Lead amides

As the result of a screening program examining microbial fermentation products for pharmacological activity (other than antibiotic activity), fusaric acid (10) was isolated from Fusarium oxysporum following the discovery that extracts were potent inhibitors of dopamine p-hydroxylase, and thus interfered with the biosynthesis in vivo of the pressor neurohormone, norepinephrine. To refine this lead, amidation of 10 via the acid chloride was carried out... 

C. Cyclopropenylidene Complexes of Divalent Germanium, Tin, and Lead Amides... 

Metal amides Lead amide, potassium amide, silver amide, sodium amide... 

A simple route to obtain Mo-Pb(II) complexes involves the elimination reaction between the lead amide Pb[N(SiMe3)2]2 and two equivalents of molybdenum hydride [CpRMo(CO)3H] (R = H, Me5 or (SiMe3)2) (equation 189)517. 

Thus 2,4,6-trimethylaniline (490) was reacted with phenyllead(IV) triacetate (482) in the presence of a catalytic amount of copper(II) acetate affording the A -phenyl derivative 491 in 94% yield [66], Contrarily, the C-arylation of, for example, 3,5-dimethylaniline (492) was accomplished by treatment with t-BuMgCl to give the magnesium amide 493, which subesquently reacts with aryllead compound 494, via lead-amide 495, to produce the respective 2-aminobiphenyl 496 in 88% yield [68], Scheme 35. 

Figure 3.5 Structures of the lead amide-containing CCR5 antagonis 6 and piperidine 7 and...

Figure 3.6 Structures of the lead amide 9, and A2B adenosine receptor antagonist, and its bioisosteric analogues 10-13.

Lead(fV) ethanoate, Pb(02CCH3)4, (Pb(ll)ethanoate plus CI2) is a powerful oxidizing agent which will convert vicinal glycols to aldehydes or ketones and 1,2-dicarboxylic acids into alkenes. Primary amides give ketones and amines give nitriles. 

For those nitriles which yield water-insoluble amides e.g., the higher alkyl cyanides), hydrolysis to the amide often leads to a satisfactory derivative. The hydration is eflfected by warming a solution of the nitrile in concentrated sulphuric acid for a few minutes, cooling and pouring... 

The mechanism of the reaction probably involves the production of bivalent carbon during the initial loss of nitrogen the group R shifte from an adjacent position to this carbon leading to the production of a keten the latter then reacts with the solvent to give an acid, an amide or an ester. 

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. 

In his cephalosporin synthesis methyl levulinate was condensed with cysteine in acidic medium to give a bicyclic thiazolidine. One may rationalize the regioselective formation of this bicycle with the assumption that in the acidic reaction mixture the tMoI group is the only nucleophile present, which can add to the ketone. Intramolecular amide formation from the methyl ester and acid-catalyzed dehydration would then lead to the thiazolidine and y-lactam rings. The stereochemistry at the carboxylic acid a-... 

All these reactions proceed by nucleophilic addition of the amine to the carbonyl group Dissociation of the tetrahedral intermediate proceeds m the direction that leads to an amide... 

The characteristic reaction of acyl chlorides acid anhydrides esters and amides is nucleophilic acyl substitution Addition of a nucleophilic reagent Nu—H to the carbonyl group leads to a tetrahedral mtermedi ate that dissociates to give the product of substitution... 

The amide formation reaction (highlighted by the circle) leads to the production of a hydrogen-bonded dimer (ZZ) of the reaction product Z with the template Z. The dimer is in thermodynamic equilibrium with free template in the reaction medium. 

Formic acid exhibits many of the typical chemical properties of the aHphatic carboxyHc acids, eg, esterification and amidation, but, as is common for the first member of an homologous series, there are distinctive differences in properties between formic acid and its higher homologues. The smaller inductive effect of hydrogen in comparison to an alkyl group leads, for example, to formic acid = 3.74) being a considerably stronger acid than acetic acid... 

MPD-1 fibers may be obtained by the polymeriza tion of isophthaloyl chloride and y -phenylenediamine in dimethyl acetamide with 5% lithium chloride. The reactants must be very carefully dried since the presence of water would upset the stoichiometry and lead to low molecular weight products. Temperatures in the range of 0 to —40° C are desirable to avoid such side reactions as transamidation by the amide solvent and acylation of y -phenylenediamine by the amide solvent. Both reactions would lead to an imbalance in the stoichiometry and result in forming low molecular weight polymer. Fibers are dry spun direcdy from solution. 

Reactions. The chemical properties of cyanoacetates ate quite similar to those of the malonates. The carbonyl activity of the ester function is increased by the cyano group s tendency to withdraw electrons. Therefore, amidation with ammonia [7664-41-7] to cyanoacetamide [107-91-5] (55) or with urea to cyanoacetylurea [448-98-2] (56) proceeds very easily. An interesting reaction of cyanoacetic acid is the Knoevenagel condensation with aldehydes followed by decarboxylation which leads to substituted acrylonitriles (57) such as (29), or with ketones followed by decarboxylation with a shift of the double bond to give P,y-unsaturated nitriles (58) such as (30) when cyclohexanone [108-94-1] is used. 

---