Acid amides, preparation tables

The mechanism of the aminolysis and the electronic effects of substituents at C-2 or C-4 on the kinetics of amide bond formation have been studied. In some cases, ring opening with amines occurs with partial isomerization of the exocyclic double bond. However, with more hindered compounds, such as unsaturated oxazolones derived from ketones, ring opening is stereospecific.Ring opening using diamines has also been described. Selected examples of dehydroamino acid amides prepared by aminolysis of unsaturated 5(4//)-oxazolones are shown in Table 7.40 (Fig. 7.51). 

TABLE XXVn. l-Methyl-l,6-dihydropyrazolo[3,4-c]pyridin-7-ones Prepared by Cyclization of Vicinal 4-(Alkyn- l-yl)pyrazole-5-carboxylic Acid Amides [90IZV2089]. 

Activated NHS esters of carboxylic acids are prepared by reacting the acid with NHS in the presence of DCC (Table 4, Figure 16). A-Hydroxysuccinimide esters are stable when kept under anhydrous and slightly acidic conditions, and they react rapidly with amino groups to form an amide in high yield. 

TABLE 1. Physical Properties of Selected Polyhydroxyalkanoate Derivatives Containing Amide or Sulfonic Acid Components Prepared According to the Current Invention... 

As illustrated by the examples in Table 3.9, resin-bound 4-alkoxybenzylamides often require higher concentrations of TFA and longer reaction times than carboxylic acids esterified to Wang resin. For this reason, the more acid-sensitive di- or (trialkoxy-benzyl)amines [208] are generally preferred as backbone amide linkers. The required resin-bound, secondary benzylamines can readily be prepared by reductive amination of resin-bound benzaldehydes (Section 10.1.4 and Figure 3.17 [209]) or by A-alkyla-tion of primary amines with resin-bound benzyl halides or sulfonates (Section 10.1.1.1). Sufficiently acidic amides can also be A-alkylated by resin-bound benzyl alcohols under Mitsunobu conditions (see, e.g., [210] attachment to Sasrin of Fmoc cycloserine, an O-alkyl hydroxamic acid). 

Various approaches have been used to prepare pyrroles on insoluble supports (Figure 15.1). These include the condensation of a-halo ketones or nitroalkenes with enamines (Hantzsch pyrrole synthesis) and the decarboxylative condensation of N-acyl a-amino acids with alkynes (Table 15.3). The enamines required for the Hanztsch pyrrole synthesis are obtained by treating support-bound acetoacetamides with primary aliphatic amines. Unfortunately, 3-keto amides other than acetoacetamides are not readily accessible this imposes some limitations on the range of substituents that may be incorporated into the products. Pyrroles have also been prepared by the treatment of polystyrene-bound vinylsulfones with isonitriles such as Tosmic [28] and by the reaction of resin-bound sulfonic esters of a-hydroxy ketones with enamines [29]. 

Selected y-hydroxybutyric acid amide derivatives, (I), prepared by Cacciaglia (1) were effective in the treatment of alcoholism and illustrated in Table 1. 

Table 1 y-Hydroxybutyric acid amide derivatives effective in treating alcoholism prepared by Cacciaglia (1)... 

Acid amide-acid halide adducts have been used in synthetic organic chemistry to prepare various types of compounds (see Table 2). 

Table 2 Preparative Applications of Acid Amide-Acid Chloride Adducts...

Prof. Audrieth, with this new lead, decided to expand his program on synthetic sweeteners and to study the relationship between chemical structure and sweetness. Since phosphorus is the next door neighbor to sulfur in the periodic table, I was assigned the project of looking into the synthesis and properties of the organic amides of phosphoric acid. I prepared many such amides of phosphoric acid, including cyclohexylphosphoramide ... 

Reaction was also applied on coupling of aliphatic carboxyUc acids and amines (Table 3.14), and the chiral bis-amides were likewise obtained from diamines without the loss of chirality, suggesting that mechanochemical conditions are apphcable for the synthesis of chiral amides. In addition, several dipeptides 114 were prepared (Scheme 3.31). Racemization was not noticed which is the usual drawback of conventional solution-based procedures (Table 3.15). In dipeptide synthesis 2 equiv. of DMAP were used as the base to deprotonate the unprotected amino acid, and as the activator of EDC HCl and sodium chloride were added as the grinding auxiUary. 

The Pb—N bond is highly reactive. Plumbylamines of the simplest type, BujPb—NEt2, are very susceptible to hydrolysis and are slowly decomposed at 20° C. Therefore they cannot be purified by distillation and should be prepared just before use (Section IV,B). On the other hand, the A -plumbyl-carboxylic acids and sulfonic acid amides are stable towards moisture and can be crystallized (Table XIII). 

To shed further light on the possible opportunity to use NVP, we prepared a poly(AA-co-IA-co-NVP) material with a 7 3 1 ratio, respectively, and ev uated the FS, CS, DTS, fracture toughness (FT), working (WT) and setting (ST) times of the possible new matrix resin. Elemental analysis showed the synthesized copolymer as having 1.34 % N (theory, 1.39 % N). The IR spectra of the copolymer showed bands at 1717 and 1651 cm indicative, respectively, of carboxylic acid and cyclic amide groups (Table 1). The and C NMR spectra, with bands at 8.32 and 12.10-12.25 and 172.0 and 176.0 ppm (Table 1), also supported the copolymer structure(s). An... 

From the list of melting points of derivatives of halo acids given in Table 10 it is evident that for the identification of halo acids, amides, anilides and /7-toluides are suitable / -bromophenacyl esters were prepared only in a few cases. If satisfactory results cannot be obtained by the application of procedures given for the preparation of carboxylic acid derivatives (see p. 249), original literature should be consulted. Identification of aromatic, halo acids is easy because they are well-crystallized solids, and, in addition the preparation of derivatives, for example, p-bromophenacyl esters, causes no difficulty. 

One of the virtues of the Fischer indole synthesis is that it can frequently be used to prepare indoles having functionalized substituents. This versatility extends beyond the range of very stable substituents such as alkoxy and halogens and includes esters, amides and hydroxy substituents. Table 7.3 gives some examples. These include cases of introduction of 3-acetic acid, 3-acetamide, 3-(2-aminoethyl)- and 3-(2-hydroxyethyl)- side-chains, all of which are of special importance in the preparation of biologically active indole derivatives. Entry 11 is an efficient synthesis of the non-steroidal anti-inflammatory drug indomethacin. A noteworthy feature of the reaction is the... 

Amide-Based Sulfonic Acids. The most important amide-based sulfonic acids are the alkenylarnidoalkanesulfoiiic acids. These materials have been extensively described ia the Hterature. A variety of examples are given ia Table 5. Acrylarnidoalkanesulfoiiic acids are typically prepared usiag technology originally disclosed by Lubrizol Corporation ia 1970 (80). The chemistry iavolves an initial reaction of an olefin, which contains at least one aHyhc proton, with an acyl hydrogen sulfate source, to produce a sulfonated intermediate. This intermediate subsequendy reacts with water, acrylonitrile, and sulfuric acid. 

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