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A safe and scalable procedure for the synthesis of 2-oxopropanethioamide, an intermediate in the synthesis of a potent β-secretase (BACE-1) inhibitor, from the reaction of acetyl cyanide with hydrogen sulfide gas under continuous-flow conditions has been developed. The toxic gas could be accurately dosed using a mass-flow controller or a peristaltic pump. The reaction proceeded smoothly at room temperature in the presence of a small amount of triethylamine as basic catalyst. After a residence time of 15 min, excellent yield (96%) and purity (>99%) were obtained for the target compound. The high reaction selectivity permitted a simple workup procedure consisting of evaporation of all volatiles.

Central topics of carbohydrate chemistry embrace structural modifications of carbohydrates and oligosaccharide synthesis. Both require regioselectively protected building blocks that are mainly available via indirect multistep procedures. Hence, direct protection methods targeting a specific hydroxy group are demanded. Dual hydrogen bonding will eventually differentiate between differently positioned hydroxy groups. As cyanide is capable of various kinds of hydrogen bonding and as it is a quite strong sterically nondemanding base, regioselective O-acylations should be possible at low temperatures even at sterically congested positions, thus permitting formation and also isolation of the kinetic product. Indeed, 1,2-cis-diols, having an equatorial and an axial hydroxy group, benzoyl cyanide or acetyl cyanide as an acylating agent, and DMAP as a catalyst yield at -78 °C the thermodynamically unfavorable axial O-acylation product; acyl migration is not observed under these conditions. This phenomenon was substantiated with 3,4-O-unproteced galacto- and fucopyranosides and 2,3-O-unprotected mannopyranosides. Even for 3,4,6-O-unprotected galactopyranosides as triols, axial 4-O-acylation is appreciably faster than O-acylation of the primary 6-hydroxy group. The importance of hydrogen bonding for this unusual regioselectivity could be confirmed by NMR studies and DFT calculations, which indicate favorable hydrogen bonding of cyanide to the most acidic axial hydroxy group supported by hydrogen bonding of the equatorial hydroxy group to the axial oxygen. Thus, the "cyanide effect" is due to dual hydrogen bonding of the axial hydroxy group which enhances the nucleophilicity of the respective oxygen atom, permitting an even faster reaction for diols than for mono-ols. In contrast, fluoride as a counterion favors dual hydrogen bonding to both hydroxy groups leading to equatorial O-acylation.

A mechanistic investigation, which included a Hammett correlation analysis, evaluation of the effect of variation of catalyst composition, and low-temperature NMR spectroscopy studies, of the Lewis acid-Lewis base catalyzed addition of acetyl cyanide to prochiral aldehydes provides support for a reaction route that involves Lewis base activation of the acyl cyanide with formation of a potent acylating agent and cyanide ion. The cyanide ion adds to the carbonyl group of the Lewis acid activated aldehyde. O-Acylation by the acylated Lewis base to form the final cyanohydrin ester occurs prior to decomplexation from titanium. For less reactive aldehydes, the addition of cyanide is the rate-determining step, whereas, for more reactive, electron-deficient aldehydes, cyanide addition is rapid and reversible and is followed by rate-limiting acylation. The resting state of the catalyst lies outside the catalytic cycle and is believed to be a monomeric titanium complex with two alcoholate ligands, which only slowly converts into the product.

The cyanation-esterification reaction of α-keto esters catalysed by N-heterocyclic carbenes (NHCs) is developed. Under the catalysis of 10 mol% 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, aromatic and aliphatic α-keto esters reacted with ethyl cyanoformate or acetyl cyanide to produce the corresponding cyano esters with a tetrasubstituted carbon center in high yields.

A concise one-pot 3-step cascade reaction to biologically significant imidazo[1,2-a]heterocycles is described. The methodology utilizes acetyl cyanide as a non-classical isocyanide replacement for TMSCN in a microwave-assisted [4+1] cycloaddition (the Groebke–Bienayme–Blackburn reaction) followed by a Strecker reaction under catalysis free conditions. The methodology proceeds with operational simplicity, short reaction times, and high bond forming efficiency.

Central topics of carbohydrate chemistry embrace structural modifications of carbohydrates and oligosaccharide synthesis. Both require regioselectively protected building blocks that are mainly available via indirect multistep procedures. Hence, direct protection methods targeting a specific hydroxy group are demanded. Dual hydrogen bonding will eventually differentiate between differently positioned hydroxy groups. As cyanide is capable of various kinds of hydrogen bonding and as it is a quite strong sterically nondemanding base, regioselective O-acylations should be possible at low temperatures even at sterically congested positions, thus permitting formation and also isolation of the kinetic product. Indeed, 1,2-cis-diols, having an equatorial and an axial hydroxy group, benzoyl cyanide or acetyl cyanide as an acylating agent, and DMAP as a catalyst yield at −78 °C the thermodynamically unfavorable axial O-acylation product; acyl migration is not observed under these conditions. This phenomenon was sub...

Cyanation reactions of carbonyl compounds with methyl cyanoformate or acetyl cyanide catalyzed by 5 mol % of 1,5,7-triazabicyclo[4,4,0]dec-5-ene (TBD) were examined. Using methyl cyanoformate, the corresponding cyanohydrin carbonates were readily obtained in high yield for aromatic and aliphatic aldehydes and ketones. Similar results were obtained when acetyl cyanide was used as the cyanide source. The polymer-supported catalyst, PS-TBD, also acted as a good catalyst for this reaction. PS-TBD was easily recovered and reused with minimal activity loss.

Carbonyl compounds studied are confined to acetyl halide (CH3COCl), acetyl cyanide (CH3COCN), acetyl sulfide (CH3COSH), acetaldehyde (CH3CHO), and methyl formate (HCOOCH3). They are asymmetrically substituted, but do not follow the well-known Norrish type I reactions. Each compound ejected in an effusive beam at about 300 K is commonly excited to the 1(n, π*)CO lower state; that is, a nonbonding electron on O of the CO group is promoted to the antibonding orbital of π*CO. The photolysis experiments are conducted in the presence of Ar gas and the corresponding fragments are detected using time-resolved Fourier-transform Infrared (FTIR) emission spectroscopy. The enhancement of the collision-induced internal conversion or intersystem crossing facilitates the dissociation channels via highly vibrational states of the ground singlet (So) or triplet (T1) potential energy surfaces. In this manner, an alternative nonadiabatic channel is likely to open yielding different products, even if the diabatic coupling strength is strong between the excited state and the neighboring state. For instance, the photodissociation of CH3COCl at 248 nm produces HCl, CO, and CH2 fragments, in contrast to the supersonic jet experiments showing dominance of the Cl fragment eliminated from the excited state. If the diabatic coupling strength is weak, dissociation proceeds mainly through internal conversion, such as the cases of CH3COCN and CH3COSH. The photodissociation of CH3COCN at 308 nm has never been reported before, while for CH3COSH matrix-isolated photodissociation was conducted that shows a distinct spectral feature from the current FTIR method. The CH3CHO and HCOOCH3 molecules belong to the same type of carbonyl compounds, in which the molecular products, CO + CH4 and CO + CH3OH, are produced through both transition state and roaming pathways. Their products are characterized differently between molecular beam and current FTIR experiments. For instance, the photodissociation of HCOOCH3 at 248 nm yields CO with the vibrational state v ≥ 4, in contrast to the molecular beam experiments producing CO at v = 1. The photodissociation of CH3CHO at 308 nm intensifies a low energy component in the CH4 vibrational distribution, thus verifying the transition state pathway for the first time.

Carbonyl compounds studied are confined to acetyl halide (CH3COCl), acetyl cyanide (CH3COCN), acetyl sulfide (CH3COSH), acetaldehyde (CH3CHO), and methyl formate (HCOOCH3). They are asymmetrically substituted, but do not follow the well-known Norrish type I reactions. Each compound ejected in an effusive beam at about 300 K is commonly excited to the (1)(n, π*)CO lower state; that is, a nonbonding electron on O of the C[double bond, length as m-dash]O group is promoted to the antibonding orbital of π*CO. The photolysis experiments are conducted in the presence of Ar gas and the corresponding fragments are detected using time-resolved Fourier-transform Infrared (FTIR) emission spectroscopy. The enhancement of the collision-induced internal conversion or intersystem crossing facilitates the dissociation channels via highly vibrational states of the ground singlet (So) or triplet (T1) potential energy surfaces. In this manner, an alternative nonadiabatic channel is likely to open yielding different products, even if the diabatic coupling strength is strong between the excited state and the neighboring state. For instance, the photodissociation of CH3COCl at 248 nm produces HCl, CO, and CH2 fragments, in contrast to the supersonic jet experiments showing dominance of the Cl fragment eliminated from the excited state. If the diabatic coupling strength is weak, dissociation proceeds mainly through internal conversion, such as the cases of CH3COCN and CH3COSH. The photodissociation of CH3COCN at 308 nm has never been reported before, while for CH3COSH matrix-isolated photodissociation was conducted that shows a distinct spectral feature from the current FTIR method. The CH3CHO and HCOOCH3 molecules belong to the same type of carbonyl compounds, in which the molecular products, CO + CH4 and CO + CH3OH, are produced through both transition state and roaming pathways. Their products are characterized differently between molecular beam and current FTIR experiments. For instance, the photodissociation of HCOOCH3 at 248 nm yields CO with the vibrational state v ≥ 4, in contrast to the molecular beam experiments producing CO at v = 1. The photodissociation of CH3CHO at 308 nm intensifies a low energy component in the CH4 vibrational distribution, thus verifying the transition state pathway for the first time.

In an effort to provide an accurate structural and spectroscopic characterization of acetyl cyanide, its two enolic isomers and the corresponding cationic species, state-of-the-art computational methods, and approaches have been employed. The coupled-cluster theory including single and double excitations together with a perturbative treatment of triples has been used as starting point in composite schemes accounting for extrapolation to the complete basis-set limit as well as core-valence correlation effects to determine highly accurate molecular structures, fundamental vibrational frequencies, and rotational parameters. The available experimental data for acetyl cyanide allowed us to assess the reliability of our computations: structural, energetic, and spectroscopic properties have been obtained with an overall accuracy of about, or better than, 0.001 Å, 2 kcal/mol, 1-10 MHz, and 11 cm(-1) for bond distances, adiabatic ionization potentials, rotational constants, and fundamental vibrational frequencies, respectively. We are therefore confident that the highly accurate spectroscopic data provided herein can be useful for guiding future experimental investigations and/or astronomical observations.

N-heterocyclic carbene (NHC) has been employed as an efficient catalyst for cyanation reaction of carbonyl compounds. Under catalysis of 1 mol % NHCs, various aldehydes and 2,2,2-trifluoroacetophenone coupled with ethyl cyanoformate in THF to provide cyanohydrins ethyl carbonates in excellent yields. While in the presence of 10 mol % catalyst, different types of aldehydes and 2,2,2-trifluoroacetophenone reacted with acetyl cyanide in dichloroethane to give acylated cyanohydrins in moderate to high yields.

The room-temperature rotational spectrum of pyruvonitrile (acetyl cyanide, CH 3 COCN) was measured up to 324 GHz, and additional measurements were also made in supersonic expansion in the region 7–19 GHz. The available data sets for the A and E torsional sublevels were extended to over 1200 transitions, J = 65 and K a = 38 for the ground vibrational state, and to comparable numbers of transitions for first excited states of the methyl torsional mode ν 18 , and the in-plane CCN bending mode ν 12 . The collected experimental measurements were fitted with several different computer programs for dealing with the effects of methyl torsional motion on the rotational spectrum and many spectroscopic constants have been determined. The experimental results are discussed in detail and are augmented by ab initio computations. Stark effect measurements in supersonic expansion were used to precisely determine the electric dipole moment of pyruvonitrile, ∣ μ a ∣ = 2.462(2) D, ∣ μ b ∣ = 2.442(2) D, μ tot = 3.468(2) D. Pyruvonitrile, as an 8-atom molecule with a sizable dipole moment, is a possible candidate for astrophysical detection and the present work provides the laboratory data necessary for that purpose.

Acetyl cyanide adds to alkyl benzoylformates and to 2-oxoalkanoates to yield enantioenriched acylated cyanohydrins in one step in the presence of a catalytic amount of a chiral base. The reaction i ...

The catalytic acylcyanation of aldimines with acylcyanides and a direct three-component variant involving the generation of an imine in situ have been developed. Furthermore, a highly enantioselective version has been established, culminating in the first organocatalytic asymmetric three-component Strecker reaction. Jacobsen thiourea catalysts were found to catalyze the reaction with excellent enantioselectivities, whereas binol phosphates (binol=1,1′-bi-2,2′-naphthol) proved to be catalytically active but only modestly enantioselective. A large number of different substrates could be used in the processes described, thus illustrating the potential of our reaction for the generation of diversity within the attractive α-amino carbonyl framework. Furthermore, a novel cyclic amidine was obtained from the reaction of acetyl cyanide with ketimines. Die katalytische Acylcyanierung von Iminen mit Acetylcyanid und ihre direkte Dreikomponentenvariante wurden entwickelt. Daruber hinaus konnte eine hoch-enantioselelektive Version beschrieben werden, die schlieslich zur Entdeckung der ersten organokatalytischen asymmetrischen Dreikomponenten-Strecker-Reaktion fuhrte. Jacobsens Thioharnstoff-Katalysatoren katalysieren die Reaktion mit hohen Enantioselektivitaten wahrend Binol-Phosphorsauren die Reaktion zwar katalysieren, aber dabei nur masige Enantioselektivitaten liefern. Eine Reihe verschiedener Substrate konnten in den beschriebenen Verfahren eingesetzt werden, wobei das Potential der Reaktion fur die Erzeugung von Diversitat innerhalb der attraktiven α-Aminocarbonyl Substratklasse illustriert wurde. Daruber hinaus wurde eine neue Klasse zyklische Amidine in der Reaktion von Acetylcyanid mit Ketiminen erzeugt.

The operationally simple one-pot three-step cascade reaction allows the synthesis of biologically significant imidazoheterocycles in short reaction times.

Reaction of benzaldehyde with ethyl cyanoformate in the presence of Lewis acidic Ti(IV) complexes of bispyridylamide or salen ligands and Lewis basic amines affords the O-alkoxycarbonylated cyanohydrin. In the presence of the salen-based catalytic system, acetyl cyanide can also be added to benzaldehyde, providing a highly enantioselective direct route to the O-acetylated cyanohydrin.

The covalent binding of acetyl cyanide on Si(1 0 0)-2 × 1 has been investigated using high-resolution electron energy loss spectroscopy, X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT) calculations. The absence of the C O and C N stretching modes in the EELS spectra for chemisorbed molecules indicates the direct interactions between carbonyl, cyano groups and the dangling bonds on Si(1 0 0)-2 × 1. The characteristic C C N asymmetric stretching mode at 2031 cm−1 and C N stretching mode at 1667 cm−1 suggest the existence of both ketenimine species and tetra-σ adduct at the interface, further supported by XPS results and DFT calculations.

Nucleophilic attack of cyanide anion at the carbonyl carbon was studied computationally at the MP2/6-311+G** level for ketene and at the MP2/6-31+G* and MP2/6-31+G*//HF/6-31+G* levels for all four title compounds. Heats of addition were computed for formation of in-plane adducts and perpendicular adducts where the terms 'in-plane' and 'perpendicular' indicate the direction of nucleophilic attack relative to the ketene plane. Heats of activation were also computed for the two modes of attack. For ketene (1) the in-plane adduct is favored by 37.6 kcal mol - 1 and the in-plane transition state by 18.8 kcal mol - 1 . For the 6-methylene compound (2) the in-plane adduct is favored by 20.1 kcal mol - 1 and the in-plane transition state by 7.3 kcal mol - 1 For the 6-oxo compound (3) the in-plane adduct is more stable by 11.2 kcal mol - 1 whereas the in-plane transition state is preferred by 8.8 kcal mol - 1 . For the 4-oxo compound (4) the in-plane adduct is favored by 19.3 kcal mol - 1 but its transition state by only 2.8 kcal mol - 1 '. The in-plane adduct for ketene is the enolate of acetyl cyanide while the perpendicular adduct is a pyramidalized carbanion attached to a cyanocarbonyl group. Calculated NPA charges support this conclusion. The perpendicular adduct is actually the transition state for rotation about the C-C bond of the ketene moiety in the in-plane adduct, and the 37.6 kcal mol - 1 enthalpy difference is closely matched by the calculated activation enthalpy for rotation about the C-C bond of acetaldehyde enolate: ΔH = 33.6 kcal mol - 1 . The smaller differences found for in-plane vs perpendicular adduct formation for the 6-methylene, 6-oxo and 4-oxo compounds are correlated with decreases in bond length alternation within the six-membered rings which occur upon addition of the nucleophile. Less alternation may be associated with an approach to aromaticity, hence an increase in stability. Both modes of attack lead to reduced bond length alternation, but the amount of alternation is lowered more for the perpendicular adducts than for the in-plane adducts. Changes in the C-O bond lengths are also diagnostic. For all four ketenes the ketenyl C=O length in the in-plane adducts is greater than in the perpendicular adducts reflecting more single bond (enolate) character in the former and more double bond (carbonyl) character in the latter. On the other hand the lengths of the 6-oxo and 4-oxo C-O bonds in their in-plane adducts are smaller than in the perpendicular adducts, consistent with increased conjugation with the oxo substituent in the latter. The greater NPA charge on the 6-oxo and 4-oxo oxygens of the perpendicular adducts supports this conclusion. Calculated enthalpies of activation are in the order ketene > 6-methyleneketene > 6-oxoketene, in qualitative agreement with experimentally determined rates of hydration.

Aroyl cyanides were readily synthesized in moderate yields by the cyanation of aroyl chlorides with dry powdered potassium cyanide under the catalysis of PEG400 and zinc iodide in dichloromethane at room temperature. A preliminary study on the one‐pot preparation of acetyl cyanide was also reported.

Dissociative excitation of CH3COCN to produce CN(B-X) and CN(A-X) fluorescence was studied by resonance enhanced multiphoton excitation at 292 nm. The laser power dependence of the CN(B-X) fluorescence intensity and the lifetime of the one-photon excited S1 state showed that CN(B) formation takes place in the direct two-photon and two-body dissociation mechanism, CH3COCN+2hν →CH3CO(X)+CN(B). Vibrational and rotational energy distributions of the nascent CN(B) fragment were determined by a simulation analysis of the dispersed fluorescence spectrum. The vibrational distribution was found to be of the relaxed type and rotational distribution in each vibrational state could be approximated by a Boltzmann distribution. The best-fit vibrational distribution of CN(B) was Nv′=0: Nv′=1:Nv′=2=1.00: 0.25: 0.07 with the respective rotational temperatures of Tr(v′=0)=2600 K, Tr(v′=1)=1000 K, and Tr(v′=2)=900 K. The internal state distributions were found to be hotter than those predicted by the statistical model with...

A HeI photoelectron spectrum of acetyl cyanide (pyruvonitrile: CH 3 COCN) in the gas phase has been observed for the first time in the region up to 19 eV, and interpreted in terms of a total of eight ionization bands on the basis of ab initio MP2/6-31G(d) and G3 calculations. The first ionization energy is much lower (1.8 eV) than the second one in spite of nearly the same orbital energies. The first and second adiabatic ionization energies have well been reproduced especially by the G3 calculations, attributable to {15a′(n O, π′ CN )} −1 and {3a″(π CN , π CO )} −1 , respectively. The molecular geometries and vibrational frequencies at the neutral ground state ( 1 S 0 ) as well as at the cationic states ( 2 D 0 , 2 D 1 ) were also calculated, in good agreement with available experimental data.

A nonstatistical behavior has been observed in the photodissociation of two acyl cyanide compounds, R-C(O)-CN, where R = methyl and tert-butyl groups. The initial activation was achieved by femtosecond two-photon excitation followed by ultrafast internal conversion. The excited-state dissociation dynamics was followed in real time by monitoring the temporal evolution of CN (X) products. The observed product appearance time constants are in picosecond time scales and are markedly similar for the two compounds studied. Our analyses revealed that the excited-state dissociation rate does not decrease with molecular size as much as statistical rate theory predicts, suggesting a nonergodic system in which the available vibrational energy does not redistributed statistically among all modes before the bond breakage occurs.

The photodissociation of a series of four cyano carbonyl compounds NCC(O)X with X = methyl, isopropyl, tert-butyl, and methoxy was studied after excitation at 193 nm using photofragment translational energy spectroscopy. For all the fragments generated (OCCN, XCO, CO, CN, X) the kinetic energy distributions were measured and the two radical decay channels, NCC(O)X → CN + OCX and NCC(O)X → OCCN + X, were identified. Dissociation leading to CN + OCX is the main decay path (∼85%) for acetyl cyanide (X = methyl), but is the minor pathway for X = isopropyl (30%), X = tert-butyl (17%), and X = methoxy (

Unimolecular decomposition rates for acetyl radical following the photodissociation of acetyl cyanide and acetic acid near 193 nm have been studied using ultrafast mass-resolved photoionization spectroscopy. In both cases, the parent decays with an instrumentally limited lifetime, while the acetyl radical behaves in a manner consistent with an RRKM mechanism, in contrast to our previous results on acetone. It is necessary to convolute the population distribution with the microcanonical RRKM rates in order to achieve this agreement. We have also undertaken an ab initio study of the excited states of acetyl cyanide to clarify the assignments of these states. The state excited at 193 nm arises from a π→π* transition with a calculated transition velocity dipole moment oriented at an angle of 57° with respect to the C–C≡N bond, resulting in an anisotropy parameter of −0.22. This is in reasonable agreement with the previous data of North et al. [J. Phys. Chem. A 101, 9224 (1997)]. The apparent RRKM behavior of ...

Fluorescence excitation spectrum of acetyl cyanide (CH3COCN) in a supersonic jet has been obtained for the 1(n,π*) transition (S1–S0). A spectral origin band is located at 27 511 cm−1, and its fluorescence lifetime is measured to be 3.5±0.3 μs. The S1 state vibrational modes associated with CH3 torsion, CCO bend, CCN bend, and CO wag are found to be optically active. The fluorescence intensity decreases with increasing the energy from the origin up to ∼2000 cm−1, while the fluorescence lifetime changes little over the same energy region. Instead, a broad background signal appears in the high energy region, indicating that the intramolecular vibrational redistribution (IVR) process becomes important in the S1 state as the density of states increases.

The potential energy surfaces of acetyl cyanide and its functional isomer acetyl isocyanide in their electronic ground state have been investigated using ab initio molecular orbital MP2(FU)/6-311G** and QCISD(T)/6-311G** calculations. The molecular eliminations of CH3COX (X = CN,NC) to CH3X + CO, HX + CH2CO, and CH2 + HCOX, the unimolecular rearrangements to CH3C−OX and CH3O−CX carbenes, 1,3-hydrogen migration to CH2C(OH)X, 1,3-methyl migration to CH3NCCO, and radical decompositions to X• + CH3CO and CH3• + COX have been examined. Also the secondary decomposition processes of COCN and CONC radicals in their ground states and the secondary elimination of HX from CH2C(OH)X have been investigated. Cyanide−isocyanide isomerization is found to be the predominant channel in the unimolecular reactions of acetyl cyanide. Despite being exothermic, the decomposition of acetyl cyanide into CH3CN + CO is found to be kinetically unfavorable. Decomposition into HCN + CH2CO, the reverse reaction of CH3COCN synthesis, is...

Pathways, energetics, and mechanisms of the 193 nm photodissociation of acetyl cyanide (CH3COCN) have been investigated using high-resolution transient frequency modulation (FM) spectroscopy and photofragment translational spectroscopy. Vibrational and rotational state distributions of CN fragments measured by FM spectroscopy are in good agreement with previous work. The quantum yield of CN is found to be 0.9 ± 0.2. State-dependent translational energy distributions are nonstatistical. The laboratory-frame anisotropy of both velocity and angular momentum of CN fragments is vanishingly small, yet significant v·j correlations are observed, indicating a preference for the CN angular momentum to be perpendicular to the recoil velocity. Photofragment translational spectroscopy provided independent confirmation of kinetic energy distributions and fragmentation pathways. The combined measurements are consistent with the strong preference for primary CN elimination over CH3 elimination, despite a large difference...

Some possible unimolecular reactions of CH 3 C(O)CN in its ground electronic state have been studied with the G2 molecular orbital method. Among the reactions considered, only its decomposition to CO and CH 3 CN is exothermic ( ΔH = −7.66 kcal mol −1 ) and its isomerization to CH 3 C(O)NC has an activation barrier (40.77 kcal mol −1 ) accessible at low temperature. CH 3 C(O)CN is predicted to be rather stable at room temperature in line with experiment since the former reaction channel and the second step of the latter channel by which CH 3 C(O)NC decomposes to CO and CH 3 NC both have very high barriers, viz. 109.47 and 100.31 kcal mol −1 , respectively.

The photodissociation of gaseous acetyl cyanide has been examined following excitation at 193 nm. CN X2Σ+ photofragments were probed via laser fluorescence excitation to determine their rotational, vibrational, and translational energy distributions. CN was produced in v‘‘ = 0 and 1 with mean rotational energy (13.5 ± 2) kJ mol-1, and v‘‘ = 2 with mean rotational energy (10 ± 4) kJ mol-1. Mean translational energies of the CN fragments were (32 ± 10) kJ mol-1. Ab initio electronic structure theory has been used to characterize the heat of formation for acetyl cyanide along with its geometries and vibrational frequencies. The acetyl cyanide heat of formation, ΔH0f,0, is predicted to be (−0.4 ± 8) kJ mol-1 using Gaussian-2 theory (G2). The theoretical results are used to compute bond dissociation energies of acetyl cyanide for further interpretation of the experimental photodissociation data. Evidence is presented that the majority of CN fragments are produced via dissociation of the parent acetyl cyanide t...

This Note aims to clarify the source of CO in photodissociation of acetyl cyanide (CH3COCN) at 308 nm. From the theoretical aspects, a new pathway via isomerization transition state (TS) at 391 ± 8 kJ/mol is found leading to the CO + CH3NC products. An amount of 60% reactant molecules at 300 K is estimated to successfully surpass the average TS barrier lying above the excitation energy by 3.5 kJ/mol. Further, a prior distribution method is conducted to characterize the vibrational energy distribution of CO on a statistical basis. The pathway to CH3NC + CO yields a vibrational branching ratio (v = 0:v = 1:v = 2:v = 3∼0.63:0.25:0.093:0.032) in excellent agreement with the observation (0.62:0.25:0.09:0.05).

The asymmetric cyanation across C C, C O, and C N bonds ranks among the most important and well-studied reactions in asymmetric catalysis to achieve useful chiral building blocks for pharmaceuticals, agrochemicals, and specialty materials. The asymmetric cyanation reaction demands careful selection of a chiral catalyst and a cyanide source. A number of efficient and successful synthetic strategies have been developed that include asymmetric cyanation-utilizing enzyme, organocatalyst, and metal complexes as catalysts. As for the concern of the source of cyanide, inorganic cyanides, for example, NaCN and KCN; and organic cyanides, for example, trimethylsilyl cyanide, alkyl cyanoformates, acetone cyanohydrin, acetyl cyanide, alkyl cyanophosphorylates, etc. have been employed, depending upon the targeted substrates. Since the subject is vast, this chapter discusses in detail chiral-metal-complex-based catalytic asymmetric synthesis of cyanohydrins using different cyanide sources. An attempt is made to discuss the reaction mechanism involved in enantioselective cyanation reactions.

N-heterocyclic carbene (NHC) has been employed as an efficient catalyst for cyanation reaction of carbonyl compounds. Under catalysis of 1 mol % NHCs, various aldehydes and 2,2,2-trifluoroacetophenone coupled with ethyl cyanoformate in THF to provide cyanohydrins ethyl carbonates in excellent yields. While in the presence of 10 mol % catalyst, different types of aldehydes and 2,2,2-trifluoroacetophenone reacted with acetyl cyanide in dichloroethane to give acylated cyanohydrins in moderate to high yields.

By using time-resolved Fourier-transform infrared emission spectroscopy, the fragments of HCN(v = 1, 2) and CO(v = 1-3) are detected in one-photon dissociation of acetyl cyanide (CH(3)COCN) at 308 nm. The S(1)(A(")), (1)(n(O), π(∗) (CO)) state at 308 nm has a radiative lifetime of 0.46 ± 0.01 μs, long enough to allow for Ar collisions that induce internal conversion and enhance the fragment yields. The rate constant of Ar collision-induced internal conversion is estimated to be (1-7) × 10(-12) cm(3) molecule(-1) s(-1). The measurements of O(2) dependence exclude the production possibility of these fragments via intersystem crossing. The high-resolution spectra of HCN and CO are analyzed to determine the ro-vibrational energy deposition of 81 ± 7 and 32 ± 3 kJ∕mol, respectively. With the aid of ab initio calculations, a two-body dissociation on the energetic ground state is favored leading to HCN + CH(2)CO, in which the CH(2)CO moiety may further undergo secondary dissociation to release CO. The production of CO(2) in the reaction with O(2) confirms existence of CH(2) and a secondary reaction product of CO. The HNC fragment is identified but cannot be assigned, as restricted to a poor signal-to-noise ratio. Because of insufficient excitation energy at 308 nm, the CN and CH(3) fragments that dominate the dissociation products at 193 nm are not detected.

The first three-component organocatalyzed Strecker reaction operating on water has been developed. The manifold utilizes ketones (aldehydes) as the starting carbonyl component, aniline as the primary amine, acetyl cyanide as the cyanide source and N,N-dimethylcyclohexylamine as the catalyst.

The first three-component organocatalyzed Strecker reaction operating on water has been developed. The manifold utilizes ketones (aldehydes) as the starting carbonyl component, aniline as the primary amine, acetyl cyanide as the cyanide source and N,N-dimethylcyclohexylamine as the catalyst. © 2009 The Royal Society of Chemistry., This work was supported by the Spanish by the Spanish Ministerio de Ciencia e Innovación and the European Regional Development Fund (CTQ2005-09074-C02-02 and CTQ2008-06806-C02-02), the Spanish MSC ISCIII (RETICS RD06/0020/1046) and Fundación Instituto Canario de Investigación del Cáncer (FICIC-REDESFAC). F.C. A thanks CSIC for a predoctoral JAE grant.

The far-IR spectrum has been recorded from 50 to 360 cm −1 at a resolution of 0.10 cm −1 for acetyl cyanide, CH 3 C(O)CN. The fundamental methyl torsion is observed at 126.06 cm −1 from which a periodic barrier to internal rotation is calculated to be 400 cm −1 (1144 cal mol −1 ). Utilizing previously reported rotational constants for eight isotopic species, r 0 structural parameters are determined. The fundamental vibrational frequencies, barrier to internal rotation, and structural parameters are obtained from ab initio Hartree—Fock calculations employing 3-21G, 6-31G and DZ basis sets. These calculated parameters are compared to the experimentally determined values as well as to the corresponding quantities for some similar molecules.

Aldimines react with acetyl cyanide in the presence of a catalytic amount of a thiourea catalyst to give the corresponding N-acetylated amino nitriles in high yields. The scope of the reaction is broad and both aromatic as well as aliphatic aldimines can readily be used.

Dual activation by a chiral Lewis acid and an achiral or chiral Lewis base enabled cyanation of both aromatic and aliphatic aldehydes with acetyl cyanide and ethyl cyanoformate to provide direct access to O-acetylated and O-alkoxycarbonylated cyanohydrins, respectively, under mild conditions. With a combination of a Ti-salen catalyst and Et3N, benzaldehyde was converted to the O-acetylated cyanohydrin with 94% ee within 10 h at -40 degrees C in 89% isolated yield.

A detailed analysis of the vibrational spectra of carbonyl cyanide, diethynyl ketone and acetyl cyanide has been conducted in harmonic and anharmonic approximations. RHF, MP2 and density functional theory (DFT) methods with 6-311++G(2df,2p) basis sets and B3LYP functionals have been employed. Spectroscopic constants such as anharmonicity constants, rotational and centrifugal distortion constants, rotation-vibration coupling constants and Coriolis coupling coefficients have been calculated for each molecule and compared with the experimental data, where available. A close agreement between the calculated and experimental values of the spectroscopic constants has been obtained. Complete assignments have been provided to the fundamental bands, overtones and combination tones of the molecules. Density functional theory based anharmonic frequencies compare well with the experimental frequencies within +/-18 cm(-1) on an average. RHF and MP2 methods, however, give much higher values for the frequencies that need scaling even in the anharmonic approximation.

Irradiations at lambda > 180 nm and lambda > 230 nm of CH3COCN (CD3COCN) trapped in an argon matrix at 10 K have been performed and monitored by Fourier transform infrared spectroscopy. For both wavelengths, the first photoreaction product is acetyl isocyanide. At lambda > 180 nm acetonitrile and methyl isocyanide are obtained as final products. They are formed by photolysis of acetyl isocyanide and acetyl cyanide, respectively. Unstable intermediates, such as ketene:HCN and ketene:HNC complexes, H2CNCH zwitterion, and H2C2NH keteneimine, not observed in the gas phase, are trapped and identified at our experimental temperature. The complexes have an L-shaped structure with a hydrogen bond between the oxygen atom of ketene and the hydrogen atom of HCN or HNC. A pathway process is proposed and compared with the ones determined in the ground state by ab initio calculations.

International audience; The present combined theoretical and experimental investigation concerns the single photoionization of gas-phase acetyl cyanide and the fragmentation pathways of the resulting cation. Acetyl cyanide (AC) is inspired from both the chemistry of cyanoacetylene and the Strecker reaction which are thought to be at the origin of medium sized prebiotic molecules in the interstellar medium. AC can be formed by reaction from cyanoacetylene and water but also from acetaldehyde and HCN or the corresponding radicals. In view of the interpretation of vacuum ultraviolet (VUV) experimental data obtained using synchrotron radiation, we explored the ground potential energy surface (PES) of acetyl cyanide and of its cation using standard and recently implemented explicitly correlated methodologies. Our PES covers the regions of tautomerism (between keto and enol forms) and of the lowest fragmentation channels. This allowed us to deduce accurate thermochemical data for this astrobiologically relevant molecule. Unimolecular decomposition of the AC cation turns out to be very complex. The implications for the evolution of prebiotic molecules under VUV irradiation are discussed.

The selectivity of the C-CH(3) and C-CN bond fissions upon excitation of acetyl cyanide at 193 nm has been investigated at the theoretical level of multistate complete active space self-consistent field second order perturbation. The calculated results indicated that the initially excited S(3) state relaxes to S(2) via ultrafast internal conversion. The S(2) state could dissociate via two pathways. One, adiabatically dissociates to CH(3)CO(X)+CN(A). The other one internally converts to S(1) before S(1) intersystem crossing to T(1). The T(1) state subsequently dissociates to two groups of products: CH(3)(X)+OCCN(X) and CH(3)CO(X)+CN(X). The experimentally observed preference branching of CN elimination over CH(3) one and bond selectivity are the results of the competition between the adiabatic and nonadiabatic dynamics of the S(2) state.

Ozonolyses of 2-cyanopropene (1a) and of 2,4-dicyano-1-butene (1b) gave the corresponding ozonides 3-cyano-3-methyl-(2a) and 3-cyano-3-(2-cyanoethyl)-1,2,4-trioxolane (2b) as the first examples of their kind. Reduction with DMS yielded the expected fragments acetyl cyanide (4a) and β-cyanopropionyl cyanide (4b), along with fomaldehyde. Reduction with triphenylphosphine, however, gave cyanomethyl acetate (6a) and cyanomethyl-β-cyanopropionate (6b), respectively.

The side chain geometry and some adjacent bond lengths and angles of the ring are optimized at the STO-3G level of molecular orbital theory for the planar and orthogonal forms of benzoyl X(X = H, F, CN, CH3, OCH3). Similar calculations are reported for acetyl fluoride, acetyl cyanide, and carbonyl cyanide, for which experimental structures and reliable internal barriers are available. The calculated barriers for the benzoyl compounds suggest steric hindrance by X in the ground state as a major cause of the variation in the barrier magnitudes. Good agreement between calculated and experimental geometries for acetyl cyanide and carbonyl cyanide, as well as for the internal rotational barrier in the former, are taken to imply a reliable calculated geometry for benzoyl cyanide. A total geometry optimization for phenol agrees fairly well as for the internal rotational barrier in the ture and also with the direction and magnitude of the dipole moment. Optimization of the ring geometry does not lower the calculated internal rotation barrier.

Sowohl das β-D-Ribofuranosylazid 1 als auch das α-Anomere 3 liefern bei der Staudinger-Reaktion das gleiche P-N-Ylid 2. Mit Alkylisocyanaten RNCO [R - CH3, (CH3)2CH, C2H5OCOCH2 und (S)-C2H5OCOCH(CH3)] entstehen die Carbodiimidderivate als Diastereomerengemische 5, welche mit HN3 in die 1-(β-Ribofuranosyl)-5-(alkylamino)tetrazole 6 umgewandelt werden. Teilweise oder ganzliche Entfernung der Schutzgruppen fuhrt zu den Produkten 7a, c, d und 7d′–d′". Vom β-D-Mannofuranosylazidderivat 8 aus gelangt man uber das P-N-Ylid 9 zum Carbodiimidderivat 10 und schlieslich zum Aminotetrazolderivat 11. Die Umsetzung von 2 mit Phenylisocyanat liefert die 5-[(β- und 5-[(α-D-Ribofuranosyl)amino]-1-phenyltetrazole 18 bzw. 19 uber die Carbodiimidzwischenstufen 12 und 13. Ferner entstehen die 1-Isocyanatozuckerderivate 14 und 15, welche fur die Entstehung der Folgeprodukte 16, 17 und 20–22 verantwortlich sind. Aus 2 und Malonsaure-monoethylester-azid entsteht das Nucleosidderivat 23. Die Darstellung der Ribosyltetrazole 26 und 27 aus 2 last sich nur mit Acetylcyanid uber das syn/anti-Gemisch 24a/24a′ durch Umsetzung mit HN3 verwirklichen. Als Zwischenstufe wird das (α-Ribosylimino)nitril 25 postuliert. Glycosyl Azides as Starting Materials for the Synthesis of Nucleoside Analogues, 2. — Synthesis of Tetrazole Nucleosides The β-D-ribofuranosyl azide derivative 1 as well as the corresponding α-anomeric compound 3 yield via Staudinger reaction the same P-N-ylide 2. Treatment with alkyl isocyanates RNCO [R = CH3, (CH3)2CH, C2H5OCOCH2, (S)-C2H5OCOCH(CH3)] affords the diastereomeric carbodiimide derivatives 5 which can be transformed by HN3 regioselectively into the 1-(β-ribofuranosyl)-5-(alkylamino)tetrazole derivatives 6. Partial or total removal of the protecting groups affords the products 7a, c, d, and 7d′–d′". The β-D-mannofuranosyl azide derivative 8 is converted via the P-N-ylide 9 into the carbodiimide 10 and the aminotetrazole derivative 11. The reaction of 2 with phenyl isocyanate yields the 5-[(β- and 5-[(α-D-ribofuranosyl)amino]-1-phenyltetrazoles 18 and 19 passing the carbodiimide intermediates 12 and 13. Additionally the 1-isocyanato sugar derivatives 14 and 15 arise which provide for the formation of the products 16, 17, and 20–22. The ethyl [(β-D-ribofuranosyl)-5-tetrazolyl]acetate 23 is formed by reaction of 2 with the azide of monoethyl malonate. The preparation of the ribosyltetrazole derivatives 26 and 27 can be achieved only by preceding synthesis of the syn/anti mixture 24a/24a originating from 2 and acetyl cyanide followed by treatment with HN3. The α-ribosyliminonitrile 25 is assumed to be an intermediate.

Microwave spectra of symmetric and asymmetric forms of monodeuterated acetyl cyanide CH2DCOCN have been observed and measured. Significant differences occur between our assign­ment and those of Krisher and Wilson1. We have confirmed all our assignments with the help of microwave - microwave double resonance (MW-MW-DR) experiments. By fitting about twelve low J transition frequencies to a rigid rotator, accurate values for the rotational constants have been obtained. From the analysis of the quadrupole hyperfine splittings of some of the tran­sitions, the nuclear quadrupole coupling constants are also determined. Using the measured rotational constants for a number of molecular isotopic species of Refer­ence (1), and in addition those measured in this laboratory for the 15N, monodeuterated and normal species (determined with greater accuracy), a complete rs-and ro-structure has been calculated. The important conclusions are - i) the methyl group does not possess C3V symmetry and ii) the Ccarbonyl, - Ccyanide and C - N bonds are collinear within the accuracy of measurements.