Mechanistic Investigations and Secondary Coordination Sphere Effects in the Hydration of Nitriles with [Ru(η⁶-arene)Cl₂PR₃] Complexes

Abstract

The mechanism of the nitrile-to-amide hydration reaction using [Ru(η 6 -arene)Cl 2 (PR 3 )] complexes as catalysts was investigated (η 6 -arene = C 6 H 6 , p-cymene, C 6 Me 6 ; R = NMe 2 , OMe, OEt, Et, iPr). Experiments showed that the mechanism involves the following general sequence of reactions: substitution of a chloride ligand by the nitrile substrate, intermolecular nucleophilic attack by water to form an amidate intermediate, and dissociation of the resulting amide. The effects of secondary coordination sphere interactions on the rates and yields of the hydration reaction were investigated. Ligands that are capable of acting as hydrogen bond acceptors with the entering water molecule result in faster rates and higher yields than nonhydrogen-bonding ligands. The faster rates are attributable to the H-bonding-facilitated deprotonation of the water as the oxygen of the water bonds to the coordinated nitrile. DFT calculations on the proposed H-bonding intermediates support this interpretation. Most homogeneous catalysts will not hydrate cyanohydrins because of the equilibrium amounts of cyanide that are present in solutions of cyanohydrins; the cyanide poisons the catalyst. Because of its increased catalytic reactivity due to secondary coordination sphere effects, the [Ru(η 6 -arene)Cl 2 (P(NMe 2 ) 3 )] catalyst gives significant yields of cyanohydrin hydration products with glycolonitrile, lactonitrile, acetone cyanohydrin, and mandelonitrile. A Taft plot showed that an increase in the steric bulk of the nitrile results in a decrease in the hydration rate, and a Hammett plot showed that electron-withdrawing groups facilitate nitrile hydration. The decrease in rate as the size of the cyanohydrin increases is likely due to both increased steric bulk and to the addition of electron-donating groups on the nitrile. The [Ru(η 6 -arene)Cl 2 (PR 3 )] catalysts are initially less susceptible to cyanide poisoning than other homogeneous nitrile hydration catalysts because [Ru(η 6 -p-cymene)(CN)(Cl)(P-(NMe 2 ) 3 )] forms in the presence of cyanide. The electron-withdrawing cyanide ligand facilitates nucleophilic attack of water on a coordinated nitrile in this molecule.

Synthetic Applications of the Parkins Nitrile Hydration Catalyst [PtH{(PMe2O)2H}(PMe2OH)]: A Review

“…The poor reactivity observed was ascribed to the low stability of the cyanohydrin substrates, which slowly equilibrate in solution with HCN and the corresponding aldehyde or ketone (Scheme 23), and the irreversible coordination of the cyanide anion to platinum leads to the deactivation of the catalyst. In fact, most of the nitrile hydration catalysts reported to date are poisoned by cyanide and, therefore, with some notable exceptions [84][85][86][87][88][89], are inoperative with this particular class of nitriles. Although with only one example, Parkins and co-workers showed that this limitation can be circumvented, protecting the OH group of the cyanohydrin prior to the hydration reaction [90].…”

Aqueous‐Phase Nitrile Hydration Catalyzed by an In Situ Generated Air‐Stable Ruthenium Catalyst

“…[15,21] In the case of acetonitrile hydration catalyzedb y[ ( h 6 -p-cymene)RuCl 2 (P(NMe 2 ) 3 )],t he reaction rate increased when 1equivalent of CN À was added and decreasedw ith increasing [CN À ]. [21] The effect of cyanideo nt he catalytic activity of RuCl 2 (PTA) 4 and the in situ generated catalyst (RuCl 3 + 6PTA)w as examined. [21] The effect of cyanideo nt he catalytic activity of RuCl 2 (PTA) 4 and the in situ generated catalyst (RuCl 3 + 6PTA)w as examined.…”

“…With water as a reagent, and many of the product amides having modest water solubility,n itrile hydration is well suited towardsa queous-phase catalysis. [9,[13][14][15][16][17][18][19][20][21][22] Our group has been interested in the development of water-soluble phosphine ligandsf or use in catalysis. [1,[12][13][14][15][16][17] Ru II and Ru IV complexes with nitrogen-containing phosphine ligands (for example, [RuCl 2 (h 6 -arene)(P(NMe 2 ) 3 )]) have shown significant activity for nitrile hydration.…”

Ruthenium-Catalyzed Amide-Bond Formation

“…The synthetic utility of complexes [RuCl 2 ( 6 -arene){P(NMe 2 ) 3 }] was further demonstrated in the challenging hydration of cyanohydrins (-hydroxynitriles), substrates usually difficult to hydrate because they degrade to produce cyanide which poisons the catalysts. As shown in Scheme 7, using 5 mol% of the pcymene complex [RuCl 2 ( 6 -p-cymene){P(NMe 2 ) 3 }] (11), and performing the catalytic reactions at room temperature within the pH range 3.5-8.5 to minimize the decomposition of the substrates into the corresponding aldehydes and HCN, glycolonitrile and lactonitrile could be completely transformed into the corresponding -hydroxyamides [48,49]. The H-bond accepting properties of tris(dimethylamino)phosphine were again evoked to explain the excellent catalytic activities observed, a cooperative effect that was supported by DFT calculations (Figure 4) [49].…”

“…As shown in Scheme 7, using 5 mol% of the pcymene complex [RuCl 2 ( 6 -p-cymene){P(NMe 2 ) 3 }] (11), and performing the catalytic reactions at room temperature within the pH range 3.5-8.5 to minimize the decomposition of the substrates into the corresponding aldehydes and HCN, glycolonitrile and lactonitrile could be completely transformed into the corresponding -hydroxyamides [48,49]. The H-bond accepting properties of tris(dimethylamino)phosphine were again evoked to explain the excellent catalytic activities observed, a cooperative effect that was supported by DFT calculations (Figure 4) [49]. Secondary coordination sphere activation of water, via hydrogen bonding with the OH group of the ligand, also explains the outstanding performances of the related phosphiniteruthenium(II) complex [RuCl 2 ( 6 -p-cymene){PMe 2 (OH)}] (12), which was also able to hydrate cyanohydrins [50,51].…”