Ethylenic acyl cyanides IV : Intramolecular ene cyclisation of 5-methyl-5-hexenoyl cyanides to 3-methyl-2-cyclohexenones

Condensation of methallyltrimethylsilanes with α,β-ethylenic acyl cyanides leads to 5-methyl-5-hexenoyl cyanides which after thermal cyclisation give 3-methyl-2-cyclohexenones and hydrogen cyanide.     

DBU catalyzed cyanoacylation of ketones with acyl cyanides

The reaction of cyclohexanone with benzoyl cyanide catalyzed by amines provides the corresponding O-benzoyl cyanohydrin adducts in moderate to good yields under mild conditions. Among the catalysts, DBU was found to be the most effective promoter allowing the reaction to proceed smoothly at room temperature and to give the corresponding O-acyl cyanohydrin adducts in higher yields for a variety of substituted cyclohexanones, cyclopentanone, acetone or pentan-3-one and various acyl cyanides.     

Synthesis of α-aminoketones via selective reduction of acyl cyanides

Reduction of acyl cyanides with zinc in acetic acid in the presence of excess acetic anhydride leads to N-acetyl-α-aminoketones in good yields. An efficient three-step synthesis of 5-aminolevulinic acid by this method is described.     

Ruthenium catalyzed oxidation of cyanohydrins to acyl cyanides useful reagents for selective N-benzoylation of aminoalcohols

Ruthenium catalyzed oxidation of cyanohydrins with tert-butyl hydroperoxide gives the corresponding acyl cyanides in good to excellent yields. Acyl cyanides thus obtained are useful reagents for selective N-benzoylation of aminoalcohols.     

Proline-catalyzed aldol reactions of acyl cyanides with acetone: an efficient and convenient synthesis of 1,3-diketones

The aldol-type addition of acetone towards (un)substituted benzoyl, heteroarylcarbonyl or α,β-unsaturated acyl cyanides was efficiently catalyzed by l-proline (30 mol %) to give 2-hydroxy-4-oxo-2-substituted pentanenitriles. Upon the treatment with sodium hydroxide, the adducts transformed to 1,3-diketones in good-to-excellent yield, furnishing an efficient and convenient method for the regioselective synthesis of 1,3-diketones.     

Alkyl phosphines promoted reductive coupling of acyl cyanides: formation of O-acyl cyanohydrins

The reductive coupling of acyl cyanides promoted by alkyl phosphines has been discovered. Under mild reaction conditions, the substituted cyanohydrins were obtained in moderate to high yields by using trimethylphosphine or tributylphosphine as a promoter. The possible mechanism involved in the reaction was discussed on the basis of deuterium labeling and control experiments, indicating that one hydride transfer took place from alkyl phosphine to O-acyl cyanohydrin.     

Reactions of acetylenic β-keto cyanides and β-keto esters with different ammonia derivatives

Different aryl substituted acetylenic β-keto cyanides (IAa-o) and β-keto esters (IBa-o) reacted with each of hydrazine hydrate, phenylhydrazine, hydroxylamine hydrochloride and semicarbazide hydrochloride in boiling alcohol to give the same heterocyclic nucleus for each type of ammonia derivative. In certain cases, intermediate acetylenic hydrazides were isolated at room or zero temperatures and cyclized to give the appropriate pyrazol-5-one compounds when healed above their melting points. It is concluded that Michael addition is favoured at elevated temperatures and Claisen addition is favoured at lower temperatures.     

Tributyltin cyanide: A facile cyanating agent of acyl chlorides

Tributyltin cyanide was prepared from tributyltin chloride and potassium cyanide, and was found to be an efficient cyanation agent for acyl chlorides to give acyl cyanides in excellent yields.     

Halodephosphorylation of α,β-unsaturated phosphonic acid monoesters

Reaction of α,β-ethylenic and acetylenic phosphonic acid monoesters with (biscollidine)iodine(I) or (biscollidine)bromine(I) hexafluorophosphate led to α,β-unsaturated halides by, without precedent, dephosphorylation reactions.     

Room temperature palladium catalysed coupling of acyl chlorides with terminal alkynes

Conditions are reported for the facile, high-yielding coupling of acyl chlorides with terminal alkynes in a reaction involving palladium and copper iodide; the reaction is tolerant of a wide variety of acyl chlorides and terminal alkynes and provides a convenient one-pot route to acetylenic ketones.     

Hetero-Diels-Alder cycloadditions of α,β-unsaturated acyl cyanides. Part 2. Reactions with N,N-dimethyluracils,a new route to 5-substituted uracil derivatives

The [4 + 2] cycloadditions of 2-oxobut-3-enenitrile ( 1a ), 2-oxopent-3-enenitrile ( 1b ), and ethyl 4-cyano-4-oxobut-2-enoate ( 1c ) with 1,3-dimethyluracil ( 2 ), 1,3, 6-trimethyluracil ( 9 ), or 1,3,5-trimethyluracil ( 16 ) were investigated. The reactions of 1a with 2 or with 9 lead to bicyclic adducts 3 and 10 , respectively. These hexahydro-cis-pyranopyrimidines undergo ring opening under acidic conditions, restoring in 4 and 11 , respectively, an uracil system comprising 2-hydroxybut-2-enenitrile as a side chain at C(5). The surprisingly stable enols tautomerize slowly to the corresponding acyl cyanides 6a and 13a , respectively. Reacting 1b or 1c with 2 and with 9 does not afford cycloadducts; instead the uracil derivatives 6b, c and 13b, c , respectively, show up, carrying at C(5) α-oxobutanenitrile side chains. Cleavage of the acyl cyanide functions in 6a–c and 13a–c with nucleophilic agents produces various acids, esters, or amides, i.e. derivatives 8a–c and 15–c , respectively. The methyl esters 8a (X ? MeO, R ? H) and 15a (X ? MeO, R ? H) are also formed directly from the adducts 3 and 10 , respectively, with acid or base catalysis in presence of MeOH. The cycloadducts 17a and 17c , resulting from the reaction of 1a and 1c with 16 , respectively, have a Me group at the ring junction C(4a) and are stable. The structure of 17c proves that this hetero-Diels-Alder addition of inverse electron demand follows the endo-mode.     

Tandem nucleophilic addition/fragmentation reactions and synthetic versatility of vinylogous acyl triflates

A thorough analysis of the chemistry of vinylogous acyl triflates provides insight into important chemical processes and opens new directions in synthetic technology. Tandem nucleophilic addition/C-C bond cleaving fragmentation reactions of cyclic vinylogous acyl triflates 1 yield a variety of acyclic acetylenic compounds. Full details are disclosed herein. A wide array of nucleophiles, such as organolithium and Grignard reagents, lithium enolates and their analogues, hydride reagents, and lithium amides, are applied. The respective reactions produce ketones 2, 1,3-diketones and their analogues 3, alcohols 4, and amides 5. The present reactions are proposed to proceed through a 1,2-addition of the nucleophile to the carbonyl group of starting triflates 1 to form tetrahedral alkoxide intermediates C, followed by Grob-type fragmentation, which effects C-C bond cleavage to yield acyclic acetylenic compounds 2-5 and 7. The potent nucleofugacity of the triflate moiety is channeled through the sigma-bond framework of 1, providing direct access to the fragmentation pathway without denying other typical reactions of cyclic vinylogous esters. The synthetic versatility of vinylogous acyl triflates, including functionalization reactions of the cyclic enone core (1 --> 6 or 8), is also illustrated.     

Mass spectrometry in structural and stereochemical problems. Part CLIII. Electron impact-promoted fragmentation of n-alkyl cyanides

In spite of previous extensive studies on the mass spectrometry of alkyl cyanides, no good mechanistic insight has as yet been gained into the behavior of straight chain alky1 cyanides. For this reason the possible origins for the principal ions in the mass spectrum of a typical alkyl cyanide (n-hexyl cyanide) have been determined using high resolution mass spectrometry anddeuterium labeling of every carbon atom. The results lead to the conclusion that most of the typical fragmentation processes of n-alkyl cyanides proceed through cyclic intermediates.     

A controllable synthesis of homoallyl ketones and multiply substituted cyclopentadienes by direct insertion of aroyl cyanides to zirconacyclopentenes

[reaction: see text] The direct reaction of aroyl cyanides with zirconacyclopentenes was achieved cleanly under controlled reaction conditions. This methodology provided an extremely efficient, one-pot, and high-yield route for the synthesis of homoallyl ketones when the reaction was carried out at -50 degrees C. Trapping of the zirconium intermediate by a variety of electrophiles afforded functionalized homoallyl ketones. Remarkably, the insertion reaction occurred with complete chemoselectivity, that means, the Zr-sp3 carbon bond reacted preferentially, which is different from Cu-mediated elaboration of zirconacycles. Surprisingly, when the reaction was done at room temperature, 1,2,3-trisubstituted cyclopentadiene derivatives were readily formed in high yields. The direct insertion reaction of zirconacyclopentanes with acyl cyanides was also described. When bicyclic zirconacyclopentanes were used, cyclopentanol derivatives were obtained with high stereoselectivity.     

Synthesis and biological activities of 5′-ethylenic and acetylenic modified l-nucleosides and isonucleosides

Two series of 6′-halovinyl-adenosine stereoisomers including 5′-ethylenic and acetylenic substituted l-adenosine, 5′-ethylenic and acetylenic substituted isonucleosides were synthesized. In the l-nucleoside series, compounds 6b, 8b, 10b and 13b showed modest inhibition of SAH hydrolase (21, 44, 50 and 26% respectively) at 100 μM. The l-isomers of 5′-ethylenic and acetylenic modified isonucleoside 23, 24 exhibited no activity for the inhibition of SAH hydrolase, however, the d-isomers 30 and 31 showed some activities in the same test (35 and 21%). It indicated clearly the strict stereochemical requirement for the substrate of SAH hydrolase. Compounds 6b, 8b, 8c, 11b exhibited modest to good inhibition effects on the growth of HeLa cells or Bel-7420 cells at 1 μM (64, 44, 53 and 82% respectively).     

Étude de l'addition des organozinciques α-éthyléniques aux amines éthyléniques,acétyléniques et alléniques

The general features and the field of application of a new reaction, that of addition of α-ethylenic organozinc compounds to unsaturated (ethylenic, acetylenic and allenic) amines, have studied. It is shown by numerous examples that this reaction constitutes a general method of synthesis for mono- and di-ethylenic amines.     

Removal of cyanides by electrooxidation

The paper describes a study on electro-oxidation of cyanides complexed with copper, present in metal plating wastewater. A detailed voltammetric study has indicated that formation in situ of the electrocatalytic film of copper oxide and electro-oxidation of cyanides probably occurs at the same anode potential. By contrary to other materials at which electro-oxidation of cyanide also occurs, at copper oxide elimination of cyanide occurs at a potential lower then the potential of hydroxide ion discharge.     

Selective separations by reactive ion exchange: Part II. preconcentration and determination of complex iron cyanides in waters

Reactive ion exchange has been applied to the determination of p.p.b. concentrations of hexacyanoferrate(II) and hexacyanoferrate(III) in various water matrices. The in situ precipitation of copper hexacyanoferrate(II) or hexacyanoferrate(III) preconcentrates the complex cyanides on shallow beds of sulfonated cation-exchange resin in the copper(II) form. Hydrochloric acid reactively elutes other cations including concomitant iron species from the resin bed and, finally, aqueous ammonia reactively releases and elutes the hexacyanoferrate(II) (or III) species through the formation of the copper-ammine complex. Preconcentration factors of 100 or more are possible when 1-1 samples are used. Final determination of the complex cyanides is performed by atomic absorption spectrometry (for iron).     

A novel stereospecific synthesis of glycosyl cyanides from 1,2-O-sulfinyl derivatives

[reaction: see text] An efficient synthesis of 1,2-trans-glycosyl cyanides via 1,2-O-sulfinyl monosaccharides is described. Such S(N)2-type displacements at the anomeric center are stereospecific and are best performed with sodium cyanide in the presence of ytterbium triflate. Significantly, the resulting 1,2-trans-glycosyl cyanides have a free hydroxyl group at C-2 ready for further modification.     

Synthesis of 1,2-Dihydropyridines, 2,3-Dihydro-4(1H)-pyridinone,and 1,2,3,4-Tetrahydropyridines via N-Acyl N,O-Hemiacetal Formation

New procedures are described for the synthesis of α,β-ethylenic and acetylenic aldehydes from 2-butene- and 2-butyne-1,4-diol, respectively (see Scheme 1). These are applied to the preparation of a particular δ-acetylamino-α,β-ethylenic aldehyde ((E)- 5 ) as well as of its acetylenic analogue 15 . On heating in the presence of a silyl enol ether, the former undergoes a complete dehydrative cyclization affording the N-acetyl-1,2-dihydropyridine 19 . The addition of HCl to aldehyde (E)- 5 results in the production of the 4-chloro-1,2,3,4-tetrahydropyridine 22 which is hydrolyzed to the corresponding alcohol 23 on silica gel. Similarly, the addition of HCl or HBr to the δ-acetyl-amino-α,β-acetylenic aldehyde 15 leads to the previously unknown 4-halo-1,2-dihydropyridines 26 ; these are easily hydrolyzed to the 2,3-dihydro-4(1H)-pyridinone 27 . The ring-forming process involves a N-acyl N,O-hemiacetal as intermediate which is eventually dehydrated.