Acetic acid, protonated condensations

A mild procedure which does not involve strong adds, has to be used in the synthesis of pure isomers of unsymmetrically substituted porphyrins from dipyrromethanes. The best procedure having been applied, e.g. in unequivocal syntheses of uroporphyrins II, III, and IV (see p. 251f.), is the condensation of 5,5 -diformyldipyrromethanes with 5,5 -unsubstituted dipyrromethanes in a very dilute solution of hydriodic add in acetic acid (A.H. Jackson, 1973). The electron-withdrawing formyl groups disfavor protonation of the pyrrole and therefore isomerization. The porphodimethene that is formed during short reaction times isomerizes only very slowly, since the pyrrole units are part of a dipyrromethene chromophore (see below). Furthermore, it can be oxidized immediately after its synthesis to give stable porphyrins. 

A rather more complex amino alcohol side chain is accessible by a variation of the Mannich reaction. Taking advantage of the acidic proton in acetylenes, propargyl acetate (62) is condensed with formaldehyde and dimethylamine to give the acetylated amino... 

Condensation products of 4(5//)-oxazolonium salts with aldehydes and orthoesters are the subject of a series of papers by Kosulina and co-workers Reaction of 2-methyl-4(5//)-oxazolonium perchlorates 44 with an ortho ester gives rise to an enol ether, which reacts with furanamides to afford the frani-eneamides 45 (Scheme 6.14). " Using electron deficient anilines in a three component condensation affords either 46 or 47 in 64-80% and 78-84% yields, respectively, depending on whether the reaction is performed in acetic acid or acetic anhydride. Electron-rich anilines are unreactive since they are merely protonated by the perchloric acid present in the reaction medium. ... 

A similar type of acid-catalyzed condensation of aldehydes with 4-methylene-2-oxetanone (diketene), giving 4-oxo-6-methyl-l,3-dioxins, has been patented (73GEP2149650). However, other work has established that <5-hydroxy-/3-keto acids or unsaturated keto acids are formed as the principal products (equation 24) (78CPB3877, 78CL409). The latter reaction probably involves electrophilic attack of the protonated aldehyde on the nucleophilic exocyclic methylene carbon atom of the diketone. A closely related reaction of acetals with diketene, catalyzed by titanium tetrachloride, gives the corresponding <5-alkoxy-/3-keto esters (74CL1189). 

Trifluoroacetylacetone (152) reacts by a condensation reaction 30 with aromatic aldehydes218 in the presence of piperidine and acetic acid, in benzene. Triethylamine does not catalyse this reaction. Probably, the product 153 is obtained via the carbinolamine (154), which in turn yields the carbonyl group of the aldehyde. Obviously, the tertiary amine cannot displace a proton and the interaction forms a zwitterionic adduct (see 148). 

Finch and Symons,87 on reinvestigation of the absorption of aliphatic alcohols and alkenes in sulfuric acid solution, showed that the condensation products formed with acetic acid (used as solvent for the precursor alcohols and alkenes) were responsible for the spectra and not the simple alkyl cations. Moreover, protonated mesityl oxide was identified as the absorbing species in the system of isobutylene, acetic acid, and sulfuric acid. 

A different approach to alkoxysilane or alkoxysiloxane waterproofing agents for masonry is represented by the use of self-emulsifying Hquid concentrates (88) intended to be diluted into water and appHed within 24—48 h of mixing. These materials owe their ready water-dispersibiUty to incorporation of low levels of amine functionaUty protonated by acetic acid upon drying, the alkoxysilanes hydrolyze and condense, and the acetic acid is lost by volatilization, leaving no residual surfactant behind. 

The imine and iminium functional groupings are, of course, the nitrogen equivalents of carbonyl and O-protonated carbonyl groups, and their reactivity is analogous. The Mannich reaction of pyrrole produces dialkylaminomethyl derivatives, the iminium electrophile being generated in situ from formaldehyde, dialkylamine and acetic acid. There are only a few examples of the reactions of imines themselves with pyrroles the condensation of 1-pyrroline with pyrrole as reactant and solvent is one such example. N-Tosyl-imines react with pyrrole with Cu(OTf>2 as catalyst. ... 

Control of the pH is also of importance for the Mannich-based bispidine synthesis. Formation of an aldol product competes with the Mannich condensation in the basic pH region. It is for this reason that, in some cases, the reaction is sensitive to the order in which the reactants are added to the reaction mixture. It is possible to add the aldehyde and amine components one after another to a solution of the CH-acidic compound, but sometimes the aldol reaction can be disfavored by changing the order. This allows the imminium ion to be formed in advance. The precursors of 45 and 46 have been prepared by this method. In some cases, it has been useful to use a protonated amine component as the acetate salt (e.g., 49 or precursors for 44, 47, and 48), as the chloride salt (e.g., 11) or to carry out the reaction in acetic acid. Aromatic amines (e.g., aniline) give rise to para-substituted aromatic amines if the solution is not approximately neutral. In a very elegant procedure, a condensate of formaldehyde and aniline, which is the trimeric methyleneaniline, was prepared separately, and treated in the Mannich reaction with dimethyl acetonedicarboxylate and formaldehyde to yield the 3,7-diphenylbispidone... 

Acetic acid is known to undergo a vapor-phase ketonization reaction with formation of acetone on Brpnsted acids in general, and on proton-zeolites in particular. On large-pore zeolites in their proton form, the ketonization reaction is followed by acid-catalysed self-condensation amounting to mesitylene, mesityl oxide and phorone as main products [1], the chemistry being essentially identical to that in mineral acids. In H-pentasil zeolites with suitable acid site density, phorone isomerises to isophorone, which is cracked to yield 2,4-xylenol [1]. With propionic acid a similar chemistry occurs, but the formation of phenolics is severely suppressed by transition-state shape-selectivity effects... 

Perchloric acid acetic anhydride Condensation by protonated acetic acid... 

The next stage of the synthesis required reduction of the Cj-Cs double bond with control over stereochemistry at Cs- The tactics ultimately used to accomplish this transformation involved conjugate addition of thiophenoxide to the enone to provide 58 with Cj stereochemistry that was never established. The critical stereochemistry (Cs), however, was clean and presmnably controlled by kinetic protonation of the intermediate enolate. Reduction of the C9 ketone was followed by esterification to provide acetate 59 as a single stereoisomer (C7 stereochemistry still not defined). Reduction of the C7 thiol was followed by excision of the extra carbon in the usual manner to provide aldehyde 60. The final carbons of the seco- dA were introduced via crossed condensation of the enolate derived from a thioester of propionic acid, with aldehyde 60. This reaction provided the proper stereochemistry at C3, but the undesired stereoisomer at C2. The C2 stereochemistry was corrected by kinetic protonation of the enolate derived from 61 with acetic acid. The structure of the resulting seco-zcid derivative (62) was established by X-ray crystallography. 

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