially an iV-bromoamide 4 is formed. With two electron-withdrawing substituents at nitrogen the A -bromoamide shows NFI-acidity, and can be deprotonated by hydroxide to give the anionic species 5. 

An aryl alkyl ketone 1 can be converted into an tn-arylalkane carboxylic amide 2 by employing the Willgerodt reaction The number of carbon centers is retained. The reaction is carried out by treating the ketone with an aqueous solution of ammonium polysulfide. A variant that has been developed by Kindler, and which is called the Willgerodt-Kindler reaction, uses a mixture of sulfur and a secondary amine instead of the ammonium polysulfide. 

The ketocarbene 4 that is generated by loss of Na from the a-diazo ketone, and that has an electron-sextet, rearranges to the more stable ketene 2 by a nucleophilic 1,2-shift of substituent R. The ketene thus formed corresponds to the isocyanate product of the related Curtius reaction. The ketene can further react with nucleophilic agents, that add to the C=0-double bond. For example by reaction with water a carboxylic acid 3 is formed, while from reaction with an alcohol R -OH an ester 5 is obtained directly. The reaction with ammonia or an amine R -NHa leads to formation of a carboxylic amide 6 or 7 ... 

S,3R)-Aziridine-2-carboxylic amide 258 (Scheme 3.95) has been used in the synthesis of the cyclic guanidino amino acid, L-epicapreomycidine (260) [145]. Treatment of 258 with saturated ammonia in methanol at 30 °C for 4 days in a pressure bottle resulted in the aziridine ring-opening product, which afforded 259 in 52 % yield after removal of the Cbz protecting group. 

In the course of this study, the authors determined /Lvalues for dibenzyl, methyl phenyl, methyl p-nitrophenyl, di-p-tolyl, di-isopropyl and tetramethylene sulphoxides and for diethyl, dipropyl and dibutyl sulphites. The /Lscales are applied to the various reactions or the spectral measurements. The /Lscales have been divided into either family-dependent (FD) types, which means two or more compounds can share the same /Lscale, family-independent (FI) types. Consequently, a variety of /Lscales are now available for various families of the bases, including 29 aldehydes and ketones, 17 carboxylic amides and ureas, 14 carboxylic acids esters, 4 acyl halides, 5 nitriles, 10 ethers, 16 phosphine oxides, 12 sulphinyl compounds, 15 pyridines and pyrimidines, 16 sp3 hybridized amines and 10 alcohols. The enthalpies of formation of the hydrogen bond of 4-fluorophenol with both sulphoxides and phosphine oxides and related derivatives fit the empirical equation 18, where the standard deviation is y = 0.983. Several averaged scales are shown in Table 1588. 

C for 6 h afforded the alkylated imides in 60-84% yields. The last approach was extended to unsaturated carboxylic amides. The diene 0,N-acetal 86 was prepared from the amide 85 in high yields and subsequently treated with azoinitiator V-70 to afford the desired products (Scheme 13). ... 

Secondary carboxylic amides of the type PhC(0)NR(H) were rapidly deprotonated with dimethylzinc to furnish mainly tetrameric and hexameric mono(methylzinc) derivatives.147... 

Another interesting asymmetric epoxidation technique using metal catalysis involves the vanadium complexes of A-hydroxy-[2.2]paracyclophane-4-carboxylic amides (e.g., 19), which serve as catalysts for the epoxidation of allylic alcohols with f-butyl hydroperoxide as... 

In addition to carbonyl substrates, imines have been used extensively with phosphorus-halogen reagents for the preparation of a variety of phosphonates and phosphinates. Combined in a reaction medium, secondary amines react with formaldehyde and phosphorus trichloride134 135 or alkyldichlorophosphines136 to produce N,N-disubstituted aminomethylphosphonates or -phosphinates. These reactions occur under mild conditions with good yield. Similarly, aliphatic carboxylic amides react with aldehydes to generate imines, which can be used in situ with diphenylchlorophosphine to produce... 

Examples of this motif include the carboxylate, amide, and imidazole derivatives shown below ... 

Other functional groups which have a heteroatom rather than a hydroxyl group capable of directing the hydrogenation include alkoxyl, alkoxycarbonyl, carboxylate, amide, carbamate, and sulfoxide. The alkoxy unit efficiently coordinates to cationic iridium or rhodium complexes, and high diastereoselectivity is induced in the reactions of cyclic substrates (Table 21.3, entries 11-13) [25, 28]. An acetal affords much lower selectivity than the corresponding unsaturated ketone (Table 21.3, entries 14 and 15) [25]. 

Oxidation by ultra-hot-air treatment for polyolefins exposition to a blast of hot air (roughly 500°C) for a short time to oxidize the surface and create reactive sites such as hydroxyl, carbonyl, carboxyl, amides... Rather similar to flame treatment, it is particularly used for polyethylene and polypropylene. 

Base-induced cleavage of non-enolizable ketones leading to carboxylic amide derivative and a neutral fragment in which the carbonyl group is replaced by a hydrogen. 

The electrophile for the cyclization reaction of an a-amino-organolithium compound is not restricted to a terminal (or phenylthio-substituted) ahcene and examples have been reported using carboxylic amides, alkynes and allyhc ethers." " For example, Fautens and Kumanovic reported that treatment of the bicyclic stannane shown in Scheme 24... 

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