Nitriles hydration

Jensen, C.M. and Trogler, W.C. (1986) Kinetics and mechanism of nitrile hydration catalyzed by unhindered hydridobis(phosphine)platinum(ll) complexes. Regioselective hydration of acrylonitrile. J. Am. Chem. Soc., 108, 723-729. 

Hydration reactions of alkynes and nitriles were studied over various zeolites in liquid phase, with ethanol as solvent. Alkyne hydration led to expected carbonyl compounds whereas the formation of the amide and of the corresponding ester was observed during nitrile hydration. 

In the case of nitrile hydration, only few examples are given using zeolite catalysts. Whatever the nature of the zeolite, acidic (ref. 12), basic (ref. 13) or metal-supported (ref. 14), amide formation is always observed. 

We have already shown that Y zeolites are efficient catalysts for alkyne hydration (ref. 15). Such zeolites can also be used for nitrile hydration, but, in this case, the occurence of ester formation in alcoholic medium constitutes a new and interesting result. 

This order of activity is, in this case, different from that observed with alkynes, especially the somewhat unexpected higher activity of mordenite in nitrile hydration. 

Figure 6.9 Metal hydroxides in nitrile hydration (8 and 9) and amide hydrolysis (9 and 10).

The kinetics of nitrile hydration by H4Ru4(n4-0)(n3-0H)(n2-0H)(PCy3)4 (CO)4 has been examined the nitrile-containing tetranuclear cluster 44 was reported to have four times the catalytic activity of its precursor in the hydration of benzonitrile.34... 

The nitrile hydrates employed are selective and stop at the amide stage. However, they display no relevant enantioselectivity. The enantioselectivity in the processes is always introduced by an amidase (see for instance Schemes 6.27 and 6.28) in a second hydrolysis step. Overall the syntheses are, remarkably, often purely catalytic and combine chemical catalysis for reductions with biocatalysis for hydrolyses and the introduction of stereoinformation (Scheme 6.38). 

It has been noted already that reports can be found in the literature, as far back as the 1960s, of modest amounts of amides being formed in the presence of nitrilases [20-22]. This side activity (see Figure 16.7) could not be accounted for by the commonly accepted nitrilase mechanism [21] and was largely neglected until quite recently. It was then shown, for example, that nitrile hydration in the presence of recombrnantly expressed and purified nitrilases from Arahidopsis thali-ana was a major pathway with some nitriles, in particular electron-deficient ones [23-25]. 

We found that nitrile hydration in the presence of PfNLase is Hkewise subject to electronic effects. Hardly any amide was formed from 2-phenylpropionitrile (Id) in the presence of this latter enzyme but the hydration pathway predominated, in contrast, with the electron-deficient 2-chloro-2-phenylacetonitrile (le) the extent... 

With the help of metal catalysis amidation takes place at room temperature under apparently neutral conditions. Manganese dioxide in large quantities, or, even better, manganese dioxide on silica gel, is well suited to this conversion. Even compounds with functional groups labile to manganese dioxide, for example benzylic groups, are suited for the hydration. With pentacarlwnylmanganese bromide, nitrile hydration takes place under PTC conditions. ... 

Regioselective aza-annulation with acrylonitrile met with somewhat limited success. Aza-annulation of 10 with acrylonitrile resulted in the formation of a 75 25 mixture of 11 (eq. I).4 The mixture of 11 was taken on to 12, which was used in the synthesis of optically active 2,2 -bipyridines and 1,10-phenanthrolines. A more selective route to 11a was reported, and this approach started from optically pure (/ )-(+)-pu egone (13, eq. 2).5 In this case, regioselective Michael addition to give 14 was accomplished due to the presence of the isopropylidene moiety of the (/ )-(+)-pulegone. Subsequent rhodium catalyzed deisopropylidenation, nitrile hydration, and cyclization gave lib, which was taken on to (-)-pumiliotoxin C (15). 

Production of acrylamide (Fig. 13) by hydration of acrylonitrile under the action of the intracelluar nitrile hydratase in Rhodococcus rhodochrous (Nitto Chemical Industry Co., Ltd., fed-batch process). The annual production amounts to >30000 tons (see also Table 6). Acrylamide is one of the most important commodity chemicals and is required in large quantities as the pre-polymer of polyacrylamide that is widely used in polymer and floccu-lent applications. The advantages of this hydratase approach in comparison with the classical chemical nitrile hydration are higher product end concentration, quantitative yields, no formation of acrylic acid, no need for copper catalyst, and only five chemical/technical operations instead of seven [73,112,113,171]. An analogous process for nicotinamide is being commercialized by Lonza (see also section 6). 

A close analog, 115, is critical in establishing the stereochemistry of the tetramic acid subunit (119) of streptolydigin [44]. Amination of 115 followed by nitrile hydration of 116... 

Keywords Amide-bond formation Dehydrogenative amidation Hydrolytic amidation Nitrile hydration Rearrangements Ruthenium catalysts... 

Scheme 1 The nitrile hydration and amide hydrolysis reactions...

Additional examples of nitrile hydration reactions catalyzed by homogeneous ruthenium catalysts in organic media are (Scheme 8) (1) The hydration of benzoxazolylacetonitrile by the arene-ruthenium(II) dimer [ RuCl(p-Cl)(r -p-cymene) 2], which led to benzoxazolylacetamide in high yield [58], and (2) the asymmetric hydration of a-benzyl-a-methylmalononitrile by the chiral catalysts 13 [59]. Modest yields and low enantiomeric excesses were obtained in this latter reaction. However, we must note that this is the first example of a nonenzymatic asymmetric nitrile hydration process reported to date in the literature. 

Scheme 8 Some nitrile hydrations catalyzed by ruthenium(II) complexes...

Despite the great advances reached in the catalytic nitrile hydration, reactions to form A-substituted amides from nitriles have few precedents. In this context, although little studied, the catalytic amidatimi of nitriles with amines in the presence of water has emerged in recent years as a useful tool for the straightforward generation of secondary and tertiary amides (Scheme 10) [71-77]. 

Garcia-Alvarez R, Crochet P, Cadiemo V (2013) Metal-catalyzed amide bond forming reactions in an environmentally friendly aqueous medium Nitrile hydrations and beyond. Green Chem 15 46... 

Ahmed TJ, Knapp SMM, Tyler DR (2011) Frontiers in catalytic nitrile hydration nitrile and cyanohydrin hydration catalyzed by homogeneous organometallic complexes. Coord Chem Rev 255 949... 

Garcia-Alvarez R, Diez J, Crochet P, Cadiemo V (2010) Arene-mthemijm(n) ctunplexes containing amino-phosphine ligands as catalysts for nitrile hydration reactions. Organometallics 29 3955... 

Lee WC, Frost BJ (2012) Aqueous and biphasic nitrile hydration catalyzed by a recyclable Ru(II) complex under atmospheric conditions. Green Chem 14 62... 

Frost BJ, Lee WC (2013) Nitrile hydration catalyzed by recyclable mthenium ctnnplexes. US Pat Appl US2013/0,096,344... 

Lee WC, Sears JM, Enow RA, Eads K, Krogstad DA, Frost BJ (2013) Hemilabile P-aminophosphine ligands derived from l,3,5-triaza-7-phosphaadamantane Applicatitnt in aqueous mthenium catalyzed nitrile hydration. Inorg Chem 52 1737... 

Garcia-Alvarez R, Zablocka M, Crochet P, Duhayon C, Majoral JP, Cadiemo V (2013) Thiazolyl-phosphine hydrochloride salts effective auxiliary ligands ftn mthenium-catalyzed nitrile hydration reactions and related amide bond forming processes in watea-. Green Chem 15 2447 ... 

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