Amides and nitriles

The synthesis of the acyclic dimethyl, 2-p-tolylsulfinyl acrylamide and its use as a dienophile was reported in 1990 [62]. A rather low reactivity toward cyclopentadiene (long reaction times under catalytic conditions were required to obtain moderate yields) and the lack of diastereoselectivity (a mixture was formed of the four possible adducts in significant amounts) were the most relevant findings from the use of this dienophile. 

The complete 7r-facial selectivity observed for these reactions, which is probably the highest so far reported with acyclic sulfinyl dienophiles, can be rationalized by assuming that conformational equilibrium around the C-S bond was completely restricted as a consequence of an important dipolar repulsion between cyano and sulfinyl groups. It determines that the latter one adopts the s- 

The sulfonyl group has also been incorporated into the vinyl sulfoxide moiety in order to increase both its reactivity and selectivity. Thus, (S)-l-f-butylsul-fonyl-1 -p-tolylsulfonyl ethene 65 was used as a masked chiral ketene equivalent 

The reactions of 1-thioderivatives of 1-trifluormethyl ethylenes have been recently reported [68]. The results obtained from racemic phenylsulfoxide (a mixture of the four possible adducts was isolated) indicate the small influ- 

PROBLEMS Predict the products of each of the following reactions  

We have said before that a carboxylic acid derivative can be prepared from any other carboxylic acid derivative that is more reactive. Let s go back to our reactivity chart to see what this means practically  

Since amides are the least reactive of the carboxylic acid derivatives (shown on the chart above), we can therefore make amides from any carboxylic acid derivatives that are higher on the chart. In other words, we can make amides from acid halides, from anhydrides, or from esters. 

Earlier in this chapter, we saw how to make amides from acid halides or anhydrides  

But now the question is how do we make amides from esters Esters are less reactive than acid halides or anhydrides. So, we have to use some kind of trick to coax the reaction along. We cannot use acid or base (an acid would just protonate the attacking atnine, rendering it useless and a base would cause other side reactions that we will learn in the next chapter). Instead, we use brute force and patience. We just heat the reaction for a long time, and a reaction is observed, which can occur via the following mechanism  

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FS(0)20CH3. Colourless liquid, b.p. 94°C. Functions as a powerful methylating agent, even for amides and nitriles which are not attacked by conventional alkylating agents like dialkyl sulphates. 

The lower members of other homologous series of oxygen compounds— the acids, aldehydes, ketones, anhydrides, ethers and esters—have approximately the same limits of solubility as the alcohols and substitution and branching of the carbon chain has a similar influence. For the amines (primary, secondary and tertiary), the limit of solubility is about C whilst for the amides and nitriles it is about C4. 

Acid chlorides and bromides, allyl halides, a-halo-ketones, esters, amides and nitriles react at 25° within 3 minutes. Vinyl and aryl halides are inert. 

Carboxylic acids and derivatives (including amides and nitriles). 

This chapter concerns the preparation and reactions of acyl chlorides acid anhydrides thioesters esters amides and nitriles These com pounds are generally classified as carboxylic acid derivatives and their nomenclature is based on that of carboxylic acids... 

Esters, amides, and nitriles are not readily hydrolyzed under neutral conditions, but they are hydrolyzed by aqueous acid. 

The influence of other groups in a pyridine or similar ring system is more difficult to assess because no kinetic data are available. The deactivating effect of the bromine atom in the 2-position is greater than that in the 3-position, while 2,6-dibromopyridine is very slow to react with dimethyl sulfate. Esters, amides, and nitriles of nicotinic and isonicotinic acids undergo fairly easy quaternization at about... 

The acids can be esterified or converted to acid chlorides and hence to amides and nitriles [107] Scheme XXIII ... 

Alkali metal amides and Nitriles and ethylene diamines ... 

Alkylation of Aldehydes, Esters, Carboxylic Acids, Amides, and Nitriles... 

Among the compounds capable of forming enolates, the alkylation of ketones has been most widely studied and applied synthetically. Similar reactions of esters, amides, and nitriles have also been developed. Alkylation of aldehyde enolates is not very common. One reason is that aldehydes are rapidly converted to aldol addition products by base. (See Chapter 2 for a discussion of this reaction.) Only when the enolate can be rapidly and quantitatively formed is aldol formation avoided. Success has been reported using potassium amide in liquid ammonia67 and potassium hydride in tetrahydrofuran.68 Alkylation via enamines or enamine anions provides a more general method for alkylation of aldehydes. These reactions are discussed in Section 1.3. 

Scheme 1.6 gives some examples of alkylation of esters, amides, and nitriles. Entries 1 and 2 are representative ester alkylations involving low-temperature... 

Scheme 9.31 Interconversion of primary amide and nitrile groups.

Enantioselective hydrolysis reactions, especially esters, amides and nitriles. 

A number of 4-pyrimidinecarboxylic acids of the general formula (XVI) and their esters, amides and nitriles are claimed to possess cardiovascular, hypotensive, and spasmolytic properties [214]. Other biological activities and medicinal uses of 5-halo-substituted orotic acids, as well as those of uracil-6-sulphonic acid and related compounds, have been discussed in Part I of this review [215]. 

If the reduction has been carried out in ether, the ether layer is separated after the acidification with dilute hydrochloric or sulfuric acid. Sometimes, especially when not very pure lithium aluminum hydride has been used, a gray voluminous emulsion is formed between the organic and aqueous layers. Suction filtration of this emulsion over a fairly large Buchner funnel is often helpful. In other instances, especially in the reductions of amides and nitriles when amines are the products, decomposition with alkalis is in order. With certain amounts of sodium hydroxide of proper concentration a granular by-product - sodium aluminate - may be separated without problems [121],... 

The third group of target molecules comprises chiral carboxylic acid and their derivatives esters, amides and nitriles. Enantiomerically pure esters are prepared in an analogous manner to the enantiomerically pure alcohols discussed earlier [i.e. by esterase- or lipase-catalyzed hydrolysis or (trans)esterification]. However, these reactions are not very interesting in the present context of cascade reactions. Amides can be produced by enantioselective ammoniolysis of esters or even the... 

SECTION 1.8. ALKYLATION OF ALDEHYDES, ESTERS, AMIDES, AND NITRILES... 

The suffixes -oic acid, -al, -amide and -nitrile are used to name acyclic compounds having one or two characteristic groups. Locants are not necessary, as these groups must be at the end of a chain. The suffixes -carboxylic acid, -carbaldehyde, -carboxamide and -carbonitrile are used when more than two groups are attached to chains or one or more groups are attached to cycles. 

The carboxylic acids of triazoles are readily decarboxylated on heating but are otherwise stable. Esters, amides, nitriles, and hydrazides react normally. This is illustrated in Scheme 18 for the amide and nitrile functions (88JMC330). 

Carboxylic acids are prepared hy the hydrolysis of acid chlorides and acid anhydrides, and acid- or hase-catalysed hydrolysis (see Section 5.6.1) of esters, primary amides and nitriles (see Section 5.6.1). 

Monolayers are best formed from water-insoluble molecules. This is expressed well by the title of Gaines s classic book Insoluble Monolayers at Liquid-Gas Interfaces [104]. Carboxylic acids (7-13 in Table 1, for example), sulfates, quaternary ammonium salts, alcohols, amides, and nitriles with carbon chains of 12 or longer meet this requirement well. Similarly, well-behaved monolayers have been formed from naturally occurring phospholipids (14-17 in Table 1, for example), as well as from their synthetic analogs (18,19 in Table 1, for example). More recently, polymerizable surfactants (1-4, 20, 21 in Table 1, for example) [55, 68, 72, 121], preformed polymers [68, 70, 72,122-127], liquid crystalline polymers [128], buckyballs [129, 130], gramicidin [131], and even silica beads [132] have been demonstrated to undergo monolayer formation on aqueous solutions. 

The MoOPH reagent also hydroxylates branched or unbranched ester, amide, and nitrile anions. 7 For unknown reasons, MoOPH hydroxylations often do not give complete conversion of enolates into products, and recovery of 5-15% of the starting carbonyl substrate is to be expected. 

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