Nitrile From unsaturated amide

Phenyl-l,3,4-oxathiazol-2-one (370), prepared from primary amides and tri-chloromethanesulfenyl chloride, undergoes a ready thermal elimination of carbon dioxide with the formation of the nitrile sulfide ylide (371). This can be trapped by a wide variety of unsaturated dipolarophiles, and with an alkyne provides a ready route to isothiazoles (372) (see Chapter 4.17). Applications to 1,2,4-thiadiazole synthesis are described in Chapter 4.25. Thermolysis of l,3,4-oxadiazolin-5-ones (500 C/10 mmHg) results in the loss of CO2 and generation of the corresponding nitrilimine (78JOC2037). 

Addition of diazoalkanes to a, -unsaturated amides and nitriles, although less frequently exploited than additions to esters, proceeds in a similar manner. Hence, the addition of diazomethane to 2-methylpropenenitrile (a-methylacrylonitrile) followed by thermal deazetization gave a good yield of 1-methylcyclopropanecarbonitrile (Houben-Weyl, Vol. 4/3, p 48). Similar problems with alkene formation are encountered to those noted in the ester series for example, in the thermolysis of 3,3-dicyano-4-isopropyl-4,5-dihydro-3/f-pyrazole 21, prepared from 20 by the addition of diazomethane. In this case, however, not only does the addition of copper(II) chloride accelerate the elimination of nitrogen, but it also reverses the product ratio in favor of the cyclopropane 23. " ... 

So far we have shown you conjugate additions mainly of a,P-unsaturated aldehydes and unsaturated a,P-ketones. You won t be at all surprised to learn, however, that unsaturated acids, esters, amides, and nitriles—in fact all carboxylic acid derivatives—can also take part in conjugate addition reactions. Two examples, an amide and an ester, are shown on the right below. But notice how the selectivity of these reactions depends on the structure of the unsaturated compound compare the way butyllithium adds to this a,P-unsaturated aldehyde and a,P-unsaturated amide. Both additions are irreversible, and BuLi attacks the reactive carbonyl group of the aldehyde, but prefers conjugate addition to the less reactive amide. Similarly, ammonia reacts with this acyl chloride to give an amide product that derives from direct... 

The highly stereoselective synthesis of ( )-a,P-unsaturated amides bearing (5)-a-methylbenzylamine has been achieved from readily available 2-phosphona-mides via Horner-Wadsworth-Emmons (H-W-E) reaction. " A broad range of substituted dihydropyrimidines (222) and thiazolines can be efficiently prepared using a four-component reaction involving phosphonates, nitriles, aldehydes and... 

Kumar and Das (2013) observed that solid supported ruthenium can be used as a heterogeneous catalyst for the reduction of aromatic, a,p-unsaturated and aliphatic nitriles to primary amides at 130-140°C for 0.5-2 h in microwave. The catalyst was found to be very stable under moisture and microwave irradiation, easily separable from the reaction mixture and recyclable up to ten times without any loss of catalytic activity. 

Aziridines can add to carbon—carbon multiple bonds. Elevated temperature and alkali metal catalysis are required in the case of nonpolarized double bonds (193—195). On the other hand, the addition of aziridines onto the conjugated polarized double or triple bonds of a,p-unsaturated nitriles (196—199), ketones (197,200), esters (201—205), amides (197), sulfones (206—209), or quinones (210—212) in a Michael addition-type reaction frequendy proceeds even at room temperature without a catalyst. The adducts obtained from the reaction of aziridines with a,p-unsaturated ketones, eg, 4-aziridinyl-2-butanone [503-12-8] from 3-buten-2-one, can be converted to 1,3-substituted pyrrolidines by subsequent ring opening with acyl chlorides and alkaline cyclization (213). 

A large part of the usefulness of the Michael reaction in organic synthesis derives from the fact that almost any activated alkene can serve as an acceptor7—a, 3-unsaturated ketones, esters, aldehydes, amides, acids, lactones, nitriles, sulfoxides, sulfones, nitro compounds, phosphonates, phosphoranes, quinones,... 

Carboxylic amides. Gilman has extended the procedure of Corey et at. (2, 261) for oxidation of allylic alcohols to carboxylic esters to the preparation of carboxylic amides. Thus oxidation of aromatic and a,/ -unsaturated aldehydes with Mn02 in the presence of sodium cyanide and an amine gives the corresponding carboxylic amides in high yield. In the absence of sodium cyanide, high yields of nitriles are formed from aldehydes, ammonia, and manganese dioxide. 

Ylides can cyclopropanate unsaturated systems which are susceptible to Michael additions, i.e. a,jS-unsaturated ketones, esters, amides, nitriles, sulfones, sulfonamides, and nitro compounds. Enhancement of electron withdrawal from the carbon-carbon double bond facilitates the reaction. The reaction is non-stereospecific. The intermediacy of zwitterions has generally been accepted, and hence the stereochemistry of the product may be predictable on the basis of the stepwise mechanism. Namely, the Michael addition of the ylide will occur predominantly from the less hindered side of the double bond in a given molecule and the subsequent cyclization will take place in the conformation which minimizes the non-bonded repulsions. 

From a historical perspective, the a-(dialkylamino)nitrile anions were the first acyl anion equivalents to undergo systematic investigation. More recent studies indicate that anions of a-(dialkylamino)nitriles derived from aliphatic, aromatic or heteroaromatic aldehydes intercept an array of electrophiles including alkyl halides, alkyl sulfonates, epoxides, aldehydes, ketones, acyl chlorides, chloroformates, unsaturated ketones, unsaturated esters and unsaturated nitriles. Aminonitriles are readily prepared and their anions are formed with a variety of bases such as sodium methoxide, KOH in alcohol, NaH, LDA, PhLi, sodium amide, 70% NaOH and potassium amide. Regeneration of the carbonyl group can be achieved... 

The compounds indicated in Table 13.3.2 corresponding to some of the peaks shown in Figure 13.3.3 belong to compounds resulting from the cleavage of various bonds in the polymer besides the peptide bond C(0)-NH, including C-N, C-C(O) and C-C bonds. The breaking of the C-N bond leads to the formation of an amide and an unsaturated hydrocarbon end. Further elimination of water leads to the formation of nitriles. These types of reactions are shown below ... 

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