Nitriles, catalytic hydrogenation substitution

Adiponitrile undergoes the typical nitrile reactions, eg, hydrolysis to adipamide and adipic acid and alcoholysis to substituted amides and esters. The most important industrial reaction is the catalytic hydrogenation to hexamethylenediarnine. A variety of catalysts are used for this reduction including cobalt—nickel (46), cobalt manganese (47), cobalt boride (48), copper cobalt (49), and iron oxide (50), and Raney nickel (51). An extensive review on the hydrogenation of nitriles has been recendy pubUshed (10). 

Lithium aluminum hydride is a convenient reagent for reduction of nitro compounds, nitriles, amides, azides, and oximes to primary amines. Catalytic hydrogenation works also. Aromatic nitro compounds are reduced best by reaction of a metal and aqueous acid or with ammonium or sodium polysulfides (see Section 23-12B). Reduction of /V-substituted amides leads to secondary amines. 

As the Heck reaction protocol is quite robust to the presence of various electrophihc and nucleophilic functional groups and reagents, its combination with other reaction types is highly appealing. The one-pot performance of a Heck reaction and a catalytic hydrogenation is definitely one of the most useful approaches to P-aryl-substituted esters and nitriles (Section 8.8). 

Substituents such as alkene units, alkyne units, and carbonyls can be reduced by catalytic hydrogenation. Lithium aluminum hydride reduces many heteroatom substituents, including nitrile and acid derivatives 56, 57, 104, 105, 106, 107, 108, 109. Polycyclic aromatic compounds such as naphthalene, anthracene, and phenanthrene give electrophilic aromatic substitution reactions. The major product is determined by the number of resonance-stabilized intermediates for attack at a given carbon and the number of fully aromatic rings (intact rings) in the resonance structures 59, 60, 61, 62, 63, 64, 65, 85, 104, 106, 107, 108,109,110,113,114,118. 

A thioamide of isonicotinic acid has also shown tuberculostatic activity in the clinic. The additional substitution on the pyridine ring precludes its preparation from simple starting materials. Reaction of ethyl methyl ketone with ethyl oxalate leads to the ester-diketone, 12 (shown as its enol). Condensation of this with cyanoacetamide gives the substituted pyridone, 13, which contains both the ethyl and carboxyl groups in the desired position. The nitrile group is then excised by means of decarboxylative hydrolysis. Treatment of the pyridone (14) with phosphorus oxychloride converts that compound (after exposure to ethanol to take the acid chloride to the ester) to the chloro-pyridine, 15. The halogen is then removed by catalytic reduction (16). The ester at the 4 position is converted to the desired functionality by successive conversion to the amide (17), dehydration to the nitrile (18), and finally addition of hydrogen sulfide. There is thus obtained ethionamide (19)... 

The percent ring substitution (% RS) of the polymer with active sites affects catalytic activity. Polystyrenes with < 25 % RS with lipophilic quarternary onium ions are swollen in triphase mixtures almost entirely by the organic phase. Water reduces the activity of anions by hydrogen bonding. In most triphase nucleophilic displacement reactions onium ion catalysts with <25% RS are highly active, and those with >40% RS, such as most commercial ion exchange resins, are much less active. However, low % RS is not critical for the reactions of hydroxide ion with active methylene compounds, as commericial ion exchange resins work well in alkylation of active nitriles. 

A related reaction involves a-substituted aryl nitriles having a sufficiently acidic a hydrogen, which can be converted to ketones by oxidation with air under phase transfer conditions. The nitrile is added to NaOH in benzene or DMSO containing a catalytic amount of triethylbenzylammonium chloride (TEBA). " This reaction could not be applied to aliphatic nitriles, but an indirect method for achieving this conversion is given in 19-60. a-Dialkylamino nitriles can be converted to ketones, R2C(NMe2)CN —> R2C=0, by hydrolysis with Q1SO4 in aqueous methanol or by autoxidation in the presence of r-BuOK. ... 

Raney copper is prepared from the commercially available copper aluminum alloy. It does not have much to offer the synthetic chemist as only a few reactions are reported to be affected by this catalyst. Raney copper, as well as Raney cobalt, generally produces fewer side reactions than Raney nickel even though they usually require higher reaction temperatures for the same reaction. Raney copper is, however, quite usefiil for the selective hydrogenation of substituted dinitro benzenes (Eqn. 8.6) with its activity apparently increasing with continued reuse. Raney copper can also be used for the catalytic hydrolysis of hindered nitriles to the amides (Eqn. 12.13). "2... 

Low-pressure hydrogenation of a-aminonitriles occurs without hydrogenolysis over platinum oxide in acetic anhydride (to the a,j8-diacetamido compound) or in alcohol-HCl (to the a,jS-diamine) . This procedure is not applicable to N-substituted amino-nitriles that are efficiently reduced using rhodium-on-alumina in alcoholic ammonia [equation (h)] the catalytic system also reduces )8-, y-, 5-aminonitriles to diamines. 

Ammonia reacts catalytically with alkyl or alkanyl side chains on aromatic hydrocarbons to form aromatic nitriles, or with olefins, and to some extent alkanes, to form aliphatic nitriles. It also reacts catalytically with methane (natural gas) in the presence of a regulated amount of oxygen to form hydrogen cyanide. The following equations illustrate the reactions involved with substituted aromatic compounds ... 

The diamines were synthesized through the aromatic nucleophilic substitution of corresponding diols with / -chloronitrobenzene or /7-fluoronitrobenzene in the presence of potassium carbonate, followed by catalytic reduction with hydrazine monohydrate and Pd/C (such as synthesis of DBAPB and DBTFAPB in Scheme 2.6). As illustrated in Scheme 2.7, bis(ether anhydride)s were prepared by a three-stage synthetic procedure starting from the nucleophilic nitrodisplacement reaction of 4-nitrophthalonitrile with diols (15A 15F, Scheme 2.7) in dry DMF in the presence of potassium carbonate at room temperature. Use of high temperature (in excess of 100 °C) was avoided as it led to dark colored products in the case of 16A 16F. The nitrodisplacement reactions led to a series of new bis(ether nitrile)s (16A 16F, Scheme 2.7). The bis(ether dinitrile)s were then hydrolyzed in an alkaline solution in the presence of hydrogen peroxide to obtain the corre-... 

As an alternative, iridium complexes show exciting catalytic activities in various organic transformations for C-C bond formation. Iridium complexes have been known to be effective catalysts for hydrogenation [1—5] and hydrogen transfers [6-27], including in enantioselective synthesis [28-47]. The catalytic activity of iridium complexes also covers a wide range for dehydrogenation [48-54], metathesis [55], hydroamination [56-61], hydrosilylation [62], and hydroalkoxylation reactions [63] and has been employed in alkyne-alkyne and alkyne - alkene cyclizations and allylic substitution reactions [64-114]. In addition, Ir-catalyzed asymmetric 1,3-dipolar cycloaddition of a,P-unsaturated nitriles with nitrone was reported [115]. 

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