Metals, activated nitriles

Under neutral conditions Ru(II) complexes catalyze the nucleophilic addition of water to nitriles to yield amides [155], The reaction proceeds via external nucleophilic attack of water to the transition metal-activated nitrile. Under similar conditions <5-ketonitriles are converted into ene-lactams, a reaction that has found elegant application in a short diastereoselective synthesis of (-)-pumiliotoxin C (Sch. 37) [156]. 

At first sight these reactions are simple examples of metal-activated nucleophilic attack upon the nitrile carbon atom. However, the geometry of the co-ordinated chelating ligand is such that the nitrile nitrogen atom is not co-ordinated to the metal ion (4.3 and 4.4) It was initially thought that this provided evidence for a mechanism involving intramolecular attack by co-ordinated water or hydroxide (Fig. 4-10). However, detailed mechanistic studies of the pH dependence of the reaction have demonstrated that the attack is by external non-co-ordinated water (or hydroxide) (Fig. 4-11). 

An important feature of the present reaction is the chemoselective addition of activated nitriles to the CN triple bonds of nitriles in the presence of carbonyl groups, because of the strong coordination ability of nitriles toward metals. The iridium-catalyzed addition of ethyl cyanoacetate to 4-acetylbenzonitrile (30) gives ethyl (Z)-3-(4-acetylphenyl)-3-amino-2-cyano-2-propenoate (31, 59%) chemoselec-tively, while the same reaction promoted by a conventional base such as AcONH4 and NaOH gives ethyl 2-cyano-3-(4-cyanophenyl)-2-butenoate (32) ( Z= 55 45) [20]. 

Murahashi reported the first example of transition metal-catalyzed addition of activated nitriles to aldehydes and ketones, giving a,/3-unsaturated nitriles (Eq. 9.55)... 

Starting from optically active nitriles, Botteghi and co-workers [32] have applied the cobalt-catalyzed reaction for the prepartion of optically active 2-substituted pyridines (eq. (8)). The chiral center is maintained during the alkyne-nitrile co-cyclization reaction. This reaction has recently been extended to the synthesis of bipyridyl compounds having optically active substituents [33] and provides an access to chiral ligands of potential interest in transition metal-catalyzed asymmetric synthesis. 

Asymmetric water-soluble ligands are known for the metal-catalyzed hydrocyanation of achiral alkenes. However, neither Jenck [21] or Davis [22] actually provides any examples of hydrocyanation catalysis in these patents so the performance of these mono- and bisphosphines in aqueous and supported aqueous media cannot be assessed although this may be a promising route for the synthesis of biologically active nitrile intermediates and products. 

Orthoesters and carbonic acid derivatives can be employed in lieu of carbonyl compounds. For example, 2,2-diethoxy-2//-chromene (178) and mediyl cyanoacetate give the 2//-chromene derivative (179 Scheme 31). (Methylthio)alkylideniminium salts (180) react with active methylene compounds under basic conditions (K2CO3 or EtsN) to give the corresponding condensation products (181 Scheme 32) 240 jjjis method is an alternative to the Eschenmoser procedure for synthesizing vinylogous lactams and urethanes. A(-Alkyl and A(-acylpyridinium salts can also serve as electrophiles in the Knoevena-gel condensation with activated methylenes. " Suitably activated nitriles (R CN) such as trichloroacetonitrile or ethyl cyanoformate react with various 1,3-dicarbonyl compounds to afford (182) in the presence of catalytic amounts of metal acetylacetonates [M(acac)n]. In the presence of TiCU non-... 

While the most direct method to form tetrazoles proceeds via concerted (uncatalyzed) [2-1-3] cycloaddition between organic azides and organic nitriles, this cycloaddition is too slow for synthetic purposes (except in the case of activated nitriles). This disadvantage can be avoided if azide salts are used and if the cycloaddition is catalyzed. This variant might be of greater synthetic interest since the range of nitriles is broader and a wide variety of metal-azide complexes can serve as azide donors [188,212-219]. 

TABLE 9.7 Cycloaddition of a Nitrile Oxide with Metal-Activated Ethyl Acetoacetate... 

Even ia 1960 a catalytic route was considered the answer to the pollution problem and the by-product sulfate, but nearly ten years elapsed before a process was developed that could be used commercially. Some of the eadier attempts iacluded hydrolysis of acrylonitrile on a sulfonic acid ion-exchange resia (69). Manganese dioxide showed some catalytic activity (70), and copper ions present ia two different valence states were described as catalyticaHy active (71), but copper metal by itself was not active. A variety of catalysts, such as Umshibara or I Jllmann copper and nickel, were used for the hydrolysis of aromatic nitriles, but aUphatic nitriles did not react usiag these catalysts (72). Beginning ia 1971 a series of patents were issued to The Dow Chemical Company (73) describiag the use of copper metal catalysis. Full-scale production was achieved the same year. A solution of acrylonitrile ia water was passed over a fixed bed of copper catalyst at 85°C, which produced a solution of acrylamide ia water with very high conversions and selectivities to acrylamide. 

Nitriles. Nitriles can be prepared by a number of methods, including ( /) the reaction of alkyl haHdes with alkaH metal cyanides, (2) addition of hydrogen cyanide to a carbon—carbon, carbon—oxygen, or carbon—nitrogen multiple bond, (2) reaction of hydrogen cyanide with a carboxyHc acid over a dehydration catalyst, and (4) ammoxidation of hydrocarbons containing an activated methyl group. For reviews on the preparation of nitriles see references 14 and 15. 

Tin metal also reacts directly with a number of activated organic haUdes, including aHyl bromide, benzyl chloride, chloromethyl methyl ether, and P-halocarboxyhc esters and nitriles giving fair-to-good yields of diorganotin dihaUdes (97,111—114). 

The chemistry of indium metal is the subject of current investigation, especially since the reactions induced by it can be performed in aqueous solution.15 The selective reductions of ethyl 4-nitrobenzoate (entry 1), 2-nitrobenzyl alcohol (entry 2), l-bromo-4-nitrobenzene (entry 3), 4-nitrocinnamyl alcohol (entry 4), 4-nitrobenzonitrile (entry 5), 4-nitrobenzamide (entry 6), 4-nitroanisole (entry 7), and 2-nitrofluorenone (entry 8) with indium metal in the presence of ammonium chloride using aqueous ethanol were performed and the corresponding amines were produced in good yield. These results indicate a useful selectivity in the reduction procedure. For example, ester, nitrile, bromo, amide, benzylic ketone, benzylic alcohol, aromatic ether, and unsaturated bonds remained unaffected during this transformation. Many of the previous methods produce a mixture of compounds. Other metals like zinc, tin, and iron usually require acid-catalysts for the activation process, with resultant problems of waste disposal. 

K. Tani and Y. Kataoka, begin their discussion with an overview about the synthesis and isolation of such species. Many of them contain Ru, Os, Rh, Ir, Pd, or Pt and complexes with these metals appear also to be the most active catalysts. Their stoichiometric reactions, as well as the progress made in catalytic hydrations, hydroal-coxylations, and hydrocarboxylations of triple bond systems, i.e. nitriles and alkynes, is reviewed. However, as in catalytic hydroaminations the holy grail", the addition of O-H bonds across non-activated C=C double bonds under mild conditions has not been achieved yet. 

As noted in Section 11.2.2, nucleophilic substitution of aromatic halides lacking activating substituents is generally difficult. It has been known for a long time that the nucleophilic substitution of aromatic halides can be catalyzed by the presence of copper metal or copper salts.137 Synthetic procedures based on this observation are used to prepare aryl nitriles by reaction of aryl bromides with Cu(I)CN. The reactions are usually carried out at elevated temperature in DMF or a similar solvent. 

Crabtree s catalyst is an efficient catalyst precursor for the selective hydrogenation of olefin resident within nitrile butadiene rubber (NBR). Its activity is favorably comparable to those of other catalyst systems used for this process. Under the conditions studied the process is essentially first order with respect to [Ir] and hydrogen pressure, implying that the active complex is mononuclear. Nitrile reduces the catalyst activity, by coordination to the metal center. At higher reaction pressures a tendency towards zero order behavior with respect to catalyst concentration was noted. This indicated the likelihood of further complexity in the system which can lead to possible formation of a multinuclear complex that causes loss of catalyst activity. 

A large batch exploded violently (without flame) during vacuum distillation at 90-100°C/20-25 mbar. Since the distilled product contained up to 12% butyroni-trile, it was assumed that the the oxime had undergone the Beckman rearrangement to butyramide and then dehydrated to the nitrile. The release of water into a system at 120°C would generate excessive steam pressure which the process vessel could not withstand. The rearrangement may have been catalysed by metallic impurities [1]. This hypothesis was confirmed in a detailed study, which identified lead oxide and rust as active catalysts for the rearrangement and dehydration reactions [2],... 

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