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A chemodosimteric reagent (1) for the efficient detection of cyanide species (CN- and/or HCN) in aq. medium as well as under physiological conditions has been described. Selective reaction of the cyanide species with this reagent in the presence of all common interfering anions, amino acids and glutathione (GSH) led to the generation of the corresponding cyanohydrin derivative. The formation of the cyanohydrin derivative of the probe is associated with a visually detectable change in solution fluorescence in aq. buffer medium with 1.9 mu M NaCN, the threshold limit set by WHO for the safe drinking water and this makes this fluorogenic sensor an ideal candidate for in-field applications. An apparent switch on the luminescence response, ultralow detection limit, low response time, cell membrane permeability and insignificant toxicity are key features of a probe molecule, which gives it a distinct edge over previously reported chemodosimetric reagents for the detection of cyanide species (CN- or HCN) in an aqueous environment. This methodology could be used for developing a generalized and efficient fluorescence-based assay for crucial enzymes like beta-glucosidase and hydroxynitrile lyase. Furthermore, spectrally-resolved fluorescence microscopy measurements on single-cells revealed that this sensor molecule could also be used for imaging the cellular uptake of cyanide species from aq. solution contaminated with NaCN. Our results confirmed that statistical analysis of integrated intensity and transition energy obtained from the emission spectra collected over various microscopic sub-cellular regions can potentially be used to discriminate the effects of local cellular environments and that due to cyanide detection.

Here we present a systematic investigation of the cyanosilylation of aldehydes with trimethylsilyl cyanide (TMSCN) by using metal–organic frameworks (MOFs) as catalysts. Four types of thermally stable MOFs (MIL-47 (V), MIL-53 (Al), MIL-101 (Cr), and UiO-66 (Zr)) constructed with the same organic linker, terephthalic acid, were studied, among which MIL-101 (Cr) exhibits the highest catalytic activity. Experimental results revealed that the catalytic activities are in close relation with the types of coordinatively unsaturated metal ions, pore sizes as well as solvents. Using MIL-101 (Cr) as the catalyst, both aliphatic and aromatic aldehydes were efficiently transformed to cyanohydrin trimethylsilyl ether, meanwhile significant size selectivities and electronic effects have also been observed. The solvent-free reaction conditions not only provide a high TON for MOF catalyzed cyanosilylation, but also render the current protocol more attractive to industrial applications.

Hydroxynitrile lyases (HNLs) catalyse the reversible cleavage of cyanohydrins to carbonyl compounds and HCN. The recent discovery of bacterial HNLs with a cupin fold gave rise to a new promising class of these enzymes. They are interesting candidates for the synthesis of cyanohydrins on an industrial scale owing to their high expression levels in Escherichia coli. The activity and enantioselectivity of the manganese-dependent HNL from Granulicella tundricola (GtHNL) were significantly improved by site-saturation mutagenesis of active site amino acids. The combination of beneficial mutations resulted in a variant with 490-fold higher specific activity in comparison to the wild-type enzyme. More importantly, GtHNL-A40H/V42T/Q110H is a highly competitive alternative for the synthesis of chiral cyanohydrins, such as 2-chlorobenzaldehyde cyanohydrin, (R)-2-hydroxy-4-phenylbutyronitrile, and (R)-2-hydroxy-4-phenyl-3-butene nitrile, which serve as intermediates for the synthesis of pharmaceuticals.

Cyanide ions are shown to interact with lanthanide complexes of phenacylDO3A derivatives in aqueous solution, giving rise to changes in the luminescence and NMR spectra. These changes are the consequence of cyanohydrin formation, which is favored by the coordination of the phenacyl carbonyl group to the lanthanide center. These complexes display minimal affinity for fluoride and can detect cyanide at concentrations less than 1 μm. By contrast, lanthanide complexes with DOTAM derivatives display no affinity for cyanide in water, but respond to changes in fluoride concentration.

Hydroxynitrile lyases (hnls) catalyze the conversion of chiral cyanohydrins to hydrocyanic acid (hcn) and aldehyde or ketone. hydroxynitrile lyase from arabidopsis thaliana (athnl) is the first r-selective hnl enzyme containing an /-hydrolases fold. in this article, the catalytic mechanism of athnl was theoretically studied by using qm/mm approach based on the recently obtained crystal structure in 2012. two computational models were constructed, and two possible reaction pathways were considered. in path a, the calculation results indicate that the proton transfer from the hydroxyl group of cyanohydrin occurs firstly, and then the cleavage of c1-c2 bond and the rotation of the generated cyanide ion (cn-) follow, afterwards, cn- abstracts a proton from his236 via ser81. the c1-c2 bond cleavage and the protonation of cn- correspond to comparable free energy barriers (12.1 vs. 12.2 kcal mol(-1)), suggesting that both of the two processes contribute a lot to rate-limiting. in path b, the deprotonation of the hydroxyl group of cyanohydrin and the cleavage of c1-c2 bond take place in a concerted manner, which corresponds to the highest free energy barrier of 13.2 kcal mol(-1). the free energy barriers of path a and b are very similar and basically agree well with the experimental value of hbhnl, a similar enzyme of athnl. therefore, both of the two pathways are possible. in the reaction, the catalytic triad (his236, ser81, and asp208) acts as the general acid/base, and the generated cn- is stabilized by the hydroxyl group of ser81 and the main-chain nh-groups of ala13 and phe82. proteins 2015; 83:66-77. (c) 2014 wiley periodicals, inc.

This thesis describes the development and rationalization of processes involved in a new methodology developed in our group, minor enantiomer recycling.The first part of the thesis addresses mechanistic studies of one of the reactions involved in minor enantiomer recycling, dual Lewis acid-Lewis base catalyzed acetylcyanation of aldehydes. The methodology uses a combination of a chiral titanium-salen complex with a tertiary amine as a catalytic system in the enantioselective synthesis of O-acylated cyanohydrins from aldehydes and ketonitriles. Mechanistic investigations revealed that the rate-determining step in the reaction changes, depending on the nature of the aldehyde that was used. It was also concluded that cyanohydrin is coordinated to the Lewis acid in the acylation step.The second part of the thesis deals with minor enantiomer recycling, a highly selective one-pot recycling system. In a first step the product is formed as a minor and a major enantiomer by asymmetric catalysis. Recycling of the minor enantiomer, by selective kinetic resolution, regenerates the starting material. Continuous addition of a second reagent, also involved in a coupled exergonic process, leads to an increase of both yield and enantiomeric excess. Recycling procedures for the synthesis of O-acylated and O-formylated cyanohydrins have been developed with high yield and high enantiomeric excess of the products. The study includes development of the systems, comparison to other methodologies in asymmetric catalysis, and attempts to understand the processes involved.

The mechanism by which tertiary amines catalyse the formation of cyanohydrin carbonates from aldehydes and alkyl cyanoformates is investigated by means of a kinetic study. The reaction rate shows a second order dependence on amine concentration unless the amine is sterically hindered, when the rate has a first order dependence on amine concentration. The catalytic activity of the amine correlated with its pKaH. On the basis of these results, a mechanism is proposed in which the amine acts as a base to activate a water molecule, which reacts with the ethyl cyanoformate generating cyanide in situ.

The trans-PtH2(P(OMe)3)2 complex was synthesized and tested as a nitrile hydration catalyst. Under nitrile hydration reaction conditions, the complex degrades to Pt nanoparticles, which are catalytically active for nitrile hydration. TEM analysis shows that the Pt nanoparticles are approximately 2 nm in diameter. 31P NMR and XPS studies of the nanoparticles show that the stabilizing ligand on the surface of the nanoparticles is either P(OMe)3 or OP(OMe)3. The Pt nanoparticles are catalytically active for the hydration of cyanohydrins, a class of nitriles that are difficult to hydrate because homogeneous catalysts are susceptible to cyanide poisoning. The Pt nanoparticles are inhibited slightly by large excesses of cyanide but still remain catalytically active. Glycolonitrile and lactonitrile were quantitatively converted to their respective amides, and acetone cyanohydrin was converted to α-hydroxyisobutyronitrile in 30 % yield.

The authors described a short and highly enantioselective route to (R)-salmeterol involving asymmetric synthesis of cyanohydrin followed by nucleophilic substitution with 6-(4-phenylbutoxy) hexyl methanesulfonate.

A new simple and practical protocol for scalable synthesis of a novel library of propargylated and PEGylated α-hydroxy acids toward the preparation of “clickable” polylactides was described. The overall synthesis starting from readily available propargyl alcohol, bromoacetaldehyde diethyl acetal, and OEGs or PEGs was developed as a convenient procedure with low cost and no need of column chromatographic purification. The terminal alkyne functionality survives from hydrolysis of the corresponding easily accessible cyanohydrin derivatives in methanolic sulfuric acid. Facile desymmetrization, monofunctionalization, and efficient chain-elongation coupling of OEGs further enable the incorporation of OEGs to α-hydroxy acids in a simple and efficient manner. At the end, synthesis of allyloxy lactic acid indicates that an alkene group is also compatible with the developed method.

A novel series of fluorescent probes containing diphenylacetylene as fluorogenic units and salicylaldehyde as a CN(-) receptor were successfully synthesized by using sonogashira coupling. In the presence of Triton-X 100 non-ionic surfactant, the fluorophores exhibited fluorescence "turn-on" in response to CN(-) in aqueous media with the detection limit of 1.6 μM. The turn-on signal is the result of the conversion of the aldehyde to cyanohydrin via the internal acid catalyzed addition of cyanide. Using paper sensor strips, a naked eye detection of cyanide is possible down to 5 nmol.

A straightforward synthesis of water-soluble silver nanoparticles stabilized by PTA (1,3,5-triaza-7-phosphaadamantane, a water-soluble phosphine ligand) ligands was developed. The nanoparticles were thoroughly characterized by ultraviolet–visible spectroscopy, 31P nuclear magnetic resonance spectroscopy, transmission electron microscopy, and energy dispersive X-ray spectroscopy. The effectiveness of the Ag–PTA nanoparticles as catalysts for the hydration of nitriles to amides in water under mild conditions was explored using a series of substituted benzonitriles and cyanohydrins. In comparison to all previously investigated homogeneous catalysts, the Ag–PTA system excels at cyanohydrin hydration, including acetone cyanohydrin hydration. Cyanohydrins are in equilibrium with small amounts of cyanide, and experiments revealed that the Ag–PTA nanoparticles disassemble in the presence of cyanide. The catalyst solution, which is proposed to contain a soluble Ag(CN)n1–n complex (with n likely equal to 2), remain...

An efficient method for the synthesis of 2-aminoindolizines by the 5-exo-dig cyclization of 2-alkyl-1-(1-cyanoalkyl)pyridinium salts has been developed. These substrates were prepared by N-alkylation of 2-alkylpyridines with readily available cyanohydrin triflates. The method allows the introduction of various substituents at the 1-, 3-, 6-, 7-, and 8-positions and leaves no undesired acceptor groups in the products.

Total synthesis of SB-203207 (1) was achieved, beginning with a desymmetrical C-H insertion reaction of a diazoester bearing our recently developed chiral auxiliary. Utilizing the optically active bicyclo[3.3.0]octane ring, four stereogenic centers were efficiently constructed in sequence. Finally, mild oxidation of 27 to carboxylic acid via a cyanohydrin intermediate and hydrolysis of cyanide to carboxyamide in the presence of the labile enamide group completed an efficient total synthesis of 1.

Continuous recycling of the minor product enantiomer obtained from the acetylcyanation of prochiral aldehydes provided access to highly enantiomerically enriched products. Cyanohydrin derivatives, which under normal conditions are obtained with modest or poor enantiomeric ratios, were formed with high enantiomeric purity by using a reinforcing combination of a chiral Lewis acid catalyst and a biocatalyst. The primarily obtained products were transformed into β-adrenergic antagonists (S)-propanolol, (R)-dichloroisoproterenol, and (R)-pronethalol by means of a two-step procedure.

The cyano-rich borate anion [B(tceg)2]– (tceg = tetracyanoethylene glycolate) has been synthesized in a two-step reaction from Na[B(OMe)4] with two equivalents of the cyanohydrin analogue Me3SiOC2(CN)4OSiMe3. The structures of the starting materials, an isolated intermediate Na2[B2(OMe)2(tceg)3], and Na[B(tceg)2] are discussed. Thermal studies of WCC[B(tceg)2] [WCC = 1-ethyl-3-methylimidazolium (EMIm), 1-butyl-3-methylimidazolium (BMIm), 1-octyl-3-methylimidazolium (OMIm), Me4N, Et4N, and Bu4N], synthesized by salt metathesis, showed that the compounds with EMIm, BMIm, OMIm, and Bu4N have ionic liquid properties. The synthesis, structure, and analytical results of Me3SiOC(CN)3 are discussed as well as the results of its conversion with Na[B(OMe)4].

A simple quinoline derived probe 3 has been described. Probe 3 having aldehyde function upon interaction with cyanide undergo nucleophilic addition reaction to form cyanohydrin derivative 4 in which fluorescence intensity enhances significantly, ‘ turn-on ’ by photoinduced electron transfer (PET) OFF–ON mechanism. The color of probe solution switched-on to fluorescent blue which is visible to the naked-eye. Job’s plot analysis revealed a 1:1 stoichiometry for an interaction between 3 and cyanide along with detection limit 0.058 μM (1.5 ppb). The mode of interaction to detect cyanide in aqueous medium through a reaction based chemodosimeter approach has been confirmed by NMR, mass, FTIR, and DFT data analysis.

The consecutive radical/ionic reaction consisting of radical formylation of alkyl bromides and nucleophilic addition of a cyanide ion was investigated, which gave moderate to good yields of cyanohydrin derivatives in one-pot.

A new 6,6′-dicarboxyl-BINOL type ligand, was synthesized and anchored onto a aminated silica. Full characterization of the solids was carried out by means of thermogravimetry/differential scanning calorimetry, N2 adsorption, infra red and UV–vis diffuse reflectance spectroscopy techniques. Comparative studies between homogeneous versus heterogeneous catalytic cyanosilylation reactions of aldehydes were carried out, and similar activities were obtained. Furthermore, an efficient sequential process to promote the hydroformylation of 1-octene into nonanal followed by in situ cyanosilylation of the aldehyde, catalyzed by titanium immobilized BINOL derivative, is described. Reutilization studies of cyanosilylation catalyst revealed that the new titanium immobilized catalyst could be reused with 25% loss of activity after 3 reuses.

The construction of enantiomerically enriched acyclic quaternary substituted ketones via the regio- and enantiospecific rhodium-catalyzed allylic alkylation reaction of chiral nonracemic tertiary alcohols with cyanohydrin pronucleophiles is described. This approach provides an alternative method to the α-arylation and vinylation of acyclic disubstituted ketone enolates, which remains a challenging endeavor. The combination of the allylic alkylation with ring-closing metathesis facilitates the preparation of enantiomerically enriched 2,2-disubstituted naphthalene-1-ones, which have proven very difficult to prepare using a more conventional dearomatization strategy.

The identity of the major product of Ru-catalysed alkene metathesis of two polyene substrates has been determined using density functional theory (DFT) NMR prediction, a1H–1H Total Correlated Spectroscopy (TOCSY) NMR experiment and ultimately by single-crystal X-ray crystallography. The substrates were designed as those that would potentially allow expedient access to thetrans-decalin skeleton of the natural product (−)-euonyminol, but the product was found to be a bis-cyclopentenyl-β-cyanohydrin [1-(1-hydroxycyclopent-3-en-1-yl)cyclopent-3-ene-1-carbonitrile, C11H13NO] rather than thetrans-2,3,6,7-dehydrodecalin-β-cyanohydrin.

A direct synthetic method for cyanohydrin esters from aroyl chlorides using potassium hexacyanoferrate(II) as an eco-friendly cyanide source and tributylphosphine as a promoter is described. This protocol has advantages of no use of strong toxic cyanating agents, high yield, and simple work-up procedure.

Vinyl ethers can be protonated to generate oxocarbenium ions that react with Me3SiCN to form cyanohydrin alkyl ethers. Reactions that form racemic products proceed efficiently upon conversion of the vinyl ether to an α-chloro ether prior to cyanide addition in a pathway that proceeds through Brønsted acid-mediated chloride ionization. Enantiomerically enriched products can be accessed by directly protonating the vinyl ether with a chiral Brønsted acid to form a chiral ion pair. Me3SiCN acts as the nucleophile and PhOH serves as a stoichiometric proton source in a rare example of asymmetric bimolecular nucleophilic addition into an oxocarbenium ion. Computational studies have provided a model for the interaction between the catalyst and the oxocarbenium ion.

Determination of exposure to cyanide can be accomplished by direct cyanide analysis or indirectly by analysis of cyanide detoxification products, such as thiocyanate and 2-amino-2-thiazoline-4-carboxylic acid. A potentially important marker and detoxification product of cyanide exposure, α-ketoglutarate cyanohydrin (α-KgCN), is produced by the reaction of cyanide and α-ketoglutarate. Therefore, an ultra high-performance liquid chromatography tandem mass spectrometry method to determine α-KgCN in plasma was developed. Swine plasma was spiked with α-KgCN and α-KgCN-d4 (internal standard) and proteins were precipitated with 1% formic acid in acetonitrile. After centrifugation, the supernatant was dried, reconstituted, separated by reversed phase high performance liquid chromatography and analyzed by tandem mass spectrometry. The method produced a dynamic range of 0.3-50μM and a detection limit of 200nM for α-KgCN. Furthermore, the method produced a %RSD of less than 13% for all intra- and inter-assay analyses. The stability of α-KgCN was poor for most storage conditions tested, except for -80°C, which produced stable concentrations of α-KgCN for the 30days tested. The validated method was tested by analysis of α-KgCN in the plasma of cyanide-exposed swine. α-KgCN was not detected pre-exposure, but was detected in all post-exposure plasma samples tested. To our knowledge, this method is the first reported analytical method for detecting α-KgCN in any matrix.

Introduction of a spiro-phosphorus cycle in position 3 of monosaccharidic derivatives was studied starting from cyanohydrin or aminonitrile A. A two-step procedure involving (i) phosphonylation and (ii) carbanion-mediated phosphonate intramolecular cyclization (denoted CPIC) was used. The necessity of having an electron-withdrawing group α to the phosphorus atom in order to avoid undesired reactions was demonstrated.

The asymmetric synthesis of two well-known anti-depressant drugs, fluoxetine and duloxetine has been accomplished in a chemoenzymatic manner. The main highlight of the synthesis is the enantioselective cyanohydrin formation by a plant (R)-HNL (hydroxynitrile lyase). The enantiopure cyanohydrins are then synthetically manipulated into the above two drug molecules and two of their structural analogues, atomoxetine and nisoxetine.

Synthetic studies on the antibiotic natural product ripostatin A have been carried out with the aim to construct the C9−C10 bond by a nickel(0)-catalyzed coupling reaction of an enyne and an epoxide, followed by rearrangement of the resulting dienylcyclopropane intermediate to afford the skipped 1,4,7-triene. A cyclopropyl enyne fragment corresponding to C1−C9 has been synthesized in high yield and demonstrated to be a competent substrate for the nickel(0)-catalyzed coupling with a model epoxide. Several synthetic approaches toward the C10−C26 epoxide have been pursued. The C13 stereocenter can be set by allylation and reductive decyanation of a cyanohydrin acetonide. A mild, fluoride-promoted decarboxylation enables construction of the C15−C16 bond by an aldol reaction. The product of this transformation is of the correct oxidation state and potentially three steps removed from the targeted epoxide fragment., National Institute of General Medical Sciences (U.S.), Novartis (Firm)

Chiral keto nitriles (β-cyano ketones) have been prepared by a facile and efficient asymmetric conjugate hydrocyanation of poorly active chalcone-type enones with benzophenone cyanohydrin. Using in situ generated 5–10 mol-% of sodium (S)-6,6′-di(1-adamantyl)-1,1′-binaphthyl-2,2′-diyl phosphate as catalyst and 5–10 mol-% of 2-tert-butylphenol as an additive, high yields and excellent enantioselectivities were obtained within 2 h in toluene at 80 °C. The development of catalysts, optimization of the reaction parameters, and substrate scope are reported. On the basis of the experimental results, HCN is shown to be the real cyanide source and a mechanism is proposed to explain the origin of the enantioselectivity with the chiral-anion-modified nucleophile HCN.

An asymmetric Strecker-type reaction of nitrones using acetone cyanohydrin as a source of HCN has been realized. A magnesium-tartramide complex, generated from (R,R)-2,3-dihydroxy-1,4-di(pyrrolidin-1-yl)-butane-1,4-dione and MeMgBr, promoted transcyanation from the bromomagnesium salt of the cyanohydrin, in the presence of a catalytic amount of DBU, to afford the corresponding optically active (S)-α-amino nitrile derivatives. The reaction was applicable to various nitrones giving high-to-excellent enantioselectivities. © 2013 American Chemical Society.

Using an acetone precipitation method, crude ( S )-hydroxynitrile lyase [( S )-MeHNL] was separated from Munihot esculenta (cassava) leaves, and used directly as biocatalyst to catalyze asymmetric cyanohydrination and produce cyanohydrins with enantiomeric purities (⩾90% ee) significantly greater than those previously reported. The use of a water/ i -Pr2O system with an enzyme, NaCN, and appropriate amounts of acetic acid is crucial in improving the stereoselectivity of cyanohydrin formation by minimizing the non-enzymatic reaction and the racemization of the chiral products. The proposed isolation method for crude ( S )-MeHNL has a high value because of its simplicity, and low cost as well as the high activity of the crude ( S )-MeHNL.

A new bifunctional titanium/Schiff base catalyst was developed for the enantioselective cyanoformylation of aldehydes with ethyl cyanoformate. The reaction proceeded smoothly with a mild reaction condition to afford the cyanohydrin ethyl carbonates in high yields (up to 96%) and good enantioselectivities (up to 85% enantiomeric excess). Copyright © 2013 John Wiley & Sons, Ltd.

We describe efforts to achieve a multigram synthesis of the tricyclic spiroacetal core of the lituarines based on the addition of acyl anion equivalent to 4-(2-furyl)butan-2-one (18). We report the first cases of chemoselective Achmatowicz reaction in the presence of a second furan ring that lacks an α-hydroxyl group. The use of lithiated methoxyallene provides an efficient one-step conversion of ketone 18 into a tricyclic Diels-Alder adduct (27). In the final route, asymmetric cyanosilylation of ketone 29 achieved the construction of the stereogenic C(12) 3°-alcohol centre. Subsequent butenylation, diastereoselective reduction of keto-alcohol (+)-33 and alkene cross metathesis set up an oxy-Michael reaction to close the C(8-12) tetrahydropyran ring. The second ring-closure, which completed the route, was achieved by oxidative spirocyclisation following our earlier work. © 2011 Elsevier Ltd. All rights reserved.

A facile synthetic route is described to cyanogenic glycosides (R)-prunasin, linamarin and (S)-heterodendrin from O-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)trichloroace- timidate and the corresponding α-hydroxyamides by a 3-step reaction of glycosylation, cyanohydrin formation by dehydration of carboxamides, and deprotection.

The first enantioselective synthesis was the selective addition of cyanide to benzaldehyde catalysed by a hydroxynitrile lyase (HNL). Since then these enzymes have been developed into a reliable tool in organic synthesis. HNLs to prepare either the (R)- or the (S)-enantiomer of the desired cyanohydrin are available and a wide variety of reaction conditions can be applied. As a result of this, numerous applications of these enzymes in organic synthesis have been described. Here the examples of the last decade are summarised, the enzyme catalysed step is discussed and the follow-up chemistry is shown. This proves HNLs to be part of main stream organic synthesis. Additionally the newest approaches via immobilisation and reaction engineering are introduced.

A highly regio- and stereospecific rhodium-catalyzed allylic alkylation of tertiary allylic carbonates with alkenyl cyanohydrin pronucleophiles is described. This protocol offers a fundamentally novel approach toward the synthesis of acyclic quaternary-substituted α,β-unsaturated ketones and thereby provides a new cross-coupling strategy for target directed synthesis. A particularly attractive feature with this process is the ability to directly couple di-, tri- and tetrasubstituted alkenyl cyanohydrin pronucleophiles to prepare the corresponding α,β-unsaturated ketone derivatives in a highly selective manner. Additionally, the chemoselective 1,4-reduction of the enone products provides rapid access to acyclic enantiomerically enriched α,α′-dialkyl-substituted ketones, which are challenging motifs to prepare using conventional enolate alkylation.

Cyanohydrins, also be called cyanoalcohols, are important industrial precursors to carboxylic acids and some amino acids. Acetone cyanohydrin (ACH) and formaldehyde cyanohydrin (glycolonitrile, FCH), which are the typical examples of cyanohydrins, are classified as extremely hazardous substances. As the cyanohydrins can readily decompose, and it is hard to find cyanohydrins in gastric contents and heart blood, the determination study in biological samples can be divided into two parts: the first is the determination of HCN by using a Prussian blue reaction and the HS-GC-MSD after derivatization by chloramine-T. The second is the determination of acetone or formaldehyde. In this part, headspace gas chromatography with flame ionization detector (HS-GC-FID) and solid phase microextraction (SPME)-gas chromatography with mass spectrometric detectors (GC-MSD) had been used. In this report, we reported two fatal intoxication cases of ACH and FCH; one person was killed by his wife by poisoning his food and the other was suicide by poison. Two real cases of ACH and FCH in human blood and gastric contents have been analyzed by using the above-mentioned method. The Prussian blue reaction was positive in the two cases. The peaks of acetone with retention times of 0.998 min appear in specimens of the deceased are consistent with the retention times of pure acetone. The peaks of formaldehyde with a retention time of 1.658 min appear in heart blood of the deceased, and the retention time of formaldehyde of the liquid is 1.674 min, which are consistent with the retention times of pure formaldehyde (1.673 min).

Synthetic routes to new amino nitriles with the functional groups at the 2-position of the adamantane core, based on reactions of adamantanonimines with acetone cyanohydrin or of adamantanone cyanohydrin with aliphatic amines, are considered. The products can be used for preparing new biologically active substances, unsymmetrical adamantyl-containing diamines or amino acids.

The asymmetric addition of trimethylsilyl cyanide to aldehydes catalysed by chiral metal(salan) complexes has been investigated. Salan complexes of titanium and vanadium displayed only low catalytic activity, but a bimetallic aluminium(salan) complex gave high levels of catalytic activity and reasonable asymmetric induction when used with triphenylphosphine oxide as a cocatalyst. Mechanistic studies showed that the reactions were first order in catalyst and aldehyde concentrations, but zero order in trimethylsilyl cyanide and triphenylphosphine oxide concentrations. A Hammett analysis indicated that there was no significant change in the electron density at the aldehyde benzylic position during the rate determining step of the catalytic cycle. On the basis of the kinetic data, a catalytic cycle is proposed which accounts for the differences observed between [Al(salen)]2O and [Al(salan)]2O based catalysts.

The N-alkylation of pyridines with cyanohydrin triflates or α-halonitriles furnishes 1-(1-cyanoalkyl)pyridinium salts that can react with nitroolefins under basic conditions to furnish polysubstituted indolizines. Overall, the indolizine core can be constructed from a pyridine, two aldehydes, and a nitroalkane, and no undesired functional groups remain in the products. When bromoacetonitrile was used for the N-alkylation, indolizine-3-carbonitriles were obtained instead. The pyridine component may be replaced by other azines, giving rise to related heterocyclic systems.

Enantioselective reactions of simple ketones, α,α- and β,β-dialkoxy ketones, and α-alkoxy ketones with trimethylsilyl cyanide catalyzed by the bimetallic systems of amino acid/BINAP/ruthenium(II) complexes and lithium phenoxide have been studied [BINAP=2,2′-bis(diphenylphosphino)-1,1′-binaphthyl]. The Ru(PhGly)2(BINAP)-lithium phenoxide system showed high enantioselectivity for the reaction of acetophenone derivatives to afford the cyanated products in up to 90% ee [PhGly=phenylglycinate]. For the cyanosilylation of dialkoxy ketones and α-alkoxy ketones, the Ru(t-Leu)2(BINAP)-lithium phenoxide system exhibited the best catalyst performance to produce the cyanohydrin derivatives in up to 99% ee and 98% ee, respectively [t-Leu=tert-leucinate]. The excellent catalytic activity resulted in complete conversion in the reaction with a substrate-to-catalyst molar ratio (S/C) of 10,000 in the best cases.

The Kiliani reaction, i.e. the elongation of the carbon chain by means of cyanide addition to the carbonyl group of carbohydrate derivatives, is studied on lower C3-, C4- and C6-ketoses under continuous flow conditions. Depending on the process parameters, the corresponding cyanohydrins or alpha-hydroxycarboxylic acids are obtained. A simple on-line purification of the effluent is studied using cation exchange resins. Reactions provide high yields and selectivity within short residence times, emphasizing the assets of the continuous flow process versus the batch process.

6,6′-Bis(methylaminosulfonyl)-7,7′-dihydroxy-8,8′-biquinolyl (3) catalyzes (5–10 mol-%) the addition of trimethylsilyl cyanide to aldehydes (aryl, alkyl, and α,β-unsaturated; 42–92 % yields), ketones (aryl alkyl, dialkyl; 22–82 % yields), and N-benzylaldimines (14–78 % yields) in toluene (0 °C or room temp.) to give the expected cyanohydrin and Strecker adducts following desilylation. Among a series of closely related compounds lacking any one of their defining structural features, bis-sulfonamide 3 and its N,N′-dimethyl derivative are exceptional in catalyzing the silylcyanation of benzaldehyde in the absence of all other additives. Hammett analysis of the competitive silylcyanation of para-substituted benzaldehydes catalyzed by 3 showed a linear free-energy relationship (R2 = 0.928) with a modest positive reaction constant (ρ = +1.52). X-ray diffraction analysis of (±)-3 indicated a cisoid biaryl conformation and the existence of an intramolecular hydrogen bond between C7′–OH and C7–O. Resolution of (±)-3 was achieved by HPLC separation of its tetravalerate derivative on a chiral stationary phase. The absolute configurations of the optical isomers of 3 were assigned by correlation of the ECD spectra with those of related biquinolyls of known configuration. The silylcyanation of aldehydes catalyzed by (–)-(aR)-3 leads to cyanohydrins with a preference for the (S)-configured product with an ee of

The catalytic hydration of cyanohydrins to their corresponding α-hydroxyamides provides a route to industrially useful α-hydroxy amides, α-hydroxy esters, α-hydroxy carboxylic acids, and their acry...

Tin ion-exchanged montmorillonite (Sn-Mont) was found to be a powerful heterogeneous catalyst for the cyanosilylation of various ketones including congested ones with a bulky cyanide source, tert -butyldimethylsilyl cyanide (TBDMSCN), giving the corresponding cyanohydrin tert -butyldimethylsilyl ethers in good (85%) to excellent (>98%) yields at room temperature. Compared to the previously reported catalysts, Sn-Mont is easy to prepare, environmentally benign, nontoxic, noncorrosive, and recyclable.