Phenyl esters, amides from

Two transformations should be discussed in more detail (1) presence of the amino group in 275 was utilized for the synthesis of the fused isoquinolinium salt 276 bearing the bicyclic heterocycle as an A-substituent <2003JHC1041> (2) selective nucleophilic substitution of 277 with pyrrolidine was reported <2001ZOR604> to yield only substitution on the phenyl substituent without formation of an amide from the ester group 278. 

The aromatic amides have attracted considerable interest from the photochemical point of view. However, anilides are less prone to photochemical rearrangements than the analogous phenyl esters. For this reason, the side reactions involving other parts of the molecule may compete favorably with PFR. Shizuka started the study of anilides in the 1960, and thereafter a number of papers have appeared dealing with the PFR of A -acyl anilines, carbazoles, indoles, and so forth. 

Different solid-phase techniques for the synthesis of C-terminal peptide aldehydes have gained much attention and allowed greater accessibility to such compounds. Solid-phase techniques have been used to synthesize peptide aldehydes from semicarbazones, Weinreb amides, phenyl esters, acetals, and a, 3-unsaturated y-amino acids)47-50,60 63 The examples presented below use unique linkers to enhance the automated efficiency of C-terminal peptide aldehyde synthesis)47 For instance, the reduction of phenyl esters led to the aldehyde as the major product, but also a small amount of alcohol)50 The cleavage of u,p-unsaturated y-amino acids via ozonolysis yielded enantiomeric pure C-terminal peptides)49,61 The semicarbazone from reduction of peptide esters technique laid the initial foundation for solid-phase synthesis. Overall, Weinreb reduction is an ideal choice due to its high yields, optical purity, and its adaptability to a solid-phase platform)47 ... 

The best way to prepare peptide aldehydes from the corresponding N -protected amino acids is by using a handle based on the Weinreb amide.f This commercial handle allows classical solid-phase elongation of peptides using protected Boc or Fmoc amino adds and, at the end of the synthesis, the peptide aldehyde is formed by reduction and concomitant cleavage from the resin with lithium aluminum hydride. Although the 4-hydro-xybenzoic acid handle also allows the preparation of peptide aldehydes by reduction of the resin-bound phenyl ester with lithium tri-tert-butoxyaluminum hydride, a noixture of the aldehyde and the alcohol is always formed. 

Acid treatment of the substituted thioureas resulting from the treatment of esters, amides, or peptides of a-amino acids (10) with isothiocyanates (usually phenyl isothiocyanate) also affords 2-thiohydantoins (11). These reactions furnish the basis of the Edman s method for the stepwise degradation of peptides.3... 

It is clear from the above discussion that each individual base defines its own acidity function. Experience has shown that 0-values for compounds containing the same functional group lie in most cases in a narrow range, possibly within experimental error. There is a recent analysis of the behavior of ketones, which shows, however, a variety of 0-values (see Table 4). The trends in Table 4 are in conformity with these principles since, obviously, an alkyl group has less ability to disperse a positive charge than a cyclopropyl, vinyl or phenyl group. Differences in 0-values between alkyl and phenyl esters or amides are also found (see Table 4), although of smaller... 

The results in Table 4.49 also show that the method is compatible with various functional groups (ketone, ester, amide, unsaturation). However, the presence of a phenyl group on the nitrogen atom seems to prevent the reaction from occurring since, in this particular case, the starting material is entirely recovered. Interest-... 

Figure 5 Relationship between Katrp and structure of alkyl halide initiators, measured with Cu X/fPMA (X=Cl or Br) as catalyst with MeCN as solvent at 22 °C 3° red, 2° blue, 1° black R-Br solid, R-CI open, R bottom-half solid Amide , Phenyl , Ester , Nitrile o. Phenyl-ester 0, Allyl . Reprinted from Tang, W. Kwak, Y. Braunecker, W. etal. J. Am. Chem. Soc. 2008, 130,10702-10713, " with permission from the ACS.

The base serves to abstract a proton from the monomer and generate an aminyl anion, which in turn deactivates its phenyl moiety. This anion reacts preferentially with the phenyl ester group of phenyl-4-nitrobenzoate and the amide group formed has a weaker electron-donating character than the aminyl anion of the activated monomer. The reaction of monomers with each other was thus efficiently prevented so that well-defined aromatic polyamides could be obtained up to 22,000 g/mol molar mass and with a dispersity index of 1.1. 

Scheme 3 ATRP activation rate constants for various initiators with Cu X/PMDETA (where X=Br or Cl) in MeCN at 35°C. 3° initiators are in red 2° blue 1° black with isothiocyanate/ thiocyanate half-filled triangle chloride open symbols bromide filled symbols iodide half-filled square, amide T benzyl A ester nitrile O phenyl ester . Reprinted with permission from Tang and Matyjaszewski [27]...

Fig. 2 Effect of initiator structures on ATRP activation rate constants (fcact) with Cu X/ N,N,N, N, N"-pentamethyldiethylenettiamine (PMDETA) (X = Br or Cl) in MeCN at 35 °C. 3° red 2° blue 1° black isothiocyanate/thiocyanate Irft half-filled chloride open bromide filled iodide bottom half-filled amide inverted filled triangle benzyl filled triangle ester open square nitrile open circle phenyl ester open diamond. Reprinted with permission from American Chemical Society [42]...

As described in U.S. Patent 2,507,631, 80 g of pulverized sodium amide are gradually added, while stirring and cooling, to a solution of 117 g of phenyl-acetonitrile and 113 g of 2-chloropyridine in 400 cc of absolute toluene. The mixture is then slowly heated to 110° to 120°C and maintained at this temperature for 1 hour. Water is added thereto after cooling, the toluene solution is shaken with dilute hydrochloric acid and the hydrochloric acid extracts are made alkaline with concentrated caustic soda solution. A solid mass is separated thereby which is taken up in acetic ester and distilled, a-phenyl-a-pvridyl-(2)-acetonitrile passing over at 150° to 155°C under 0.5 mm pressure. When re-crystallized from ethyl acetate it melts at 88° to 89°C, the yield amounting to 135 g. 

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