Trans-3- - -nitril

Unsolvated potassium cyanide and hydrazone dissolve as the reactants are converted to the thermodynamically favored trans-nitrile. Shortly after all of the solid dissolves, a second solid precipitates from solution. This solid is presumed to be potassium mesitylenesulfinate and is usually accompanied by some foaming. An oversize flask used with efficient stirring keeps the reaction mixture from foaming into the condenser. 

Improved efficiency in the synthesis of 24 was ultimately achieved via an enzymatic desymmetrization approach (Scheme 7). In the key step of this route, an asymmetric oxidation of achiral amine 41 promoted by monoamine oxidase (MAON) under an oxygen atmosphere afforded intermediate 42. In this streamlined process, sodium bisulfite was included in the enzymatic oxidation mixture to effect direct conversion to sulfonate 44. Treatment of 44 with sodium cyanide provided the trans-nitrile 43 as a single diastereomer in approximately 90% yield from pyrrolidine 41. As in the second-generation synthesis, the nitrile is hydrolyzed to the methyl ester under Pinner conditions (HCI, methanol). In the manufacturing process, the product was converted to its free base using NaOH, then crystallized as the HCI salt from i-propanol and methyl t-... 

The oxidation of 130 by oxygen under pressure was developed af lab scale. Under optimal conditions, the substrate/bisulfite mixture was added to a solution of 130 (3.9 g/1), MAON401 and catalase over 20h. Substrate 130 (65g/l) was converted to sulfonate 133 with a small amount of 131 (<10%). The enzyme reaction stream was telescoped for cyanation to afford only trans-nitrile 134 in 90% yields from 130. Subsequenfly the nitrile was transformed to the methyl ester and the product was converted to the free base 132. In the final step the free base was crysfallized to afford 135 in 56% yield and >99% ee. The conditions of the procedure were successfully applied to pilot plant scale. Compared with the resolution method in the enzymatic process the product yield was increased by 150%, raw material use was reduced by 59.8%, consumption of water was reduced by 60.7%, and the overall process waste was reduced by 63.1% [167]. 

The trans-1,4 configuration predominates but there are also small amounts of the three other isomeric stmctures, ie, cis-1,4, -1,2, and -3,4. It was one of the first synthetic mbbers produced in the United States as early as 1931, by the Du Pont Co., because of its good solvent resistance. Its Du Pont trade name is neoprene. Even though it is not as solvent resistant as nitrile mbber, it has many other advantageous properties (see Elastomers,... 

In a copolymer of 33% acrylonitrile, the most common composition for commercial products, the butadiene occurs in the approximate ratio of 90% trans, 8% vinyl, and 2% cis. At higher acrylonitrile content the cis configuration disappears, and at lower levels it increases to about 5% the vinyl configuration remains approximately constant (6,7). Since actual compositions of commercial nitrile mbbers are between 15 and 50% acrylonitrile, they also vary somewhat in sequence distribution and in the content of the three isomeric butadiene configurations. 

In a manner analogous to classic nitrile iinines, the additions of trifluoro-methylacetonitrile phenylimine occur regiospecifically with activated terminal alkenes but less selectively with alkynes [39], The nitnle imine reacts with both dimethyl fumarate and dimethyl maleate m moderate yields to give exclusively the trans product, presumably via epimenzation of the labile H at position 4 [40] (equation 42) The nitrile imine exhibits exo selectivities in its reactions with norbornene and norbornadiene, which are similar to those seen for the nitrile oxide [37], and even greater reactivity with enolates than that of the nitnle oxide [38, 41], Reactions of trifluoroacetomtrile phenyl imine with isocyanates, isothiocyanates, and carbodiimides are also reported [42]... 

Auch ungesattigte Nitrile werden mit Chrom(II)-sulfat reduziert. So erhalt man z. B. in quantitativer Ausbeute aus Acrylnitril in Wasser Propansdure-nitril1 bzw. aus trans-2,3-Diphenyl-fumarsaure-dinitril in Dimethylformamid/Wasser (1 2) zu 84% d.Th. eine 1 1-Mischung aus meso- und u,. -2,3-Diphenyl-bemsteinsdure-dinitril. ... 

Both cis- and trans-chrysanthemic nitriles and amides were resolved into highly enantiopure amides and acids by Rhodococcus sp. whole cells [85]. The overall enantioselectivity of reactions of nitriles originated from the combined effects of a higher (lJ )-selective amidase and a (IJ )-selective nitrile hydratase (Figure 6.29). Chrysanthemic acids are related to constituents of pyrethrum flowers and insecticides. 

Chiral tricyclic fused pyrrolidines 29a-c and piperidines 29d-g have been synthesized starting from L-serine, L-threonine, and L-cysteine taking advantage of the INOC strategy (Scheme 4) [19]. L-Serine (23 a) and L-threonine (23 b) were protected as stable oxazolidin-2-ones 24a and 24b, respectively. Analogously, L-cysteine 23 c was converted to thiazolidin-2-one 24 c. Subsequent N-allylation or homoallylation, DIBALH reduction, and oximation afforded the ene-oximes, 27a-g. Conversion of ene-oximes 27a-g to the desired key intermediates, nitrile oxides 28 a-g, provided the isoxazolines 29 a-g. While fused pyrrolidines 29a-c were formed in poor yield (due to dimerization of nitrile oxides) and with moderate stereoselectivity (as a mixture of cis (major) and trans (minor) isomers), corresponding piperidines 29d-g were formed in good yield and excellent stereoselectivity (as exclusively trans isomers, see Table 3). 

The above methodology has been extremely useful for the synthesis of a variety of INOC precursors. For instance, treatment of 0-trimethylsilyl a-bro-moaldoximes 52b, e, f with F ion in presence of unsaturated alcohols 57 produces oximino ethers 58 which can be readily oxidized using NaOCl (Scheme 8) [29]. The transient nitrile oxide intermediates formed undergo spontaneous cyclization to fused isoxazolines 59. The preferred stereoisomer in the formation of the five-membered ring ethers is trans whereas in the six-membered ring ethers the cis isomer predominates (see Table 5). MM2 calculations helped rationalize the experimentally observed stereoselectivites (see Table 5). 

S (2)-hydroxy-3-butenenitrile from acrolein and HCN trans hydrocyanation using, for instance, acetone cyanohydrin Hydrolysis of nitriles to amides, e.g. acrylonitrile to acrylamide Isomerization of glucose to fructose Esterifications and transesterifications Interesterify positions 1 and 3 of natural glycerides Oxidation of glucose to gluconic acid, glycolic acid to glyoxalic acid... 

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