Hydrocyanation step

Pentenenitnles are produced as intermediates and by-products in DuPont s adiponitrile process. 3-Pentenenitrile [4635-87-4] is the principal product isolated from the isomerisation of 2-methyl-3-butenenitrile (see eq. 4). It is entirely used to make adiponitrile. i7j -2-Pentenenitrile [25899-50-7] is a by-product isolated from the second hydrocyanation step. Some physical properties are Hsted in Table 13. 

Hydrocyanation of butadiene is more complicated than that of ethene it requires two hydrocyanation steps and several isomers can be observed. The isomers obtained in the first step of the HCN addition to butadiene are shown in Figure 11.3. The addition first leads to compounds 1 and 2, in a 1 2 ratio, but they equilibrate to a favourable 1 9 ratio via the retro-reaction. The retro reaction involves a C-C bond breaking reaction, which is rare, but in this case the intermediate is a Tt-allyl species and a stable, anionic cyanide group. Electron-rich nickel species (Ni-dippe) can cleave aromatic nitrile C-C bonds... 

Figure 3.34 a Formation of the various products in the second hydrocyanation step, co-catalyzed by Lewis acids (LA) b bulky Lewis acids such as BPh3 shift the linear/branched product equilibrium toward the desired linear product. 

The hydrocyanation of alkenes [1] has great potential in catalytic carbon-carbon bond-formation because the nitriles obtained can be converted into a variety of products [2]. Although the cyanation of aryl halides [3] and carbon-hetero double bonds (aldehydes, ketones, and imines) [4] is well studied, the hydrocyanation of alkenes has mainly focused on the DuPont adiponitrile process [5]. Adiponitrile is produced from butadiene in a three-step process via hydrocyanation, isomerization, and a second hydrocyanation step, as displayed in Figure 1. This process was developed in the 1970s with a monodentate phosphite-based zerovalent nickel catalyst [6],... 

Copper catalysis presents some definite advantages over nickcl(O) complexes, since it is not verysensitive to the presenceof small amounts of water or oxygen, but the second hydrocyanation step cannot be conveniently performed with these catalysts and, thus, remains an unsolved problem. 

There are three commercial routes to ADN in use. The first method, direct hydrocyanation of 1,3-butadiene [106-99-0] has replaced an older process, cyanation via reaction of sodium cyanide with 1,4-dichlorobutane [110-56-5] owing to the lower cost and fewer waste products of the new process. During the initial steps of the direct hydrocyanation process, a mixture of two isomers is generated, but the branched isomer is readily converted to the linear 3-pentenenitrile [4635-87-4]. 

There is a discrepancy between the cyanide criteria for both aquatic and drinking water standards and the current analytical technology. The criteria are stated for free cyanide (which Includes hydrocyanic acid and the cyanide ion), but the EPA approved analytical methodology for total cyanide measures the free and combined forms (11). This test probably overestimates the potential toxicity. An alternative method (cyanides amenable to chlorination) measures those cyanide complexes which are readily dissociated, but does not measure the iron cyanide complexes which dissociate in sunlight. This method probably tends to underestimate the potential toxicity. Other methods have been proposed, but similar problems exist (12). The Department of Ecology used the EPA-approved APHA procedure which includes a distillation step for the quantification of total cyanide (13,14). A modification of the procedure which omits the distillation step was used for estimation of free cyanide. Later in the study, the Company used a microdiffusion method for free cyanide (15). 

Some companies are successfully integrating chemo- and biocatalytic transformations in multi-step syntheses. An elegant example is the Lonza nicotinamide process mentioned earlier (.see Fig. 2.34). The raw material, 2-methylpentane-1,5-diamine, is produced by hydrogenation of 2-methylglutaronitrile, a byproduct of the manufacture of nylon-6,6 intermediates by hydrocyanation of butadiene. The process involves a zeolite-catalysed cyciization in the vapour phase, followed by palladium-catalysed dehydrogenation, vapour-pha.se ammoxidation with NH3/O2 over an oxide catalyst, and, finally, enzymatic hydrolysis of a nitrile to an amide. 

The one-step condensation to convert 2-butanone, ethyl cyano-acetate, and hydrocyanic acid to ethyl 2,3-dicyano-3-methyl-pentanoate is a modification of the procedure described by Smith and Horowitz 6 in which pyridine acetate was employed as the catalyst. Higson and Thorp 6 employed a two-step procedure in which butanone was converted to its cyanohydrin, which in turn was condensed with ethyl cyanoacetate. 

The industrial use of 1,3-dienes and of their electrophilic reactions has strongly stimulated the field in recent years. Because of the low cost of butadiene, abundantly available from the naphtha cracking process, very large scale applications in the synthesis of polymers, solvents and fine chemicals have been developed, leading to many basic raw materials of the modem chemical industry. For example, the primary steps in the syntheses of acrylonitrile and adiponitrile have been the electrophilic addition of hydrocyanic acid to butadiene24. Chlorination of butadiene was the basis of chloroprene synthesis25. 

Isomerisation is also an important step in the DuPont process for making adiponitrile (Chapter 11) in which internal pentenenitriles must be converted to the terminal alkene. The catalyst is the same as that used for the hydrocyanation reaction, namely nickel(II) hydrides containing phosphite ligands. 

First we will describe the hydrocyanation of ethene as a model substrate. The catalyst precursor is a nickel(O) tetrakis(phosphite) complex which is protonated to form a nickel(II) hydride. Actually, this is an oxidative addition of HCN to nickel zero. In Figure 11.1 the hydrocyanation mechanism in a simplified form is given the basic steps are the same as for butadiene, the actual substrate, but the complications due to isomer formation are lacking. 

By analogy with the synthesis of a-hydroxy acids one can envisage a one-pot synthesis of a-hydroxy amides from aldehydes via hydrocyanation and in situ NHase-catalyzed hydrolysis to the amide. Since enantioselective NHases are very rare, the enantioselectivity should be derived from HnL-catalyzed hydrocyanation. The second step has been described for the Rhodococcus erythropolis NHase-catalyzed hydration of (R)-mandelonitrile to give the (R)-amide with retention of enantiopurity [43]. 

For some years acetone has been converted to ketene (CH2 CO) by high temperature decomposition. The ketene is reacted with acetic acid to give acetic anhydride. Since the mid-1930 s acetone has also been one of the basic raw materials for methacrylate plastics. The first step in this process involves the addition of hydrocyanic acid to acetone to produce acetone cyanohydrin (CH3)2CO + HCN(CHs)2C(OH)CN. The methacrylate ester monomers are then made by reacting with methanol or another alcohol in the presence of sulfuric acid or some other dehydrating agent. 

Among other nonaddition processes, adiponitrile may be manufactured by the direct hydrocyanation of 1,3-butadiene (DuPont process).169 172,187 196 A homogeneous Ni(0) complex catalyzes both steps of addition of HCN to the olefinic bonds (Scheme 6.4). The isomeric monocyano butenes (20 and 21) are first formed in a ratio of approximately 1 2. All subsequent steps, the isomerization of 20 to the desired 1,4-addition product (21), a further isomerization step (double-bond migration), and the addition of the second molecule of HCN, are promoted by Lewis acids (ZnCl2 or SnCl2). Without Lewis acids the last step is much slower then the addition of the first molecule of HCN. Reaction temperatures below 150°C are employed. 

The current hydrocyanation process can be broken down into two major steps. In the first, HCN is added to butadiene in the presence of an NiL4 catalyst to give 3-pentenenitrile (3PN) and 2-methyl-3-butenenitrile (2M3BN) [Eq. (7)]. Fortunately the branched 2M3BN may be isomerized to the linear 3PN isomer [Eq. (8)]. In the second step, a Lewis acid promoter is added to the NiL4 (L = a phosphorus ligand) catalyst to effect the double bond isomerization of 3PN to 4-pentenenitrile (4PN) concurrently with the... 

The isomerization of the internal olefin 3PN to the terminal olefin 4PN is a critical step in the hydrocyanation of 3PN to ADN [Eqs. (9) and (10)]. Unfortunately, there is a loss in yield because the undesirable conjugated isomer 2PN is also produced. Observations discussed below have led us to the belief that cationic nickel-hydride complexes, HNiL4, may be important in the isomerization process. 

Extension of this reaction toward a one-pot asymmetric Mannich-hydrocyanation reaction sequence was also reported by the Barbas group [29]. In this one-pot two-step process proline-catalyzed asymmetric Mannich reaction of unmodified aldehydes with the a-imino glyoxylate was performed first, then diastereoselective in situ cyanation. The resulting /i-cyanohydroxymethyl a-amino acids were obtained with high enantioselectivity (93-99% ee) [29]. Another one-pot two-step reaction developed by Barbas et al. is the Mannich-allylation reaction in which the proline-catalyzed Mannich reaction is combined with an indium-promoted allylation [30], This one-pot synthesis was conducted in aqueous media and is the first example of a direct organocatalytic Mannich reaction in aqueous media [28, 30]. 

It was mentioned at the beginning of this chapter that alkaloids were among the first catalysts to be used for asymmetric hydrocyanation of aldehydes. More recent work by Tian and Deng has shown that the pseudo-enantiomeric alkaloid derivatives 5/6 and 7/8 catalyze the asymmetric addition of ethyl cyanoformate to aliphatic ketones (Scheme 6.6) [50]. It is believed that the catalytic cycle is initiated by the alkaloid tertiary amine reacting with ethyl cyanoformate to form a chiral cyanide/acylammonium ion pair, followed by addition of cyanide to the ketone and acylation of the resulting cyanoalkoxide. Potentially, the latter reaction step occurs with dynamic kinetic resolution of the cyano alkoxide intermediate... 

The nickel-catalyzed hydrocyanation of butadiene is a two-step process (Figure 3.32). In the first step, HCN is added to butadiene in the presence of a nickel-tetrakis(phosphite) complex. This gives the desired linear product, 3-pente-nenitrile (3PN), and an unwanted branched by-product, 2-methyl-3-butenenitrile (2M3BN). The products are separated by distillation, and the 2M3BN is then isomerized to 3PN. In the second step, 3PN is isomerized to 4PN (using the same nickel catalyst), followed by anti-Markovnikov HCN addition to the terminal double bond. The second step is further complicated by the fact that there is another isomerization product, CH3CH2CH=CHCN or 2PN, which is thermodynamically more stable than 4PN. In fact, the equilibrium ratio of 3PN/2PN/4PN is only 20 78 1.6. Fortunately, the reaction kinetics favor the formation of 4PN [95],... 

The Strecker reaction is defined as the addition of HCN to the condensation product of a carbonyl and amine component to give a-amino nitriles. Lipton and coworkers reported the first highly effective catalytic asymmetric Strecker reaction, using synthetic peptide 43, a modification of Inoue s catalyst (38), which was determined to be inactive for the Strecker reactions of aldimines (see Scheme 6.5) [62], Catalyst 43 provided chiral a-amino nitrile products for a number of N-benzhydryl imines (42) derived from substituted aromatic (71-97% yield 64->99% ee) and aliphatic (80-81% yield <10-17% ee) aldehydes, presumably through a similar mode of activation to that for hydrocyanations of aldehydes (Table 6.14). Electron-deficient aromatic imines were not suitable substrates for this catalyst, giving products in low optical purities (<10-32% ee). The a-amino nitrile product of benzaldehyde was converted to the corresponding a-amino acid in high yield (92%) and ee (>99%) via a one-step acid hydrolysis. 

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