Amides and Thioamides

Relatively general routes to amides include the preparation of mixed anhydrides by the addition of a carboxylic acid to an 

Several routes to amides via heterocycles have been reported. 

6-Amino-Y-ketobutyric acid derivatives can be prepared by Friedel-Crafts reaction of benzene, toluene, or furan with the 

2-(bromomethyl)prop-2-enoate, and subsequent hydrolytic removal of 

Amides of acrylic and n-pentenoic acids have been prepared by a 

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Thioamides have been transformed into the corresponding nitriles. Treatment of primary thioamides by tellurium tetrachloride or selenium tetrachloride in combination with triethylamine affords nitriles.66 Treatment of primary amides and thioamides with l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) gives nitriles.67 Reactions of thioamides with metal carboxylates in organic solvents enables the selective preparation of nitriles, imides or amides depending on the substitution pattern of the starting material (Scheme 33).68... 

Investigations of hydrogen bonding of several thioamides have been carried out by calculations and spectroscopy. Characterization, hydrolysis and cyclization of thioamides have been discussed by using the results of calculations and spectroscopy. Comparison of amides and thioamides has been investigated.81 86 Rotation barriers for a series of amides and thioamides have been calculated.87 93... 

Fig. 8 Correlation between the twist angle, t, and the pyramidalization at nitrogen, yN, for anilines (O) and naphthalenes (+), enamines ( ) and amides (A). Data points for amides and thioamides are not shown. Reprinted with permission from Gilli et ul. (1986). Copyright 1986 American Chemical Society.

The points for amides and thioamides are omitted from the plot shown in Fig. 8. They fall almost exclusively in the region (boxed in the figure) of small deformations from planarity (t, 15°), as expected in view of the... 

General procedure for alkylation of amidic and thioamidic heterocyclic systems... 

In isolated examples, reactions of specific amides and thioamides with dihalo-carbenes can take unusual pathways. Thus, for example, using procedure 7.1.1, A,A-dialkylamides are converted into a-chloromethylene derivatives of the amides [48]. The initial step in which the carbene attacks the carbonyl oxygen atom is the same as for the dehydration of the A-alkyl amides, but subsequent steps, for which there is evidence from 2H/ H labelling experiments, lead to the formation of an enamine and further reaction with the carbene (Scheme 7.34). 

Thieno[4,3,2-/g]benz[l]azocine 187 is produced in high yield (79MI397) from oxime 186 by Beckman rearrangement in PPA. Transformations of amide and thioamide groups of azocines 187 and 188, lead to derivatives 189-192, as shown in Scheme 52. 

Typical examples are barriers to rotation in dimethylamino heterocycles and barriers to rotation in heterocyclic amides and thioamides. 

Particularly interesting are the barriers to rotation of the dimethylamino group in heteroaromatic amides and thioamides which can be used as a sensor for the following effects (Scheme 73). 

The synthetic utility of azolides is exemplified by many examples of their use in the synthesis of carboxylic acids, esters, and thioesters, amides and thioamides, aldehydes and ketones, and phosphorylated imidazoles and benzimidazoles. 

Substituted phenols Chlorophenoxy compounds Substituted acetic and propionic acids Amides and thioamides Substituted ureas Carbamates and dithiocarbamates Symmetrical triazines Benzoic acid derivatives Miscellaneous herbicides... 

The amides and thioamides have a low order of solubility and a somewhat greater vapor pressure than most other herbicides. They do not appear to be strongly fixed to soils having high organic matter and generally break down within a year to innocuous compounds. 

Indications. A brown-orange colour is produced quickly by aliphatic amides and thioamides. The presence of an aromatic ring slows the reaction and the nearer the amide group is to the ring, the more the reaction is inhibited. Substituents in the ring may cause a weak reaction. 

A very fast reaction occurs between dialkylzinc compounds and the more acidic amide and thioamide derivatives of the... 

Hydrogen and carbon monoxide were lost from the latter to form the Fe" complexes (XCIV x=0). The appearance of an absorption assigned to indicated the formation of an unstable Fe—H intermediate. Carbonyla-tion of (XCIV X = 0) gave the red cis complex (XCIV x = 2) 344). Noncoordinate irnine groups were postulated for the product (XCV R =/)-MeOC6H4) from the reaction of Fe2(CO)9 and p-methoxythio-benzamide, which contrasts with the normal reaction of iron carbonyls with primary amides and thioamides, w hich proceed to nitriles 16). 

In a few cases, single-bond rotation is so slowed that cis and trans isomers can be isolated even where no double bond exists (see also p. 230). One example is N-methyl-A -benzylthiomesitylide (69 and 70), the isomers of which are stable in the crystalline state but interconvert with a half-life of 25 h in CDCI3 at 50°C. This type of isomerism is rare it is found chiefly in certain amides and thioamides, because resonance gives the single bond some double-bond character and slows rota-tion. (For other examples of restricted rotation about single bonds, see pp. 230-233). 

The amides and thioamides obtained by the Willgerodt-Kindler reaction are, sometimes without isolation, converted into acids by refluxing with 15-20% sodium or potassium hydroxide or converted into esters by refluxing for 3 h with alcohols in the presence of gaseous hydrogen chloride [501]. 

Phosgene, as well as the easier to handle diphosgene (chloroformic acid trichloromethyl ester) or triphosgene (carbonic acid bis(trichloromethyl) ester) transform primary, secondary and tertiary amides and thioamides to chloromethyleneiminium chlorides (25 equation 15), whereby the reaction with thioamides is of broader scope and proceeds with fewer side reactions. The amide chlorides derived from primary and secondary amides can lose HCl, giving nitriles or imidoyl halides, respectively. /V-Sub-stituted formamides can be converted to isonitriles via amide halides. ... 

Primary and secondary amides and thioamides react with alkyl chlorofoimates with loss of CO2 or COS, forming iminium chlorides (82 equation 52). In some cases this method is complementary to the Pinner imido ester hydrochloride synthesis. The iminium salt (83 Scheme 6) formed by action of ethyl chloroformate on DMF is labile and decomposes rapidly to ethyl chloride. If the reaction is performed in the presence of NaBp4, the iminium salt (85) is isolable. Aryl chlorofoimates react in the same fashion with DMF or DMA, but in these cases the aryloxymethyleneiminium compounds are fairly stable, so this reaction is an important method for the preparation of compounds of this type. - Succinic acid monoamides, phthalic acid monoamides and related compounds are cyclized to iminium salts (86 equation 53) by treatment with acetic anhydride and HC104. ° With the aid of trifluoromethanesulfonic anhydride lactams and amides can be converted to dication ether salts (87) and (88 Scheme 7).22i.222... 

Diels-Alder reactions. C2-Symn dienophiles for asymmetric Diels-Ald Lewis acid catalyst(s) the dienophiles Aldol condensation. The reaciK ketene silyl acetals is sy -selectivc m tuted amides and thioamides behave t (i-PrO)3TiCl is used as catalyst. ... 

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