Amino Nitriles Research Articles

Cyanohydrins from methyl 6-deoxy-2,3-O-isopropylidene-α-l-lyxo-hexofuranosid-4-ulose via Bucherer–Bergs and Strecker reactions

The formation of methyl 4-cyano-6-deoxy-2,3-O-isopropylidene-α-l-talopyranoside (3), methyl 4-cyano-6-deoxy-2,3-O-isopropylidene-α-l-mannopyranoside (4), methyl 4-cyano-6-deoxy-2,3-O-isopropylidene-β-d-allopyranoside (5), and methyl 4-cyano-6-deoxy-2,3-O-isopropylidene-β-d-gulopyranoside (7) from methyl 6-deoxy-2,3-O-isopropylidene-α-l-lyxo-hexopyranosid-4-ulose (1) under Strecker amino nitrile synthesis and Bucherer–Bergs hydantoin synthesis reaction conditions, respectively, is reported. Their structures were determined on the basis of NMR and mass spectral data. The configurations of free cyanohydrins 3 and 4 and 4-O-acetylated cyanohydrins 6 and 8 (obtained by acetylation of 5 and 7, respectively) were established by single-crystal X-ray analysis. The conformations of the six-membered pyranose ring and five-membered 1,3-dioxolane ring in compounds 3, 4, 6, and 8 are also reported.

Synthesis of 2-amino-2-cyanoadamantane and its derivatives

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.

ChemInform Abstract: Light‐Mediated Heterogeneous Cross Dehydrogenative Coupling Reactions: Metal Oxides as Efficient, Recyclable, Photoredox Catalysts in C—C Bond‐Forming Reactions.

AbstractThe title TiO2‐ or ZnO‐mediated irradiation reactions are exemplified for tetrahydroisoquinolines in the presence of an equimolar amount of the metal oxide and using an 11 W fluorescent lamp, aza‐Henry, Mannich, cyanation, and phosphonylation reactions are performed to give β‐nitro amines, β‐amino ketones, amino nitriles, and amino‐phosphonates (33 examples).

Synthesis of α–amino nitriles through Strecker-type reaction using SO3H -functionalized ionic liquid as a homogeneous and water tolerant-acidic catalyst

Abstract Task-specific ionic liquid (TSIL) bearing a sulfonic acid group in imidazolium cation (10 mol %), was found to be an effective catalyst for a Strecker-type reaction in water at room temperature. A wide variety of aldehydes/ketones, amines and TMSCN as cyanide source can be easily transformed into the corresponding α-amino nitriles. The water tolerant catalyst could be recycled five times without loss of any activity.

Self‐Supported Chiral Titanium Cluster (SCTC) as a Robust Catalyst for the Asymmetric Cyanation of Imines under Batch and Continuous Flow at Room Temperature

A robust heterogeneous self-supported chiral titanium cluster (SCTC) catalyst and its application in the enantioselective imine-cyanation/Strecker reaction is described under batch and continuous processes. One of the major hurdles in the asymmetric Strecker reaction is the lack of availability of efficient and reusable heterogeneous catalysts that work at room temperature. We exploited the readily hydrolyzable nature of titanium alkoxide to synthesize a self-supported chiral titanium cluster (SCTC) catalyst by the controlled hydrolysis of a preformed chiral titanium-alkoxide complex. The isolated SCTC catalysts were remarkably stable and showed up to 98 % enantioselectivity (ee) with complete conversion of the imine within 2 h for a wide variety of imines at room temperature. The heterogeneous catalysts were recyclable more than 10 times without any loss in activity or selectivity. The robustness, high performance, and recyclability of the catalyst enabled it to be used in a packed-bed reactor to carry out the cyanation under continuous flow. Up to 97 % ee and quantitative conversion with a throughput of 45 mg h(-1) were achieved under optimized flow conditions at room temperature in the case of benzhydryl imine. Furthermore, a three-component Strecker reaction was performed under continuous flow by using the corresponding aldehydes and amines instead of the preformed imines. A good product distribution was obtained for the formation of amino nitriles with ee values of up to 98 %. Synthetically useful ee values were also obtained for challenging α-branched aliphatic aldehyde by using the three-component continuous Strecker reaction.

Enantioselective Hydrocyanation of N-Protected Aldimines

Enantioselective hydrocyanation of N-benzyloxycarbonyl aldimines catalyzed by a Ru[(S)-phgly](2)[(S)-binap]/C(6)H(5)OLi system or a bimetallic complex [Li{Ru[(S)-phgly](2)[(S)-binap]}]Cl affords the amino nitriles in 92-99% ee. The reaction is carried out in tert-C(4)H(9)OCH(3) with a substrate-to-catalyst molar ratio in the range of 500-5000 at -20 to 0 °C. Primary, secondary, and tertiary alkyl imines as well as the aryl and heteroaryl substrates are smoothly cyanated to produce the desired products in high yield.

ChemInform Abstract: Superelectrophilic Chemistry of Aminonitriles and Related Substrates.

AbstractIn the presence of superacid TfOH, Houben—Hoesch reaction of amino nitriles or cyanopyridines with benzene affords aryl ketones after aqueous hydrolysis.

Zr-MCM-41 Nanoreactors as Efficient and Reusable Catalysts in the Synthesis of New Aminonitriles by the Strecker Reaction

The synthesis and characterization of Zr-MCM-41 nanoreactors and their catalytic activity in the synthesis of new amino nitrile derivatives by the Strecker reaction in high yields and in short reaction times is reported. Synthesis and characterization of Zr-MCM-41 nanoreactors and their catalytic activity in the synthesis of new amino nitrile derivatives by the Strecker reaction in high yields and in short reaction times are reported.

Organocatalytic Enantioselective Strecker Synthesis of α‐Quaternary α‐Trifluoromethyl Amino Acids

AbstractThe first organocatalytic enantioselective Strecker synthesis of α‐quaternary α‐trifluoromethylated amino acids has been developed. Employing Takemoto’s thiourea catalyst the nucleophilic addition of trimethylsilyl cyanide to trifluoromethyl ketimines affords α‐amino nitriles in good to excellent yields (50–99%) and very good enantioselectivities (ee=83–95%). The enantiopure amino nitriles can be obtained by recrystallization. Deprotection and hydrolysis leads to the title amino acids.

Identification of potent and reversible cruzipain inhibitors for the treatment of Chagas disease

Identification of potent and reversible cruzipain inhibitors for the treatment of Chagas disease is described. The identified inhibitors bearing an amino nitrile warhead in P1 exhibit low nanomolar in vitro potency against cruzipain. Further SAR in P2 portion led to the identification of compounds, such as 26, that have a unique selectivity profile against other cysteine proteases and offering new opportunities for safer treatment of Chagas disease.

A Remarkable Titanium‐Catalyzed Asymmetric Strecker Reaction using Hydrogen Cyanide at Room Temperature

AbstractClose to perfect enantioselectivity (up to 98% ee) is obtained for the formation of amino nitriles using hydrogen cyanide (HCN) as the cyanide source at room temperature for the first time. In an operationally simple process, the catalyst generated from a partially hydrolyzed titanium alkoxide (PHTA) and (S)‐N‐salicyl‐β‐amino alcohol ligand, catalyzes the cyanation of imines in a short reaction time.

ChemInform Abstract: First Example of Epibromohydrin as an Acetone Equivalent.

In the presence of lithium diisopropylamide at low temperature, the anion of the amino nitrile 1 is alkylated with epibromohydrin to give an acetonyl derivative 3; allene oxide is invoked as the reactive intermediate.

On the Possibility of Gly and Ala Amino Acids on Titan’s Surface

In view of the possible production of formaldehyde and acetaldehyde in Titan’s atmosphere, the production of α-amino nitriles, the precursors of Glycine and Alanine amino acids, is explored in the upper atmosphere of Titan. The presence of Glycine and Alanine amino acids or their precursor amino nitriles can be used as a diagnostic, respectively for the presence or absence of water locally on the surface of Titan.

Tholinomics—Chemical Analysis of Nitrogen-Rich Polymers

The polymeric composition of Titan's tholins--laboratory analogues of Titan's aerosols--is elucidated using high-resolution mass spectrometry. This complex organic matter is produced by plasma discharge in a gaseous nitrogen-methane mixture and analyzed with a hybrid linear trap/orbitrap mass-spectrometer. The highly structured mass spectra are treated with tools developed for petroleomics (Kendrick and van Krevelen diagrams), with original adaptations for nitrogen-rich compounds. Our goal is to find the best chemical basis set to describe the compositional space that these polymers occupy, to shed light onto the chemical structure of tholins. We succeeded in assigning the molecules identified in the mass spectra of tholins to a small number of regularly distributed X-(CH(2))(m)(HCN)(n) families, where the balanced copolymer (m = n) is determined to play a central role. Within each family, the polymer lengths n and m present Poisson-type distributions. We also identify the smallest species of a subset of families as linear and cyclic amino nitrile compounds of great astrobiological interest: biguanide, guanidin, acetamidine, aminoacetonitrile, and methylimidazole.

Progress of Enantioselective Nitrile Biotransformations in Organic Synthesis

Recent progress of enantioselective biotransformations of nitriles including various functionalized nitriles, ?-hydroxy and ?-amino nitriles, oxirane- and aziridine-containing carbonitriles is summarized in this short review article.

Synthesis of New Analogues of the Tetraponerines

AbstractTo evaluate the influences of the tetraponerine alkyl chains and tricyclic ring systems on their cytotoxic activities, we have prepared a series of alkyl derivatives (3a, 3b and 4a–f) of the non‐natural tricyclic skeletons decahydro‐2H,6H‐dipyrido[1,2‐a:1′,2′‐c]pyrimidine (3, 6–6–6 skeleton) and dodecahydro‐2H‐1,8a‐diazaphenanthrene (4, iso‐6–6–6 skeleton). In this study, two ways to synthesise the 6–6–6 analogues have been developed and compared. One is based on the condensation of α‐tripiperideine with diethyl malonate (DEM) in water at pH 11. This yielded oxo ester 11, precursor of the amino nitrile 8, but only in moderate yield. In the second pathway, the key intermediate 8 was more efficiently synthesised by starting from 2‐(2‐piperidyl)ethanol. Treatment of 8 with alkyl Grignard reagents led to the 6–6–6 analogues 3a and 3b. When the one‐pot reaction between α‐tripiperideine and DEM was performed in water at pH 8, the lactam 12, precursor of the iso‐6–6–6 skeleton, was obtained in a yield of 76 %. The same lactam was also obtained in a yield of 86 % by treatment of tetrahydroanabasine 14 with DEM in water at pH 8. Lactam 12 was transformed into the iso‐6–6–6 analogues 4a–4f. The cytotoxic activities of the 6–6–6 and iso‐6–6–6 analogues against HT29 cancer cells were compared with those of the 5–6–5 and 6–6–5 tetraponerines and with those of solenopsin analogues. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Potential of Amino Acid-Derived α-Amino Nitriles for Generating molecular Diversity.

Potential of Amino Acid-Derived α-Amino Nitriles for Generating molecular Diversity.

Biocatalytic application of nitrilases from Fusarium solani O1 and Aspergillus niger K10

The nitrilases from Fusarium solani O1 and Aspergillus niger K10 showed a broad substrate specificity for carbocyclic and nonaromatic heterocyclic amino nitriles, the preferred substrates being five-membered γ-amino nitrile (±)- 1a, six-membered γ-amino nitriles (±)- 3a, (±)- 5a and (±)- 6a, pyrrolidine-3-carbonitriles (±)- 9a and (±)- 10a as well as piperidine-4-carbonitriles 14a and 15a. Both enzymes showed a strong diastereopreference for cis- vs. trans-γ-amino nitriles. The electronic and steric effects of N-protecting groups affected the reactivity of the nitriles. Amides as by-products of the nitrilase-catalyzed reaction were produced from heterocyclic amino nitriles (±)- 9a, (±)- 10a, 14a and 15a by the A. niger enzyme but only from nitrile (±)- 9a by the F. solani enzyme.

Gallium(III) Triflate Catalyzed Conversion of Aldehydes and Ketones to Hydantoins

Reported is the one-pot synthesis of hydantoins from aldehydes and ketones using gallium-catalyzed cyanoamination. Reported also is a two-pot process which showed a significant advance upon the traditional Bucherer-Bergs reaction, but suffered from problems of isolation and purification of the intermediate amino nitriles. In order to circumvent these problems, a one-pot procedure was developed. This procedure consists of addition of liquid ammonia at -78 °C to an aldehyde or ketone and gallium(III) triflate, followed by addition of HCN. Allowing the reaction mixture to warm to room temperature (evaporation of NH3) followed by addition of Hünigs base and gaseous CO2 delivered the desired hydantoins in reasonable to excellent yields. The two- and one-pot reactions were compared and the one-pot reaction gave similar or better yields. Significantly, benzaldehyde, 2-aceto­naphthalene and nonan-5-one, gave very poor (0-3%) combined yields in the two-pot reaction due to problems of isolation and purification of the amino nitriles, but good yields in the one-pot reaction.

Production of enantiomerically pure D-Phenylglycine using Pseudomonas aeruginosa 10145 as biocatalyst

Different bacterial strains were screened to detect nitrilase and/or nitrile hidratase/amidase activities towards benzonitrile, to be used as biocatalyst to produce enantiomerically pure non-proteinogenic amino acids using amino nitriles as starting material. The best biocatalyst found was Pseudomonas aeruginosa 10145, which showed high enzyme activities. Whole cells were used as catalyst for the transformation of 2-phenyl-2-amino-acetonitrile for the corresponding D-phenylglycine. The percentage conversion was followed by chiral HPLC. After 1 hour reaction 18% of 2-phenyl-2-amino-acetonitrile was converted into D-phenylglycine with an enantiomeric excess of over 95%. When an inducer was added to the media, an increase in nitrile hydrolyzing activities was detected, hence leading to total conversion of (R)-2-phenyl-2-amino-acetonitrile to the corresponding amino acid in 30 min reaction. The isolated yield of the target product was 50% and its characterization was performed by polarimetry, chiral HPLC, IR-FT spectroscopy and GC-MS.