1.4- hydrocyanation

Hydrocyanation is the addition of HCN across a C=C bond. In 1971, Dupont reported a new process that added two equivalents of HCN, in an anti-Markovnikov manner, to 1,3-butadiene to yield adiponitrile (equation 9.38).96 The process is catalyzed overall by a Ni(0) triarylphosphite complex. 

The mechanism of hydrocyanation turns out to be another classic example of a set of catalytic cycles that use many of the fundamental types of organometallic reactions that we have already encountered. In fact, the investigation of the details of this mechanism went hand in hand with the advancement of important general 

97Adipic acid is also made on an industrial scale through oxidation of cyclohexanone. The number 66 represents the number of carbons in the two different monomeric units of nylon 66 both adipic acid and 1,6-hexanediamine contain six carbon atoms. Nylon 6 is made from only one type of monomeric unit, which also contains six carbon atoms. 

Hydrocyanation of 1,3-butadiene occurs in three stages. Equation 9.39 shows the first stage, which produces a 2 1 mixture of the desired 3-pentenenitrile (68), produced by a 1,4-addition of HCN to 1,3-butadiene, and the branched isomer 2-methyl-3-butenenitrile (69), which results from Markovinikov 1,2-addition. 

The next stage requires equilibration and isomerization of 69 to 68, giving a 9 1 ratio of desired to undesired product. A Ni catalyst is also used for this reaction. Finally, the third stage consists of two transformations, where 68 is first isomer-ized to 4-pentenenitrile (70) under kinetic control, fortunately without producing much of the thermodynamically more stable 2-pentenenitrile (71). Compound 70 then undergoes a second hydrocyanation with anti-Markovnikov orientation (equation 9.40). In this last Ni-catalyzed stage of the overall process, a Lewis acid, such as Ph3B, is added to ensure that linear rather than branched product (72) forms. 

Hydrocyanation is the addition of HCN across carbon-carbon or carbon-heteroatom multiple bonds to form products containing a new C-C bond. The majority of examples from organometallic chemistry involve the addition of HCN across carbon-carbon multiple bonds, as shown in Equations 16.2 and 16.3. Lewis acids and peptides have been used to catalyze the enantioselective addition of HCN to aldehydes and imines to form cyanohydrins and precursors to amino acids.The addition of HCN to unactivated olefins requires a catalyst because HCN is not sufficiently acidic to add directly to an olefin, and the C-H bond is strong enough to make additions by radical pathways challenging. However, a large number of soluble transition metal compounds catalyze the addition of HCN to alkenes and alkynes. 

The addition of HCN to olefins catalyzed by complexes of transition metals has been studied since about 1950. The first hydrocyanation by a homogeneous catalyst was reported by Arthur with cobalt carbonyl as catalyst. These reactions gave the branched nitrile as the predominant product. Nickel complexes of phosphites are more active catalysts for hydrocyanation, and these catalysts give the anti-Markovnikov product with terminal alkenes. The first nickel-catalyzed hydrocyanations were disclosed by Drinkard and by Brown and Rick. The development of this nickel-catalyzed chemistry into the commercially important addition to butadiene (Equation 16.3) was conducted at DuPont. Taylor and Swift referred to hydrocyanation of butadiene, and Drinkard exploited this chemistry for the synthesis of adiponitrile. The mechanism of ftiis process was pursued in depth by Tolman. As a result of this work, butadiene hydrocyanation was commercialized in 1971. The development of hydrocyanation is one of tfie early success stories in homogeneous catalysis. Significant improvements in catalysts have been made since that time, and many reviews have now been written on this subject.  

Hydrocyanation of olefins and acetylenes, i.e., the addition of hydrogen cyanide to olefins, is catalyzed by iron, cobalt, and nickel carbonyls, particularly in the presence of phosphines, as well as [Ni R2P(CH2)nPR2 2], [M P(OR)3 4] (M = Ni, Pd), [Ni(CN)4] -, [Ni(C2H4) P(OC6H4Me-2)3 2], CuCl, 

Hydrogen cyanide may undergo oxidative addition to low-valent complexes or it may be coordinated as a Lewis base in the case of complexes of metals in higher oxidation states  

Hydrocyanation proceeds via hydrido metal complexes as a result of the migration reaction of hydrogen to the olefin and reductive elimination of the nitrile [equation (13.152)]. 

The addition of HCN to olefins in which the double bond is activated by substituents such as — COOR, aryl, — NO2, — CN, and —COR proceeds more easily than in the case of nonactivated olefins and is catalyzed by basic species, for example, CN. Metal carbonyls are also effective catalysts, for example, [Co2(CO)g], [Ni(CO)4], and [Ni(CO)4] + PPh3. 

Hydrocyanation of acetylene is catalyzed by an aqueous solution of copper(I) chloride and ammonium chloride however, byproducts are also formed, viz., acetaldehyde and vinylacetylene, the latter arising by dimerization of acetylenes. Hydrocyanation, followed by reduction of alkynes leading to secondary nitriles, is catalyzed by Co(CN)5 in the atmosphere of H2 or by Ni(CN)4 in the presence of BH4 cyanide. 

DuPont developed a manufacturing process for adiponitrile (ADN), a raw material for nylon 6,6, by the hydrocyanation of butadiene using homogeneous nickel catalysts. As shown by reaction 5.6.1, this involves the addition of two molecules of HCN to butadiene. 

The reaction is carried out in two stages. In the first stage, two reactions (5.6.2) and (5.6.3) take place. One molecule of HCN is added to butadiene. This gives 3-pentenenitrile (3PN) and 2-methyl 3-butenenitrile (2M3BN) by anti-Markovnikov and Markovnikov addition of the cyano group. However, under the reaction conditions 2M3BN is isom-erized to 3PN. 

As shown by reactions 5.6.4 and 5.6.5, in the second stage 3PN is isomerized to 4-pentenenitrile (4PN) and the second molecule of HCN is added. Regioselectivity is of paramount importance and the addition of the second molecule of HCN must take place again in an anti-Markovnikov manner to give ADN, the desired product. The branched product by the Markovnikov pathway, called 2-methyl glutaronitrile (2-MGN), is an unwanted side product. 

Hydrogen qianide is a remarkably versatile Cj building blocdi. Its use, however, has been limited by its relatively difficult synthesis/puriJication as well as by its high flammability, its tendency toward base-catalyzed explosive polymerization, and its toxicity, jyjost of the recent hydrocyanation literature comes from industry rather than academic laboratories. 

The addition of HCN to activated alkenes, as in Michael additions, has been known and commercially practiced for many years. Addition of HCN to isophorone [Eq. (1)] is an example [2], 

More common is the general acid- or base-catalyzed addition of HCN to ketones and aldehydes to give cyanohydrins [Eq. (2)] [1]. Because of the propensity of HCN to spontaneously and exothermically polymerize under basic conditions, general acid catalysis is sometimes favored over basic media, as was the case in the recent Sumitomo [3] and Upjohn work [4, 5]. Applications of aqueous media have been reported to lead to asymmetric hydrocyanation catalysis [Eq. (3)] [6, 7]. 

Another variant of this HCN addition to polar C=X bonds is the Strecker synthesis of aminonitriles from ketones or aldehydes, HCN, and ammonia [Eq. (4)] [8]. A number of patents to Distler and co-workers at BASF do teach the use of aqueous media to facilitate isolation of pure products [9], and researchers at Grace [10], Stauffer [11], Mitsui [12], and Hoechst [13] have reportedly used aqueous media to control the rates of formaldehyde aminohydrocyanation to isolate intermediate addition products in good yields. The use of aqueous media has also proven advantageous when amides, rather than nitriles, are the desired products. 

The addition of HCN to C=C double bonds can be effected in low yields to produce Markovnikov addition products. However, through the use of transition metal catalysts, the selective anti-Markovnikov addition of HCN to alkenes can take place. The most prominent example of the use of aqueous media for transition metal-catalyzed alkene hydrocyanation chemistry is the three-step synthesis of adiponitrile 

The evidence for the proposed mechanism and reactions 7.11 to 7.13 come from a variety of observations. First of all cleavage of the alkenes only at the double bonds, that is, generation of species such as 7.38 and 7.40, is indicated by isotope-labeling studies. A mixture of but-2-ene and perdeuterated but-2-ene on exposure to metathesis catalysts shows that the product but-2-ene is duterated only at the 1,2 positions. Second, fully characterized metal -alkylidene complexes such as 7.43 and 7.44 have been shown to be active metathesis catalysts. 

The product from reaction 7.14 has been isolated and fully characterized. This lends credence to the mechanistic postulate that metallocyclobutane rings play a crucial role in metathesis reactions. 

The hydrocyanation reaction is important not only because it is practiced industrially on a large scale, but also because it clearly illustrates some of the fundamental postulates of homogeneous catalysis. The potential of the hydrocyanation reaction in asymmetric catalysis has also been explored and appears to be promising (see Chapter 9). 

ASYMMETRIC CATA1YSIS VIA CHIRAI META COMPI EXES 

4-Coupling with a Carbanion Equivalent and Another Nucleophile 

Insertion of the diene into the Pd-R bond produces a Tt-aUylpaUadium intermediate which reacts with the nucleophile to give the 1,4-addition product. The R group in these reactions is typically an aryl or a vinyl, and the X group in RX is in most cases a halide or a triflate. 

Although 2 1 telomerization reactions can be considered as a special case of 1,4-addition to a conjugated diene by a carbon and a nucleophile (Eq. (14)), these reactions will not be covered in this chapter, and the reader is advised to consult Refs. [8] and [27] for further details on this matter. An intramolecular version of this reaction will be discussed in Section 11.2.2.3. 

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GattermaDD synthesis A method for the synthesis of aromatic hydroxyaldehydes. E.g. AICI3 is used to bring about the condensation of phenol with a mixture of gaseous hydrochloric acid and hydrocyanic acid an aldimine hydrochloride is formed and on hydrolysis gives p-hydroxybenzaldehyde... 

In the mid 1970s, Ugi and co-workers developed a scheme based on treating reactions by means of matrices - reaction (R-) matrices [16, 17]. The representation of chemical structures by bond and electron (BE-) matrices was presented in Section 2.4. BE-matrices can be constructed not only for single molecules but also for ensembles of them, such as the starting materials of a reaction, e.g., formaldehyde (methanal) and hydrocyanic add as shown with the B E-matrix, B, in Figure 3-12. Figure 3-12 also shows the BE-matrix, E, of the reaction product, the cyanohydrin of formaldehyde. 

The maximum permissible body burden for ingested polonium is only 0.03 microcuries, which represents a particle weighing only 6.8 x IO-12 g. Weight for weight it is about 2.5 x lOii times as toxic as hydrocyanic acid. The maximum allowable concentration for soluble polonium compounds in air is about 2 x lO-ii microcuries/cnu. 

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. 

Miscellaneous Reactions. Sodium bisulfite adds to acetaldehyde to form a white crystalline addition compound, insoluble in ethyl alcohol and ether. This bisulfite addition compound is frequendy used to isolate and purify acetaldehyde, which may be regenerated with dilute acid. Hydrocyanic acid adds to acetaldehyde in the presence of an alkaU catalyst to form cyanohydrin the cyanohydrin may also be prepared from sodium cyanide and the bisulfite addition compound. Acrylonittile [107-13-1] (qv) can be made from acetaldehyde and hydrocyanic acid by heating the cyanohydrin that is formed to 600—700°C (77). Alanine [302-72-7] can be prepared by the reaction of an ammonium salt and an alkaU metal cyanide with acetaldehyde this is a general method for the preparation of a-amino acids called the Strecker amino acids synthesis. Grignard reagents add readily to acetaldehyde, the final product being a secondary alcohol. Thioacetaldehyde [2765-04-0] is formed by reaction of acetaldehyde with hydrogen sulfide thioacetaldehyde polymerizes readily to the trimer. 

Complexes. In common with other dialkylamides, highly polar DMAC forms numerous crystalline solvates and complexes. The HCN—DMAC complex has been cited as an advantage ia usiag DMAC as a reaction medium for hydrocyanations. The complexes have vapor pressures lower than predicted and permit lower reaction pressures (19). 

Substances that form carbanions, such as nitro compounds, hydrocyanic acid, malonic acid, or acetylacetone, react with vinyl ethers in the presence of water, replacing the alkyl group under mild conditions (245). 

Formamide decomposes thermally either to ammonia and carbon monoxide or to hydrocyanic acid and water. Temperatures around 100°C are critical for formamide, in order to maintain the quaUty requited. The lowest temperature range at which appreciable decomposition occurs is 180—190°C. Boiling formamide decomposes at atmospheric pressure at a rate of about 0.5%/min. In the absence of catalysts the reaction forming NH and CO predominates, whereas hydrocyanic acid formation is favored in the presence of suitable catalysts, eg, aluminum oxides, with yields in excess of 90% at temperatures between 400 and 600°C. 

Methanol can be converted to a dye after oxidation to formaldehyde and subsequent reaction with chromatropic acid [148-25-4]. The dye formed can be deterruined photometrically. However, gc methods are more convenient. Ammonium formate [540-69-2] is converted thermally to formic acid and ammonia. The latter is trapped by formaldehyde, which makes it possible to titrate the residual acid by conventional methods. The water content can be determined by standard Kad Eischer titration. In order to determine iron, it has to be reduced to the iron(II) form and converted to its bipyridyl complex. This compound is red and can be determined photometrically. Contamination with iron and impurities with polymeric hydrocyanic acid are mainly responsible for the color number of the merchandized formamide (<20 APHA). Hydrocyanic acid is detected by converting it to a blue dye that is analyzed and deterruined photometrically. 

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). 

Until the 1960s, adipic acid [124-04-9] was virtually the sole intermediate for nylon-6,6. However, much hexamethylenediamine is now made by hydrodimerization of acrylonitrile (qv) or via hydrocyanation of butadiene (qv). Cyclohexane remains the basis for practically the entire world output of adipic acid. The U.S. capacity for adipic acid for 1993 was 0.97 X 10 t/yr (233). 

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). 

Nickel plays a role in the Reppe polymeriza tion of acetylene where nickel salts act as catalysts to form cyclooctatetraene (62) the reduction of nickel haUdes by sodium cyclopentadienide to form nickelocene [1271 -28-9] (63) the synthesis of cyclododecatrienenickel [39330-67-1] (64) and formation from elemental nickel powder and other reagents of nickel(0) complexes that serve as catalysts for oligomerization and hydrocyanation reactions (65). 

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). 

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]. 

Amin omethyl-3,5,5-trimethyl cyclohexyl amine (21), commonly called isophoronediamine (IPD) (51), is made by hydrocyanation of (17) (52), (53) followed by transformation of the ketone (19) to an imine (20) by dehydrative condensation of ammonia (54), then concomitant hydrogenation of the imine and nitrile functions at 15—16 MPa (- 2200 psi) system pressure and 120 °C using methanol diluent in addition to YL NH. Integrated imine formation and nitrile reduction by reductive amination of the ketone leads to alcohol by-product. There are two geometric isomers of IPD the major product is ds-(22) [71954-30-5] and the minor, tram-(25) [71954-29-5] (55). 

Dicyclopentadiene (24) [77-73-6] is an inexpensive raw material for hydrocyanation to (25), a mixture of l,5-dicarbonittile [70874-28-1] and 2,5-dicarbonittile [70874-29-2], then subsequent hydrogenation to produce tricyclodecanediamine, TCD diamine (26). This developmental product, a mixture of endo and exo, cis and trans isomers, is offered by Hoechst. 

Mandelic acid is best prepared by the hydrolysis of mandeloni-trile with hydrochloric acid. The mandelonitrile has been prepared from amygdalin, by the action of hydrocyanic acid on benzaldehyde, and by the action of sodium or potassium cyanide on the sodium bisulfite addition product of benzaldehyde. ... 

The excess nitric acid is used in order to oxidize unchanged crotonic acid. Since hydrocyanic acid may be evolved the operation should be carried out under a hood. 

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. 

Acetylene, fulminic acid (produced in ethanol - nitric acid mixtures), ammonia Acetic acid, acetone, alcohol, aniline, chromic acid, hydrocyanic acid, hydrogen sulphide, flammable liquids, flammable gases, or nitratable substances, paper, cardboard or rags Inorganic bases, amines Silver, mercury... 

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