Cyanide chain

Recent microwave measurements in the laboratory have aided the detection of many molecules in interstellar space. We mention here the linear cyanide chains. 

Cyanide ion ( C = N ) The negatively charged carbon atom of cyanide ion IS usually the site of its nucleophilic character Use of cyanide ion as a nucleophile permits the extension of a carbon chain by carbon-carbon bond formation The product is an alkyl cyanide or nitrile... 

Substitutive lUPAC names for nitriles add the suffix nitrile fo fhe name of fhe parenf hydrocarbon chain fhaf includes fhe carbon of fhe cyano group Nifriles may also be named by replacing the ic acid or oic acid ending of the corresponding carboxylic acid with omtrile Alternatively they are sometimes given functional class lUPAC names as alkyl cyanides... 

The presence of an aldehyde function m their open chain forms makes aldoses reactive toward nucleophilic addition of hydrogen cyanide Addition yields a mixture of diastereo meric cyanohydrins... 

A further improvement in the cuprate-based methodology for producing PGs utilizes a one-pot procedure (203). The CO-chain precursor (67) was first functionalized with zirconocene chloride hydride ia THF. The vinyl zirconium iatermediate was transmetalated direcdy by treatment with two equivalents of / -butyUithium or methyUithium at —30 to —70° C. Sequential addition of copper cyanide and methyUithium eUcited the /V situ generation of the higher order cyanocuprate which was then reacted with the protected enone to give the PG. 

Reactions of the Side Chain. Benzyl chloride is hydrolyzed slowly by boiling water and more rapidly at elevated temperature and pressure in the presence of alkaHes (11). Reaction with aqueous sodium cyanide, preferably in the presence of a quaternary ammonium chloride, produces phenylacetonitrile [140-29-4] in high yield (12). The presence of a lower molecular-weight alcohol gives faster rates and higher yields. In the presence of suitable catalysts benzyl chloride reacts with carbon monoxide to produce phenylacetic acid [103-82-2] (13—15). With different catalyst systems in the presence of calcium hydroxide, double carbonylation to phenylpymvic acid [156-06-9] occurs (16). Benzyl esters are formed by heating benzyl chloride with the sodium salts of acids benzyl ethers by reaction with sodium alkoxides. The ease of ether formation is improved by the use of phase-transfer catalysts (17) (see Catalysis, phase-thansfer). 

The pH of the pulp to the flotation cells is carefliUy controlled by the addition of lime, which optimizes the action of all reagents and is used to depress pyrite. A frother, such as pine oil or a long-chain alcohol, is added to produce the froth, an important part of the flotation process. The ore minerals, coated with an oily collected layer, are hydrophobic and collect on the air bubbles the desired minerals float while the gangue sinks. Typical collectors are xanthates, dithiophosphates, or xanthate derivatives, whereas typical depressants are calcium or sodium cyanide [143-33-9] NaCN, andlime. 

Addition of hydrogen cyanide to an aldose to form a cyanohydrin is the first step in the Kiliani-Fischer method for increasing the carbon chain of aldoses by one unit. Cyanohydrins react with Grignard reagents (see Grignard reaction) to give a-hydroxy ketones. 

Cyanohydrin Synthesis. Another synthetically useful enzyme that catalyzes carbon—carbon bond formation is oxynitnlase (EC 4.1.2.10). This enzyme catalyzes the addition of cyanides to various aldehydes that may come either in the form of hydrogen cyanide or acetone cyanohydrin (152—158) (Fig. 7). The reaction constitutes a convenient route for the preparation of a-hydroxy acids and P-amino alcohols. Acetone cyanohydrin [75-86-5] can also be used as the cyanide carrier, and is considered to be superior since it does not involve hazardous gaseous HCN and also virtually eliminates the spontaneous nonenzymatic reaction. (R)-oxynitrilase accepts aromatic (97a,b), straight- (97c,e), and branched-chain aUphatic aldehydes, converting them to (R)-cyanohydrins in very good yields and high enantiomeric purity (Table 10). 

Halogenomethyl, hydroxymethyl and aminomethyl groups readily undergo displacement reactions with nucleophilic reagents. Both side-chain and nuclear substitution products have been obtained (Scheme 57). These two possibilities are exemplified by the reaction of furfuryl chloride with sodium cyanide (Scheme 58). 

MILLER - SNYDER Aiyl Cyanide Synthesis Synthesis of benzonitnies from aldehydes via oxime ethers Formation of p-cyanophenol from p nrtrobenzaldoxime and p-nitiobenzonitnle (used as a sometimes recyclable chain carrier)... 

Lehn s approach is slightly more complex than that illustrated above in that the diol is chloromethylated and then treated with cyanide. Hydrolysis then affords the diacid which may be carried through as shown. It should also be noted that once the bis-acyl halide is in hand, it may be treated directly with an open-chained amine to yield a lipophilic diazacrown, after reduction ... 

Reaction type 3 (equation 10), where the complete hetero-l,3-diene skeleton is incorporated into the newly formed ring system, occurs with compounds having both a nucleophilic center and an electrophilic center If these two functionalities are in positions 1 and 2, various types of six-membered ring systems become accessible 4,4-Bis(trifluoromethyl)-I,3-diaza-1,3-butadienes require only room temperature to react with acetyl cyanide to yield l,4,5,6-tetrahydropynmidin-6-ones [96] Likewise, certain open-chain 1,3-diketones (acetylacetone and acetoacetates) and the heterodiene form six-membered nng systems [97] (equation 19)... 

The special properties of lipoic acid arise from the ring strain experienced by oxidized lipoic acid. The closed ring form is approximately 20 kj higher in energy than the open-chain form, and this results in a strong negative reduction potential of about —0.30 V. The oxidized form readily oxidizes cyanides to isothiocyanates and sulfhydryl groups to mixed disulfides. 

Campaigne et al. have used 3-thenyl bromide obtained by benzoyl peroxide-catalyzed, side-chain bromination of 3-methylthiophene with A -bromosuccinimide, as a starting material for 3-substituted thiophenes. - 22 3-Methylthiophene is now prepared commercially from itaconic acid. The reactive halogen in 3-thenyl bromide could be directly reacted with a variety of nucleophiles, such as cyanide, or malonate, to give more complex 3-substituted compounds. 3-Thenyl bromide was converted by the Sommelet reaction to 3-thio-phenealdehyde which, with silver oxide, was oxidized to 3-thio-... 

Antispasmodic activity, interestingly, is maintained even in the face of the deletion of the ethanolamine ester side chain. Reaction of anisaldehyde with potassium cyanide and dibutylamine hydrochloride affords the corresponding a-aminonitrile (72) (a functionality analogous to a cyanohydrin). Treatment with sulfuric acid hydrolyzes the nitrile to the amide to yield ambucet-amide (73). ... 

Aminonitrile formation on 125 with potassium cyanide and piperidine hydrochloride affords the derivative, 135. Hydrolysis as above gives the corresponding amide (136). Debenzylation is accomplished by catalytic reduction. Alkylation of the secondary amine with the side chain (96) used in the preparation of diphenoxylate affords pirintramide (138) This compound, interest-... 

A remarkably simple fused indole devoid of the traditional side chains is described as an antidepressant agent. Michael addition of the anion from indole ester 119 to acrylonitrile affords the cyanide 120. Selective... 

Chain extension by means of the reaction of alkyl halides with cyanide is frequently alluded to but rarely employed, mainly because of the long reaction times and poor yields usually encountered. The use of DMSO as a solvent has greatly simplified the procedures and improved the yields of many ionic reactions, and the conversion of alkyl chlorides to nitriles is a good example. 

Schemes 15 and 16 summarize the syntheses of intermediates that represent rings A and D of vitamin Bi2 by the Eschenmoser group. Treatment of lactam/lactone 51, the precursor to B-ring intermediate 8 (whose synthesis has already been described, see Scheme 8), with potassium cyanide in methanol induces cleavage of the y-lac-tone ring and furnishes intermediate 76 after esterification of the newly formed acetic acid chain with diazomethane. Intermediate 76 is produced as a mixture of diastereomers, epimeric at the newly formed stereocenter, in a yield exceeding 95%. Selective conversion of the lactam carbonyl in 76 into the corresponding thiolactam...

Although the biosynthetic cascade hypothesis predicts the co-occurrence of endiandric acids D (4) and A (1) in nature, the former compound was not isolated until after its total synthesis was completed in the laboratory (see Scheme 6). Our journey to endiandric acid D (4) commences with the desilylation of key intermediate 22 to give alcohol 31 in 95% yield. The endo side chain is then converted to a methyl ester by hydrolysis of the nitrile to the corresponding acid with basic hydrogen peroxide, followed by esterification with diazomethane to afford intermediate 32 in 92% overall yield. The exo side chain is then constructed by sequential bromination, cyanide displacement, ester hydrolysis (33), reduction, and olefination (4) in a straight-... 

The shielding effect of the vicinal phenyl substituent accounts for the favored attack of the cyanide from the opposite direction, giving rise to the (S)-diastereomers. However, it should be noted that imines of aliphatic aldehydes which bear an odd number of carbons in the main side chain surprisingly give (/ )-diastereomcrs, concluded from ORD data48. This opposite stereochemical course in the formation of these compounds has not been explained48. It might simply be due to crystallization of the (R)-diastereomer which continuously shifts the equilibrium (vide supra). 

The most important complexes with C-donors, other than organometallics, are cyanides. AgCN has a structure with Ag—C-N-Ag bonding in linear polymeric chains it dissolves in excess KCN forming K+Ag(CN)2 (digonal with Ag-C 2.13A, i[Pg.288]

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