Cyanides from aldoximes

Some reviews on the preparation of cyanides from aldoximes [1045, 1046] and from carboxamides [1047,1048] are available. Often used dehydration reagents are acetic anhydride for aldoximes and phosphorus pentoxide for carboxamides. In the following sections, dehydration reactions affording cyanides are described with various dehydration reagents, classified into acidic and basic reagents. 

The preparation of cyanides by dehydration is best accomplished from aldoximes (standard method) rather than from carboxamides, because the former require milder reaction conditions. However, carboxamides, as carboxylic acid derivatives, are more easily accessible. Phosgene has been applied in the dehydration of carboxamides rather than of aldoximes. 

General procedure. Cyanides 1379 from aldoximes 1380 [1056] To an ice-cold, stirred solution of aldoxime 1380 (3 mmol) and triethylamine (1.2 mL, 8 mmol) in absolute dichloromethane (25 mL), a solution of triphosgene (0.33 g, 1.1 mmol) in di-chloromethane (20 mL) was added dropwise at 0-5 °C over a period of 15 min. The mixture was stirred at the same temperature for 1 h, and then washed successively with water (10 mL), 0.1 N aq. HCl (20 mL), 10% aq. NaHC03 (20 mL), and brine (15 mL). The separated organic layer was dried (Na2S04) and concentrated, and the crude product was purified by passage through a short column of silica gel. 

A route to bis-annulated pyranosides has been developed involving intermediate cyanides derived from aldoximes by dehydration with TFAA [1081]. 

Then again, many elimination reactions are found to occur much, more readily in that member of a pair of geometrical isomerides in which the atoms or groups to be eliminated are trans to each other than in the isomer in which they are cis (p. 255). As is seen in the relative ease of elimination from and and syn aldoxime acetates to yield the same cyanide ... 

The methods used for preparing cyanobenzo[6]thiophenes are merely summarized in the present section they are discussed in more detail elsewhere in this review. Cyanobenzo[6]thiophenes are most conveniently prepared by heating a halobenzo[6]thiophene with cuprous cyanide in a suitable solvent (Section VI, D, 2), or by means of a Sandmeyer reaction of the appropriate diazotized amine (Section VI, F, 4 and 5). Less commonly they are prepared from aldehydes or aldoximes, by methods described in Section VI, L, 1, or from carbox-... 

When l-[14C]methyl-pyridinium aldoxime iodide or radioactive pralidoxime [14C]-labelled in the oxime group was parenterally administrated to rats, 90% of the radioactivity was recovered in urine and 6% in the faeces, irrespective of the position of the label. About 90% of the urinary radioactivity was associated with intact pralidoxime. In addition, some 5% of the dose was excreted as l-methyl-2-pyridone, indicating some cyanogenesis (Enandcret al., 1962). In humans, the l-methyl-2-cyanopyridinium ion was detected in urine of male volunteers without significantly increased urinary thiocyanate. Since 90% of pralidoxime chloride, 5 mg kg 1 IV, was recovered from urine, cyanide formation is probably of no toxicological concern (Garrigue etal., 1990). 

The cyanides 1408-1412 have all been synthesized by dehydrating their carbox-aldoximes with acetic anhydride [1070-1074]. A pteridine synthesis yielded 75% of 6-cyano-l,3-dimethyUumazine 1408 [1070]. N-Acetyl (3-phenyl-l,2,4-triazolo-5-yl)-thiolacetonitrile 1409 was obtained as the condensation product from a triazole derivative and chloro acetaldehyde, followed by oximation and dehydration, in 79% yield [1071]. endo-l-Cyano-3-acetoxy-8-oxabicyclo[3.2.1]oct-6-ene 1410 (89%) is an intermediate in the synthesis of ll-oxatricyclo[5.3.1.0 Jundecane [1072]. A synthesis of loi,25-dihydroxY-18-norvitamin Dj and la,25-dihydroxy-18,19-dinorvitamin Dj requires the 8j8-acetoxy-des-A,B-cholestane-18-nitrile 1411 (86%) [1073]. A new route to spirooxindoles, a tricyclic system found in a number of interesting natural products, requires the cyanide 1412 (72%) as a key intermediate [1074]. 

PROBLEM 18.47 In Section 18.12c, we saw that primary amides could be dehydrated to nitriles (cyanides) with P2O5. Nitriles can also be prepared by treating aldoximes (1) with dehydrating agents such as acetic anhydride. Propose a mechanism for the formation of benzonitrile from the reaction of 1 with acetic anhydride. How are oximes prepared ... 

In the presence of Triethylamine, PI3 or P2l4 effects the conversion of aldehyde oximes or primary nitro compounds to nitriles. For example, treatment of the aldoxime derived from phenylac-etaldehyde with 1 equiv of PI3 (CH2Cl2-Et3N, 25 °C, 15 min) affords benzyl cyanide in 83% yield (eq 10). Similarly, treatment of 1-nitrodecane with 2 equiv of PI3 (CH2Cl2-Et3N, 25 °C, 15 min) affords 1-cyanononane (82%) (eq 11). Other reagents for the direct conversion of primary nitro compounds to nitriles include Sn(SPh)4/Ph3P/DEAD, TMSI, Sulfur Dioxide and Phosphorus(III) Chloride. ... 

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