Amide-forming reactions

Although Lehn and his coworkers prepared a large number of cryptands and derived complexes over the years, the synthetic approach to these compounds remained essentially similar for most of them. Details are presented for a number of such compounds in ref. 26. The essential features of these syntheses were use of amide-forming reactions in the absence of templating ions with reliance on a high dilution step to form the second ring. An alternative approach for the synthesis of cryptands was developed by Dye and his coworkers. Their approach involved the use of a flow synthesis to replace the high dilution step. 

The chemistry of acid anhydrides is similar to that of acid chlorides. Although anhydrides react more slowly than acid chlorides, the kinds of reactions the two groups undergo are the same. Thus, acid anhydrides react with water to form acids, with alcohols to form esters, with amines to form amides, and with UAIH4 to form primary alcohols. Only the ester and amide forming reactions are much used, however. 

Nitrosamine formation is not the only conceivable fragmentation mechanism for compounds of structure I. By analogy to the nitrosative dealkylation reactions discussed above, one might predict that such compounds could also undergo cis elimination of nitroxyl in amide-forming reactions. Such a transformation has possibly been observed (14). During an attempt to synthesize the nitrosamino aldehyde VIII from immonium ion IX, Hecht coworkers were able to isolate only 5-10% of the desired product. The major product proved to be N-methyl-2-pyrrolidone, as shown in Fig. 10. We interpret this as evidence that an intermediate such as li can fragment not only by the Fig. 1... 

Although the intramolecular aminocarbonylation described above is an extension of the standard amide-forming reaction, a different type of intramolecular aminocarbonylation has been studied, wherein the amine moiety adds across the olefin moiety activated by a Pd catalyst to generate /3-aminoalkyl-Pd species, followed by CO insertion and alcoholysis, forming a lactone or an ester. ... 

In addition to moving the sulfonyl chloride earlier in the synthesis, the commercial route also uses an acyl imidazole to form a key amide bond (13.77 — 13.79) instead of an acid chloride (13.67 — 13.70, Scheme 13.12). Carbonyldiimidazole (13.76) is an expensive reagent, but the use of acyl imidazole 13.77 gives many advantages. The yields of the amide-forming reaction are higher, and solvent requirements are greatly simplified. The overall... 

Explain the following amide-forming reactions using arrow pushing. Specify the structures of A, B, and C and show all relevant mechanistic steps. 

This class of amides has been made enantio-selectively - albeit in low yield and low ee -by an ortholithiation reaction (Scheme 10). More successful is Uemura s demonstration [19] that the arene-chromium tricarbonyl complex chemistry that works with atroposelectivc biaryl couplings is also successful with atropose-lective amide-forming reactions (Scheme 11). 

Funclionality is dclined only for a given reaction. A glycol, HOROH, has a functionality of 2 in esterification or ether-forming reactions, but its functionality is zero in amide-forming reactions. The same is true of 1,3-butadiene. 

This is not surprising, since amide-forming reactions between amines and (activated) carboxylic acids proceed readily, and many optically active carboxylic acids are readily available. Furthermore, the diastereomeric amides produced are often well-resolved by LC or GLC. A variety of leaving groups (X in Eq, 1) have been used in the acylation reactitm, for example, chloride, imidazole, carboxylate, etc. 

Amides don t usually form well from amines and carboxylic acids (see p. 207 of the textbook). But in this case the reaction is intramolecular, and with a fair degree of heating (the product is known trivially as pyroglutamic acid ) the amide-forming reaction is all right. 

A diamine like hexamethylenediamine has a functionality of 2 in amide-forming reactions such as that shown in Equation 1.2. However, in esterification reactions a diamine has a functionality of zero. Butadiene has the following structure ... 

Figure 12.18. Examples of alcohols and phenols that are used to block the carboxyhc acid portion of amino acids so that amide-forming reactions can occur at the nitrogen. Simple alcohols that include methanol (CH3OH), ethanol (CH3CH2OH), and fert-butyl alcohol (f-butanol, (CH3)3COH) are omitted intentionally. Methyl esters or many amino acids, in particular, are often commercially available and are frequently used as received.

Figure 12.19. Examples of chloroformates and carbonates that are nsed to block the amine portion of amino acids so that amide-forming reactions can occnr at the carboxylic add. PhthaUc anhydride (Scheme 10.2) is omitted intentionally since an amino acid prepared by the Gabriel synthesis using phthalimide wonld retain the phthalimide protecting group subsequently. PhthaUc anhydride is not generally used as a protecting group with preformed amino acids.

A condensation polymerization is one in which two or more molecules combine with the loss of a small molecule, typically water or ammonia. We can anticipate that reactions such as alcohols combining with carboxylic acids to make esters with the loss of water and comparable amide-forming reactions will be important. The reactive groups, which weTl call A and B, can either be in differing, necessarily difunctional monomers, or they can be part of a single, difunctional AB molecule. 

Amide-forming reactions applied in an intramolecular way will work... 

In the past few years, microwave-assisted chemical synthesis has been used extensively as an environmental-friendly, rapid and high-yielding technique. Nomura et al. (2005) reported a base-catalysed decarboxylation and amide-forming reaction of substituted cinnamic acids via microwave heating. 

Construct an explanation for why the following amide-forming reaction analogous to the esterforming reaetion shown in S nthetie Transformation 24.2 does NOT produee the desired product. Hint. Consider what speeies in solution is most likely to reaet with the aeid eatalvst.)... 

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