Hydrocyanation process

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]. 

The transition metal catalysed addition of HCN to alkenes is potentially a very useful reaction in organic synthesis and it certainly would have been more widely applied in the laboratory if its attraction were not largely offset by the toxicity of HCN. Industrially the difficulties can be minimised to an acceptable level and we are not aware of major accidents. DuPont has commercialised the addition of HCN to butadiene for the production of adiponitrile [ADN, NC(CH2)4CN], a precursor to 1,6-hexanediamine, one of the components of 6,6-nylon and polyurethanes (after reaction with diisocyanates). The details of the hydrocyanation process have not been released, but a substantial amount of related basic chemistry has been published. The development of the ligand parameters % and 0 by Tolman formed part of the basic studies carried out in the Du Pont labs related to the ADN process [1],... 

The reaction mixture containing about 13%. 2M) of diethylaluminum cyanide and a small amount of ethylaluminum dicyanide may be used for most hydrocyanation processes without further purification. Care must be taken to have no unchanged triethylaluminum, since the submitters have observed that hydrocyanation of A -ll-keto steroids with diethylaluminum cyanide is greatly retarded by the presence of a small amount of unchanged triethylaluminum. ... 

For preparative purposes, the use of biphasic solvent systems consisting of an aqueous phase and a water-immiscible organic phase for PaHNL and llhl INI. catalysis has proven to have a broad applicability, also including, for example, pyrrole derivatives [30] (see Table 9.3, Section 9.2.2.3) and to be suitable for industrial scale. DSM established enzymatic hydrocyanation processes, e.g., for the production of (S)-m-phenoxymandelonitrile [31, 32] and large-scale production of (R) -2 - (2 -furyl) - 2 -hydroxyace tonitrile [33]. 

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... 

Interestingly, completely different types of organocatalyst have been found to have catalytic hydrocyanation properties. Among these molecules are chiral diketo-piperazine [4, 5], a bicydic guanidine [6], and imine-containing urea and thiourea derivatives [7-13]. All these molecules contain an imino bond which seems to be beneficial for catalyzing the hydrocyanation process. Chiral N-oxides also promote the cyanosilylation of aldimines, although stoichiometric amounts of the oxides are required [14]. 

Kreutzer, K. A. Tam, W. Hydrocyanation process and multidentate phosphite and nickel catalyst composition therefore. US 5,663,369,1997. 

Large-scale manufacturing processes involving isomerization reactions by homogeneous catalysts are few. Two important ones are the isomerization step in the SHOP process and the enantioselective isomerization of diethylgeranyl or diethylnerylamine as practiced by the Takasago Perfumery. The isomerization step in the SHOP process is discussed later on in this chapter. The Takasago process is discussed in Chapter 9. Isomerization of alkenes with nitrile functionalities is very important in DuPont s hydrocyanation process. The mechanism for this reaction is discussed in Section 7.7. 

All the reactions of the hydrocyanation process are catalyzed by zero-valent nickel phosphine or phosphite complexes. These are used in combination with Lewis acid promoters such as zinc chloride, trialkyl boron compounds, or trialkyl borate ester. The ability of the precatalyst to undergo ligand dissociation... 

Although for clarity the reactions of Fig. 7.13 are shown to be unidirectional, all the reactions of the catalytic cycle are in fact reversible. This is an important aspect of the first stage of the hydrocyanation process. It provides for a mechanism for the isomerization of the unwanted 2M3BN to the desired 3PN. The isomerization reaction of 2M3BN to 3PN has been studied by deuteriumlabeling experiments. The results are consistent with a mechanism where butadiene is formed in one of the intermediate steps. This means that the reversibility of all the steps allows isomerization to follow the path 7.51 — 7.50 — ... 

Obviously, the direct addition of two molecules of HCN to butadiene (a true hydrocyanation process) is a more straightforward method for the preparation of adiponitrile than the former process, which requires three steps. 

For the production of (5)-m-phenoxybenzaldehyde cyanohydrin (47) DSM established an enzymatic hydrocyanation process on an industrial scale (Scheme 31). An efficient (S)-oxynitrilase biocatalyst has been developed. This enzyme is derived from the plant Hevea brasiliensis, and has been cloned and overexpressed in a microbial host organism [117]. In the presence of this biocatalyst the desired product 47 has been obtained with high enantioselec-tivity. 

HMDA) manufacturing processes. The two sets of metrics clearly show the tradeoffs for these processes. The hydrocyanation process has lower energy-intensity and greenhouse-gases metrics, but its material-intensity, water consumption and pollutants metrics are higher than those for the electrohydrodimerization process. 

Given the efficiency and utility of the butadiene hydrocyanation process, its potential in more complex settings is underused. Whereas the range of applications has mostly been limited to simple substrates, several important developments in reaction scope and as5mimetric induction have appeared. For example, carbohydrate-derived bis-phosphine ligands allowed efficient asymmetric hydrocyanations of... 

A hydrocyanation process has been used to introduce bridged rings at angular... 

HCN is the precursor to sodium cyanide and potassium cyanide, which are used mainly in mining. Via the intermediacy of cyanohydrins, a variety of useful organic compounds are prepared from HCN including the monomer methyl methacrylate, from acetone, the amino acid methionine, via the Strecker synthesis, and the chelating agents EDTA and NTA. Via the hydrocyanation process, HCN is added to butadiene to give adiponitrile, a precursor to Nylon 66. 

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. 

In another DMF process, hydrocyanic acid reacts with methanol ia the presence of water and a titanium catalyst (16), or ia the presence of dimethylamine and a catalyst (17). 

Irradiation of ethyleneimine (341,342) with light of short wavelength ia the gas phase has been carried out direcdy and with sensitization (343—349). Photolysis products found were hydrogen, nitrogen, ethylene, ammonium, saturated hydrocarbons (methane, ethane, propane, / -butane), and the dimer of the ethyleneimino radical. The nature and the amount of the reaction products is highly dependent on the conditions used. For example, the photoproducts identified ia a fast flow photoreactor iacluded hydrocyanic acid and acetonitrile (345), ia addition to those found ia a steady state system. The reaction of hydrogen radicals with ethyleneimine results ia the formation of hydrocyanic acid ia addition to methane (350). Important processes ia the photolysis of ethyleneimine are nitrene extmsion and homolysis of the N—H bond, as suggested and simulated by ab initio SCF calculations (351). The occurrence of ethyleneimine as an iatermediate ia the photolytic formation of hydrocyanic acid from acetylene and ammonia ia the atmosphere of the planet Jupiter has been postulated (352), but is disputed (353). 

Another example is the du Pont process for the production of adiponitrile. Tetrakisarylphosphitenickel(0) compounds are used to affect the hydrocyanation of butadiene. A multistage reaction results in the synthesis of dinitrile, which is ultimately used in the commercial manufacture of nylon-6,6 (144-149). 

The first methacrylic esters were prepared by dehydration of hydroxyisobutyric esters, prohibitively expensive starting points for commercial synthesis. In 1932 J. W. C. Crawford discovered a new route to the monomer using cheap and readily available chemicals—acetone, hydrocyanic acid, methanol and sulphuric acid— and it is his process which has been used, with minor modifications, throughout the world. Sheet poly(methyl methacrylate) became prominent during World War II for aircraft glazing, a use predicted by Hill in his early patents, and since then has found other applications in many fields. 

By this process, 4-methylselenazole (2 R = CH3, R = R" = H) could be obtained by the reaction of hydrocyanic acid and hydrogen selenide with chloroacetone. This is the solitary selenazole unsubstituted in the 2-position that is known. The yield, however, was only 2.5% calculated on the chloroacetone used. 

For an exhaustive examination of the various processes proposed for the determination of hydrocyanic acid, the reader is referred to a series of papers by Eunne in the Apotheker Zeitung.-... 

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. 

Hexamethylenediamine (HMDA), a monomer for the synthesis of polyamide-6,6, is produced by catalytic hydrogenation of adiponitrile. Three processes, each based on a different reactant, produce the latter coimnercially. The original Du Pont process, still used in a few plants, starts with adipic acid made from cyclohexane adipic acid then reacts with ammonia to yield the dinitrile. This process has been replaced in many plants by the catalytic hydrocyanation of butadiene. A third route to adiponitrile is the electrolytic dimerization of acrylonitrile, the latter produced by the ammoxidation of propene. 

Hydrocyanation represents a reaction of considerable economic importance largely due to the value of the DuPont process involving HCN addition to butadiene to afford adiponitrile.61,62 The mechanism is well known, and involves (i) oxidative addition of H-CN to a coordinatively unsaturated metal complex, (ii) coordination of an alkene to the H-M-CN species, (iii) migratory... 

Addition of molecules across unsaturated organic bonds is an extremely important process that includes reactions such as hydrogenation, hydroformylation, oxidation, hydrocyanation, hydrosilylation and many others. These reactions are often most effectively catalysed by homogeneous catalysts and in this chapter we will focus on hydrogenation (addition of H2) and hydroformylation (addition of H2 and CO), which are shown generically in Scheme 8.1. 

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. 

In an extension of an early work on the nickel-catalyzed addition of hydrogen cyanide to unsaturated compounds, a basic reaction in various large-scale processes in the polymer industry, the hydrocyanation of butadiene (equation 15) and the efficiency of catalysis of this reaction by low-cost copper salts has been studied extensively by Belgium researchers47,48. 

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