Elimination of hydrogen cyanide

The stereospecific generation of enamines by -elimination reactions (187) and a vinylogous elimination, which leads to a dienamine (188), have been reported. The loss of an a substituent from a tertiary amine is seen in the generation of enamines by elimination of hydrogen cyanide from benzylic a-aminonitriles (189,190). 

An approach to isobacteriochlorins1 ln-e makes use of Pd(II) or metal-free bilatrienes 1 as starting materials. Cyclization of the corresponding bilatriene derivatives is induced by base in the presence of palladium(II) or zinc(II) which exercise a template effect. Zinc can be readily removed from the cyclized macrotetracycles by acid whereas palladium forms very stable complexes which cannot be demetalated. Prior to the cyclization reaction, an enamine is formed by elimination of hydrogen cyanide from the 1-position. The nucleophilic enamine then attacks the electrophilic 19-position with loss of the leaving group present at the terminal pyrrole ring. 

Grigg et a/.472,473 reported the first examples of the elimination of hydrogen cyanide and nitriles in retrocycloaddition reactions. The oxazoles 4 (R = H or Me) with DMAD in cold ether led directly to the furan 6 and the appropriate nitrile the expected intermediate 5 could not be isolated. The less reactive oxazole 7 was converted by DMAD into the furan 8 (69%) and benzonitrile only in boiling toluene about 10%... 

The 2-pyrazolines 199 arise from the reactions of C-heteroarylhydrazo-noyl halides 27, 28b, and 30e with a-cyanocinnamic acid derivatives 198 in chloroform in the presence of triethylamine. In some cases, products 199 undergo elimination of hydrogen cyanide as soon as they are formed... 

Two groups have independently observed an interesting product when the vinyl azide (61) is thermolyzed.30 31 Bauer and Hafner have isolated the azirine (62) by low-temperature photolysis of 61 and have shown that thermolysis of this azirine also leads to 170.31 Apparently, elimination of hydrogen cyanide occurs to give 9-fluorenylidene carbene (171), which then reacts with azirine (62) to give the final product. 

Elimination of hydrogen cyanide was favored over that of acetylene in the rearomatization step. The ratio of hydrogen cyanide to acetylene in the exit gases was not identical with that predicted from the analysis of the less volatile products this was probably due to secondary pyrolytic transformations of both gases under the reaction conditions. Such transformations were found in separate pyrolyses of hydrogen cyanide and acetylene alone. 

Bond formation through carbanions of type B has been much more widely used. A versatile isoindole synthesis (Scheme 24a) proceeds through intramolecular carbanion addition to an aryne. The subsequent aromatization is effected by base promoted elimination of hydrogen cyanide (77T2255). 

The monobenzo compound (107 R1=R2 = H) forms a stable salt with methyl iodide. Reaction with TCNE results in elimination of hydrogen cyanide and formation of the tricyanovinyl derivative (107 R1 = C(CN)=C(CN)2, R2 = H) (67JA2626). 

The bicyclic species (111) are unknown but some reactions of the monobenzo (112) and dibenzo (113) species have been described and they closely resemble those of the isomeric betaines (107) and (108) (Section 4.37.4.4). Electrophilic substitution occurs on the ben-zenoid rings of compound (113) and treatment with methyl iodide slowly gives an adduct. The monobenzo derivative is more reactive, readily giving a methiodide and rapidly undergoing electrophilic substitution reactions. Reaction of compound (112 R = H) with TCNE results in elimination of hydrogen cyanide and formation of the tricyanovinyl derivative (112 R = C(CN)=C(CN)2) (67JA2633). 

The formation of alkylselenocyanates by nucleophilic substitution at the sp carbon atom with potassium selenocyanate (KSeCN) followed by the elimination of hydrogen cyanide or its equivalent has been used for the generation of selenoaldehydes [56,57a,b],selenoketones [57c],and a-acyl selenoamides [58]. Alternatively, the acylation of KSeCN effectively takes place at the nitrogen atom to form acyl selenoisocyanates, that have been trapped with amines [59 a] or tellurols (Eq. 18) [59b]. 

Fragmentation of oxohydropurines such as hypoxanthine, xanthine and uric acid is similar to that of guanine, the main route involving elimination of hydrogen cyanide from N(l)—C(2), followed by ejection of CO and HCN. Xanthine and uric acid eject HCNO followed by decarbonylation (67JA2719, 62M632). Also see (B-72MI40902, p. 402) for a mass spectral study of N- and S-methylpurines. 

Reaction with alcohols. In the presence of urea, TCNE reacts with alcohols, for example ethylene glycol, with elimination of hydrogen cyanide. " The product. 

Dipolar addition of pyridinium dicyanomethanide to 2,3-diphenylcyclopropenone in refluxing acetonitrile produced, with elimination of hydrogen cyanide, the 2//-quinolizin-2-one 4 in 58% yield. ... 

Probably the most useful and general reaction of all these systems is the inverse-electron-demand Diels-Alder reaction with acetylenes (or equivalents) to produce either pyridines or diazines via elimination of hydrogen cyanide, a nitrile or nitrogen. ... 

Malononitrile (in THE at 20-25 °C overnight) and cyanoacetamide (in water at 20-25 °C for 5 days) react with pteridines, e.g. I, to give pyrido[2,3-6]pyrazines, e.g. 2, by addition across the 3,4-bond followed by scission of that bond and a nitrogen-eliminating recyclization. The intermediate of the reaction with cyanoacetamide can be isolated by addition of aqueous sodium hydroxide. Because the product from malononitrile can be generated under anhydrous conditions, it can be concluded that the reaction takes place by a concerted cyclization of the amidine intermediate with elimination of hydrogen cyanide, rather than via a pyridazinamine which could arise by hydrolysis of this amidine (cf. similar reactions in other fused pyrimidine series).56,64-66... 

Benzodithiazines (214) reacted with dimethyl alkynedicarboxylate in boiling o-dichlorobenzene to give 2,3-bis(methoxycarbonyl)-1,4-benzodithiins (215) in good yields with elimination of hydrogen cyanide or a nitrile <82CC612>. 

The fate of the bicyclic Diels-Alder adducts derived by the interaction of oxazoles with dienophiles containing a triple bond is very different from those considered above. In such cases ready elimination of hydrogen cyanide or a nitrile by the retro-diene cycloaddition mechanism (also called retro-Diels-Alder reaction) is generally observed. Typically, the reaction of 5-ethoxyoxazoles (199) with dimethyl acetylenedicarboxylate... 

Very closely related to decarbonylation of an -hydroxy acid is the Wohl degradation, in which an -hydroxy aldehyde is degraded to the aldehyde with one fewer carbon atoms. This starts from the oxime, which is converted by removal of water into the hydroxy nitrile, whence elimination of hydrogen cyanide — analogous to that of carbon monoxide and water from an -hydroxy acid — affords the lower aldehyde ... 

Azomethine ylides can also be trapped by aryl trifluoromethyl alkynes. When l-t-butyl-2-cyano-aziridine was used, a pyrrole was formed by elimination of hydrogen cyanide <94S287>. Use of aziridine-2-carboxylate esters with this dipolarophile gave regioisomeric mixtures of dihydropyrroles which could be converted to pyrroles by oxidation with ddq (Equation (60)). 

The mass spectra of various purine bases have been analyzed by high resolution mass spectrometry (89). The spectra are characterized by the appearance of very intense molecular ion peaks. The mass spectrum of adenine, for example, is characterized by peaks at m/e 108, 81 and 54 due to excessive elimination of hydrogen cyanide from the Mt. Another example is 6-methylaminopurine, which loses 28 or 29 mass units from... 

Scheme 11.15. An example of the Wohl degradation. The anomers of D-glucose (i.e., the isomers that are epimeric at the anomeric carbon) can be considered as the aldehyde rather than the hemiacetals. Formation of the oximes (presumably both ( )- and (Z)-oxime isomers form) followed by acetylation results in elimination to the nitrile. Hydrolysis of the remaining acetates is accompanied by elimination of hydrogen cyanide and formation of an aldehyde with one carbon less than the aldehyde with which the sequence began. Thus, both mannose and glucose yield arabinose.

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