HCN addition

The first HCN addition (eq. 3) occurs at practical rates above 70°C under sufficient pressure to keep butadiene condensed in solution and produces the 1,4- and 1,2-addition products (3-pentenenitrile [4635-87-4] 3PN, and 2-meth5i-3-butenenitrile [16529-56-9] 2M3BN) in a 2 to 1 ratio. Fortunately, thermodynamics favors 3PN (about 20 1) and 2M3BN may be isomerized to 3PN (eq. 4) in the presence of a nickel catalyst. 

The selective addition of the second HCN to provide ADN requires the concurrent isomerisation of 3PN to 4-pentenenitrile [592-51 -8] 4PN (eq. 5), and HCN addition to 4PN (eq. 6). A Lewis acid promoter is added to control selectivity and increase rate in these latter steps. Temperatures in the second addition are significandy lower and practical rates may be achieved above 20°C at atmospheric pressure. A key to the success of this homogeneous catalytic process is the abiUty to recover the nickel catalyst from product mixture by extraction with a hydrocarbon solvent. 2-Methylglutaronitrile [4553-62-2] MGN, ethylsuccinonitfile [17611-82-4] ESN, and 2-pentenenitrile [25899-50-7] 2PN, are by-products of this process and are separated from adiponitrile by distillation. 

The manufacture of hexamethylenediamine [124-09-4] a key comonomer in nylon-6,6 production proceeds by a two-step HCN addition reaction to produce adiponittile [111-69-3] NCCH2CH2CH2CH2CN. The adiponittile is then hydrogenated to produce the desired diamine. The other half of nylon-6,6, adipic acid (qv), can also be produced from butadiene by means of either of two similar routes involving the addition of CO. Reaction between the diamine and adipic acid [124-04-5] produces nylon-6,6. 

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 HCN to acetone to form the cyanohydrin is still the main route to methyl methacrylate. Hydrocyanins can be converted to amino acids as well. The nitrile group can be easily converted to amines, carboxylic acids, amides, etc. Addition to aldehydes and activated alkenes can be done with simple base, but addition to unactivated alkenes requires a transition metal catalyst. The methods of HCN addition have been discussed by Brown [2],... 

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... 

The preparation of (S)-ketone cyanohydrins has also been achieved in a one-pot procedure, using the PaHnl, by decomposition of the corresponding racemic cyanohydrins followed by stereoselective addition of the HCN that is liberated to m-bromoaldehydes [97]. This tandem reaction process yielded both (S)-ke-tone cyanohydrins (from the decomposition of the racemic cyanohydrin) and (i )-m-bromocyanohydrins (the HCN addition product), the latter being con-... 

The next milestone in the realm of enantioselective organocatalysis was reached by Inoue and coworkers, who elegantly modernized the cyanohydrin reaction, first outlined by Bredig and Fiske in 1912. In these studies, a cyclic histidine-containing dipeptide (4) catalyzed the HCN addition to aromatic aldehydes with high enantioselectivities (97% ee) [Eq. (11.4)] a result that effectively paved the way for the field of peptide-catalyzed nucleophilic addition to aldehydes and imines ... 

In an aqueous system, the only possible way to suppress the unwanted chemical HCN addition to carbonyl compounds is to work at low pH to reduce the concentration of the cyanide ion-the reactive species-and at low temperature to increase the selectivity. However, in an acidic medium, most HNLs lose activity very fast [15, 16], and it is therefore necessary to find reaction conditions to avoid these problems. 

This may be a rare example of CN transfer from the cuprate to a substrate, but more likely is a result of HCN addition formed from the acidic work-up.124... 

The addition of hydrogen cyanide to a carbonyl group results in the formation of an a-hydroxy nitrile, a so-called cyanohydrin (A, Scheme 6.1) [1]. Compounds of this type have in many instances served as intermediates in the synthesis of, e.g., a-hydroxy acids B, a-hydroxy aldehydes C, fS-amino alcohols D, or a-hydroxy ketones E (Scheme 6.1) [1], In all these secondary transformations of the cyanohydrins A, the stereocenter originally introduced by HCN addition is preserved. Consequently, the catalytic asymmetric addition of HCN to aldehydes and ketones is a synthetically very valuable transformation. Besides addition of HCN, this chapter also covers the addition of trimethylsilyl cyanide and cyanoformate to car-... 

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],... 

Scheme 12 Option. The oxynitrilase-catalyzed HCN addition to the aldehyde Xin appeared to offer an attractive prospect presuming that the R-cyanohydrin (XIV) could be formed, and this then converted to dilevalol via intermediates XV and XVI. Although the oxynitrilase-catalyzed formation of chiral aromatic and aliphatic cyanohydrins and their reduction to chiral aminoalcohols has been known for some time,16 the selective reduction of XIV to XV and the likelihood of 100% induction in the reduction of the Schiff base XVI raised many questions.

The mechanism of hydrocyanation by nickel catalysts should proceed through a nickel hydride addition on the double bonds. The nickel hydrides should result from the oxidative HCN addition to the metal, or from the above Lewis acid-assisted dissociation of HCN. The oxidative HCN addition to low-valent metal complexes has been demonstrated, particularly by NMK spectroscopy with Ni(0)(P(OF.t)3 4. 

The selective addition of the second HCN to provide ADN requires the concurrent isomerization of 3PN to 4PN (eqnation 7), and anti-Markovnikov HCN addition to 4PN (eqnation 8). A Lewis acid promoter is added to improve the selectivity and increase the rates of these latter steps. 

HCN addition to 6-methoxy-2-vinylnaphthalene occurs readily at 25 °C in the presence of these optically active Ni complexes to give the branched nitrile exclusively and in high yield. The enantioselectivity (R versus S) of the... 

Rgure 7.2.7 The HCN addition reaction is used industrially to make monomers for Perspex ... 

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