Cyanide, conjugation

Support for this hypothesis was provided by Peiser et al. [21], who prepared [carboxyl- CjACC and [1- C]ACC, and showed that the carboxyl carbon of ACC is liberated as CO2, whereas the C-1 of ACC is recovered not as free HCN but as cyanide conjugates, in an amount equivalent to that of the ethylene produced. Their results indicated that ACC is degraded into ethylene, CO2 and HCN, with HCN being rapidly metabolized to yield )S-cyanoalanine -cyanoalanine is then hydrated to asparagine, but in some plants, such as Vida sativa. y-glutamyl- -cyanoalanine is the main product [21]. This sequence of reactions is illustrated below ... 

It has also been shown that in the presence of 3-methylcyclo-hexenone, treatment of diethylaluminum cyanide with TBAT provides the cyanide conjugate addition product." The enolate can be captured when the reaction is run in the presence of triflic anhydride, providing the triflate. 

Tertiary amines capable of eliminating a secondary amine to form a conjugated system can react with hydrogen cyanide to form y-keto nitriles by amine replacement. Thus (I) yields p-benzoylpropionitrile (IV) ... 

Note 1. No cyanide was used to remove the copper salts, since the nitrile is probably very base-sensitive (isomerization to a conjugated diene). 

Cyanide is a weaker base than hydroxide because its conjugate acid HCN (pK 9 1) IS a stronger acid than water ipK 15 7)... 

Formal oxidation of pyrrolidine to the succinimide stage affords a series of compounds used as anticonvulsant agents for treatment of seizures in petit mal epilepsy. Knoevnagel condensation of benzaldehyde with ethyl cyanoacetate affords the unsaturated ester, 9. Conjugate addition of cyanide ion leads to the di-nitrile ester (10). Hydrolysis in mineral acid affords the succinic acid (11), presumably by decarboxylation of the intermediate tricarboxyllie acid. Lactamization with methylamine gives phensuximide (12). ... 

Addition (Sections 14.2, 19.13) Addition of a reactant to the ends of a conjugated tt system. Conjugated dienes yield 1,4 adducts when treated with electrophiles such as MCI. Conjugated enones yield 1,4 adducts when treated with nucleophiles such as cyanide ion. 

Conjugate addition, 34-5, 51-2,53, 132, 133 Conjugate hydroxymethylation, 59-60 Copper(n) bromide, 54 Copper([) chloride, 120 Copper(n) chloride, 120 Copper(i) cyanide, 7,52, 53 Copper(i) iodide, 54 Corey s internal quench, 104 Cyanohydrin trimethylsilyl ether, 137 Cycloaddition. 34,112 Cydobutane-l,2-dione, 135 Cyclohept-2-dione, 135 Cyclohex-2-enone, 52,123 Cyclohcxa-1,3-diene, 26 Cyclohexane carboxaldehyde, 22-3,69 73,78... 

Because HCN is the acid that forms when a proton is transferred to a cyanide ion, HCN is the conjugate acid of the base CN. In general, a conjugate acid of a base is the species formed when the base accepts a proton ... 

The cyanide ion, CN-, is the conjugate base of hydrogen cyanide, HCN. This acid is made by heating ammonia, methane, and air in the presence of a platinum catalyst ... 

Coumalic acid, 56, 51 Crotyl fluoride, 57,73 18-CROWN-6,57, 30 Curtius rearrangement, 59, 1 Cyanide ion, as catalyst for conjugate addition of aldehydes, 59, 56 p-Cyanobenzenesulfonyl cyanide, 57, 89 2-( 1 -Cyanocyclohexyljhydrazinecarboxylic acid methyl ester, 58,102 Cy a noferrocene, 56, 30 Cyanogen chloride, 57, 88... 

CYANIDE-CATALYZED CONJUGATE ADDITION OF ARYL ALDEHYDES 4-(3-PYRIDYL)-4-OXOBUTYRONITRILE... 

The mechanism of the cyanide- and thioazolium ion-catalyzed conjugate addition reactions is considered to be analogous to the Lapworth mechanism for the cyanide-catalyzed benzoin condensation. Thus the cyano-stabilized carbanion resulting from deprotonation of the cyanohydrin of the aldehyde is presumed to be the actual Michael donor. After conjugate addition to the activated olefin, cyanide is eliminated to form the product and regenerate the catalyst. 

Cyanide ion acts as a carbon nucleophile in the conjugate addition reaction. The pK of HCN is 9.3, so addition in hydroxylic solvents is feasible. An alcoholic solution of potassium or sodium cyanide is suitable for simple compounds. 

Cyanide addition has also been done under Lewis acid catalysis. Triethylaluminum-hydrogen cyanide and diethylaluminum cyanide are useful reagents for conjugate... 

Diethylaluminum cyanide mediates conjugate addition of cyanide to a, (3-unsaturated oxazolines. With a chiral oxazoline, 30-50% diastereomeric excess can be achieved. Hydrolysis gives partially resolved a-substituted succinic acids. The rather low enantioselectivity presumably reflects the small size of the cyanide ion. 

The medicinal chemists subsequently discovered an improved route to racemic acid 9 that started with 2-bromo-2-cyclopente-l-one 11 (Scheme 7.2) [5]. Suzuki-Miyaura cross-coupling of 11 with 4-fluorophenyl boronic acid 12 provided 13 in 67% yield. Conjugate addition of cyanide furnished ketone 14 in 71% yield. Reduction of 14 with NaB H4 gave a 2.8 1 mixture of desired 15 and undesired 16 which were separated by silica gel chromatography. The observed diastereoselec-tivity with the cyano group was similar to ester 6. Hydrolysis of 15 with 5 M NaOH in MeOH gave racemic acid 9 in 91% yield, which was resolved as outlined in Scheme 7.1. 

The conjugate addition of hydrogen cyanide, generated in situ from KCN and acetic acid to (i-mesityl ketones, gives high yields of the corresponding oxo nitriles in aqueous ethanol (Eq. 10.19).41... 

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