A-Deprotonation

Fig. 10. Pharmacophores for angiotension-converting enzyme. Distances in nm. (a) The stmcture of a semirigid inhibitor and distances between essential atoms from which one pharmacophore was derived (79). (b) In another pharmacophore, atom 1 is a potential zinc ligand (sulfhydryl or carboxylate oxygen), atom 2 is a neutral hydrogen bond acceptor, atom 3 is an anion (deprotonated sulfur or charged oxygen), atom 4 indicates the direction of a hydrogen bond to atom two, and atom 5 is the central atom of a carboxylate, sulfate, or phosphate of which atom 3 is an oxygen, or atom 5 is an unsaturated carbon when atom 3 is a deprotonated sulfur. The angle 1- -2- -3- -4 is —135 to —180° or 135 to 180°, and 1- -2- -3- -5 is —90 to 90°.

The 2-alkyl group of 2-alkylisoxazolium salts is also susceptible to a -deprotonation. For example, treatment of 3,5-distyrylisoxazolium salt (199) with potassium methoxide followed by acid hydrolysis gave the natural /3-diketone curcumine (77H(7)24l). 

Most diaziridines are not sensitive towards alkali. As an exception, diaziridines derived from 2-hydroxyketones are quickly decomposed by heating with aqueous alkali. Acetaldehyde, acetic acid and ammonia are formed from (162). This reaction is not a simple N—N cleavage effected intramolecularly by a deprotonated hydroxy group, since highly purified hydroxydiaziridine (162) is quite stable towards alkali. Addition of small amounts of hydroxybutanone results in fast decomposition. An assumed reaction path — Grob fragmentation of a hydroxyketone-diaziridine adduct (163) — is in accord with these observations (B-67MI50800). 

If activity increases dramatically as pH is increased, catalysis may depend on a deprotonated group that may normally act as a general base, accepting a proton from the substrate or a water molecule, for example (a). Protonation of this group at lower pH prevents it from accepting another proton (from the substrate or water, for example). 

The use of the amide ions in these reactions leads sometimes to unexpected side reactions, since besides addition amide ions can also act as a deprotonation agent. An illustrating example is the formation of... 

Acetylene and terminal alkynes are CH-acidic compounds the proton at the carbon-carbon triple bond can be abstracted by a suitable base. Such a deprotonation is the initial step of the Glaser reaction as well as the Eglinton... 

When lithiated, the ring strain of the three-membered heterocycle remains important, and this strain, combined with a weakening of the a-C-O bond, due to its greater polarization, make metalated epoxides highly electrophilic species [2], They react with strong nucleophiles (often the base that was used to perform the a-deprotonation) to give olefins following the elimination of M2O (Scheme 5.2, Path B), a process often referred to as reductive alkylation . 

On the other hand, syn-carboxylic acids are obtained from a deprotonation of the /5-silyl ester, giving the (E)-enolate, followed by reaction with different aldehydes and subsequent hydrogenolysis. No diastereomers of the aldol product are detected720. 

Iron-acyl enolates such as 1, 2, and 3 react readily with electrophiles such as alkyl halides and carbonyl compounds (see Houben-Weyl, Vol. 13/9a p418). The reactions of these enolatc species with alkyl halides and similar electrophiles are discussed in Section D.1.1.1.3.4.1.3. To date, only the simple enolates prepared by a-deprotonation of acetyl and propanoyl complexes have been reacted with ketones or aldehydes. 

With ethylenediamine, high oxidation states become a possibility (Figure 1.57), sometimes involving a deprotonated ligand (see also section 1.12.1) [148],... 

The basic principle of all diazotizations of aromatic amines with a hydroxy- or a sulfonamido group in the 4-position relative to the amino group involves a deprotonation of the OH or NH group, respectively, after diazotization of the amino group. There is also a case of a deprotonation of a CH group in the 4-position of an aniline derivative, namely in the diazotization of 4-aminophenylmalononitrile (2.41) which, by the sequence of steps shown in Scheme 2-23, yields 3-diazo-6-dicyanomethylene-1,4-cyclohexadienone (2.42), as found by Hartzler (1964). This product can also be represented by a zwitterionic carbanion-diazonium mesomeric structure. 

The first complexes of a-keto ylides and group 5 early transition metals have only recently been obtained by reaction of Nb(III) derivatives [[NbCl3(dme) (R C=CR")] with 25 (R = thiazolyl) (Scheme 16). The chelation of the ylide occurs through an N,0-coordination to the metal center and in presence of MeLi a deprotonation of a phenyl ring takes place with the loss of alkyne, leading to the formation of a new orfho-metallated binuclear compound 32. The two ylides involved in the complexation behave as tridentate anionic ligands and are mutually in a trans disposition in order to minimize the steric hindrance [71,72]. Another binuclear niobium complex 33 has been obtained from 25 (R = Me, Ph) with this time an 0-coordinated a-keto ylide [68]. 

The kinetic isotope effect of the protonation h/ d = 3.9 suggests that an in-nitrogen atom is protonated directly rather than conformational changes exposing the lone pair of a nitrogen atom to the outside prior to protonation. It is assumed that a protonated nitrogen does not invert. Inversion is only possible by a deprotonation-inversion-reprotonation sequence (Kjaer etal., 1979). 

Reaction of trietylenetetraamine (trien) with H [AuCU] at low pH leads to the water soluble dinuclear complex [Au2(trien-H)Cl3]Cl2, which features a deprotonated amino nitrogen bridging the two gold centers (Figure 2.10) [69]. 

Methyl-3-formylpyrazole 4-phenylthiosemicarbazone, 45, also coordinates as a deprotonated NNS ligand to form spin-paired cobalt(III) complexes [200]. Values of Dq and B are 2500 and 550 cm , respectively, indicating less covalency than the complexes of 40. Analogous complexes have been isolated with the related 41 having values of Dq and B of 2460 and 580 cm respectively, for [Co(41-H)2 ] [191]. 

Methyl-3-formylpyrazole A-phenylthiosemicarbazone, 45, coordinates as a deprotonated NNS tridentate ligand to form the diamagnetic, spin-paired [Ni(45-H)NCS] complex [200]. However, the complexes formed with other nickel(II) salts have stoichiometry [Ni(45)2]A2, where A = Cl, Br, NO3, CIO4, and BF4. These octahedral complexes NNS coordinated neutral hgands have Dq values between 1086 and 1150cm" ... 

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