6850-38-0

Usage

Uses

Used in Pharmaceutical Industry:
2-Aminocyclohexanol is used as a key intermediate in the synthesis of various pharmaceuticals, including the antiarrhythmic drug vernakalant, spleen tyrosine kinase inhibitors, and κ-opioid analgesics. Its unique chemical structure allows for the formation of complex molecules with specific biological activities.
Used in Chemical Synthesis:
2-Aminocyclohexanol is also used as a versatile building block in the synthesis of various chemicals, such as chiral amines, cyclohexane derivatives, and other organic compounds. Its reactivity and functional group make it a valuable component in the development of new chemical entities with potential applications in various industries.

Preparation

2-Aminocyclohexanol Synthesis: Under water bath reaction conditions, 214.3 g of ammonia water was added to a 500 mL three-necked flask. Stir and heat, and when the internal temperature reaches about 50°C, start to slowly drop 50.0 g of 1,2-epoxycyclohexane into the reaction flask. After the dropwise addition was completed, the reaction was performed at a constant temperature for 12h. After the reaction was completed, the reaction was processed to obtain a crude product, which was purified by recrystallization to obtain 2-aminocyclohexanol with a yield of 90% and an amine value (mgKOH/g) of 453.

InChI:InChI=1/C6H13NO/c7-5-3-1-2-4-6(5)8/h5-6,8H,1-4,7H2

Upstream product

• 286-20-4 cyclohexane-1,2-epoxide 
• 71559-13-2 2-azido cyclohexanol 
• 6628-80-4 trans-2-chlorocyclohexanol 
• 7664-41-7 ammonia 
• 1460-57-7 trans-1,2-cyclohexandiol 
• 931-16-8 (+/-)-trans-2-aminocyclohexanol 
• 110716-78-4 (1R,2R)-trans-2-azidocyclohexanol 
• 155975-19-2 (1R,2R)-trans-2-(N-tert-butyloxycarbonyl)amino-1-cyclohexanol 
• 177900-52-6 (2-isocyanocyclohexyloxy)trimethylsilane 
• 189942-49-2 (4R,5R)-trans-hexahydrobenzoxazolidin-2-one 
• 40571-86-6 rac-(1R,2R)-2-(benzylamino)cyclohexanol 
• 882409-01-0 (S)-mandelic acid salt of (1R,2R)-2-trans-2-(benzylamino)cyclohexanol 
• 141553-09-5 (1R,2R)-trans-2-(N-benzyl)amino-1-cyclohexanol 
• 119479-49-1 (1S,2S)-trans-2-azidocyclohexanol 

Downstream Products

• 18421-15-3 (±)-N-((1R,2R)-2-hydroxycyclohexyl)acetamide 
• 18421-17-5 (+/-)-trans-2-acetylamino-1-acetoxy-cyclohexane 
• 144383-34-6 C₈H₁₈NO₃P 
• 92645-06-2 2-cyclohexanol 
• 80509-53-1 2,9-Bis-(2-hydroxy-cyclohexyl)-anthra[2,1,9-def;6,5,10-d'e'f']diisoquinoline-1,3,8,10-tetraone 
• 23551-93-1 N-(2-Hydroxy-cyclohexyl)-benzamide 
• 786652-78-6 [(2-oxo-cyclohexylcarbamoyl)-phenyl-methyl]-carbamic acid tert-butyl ester 
• 31236-61-0 (+/-)-2-cyclohexanone 
• 123719-56-2 (1S*,2S*)-2-amino-1-ethenyl-1-cyclohexanol 
• 123719-56-2 (1R*,2S*)-2-amino-1-ethenyl-1-cyclohexanol 
• 123719-63-1 (3aS,7aR)-7a-Vinyl-hexahydro-benzooxazol-2-one 
• 123719-63-1 (3aR,7aR)-7a-Vinyl-hexahydro-benzooxazol-2-one 
• 143818-05-7 ((1S,2R)-2-Hydroxy-2-vinyl-cyclohexylamino)-acetic acid ethyl ester 
• 143818-05-7 ((1R,2R)-2-Hydroxy-2-vinyl-cyclohexylamino)-acetic acid ethyl ester 

Relevant academic research and scientific papers

One-pot production of phenazine from lignin-derived catechol

Upgrading lignin-derived monomeric products is crucial in bio-refineries to effectively utilize lignin. Herein, we report a simple strategy to convert catechol to phenazine, a useful N-heterocycle three-aromatic-ring compound, whose current synthetic procedure is complex via a petroleum-derived feedstock. The reaction uses catechol as the sole carbon source and aqueous ammonia as reaction media and a nitrogen source. Without additional solvents, phenazine was obtained in 67% yield in the form of high purity crystals (>97%) over a Pd/C catalyst after a one-pot-two-stage reaction. When cyclohexane was used as a co-solvent in the first step, a higher yield (81%) and purity (>99%) were achieved. Mechanistic investigations involving control experiments and an isotope labeling study reveal that hydrogenation, amination, coupling and dehydrogenation reactions are the key steps leading to phenazine formation. The conversion of other lignin-derived catechols highlights that the protocol is extendable to produce substituted phenazines.

Enantioselective Cascade Biocatalysis for Deracemization of Racemic β-Amino Alcohols to Enantiopure (S)-β-Amino Alcohols by Employing Cyclohexylamine Oxidase and ω-Transaminase

Optically active β-amino alcohols are very useful chiral intermediates frequently used in the preparation of pharmaceutically active substances. Here, a novel cyclohexylamine oxidase (ArCHAO) was identified from the genome sequence of Arthrobacter sp. TYUT010-15 with the R-stereoselective deamination activity of β-amino alcohol. ArCHAO was cloned and successfully expressed in E. coli BL21, purified and characterized. Substrate-specific analysis revealed that ArCHAO has high activity (4.15 to 6.34 U mg?1 protein) and excellent enantioselectivity toward the tested β-amino alcohols. By using purified ArCHAO, a wide range of racemic β-amino alcohols were resolved, (S)-β-amino alcohols were obtained in >99 % ee. Deracemization of racemic β-amino alcohols was conducted by ArCHAO-catalyzed enantioselective deamination and transaminase-catalyzed enantioselective amination to afford (S)-β-amino alcohols in excellent conversion (78–94 %) and enantiomeric excess (>99 %). Preparative-scale deracemization was carried out with 50 mM (6.859 g L?1) racemic 2-amino-2-phenylethanol, (S)-2-amino-2-phenylethanol was obtained in 75 % isolated yield and >99 % ee.

Asymmetric amination of meso-epoxide with vegetable powder as a low-toxicity catalyst

This paper describes the scope and limitation of substrates subjected to asymmetric amination with epoxides catalyzed by a soluble soybean polysaccharide (Soyafibe S-DN), which we recently discovered from the reaction of 1,2-epoxycyclohexane with cyclopropylamine. Various meso-epoxides reacted with various amines afforded the corresponding products with good enantiomeric selectivity. Since it was found that pectin was found to have a catalytic ability after screening commercially available polysaccharides, we studied 33 different vegetable powders having pectic substances, and we found that many vegetable powders showed catalytic ability. These results should guide in using vegetable components as low-toxic catalysts for the production of pharmaceuticals.

Novel process for preparing beta-aminocyclohexanol by open loop of 1,2-cyclohexene oxide

The invention discloses a novel process for preparing beta-aminocyclohexanol by open loop of 1,2-cyclohexene oxide. The process comprises the following steps: preparing the beta-aminocyclohexanol by adopting open loop of 1,2-cyclohexene oxide and ammonia in a molar ratio of 1:1-10, reacting at 0-100 DEG C for 1-48 hours to obtain a crude product; recrystallizing and purifying the crude product obtained after the reaction to obtain the beta-aminocyclohexanol having a yield of 90% or above and an amine value of about 450. The beta-aminocyclohexanol preparation method has low cost, simple process flow, mild reaction, easy operation and high yield, and has a wide application and market prospect.

Hybrid Organo- and Biocatalytic Process for the Asymmetric Transformation of Alcohols into Amines in Aqueous Medium

A hybrid organo- and biocatalytic system for the asymmetric conversion of racemic alcohols into amines was developed. Combining an organocatalyst, AZADO, an oxidant, NaOCl, and an enzyme, ω-transaminase, we implemented a one-pot oxidation-transamination sequential process in aqueous medium. The method showed broad substrate scope and was successfully applied to conventional secondary alcohols and sterically hindered β-substituted cycloalkanols, where a highly stereoselective dynamic asymmetric bioamination enabled us to set up both contiguous stereocenters with very high enantio- and diastereomeric ratio (>90% yield, >99% ee, and up to 49:1 dr).

Structure-anticonvulsant activity studies in the group of (E)-N-cinnamoyl aminoalkanols derivatives monosubstituted in phenyl ring with 4-Cl, 4-CH3or 2-CH3

A series of twenty two (E)-N-cinnamoyl aminoalkanols derivatives monosubstituted in phenyl ring with 4-Cl, 4-CH3or 2-CH3was designed, synthesized and evaluated for anticonvulsant activity in rodent models of seizures: maximal electroshock (MES) test, subcutaneous pentylenetetrazole (scPTZ) test, and 6-Hz test. There were identified three most active compounds: S-(2E)-N-(1-hydroxypropan-2-yl)-3-(2-methylphenyl)prop-2-enamide (5) (ED50MES = 42.56, ED50scPTZ = 58.38, ED506-Hz 44 mA = 42.27 mg/kg tested in mice after intraperitoneal (i.p.) administration); R,S-(2E)-3-(4-chlorophenyl)-N-(1-hydroxybutan-2-yl)prop-2-enamide (6) (ED50MES = 53.76, ED50scPTZ = 90.31, ED506-Hz 44 mA = 92.86 mg/kg mice, i.p.); and R,S-(2E)-3-(4-chlorophenyl)-N-(2-hydroxypropyl)prop-2-enamide (11) (ED50MES = 55.58, ED50scPTZ = 102.15, ED506-Hz 44 mA = 51.27 mg/kg mice, i.p.). Their structures and configurations were confirmed by crystal X-ray diffraction method. The structure-activity studies among the tested series showed that chlorine atom in position para or methyl group in position ortho of phenyl ring were beneficial for anticonvulsant activity. Methyl group in position para of phenyl ring decreased anticonvulsant activity in reported series of cinnamamide derivatives.

Method for synthesizing trans-cyclohexyldiamine

The invention discloses a method for synthesizing trans-cyclohexyldiamine. The method comprises the following steps: by using epoxy cyclohexane as the raw material, carrying out ring opening with ammonia water, adding sulfuric acid for dewatering and salification, adding free alkali, carrying out ring opening with ammonia water, and distilling to obtain the trans-cyclohexyldiamine. The method has the advantages of high repetitiveness of the synthesis route, and simple and accessible raw materials, and provides an alternative scheme for obtaining the trans-cyclohexyldiamine pure product.

Chemo- and Site-Selective Alkyl and Aryl Azide Reductions with Heterogeneous Nanoparticle Catalysts

Site-selective modification of bioactive natural products is an effective approach to generating new leads for drug discovery. Herein, we show that heterogeneous nanoparticle catalysts enable site-selective monoreduction of polyazide substrates for the generation of aminoglycoside antibiotic derivatives. The nanoparticle catalysts are highly chemoselective for reduction of alkyl and aryl azides under mild conditions and in the presence of a variety of easily reduced functional groups. High regioselectivity for monoazide reduction is shown to favor reduction of the least sterically hindered azide. We hypothesize that the observed selectivity is derived from the greater ability of less-hindered azide groups to interact with the surface of the nanoparticle catalyst. These results are complementary to previous Staudinger reduction methods that report a preference for selective reduction of electronically activated azides.

Anticonvulsant activity, crystal structures, and preliminary safety evaluation of N - trans -cinnamoyl derivatives of selected (un)modified aminoalkanols

Adequate control of seizures remains an unmet need in epilepsy. In order to identify new anticonvulsant agents, a series of N-trans-cinnamoyl derivatives of selected aminoalkanols was synthetized. The compounds were obtained in the reaction of N-acylation carried out in a two-phase system. The substances were tested in animal models of seizures induced either electrically (maximal electroshock - MES; 6-Hz test) or chemically, by subcutaneous injection of pentetrazol (scPTZ). Neurotoxicity was determined by the rotarod test. Lipophilicity of the active compounds, expressed as RM0, was determined by reversed-phase thin layer chromatography and it ranged from 1.390 to 2.219. From among the tested series of compounds, R,S-(E)-N-(1-hydroxypropan-2-yl)-3-phenylprop-2-enamide (1) and R,S-(E)-N-(2-hydroxypropyl)-3-phenylprop-2-enamide (3) exhibited the best anticonvulsant activity. Compound 1, when administered to mice by intraperitoneal (i.p.) injection, showed the ED50 values of 86.6, 60.9, and 109.6 mg/kg in the MES, 6-Hz, and scPTZ tests, respectively. For compound 3, the ED50 values were found to be 47.1 mg/kg in MES and 77.1 mg/kg in scPTZ (mice, i.p.). The distances measured in crystals of compound 1 were: 7.99 ? - from the phenyl ring to the hydroxyl group in the amide moiety, 5.729 ? - from the phenyl ring to the amide group, and 3.112 - from the amide group to the hydroxyl group in the amide moiety. The reported compounds did not exhibit mutagenic potential when assayed in the Ames test. Compounds 1 and 3 did not affect viability and morphology of human hepatocellular carcinoma cells (HepG2).

Preliminary evaluation of central nervous system activity of (E)-N-2-methyl-3-phenylprop-2-enyl ((E)-N- α-methylcinnamyl) derivatives of selected aminoalkanols

A series of (E)-α-methylcinnamyl derivatives of selected aminoalkanols was synthetized and evaluated for activity in central nervous system. All compounds were tested as anticonvulsants and one additionally in antidepressant- and anxiolytic-like assays. The compounds possessed pharmacophoric elements regarded as beneficial for anticonvulsant activity: hydrophobic unit and two hydrogen bonds donor/acceptor features. The compounds were verified in mice after intraperitoneal (i.p.) administration in maximal electroshock (MES) and subcutaneous pentetrazole (scPTZ) induced seizures as well as neurotoxicity assessments. Eight of the tested substances showed protection in MES test at the dose of 100 mg/kg. The derivative of 2-aminopropan-1-ol was also tested in 6-Hz test in mice i.p. and showed anticonvulsant activity but at the same time the neurotoxicity was noted. The derivative of 2-amino-1-phenylethanol which possessed additional hydrophobic unit in aminoalkanol moiety was tested in other in vivo assays to evaluate antidepressant- and anxiolytic-like activity. The compound proved beneficial properties especially as anxiolytic agent remaining active in four-plate test in mice at the dose of 2.5 mg/kg (i.p.). In vitro biotransformation studies of 2-amino-1-phenylethanol derivative carried out in mouse liver microsomal assay indicated two main metabolites as a result of aliphatic and aromatic hydroxylation or aliphatic carbonylation. To identify possible mechanism of action, we evaluated serotonin receptors (5-HT1A, 5-HT6 and 5-HT7) binding affinities of the compounds but none of them proved to bind to any of tested receptors.