2523-56-0

Basic information

• Product Name: cis-4-Methylcyclohexylamine.
• Synonyms: Cyclohexanamine, 4-methyl-, cis-;p-Aminocyclohexylmethane;4-cis-MethylcyclohexanaMine;cis-1-AMino-4-Methylcyclohexane;4-cis-Methylcyclohexylamine;cis-4-Methyl-1-cyclohexanamine
• CAS NO: 2523-56-0
• Molecular Formula: C₇H₁₅N
• Molecular Weight: 113.2
• Product Categories: Amines;Chiral Reagents;Intermediates
• Mol File: 2523-56-0.mol
• Article Data: 12

Chemical Properties

• Melting Point: -8.5°C (estimate)
• Boiling Point: 154℃
• Flash Point: 27℃
• Appearance: /
• Density: 0.844
• Refractive Index: 1.4550 to 1.4590
• PKA: 10.58±0.70(Predicted)
• CAS DataBase Reference: cis-4-Methylcyclohexylamine.(CAS DataBase Reference)
• NIST Chemistry Reference: cis-4-Methylcyclohexylamine.(2523-56-0)
• EPA Substance Registry System: cis-4-Methylcyclohexylamine.(2523-56-0)

Safety Data

• RIDADR: UN 2734 8/3/PG II
• HazardClass: 8/3
• PackingGroup: II
• Hazardous Substances Data: 2523-56-0(Hazardous Substances Data)

Usage

Description

cis-4-Methylcyclohexylamine is a colorless viscous oily liquid with almost no odor. It is a reagent used in the synthesis of many biologically active compounds, including kinase inhibitors, receptor agonists/antagonists, and a variety of ligands. However, it is highly toxic and can cause severe chemical burns upon contact with the skin, eyes, and mucous membranes. Toxic ammonia and nitrogen oxides may also be released upon exposure to fire.

Uses

Used in Pharmaceutical Industry:
cis-4-Methylcyclohexylamine is used as a reagent for the synthesis of various biologically active compounds, such as kinase inhibitors, receptor agonists/antagonists, and a variety of ligands. This makes it valuable in the development of new drugs and therapies.
Used in Chemical Synthesis:
cis-4-Methylcyclohexylamine is used as a reagent in the synthesis of various organic compounds, contributing to the production of a wide range of chemical products.
It is important to handle cis-4-Methylcyclohexylamine with extreme caution due to its highly toxic nature and potential to cause severe chemical burns and release toxic gases upon exposure to fire. Proper safety measures and protective equipment should be used when working with this compound.

Air & Water Reactions

Slowly decomposes in air to yield ammonia.

Reactivity Profile

cis-4-Methylcyclohexylamine. is incompatible with acids and oxidizing agents. Neutralizes acids exothermically to form salts plus water. May be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Generates flammable gaseous hydrogen in combination with strong reducing agents, such as hydrides.

Health Hazard

TOXIC; inhalation, ingestion or skin contact with material may cause severe injury or death. Contact with molten substance may cause severe burns to skin and eyes. Avoid any skin contact. Effects of contact or inhalation may be delayed. Fire may produce irritating, corrosive and/or toxic gases. Runoff from fire control or dilution water may be corrosive and/or toxic and cause pollution.

Fire Hazard

Non-combustible, substance itself does not burn but may decompose upon heating to produce corrosive and/or toxic fumes. Some are oxidizers and may ignite combustibles (wood, paper, oil, clothing, etc.). Contact with metals may evolve flammable hydrogen gas. Containers may explode when heated.

Synthetic route

4,4,5,5-tetramethyl-2-(4-methylcyclohexyl)-1,3,2-dioxaborolane → cis-4-methylcyclohexanamine (2523-56-0)

Conditions	Yield
With aminosulfonic acid; sodium hydroxide In acetonitrile at 20 - 25℃; for 16h; Inert atmosphere;	90%

cis-4-methylcyclohexylboronic acid catechol ester → cis-4-methylcyclohexanamine (2523-56-0)

Conditions	Yield
With aminosulfonic acid; potassium hydroxide In acetonitrile at 20 - 25℃; for 16h; Inert atmosphere;	86.5%

cis-4-methylcyclohexylboronic acid → cis-4-methylcyclohexanamine (2523-56-0)

Conditions	Yield
With aminosulfonic acid; sodium hydroxide In tetrahydrofuran at 20 - 25℃; for 16h; Inert atmosphere; Large scale;	85%

C12H23BO2 → cis-4-methylcyclohexanamine (2523-56-0)

Conditions	Yield
With aminosulfonic acid; lithium hydroxide In tetrahydrofuran at 20 - 25℃; for 16h; Inert atmosphere;	81%

p-toluidine (106-49-0) → trans-4-methylcyclohexanamine (2523-55-9) + cis-4-methylcyclohexanamine (2523-56-0) + 4,4'-dimethyldicyclohexylamine (84518-71-8, 109667-09-6)

Conditions	Yield
With hydrogen In tetrahydrofuran at 110℃; under 75007.5 Torr; for 3h; Kinetics; Reagent/catalyst; Temperature; Autoclave;	A 63.6% B 30.2% C n/a

p-toluidine (106-49-0) → trans-4-methylcyclohexanamine (2523-55-9) + cis-4-methylcyclohexanamine (2523-56-0)

Conditions	Yield
With hydrogenchloride; hydrogen; acetic acid; platinum at 25℃; under 2280 Torr;
With hydrogen; silica gel; rhodium In 2,2,4-trimethylpentane at 49.85℃; Product distribution; Further Variations:; Catalysts;
With hydrogen In 1,4-dioxane at 100℃; under 15001.5 Torr; for 3.33333h; Autoclave;	A n/a B n/a

formamide (77287-34-4, 77287-35-5, 60100-09-6) + 1-methylcyclohexan-4-one (589-92-4) → trans-4-methylcyclohexanamine (2523-55-9) + cis-4-methylcyclohexanamine (2523-56-0)

Conditions	Yield
With formic acid anschliessendes Erhitzen mit wss.HCl;

4-Methylacetanilide (103-89-9) → cis-4-methylcyclohexanamine (2523-56-0)

Conditions	Yield
With hydrogenchloride; acetic acid; platinum at 70 - 80℃; under 2280 Torr; anschliessend man verseift durch Erhitzen mit konz. Salzsaeure auf 130-140grad;

trans-4-methylcyclohexyl p-toluenesulfonate (34866-36-9) → cis-4-methylcyclohexanamine (2523-56-0)

Conditions	Yield
(i) NaN3, (ii) H2, Pd-C, EtOH; Multistep reaction;
With ammonia
(i) NaN3, (ii) LiAlH4; Multistep reaction;

1-methylcyclohexan-4-one (589-92-4) → trans-4-methylcyclohexanamine (2523-55-9) + cis-4-methylcyclohexanamine (2523-56-0)

Conditions	Yield
Yield given. Multistep reaction. Yields of byproduct given;
With decane; (S)-1-phenyl-ethylamine; Chromobacterium violaceum amine transaminase A W60 C In tert-butyl methyl ether at 37℃; pH=8.2; Enzymatic reaction; stereoselective reaction;	A n/a B n/a
With decane; (S)-1-phenyl-ethylamine; Vibrio fluvialis amine transaminase A In tert-butyl methyl ether at 37℃; pH=8.2; Catalytic behavior; Reagent/catalyst; Solvent; Enzymatic reaction; stereoselective reaction;	A n/a B n/a

4-methylcyclohexanone oxime (4994-13-2, 128925-57-5, 128925-58-6) → cis-4-methylcyclohexanamine (2523-56-0)

Conditions	Yield
With hydrogen; platinum

1-methyl-cyclohexanone-(4)-oxime → cis-4-methylcyclohexanamine (2523-56-0)

Conditions	Yield
With sodium amalgam; ethanol; acetic acid

ethanol (64-17-5) + 4-methylcyclohexanone oxime (4994-13-2, 128925-57-5, 128925-58-6) + acetic acid (64-19-7) + sodium amalgam → cis-4-methylcyclohexanamine (2523-56-0)

p-toluidine (106-49-0) → cis-4-methylcyclohexanamine (2523-56-0)

Conditions	Yield
With hydrogen; silica gel; rhodium In 2,2,4-trimethylpentane at 49.85℃; Activation energy; Further Variations:; Catalysts;

trans-4-methylcyclohexan-1-ol (7731-29-5) → cis-4-methylcyclohexanamine (2523-56-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: Py 2: liq. NH3 View Scheme

cis-4-methylcyclohexylamine hydrochloride (33483-66-8) → cis-4-methylcyclohexanamine (2523-56-0)

Conditions	Yield
Stage #1: cis-4-methylcyclohexylamine hydrochloride With sodium hydrogencarbonate In water Stage #2: With hydrogenchloride In water at 20℃; Stage #3: With ammonia In methanol	1.78 g

1-methyl-4-nitrobenzene (99-99-0) → trans-4-methylcyclohexanamine (2523-55-9) + cis-4-methylcyclohexanamine (2523-56-0)

Conditions	Yield
With hydrogen In tetrahydrofuran at 110℃; under 75007.5 Torr; for 3h; Kinetics; Autoclave; diastereoselective reaction;	A n/a B n/a

p-cresol (106-44-5) → trans-4-methylcyclohexanamine (2523-55-9) + cis-4-methylcyclohexanamine (2523-56-0)

Conditions	Yield
With methanol; 5% Rh/C; ammonia; hydrogen; isopropyl alcohol In Hexadecane at 140℃; under 12001.2 Torr; for 16h; Autoclave;	A n/a B n/a
With alumina-supported nickel; ammonia; hydrogen In toluene at 160℃; for 6h; Time; High pressure; Overall yield = 96 percentChromat.;	A n/a B n/a

2-(4-methylphenyl)-benzo-1,3-dioxa-2-borole (85107-38-6) → cis-4-methylcyclohexanamine (2523-56-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: rhodium contaminated with carbon; hydrogen / ethyl acetate / 12 h / 70 °C / 11251.1 Torr 2: aminosulfonic acid; potassium hydroxide / acetonitrile / 16 h / 20 - 25 °C / Inert atmosphere View Scheme

4-methylphenylboronic acid (5720-05-8) → cis-4-methylcyclohexanamine (2523-56-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: rhodium contaminated with carbon; hydrogen / 80 °C / Autoclave; Large scale 2: aminosulfonic acid; sodium hydroxide / tetrahydrofuran / 16 h / 20 - 25 °C / Inert atmosphere; Large scale View Scheme

p-tolylboronic pinacol ester (195062-57-8) → cis-4-methylcyclohexanamine (2523-56-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: rhodium contaminated with carbon; hydrogen / ethyl acetate / 8 h / 60 °C / 15001.5 Torr 2: aminosulfonic acid; sodium hydroxide / acetonitrile / 16 h / 20 - 25 °C / Inert atmosphere View Scheme

phthalic anhydride (85-44-9) + cis-4-methylcyclohexanamine (2523-56-0) → cis-1-Methyl-4-phthalimidocyclohexan (31946-74-4)

Conditions	Yield
In N,N-dimethyl-formamide at 150℃;	80%

cis-4-methylcyclohexanamine (2523-56-0) + benzoic acid (65-85-0) → cis-4-benzamino-1-methyl-cyclohexane (32175-02-3)

Conditions	Yield
Stage #1: benzoic acid With N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 0℃; for 0.166667h; Stage #2: cis-4-methylcyclohexanamine With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 5h;	80%

cis-4-methylcyclohexanamine (2523-56-0) + 3-chloroisoquinoline-7-carbaldehyde (1337879-96-5) → 3-((cis-4-methylcyclohexyl)amino)isoquinoline-7-carbaldehyde (1544664-54-1)

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos In N,N-dimethyl-formamide at 90℃; for 6h; Inert atmosphere;	51%

4,6-dichloro-1H-indole-2-carboxylic acid (101861-63-6) + cis-4-methylcyclohexanamine (2523-56-0) → 4,6-dichloro-N-(cis-4-methylcyclohexyl)-1H-indole-2-carboxamide (1473450-31-5)

Conditions	Yield
Stage #1: 4,6-dichloro-1H-indole-2-carboxylic acid With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 0.166667h; Stage #2: cis-4-methylcyclohexanamine In N,N-dimethyl-formamide at 20℃; for 16h;	50%

formaldehyd (50-00-0) + formic acid (64-18-6) + cis-4-methylcyclohexanamine (2523-56-0) → dimethyl-(cis-4-methyl-cyclohexyl)-amine (2523-66-2)

Conditions	Yield
With water

cis-4-methylcyclohexanamine (2523-56-0) + C17H19N3O4S → C23H29N3O4S (862-48-6)

Conditions	Yield
In 1,4-dioxane Heating;

cis-4-methylcyclohexanamine (2523-56-0) + benzoyl chloride (98-88-4) → cis-4-benzamino-1-methyl-cyclohexane (32175-02-3)

Conditions	Yield
With sodium hydroxide

formaldehyd (50-00-0) + cis-4-methylcyclohexanamine (2523-56-0) → dimethyl-(cis-4-methyl-cyclohexyl)-amine (2523-66-2)

Conditions	Yield
With formic acid

3,3-Diphenylpropionic acid (606-83-7) + cis-4-methylcyclohexanamine (2523-56-0) → N-(4-Methyl-cyclohexyl)-3,3-diphenyl-propionamide

Conditions	Yield
(i) ClCO2Et, Et3N, DMF, (ii) /BRN= 2203109/; Multistep reaction;

cis-4-methylcyclohexanamine (2523-56-0) → cis-N-(4-Methylcyclohexyl)-3,3-diphenylpropylamin (59182-79-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: (i) ClCO2Et, Et3N, DMF, (ii) /BRN= 2203109/ 2: LiAlH4 / tetrahydrofuran View Scheme

cis-4-methylcyclohexanamine (2523-56-0) + 3-chloroisoquinoline-7-carbaldehyde (1337879-96-5) → 4-chloro-3-((cis-4-methylcyclohexyl)amino)isoquinoline-7-carbaldehyde (1544664-57-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / N,N-dimethyl-formamide / 6 h / 90 °C / Inert atmosphere 2: N-chloro-succinimide; trifluoroacetic acid / acetonitrile / 16 h / 20 °C View Scheme

Upstream product

• 106-49-0 p-toluidine 
• 77287-34-4 formamide 
• 589-92-4 1-methylcyclohexan-4-one 
• 103-89-9 4-Methylacetanilide 
• 34866-36-9 trans-4-methylcyclohexyl-p-toluenesulfonate 
• 4994-13-2 4-methylcyclohexanone oxime 
• 64-17-5 ethanol 
• 64-19-7 acetic acid 
• 7731-29-5 trans-4-methylcyclohexan-1-ol 
• 33483-66-8 cis-4-methylcyclohexylamine hydrochloride 
• 99-99-0 1-methyl-4-nitrobenzene 
• 106-44-5 p-cresol 
• 85107-38-6 2-(4-methylphenyl)-benzo-1,3-dioxa-2-borole 
• 5720-05-8 4-methylphenylboronic acid 

Downstream Products

• 2523-66-2 dimethyl-(cis-4-methyl-cyclohexyl)-amine 
• 862-48-6 C₂₃H₂₉N₃O₄S 
• 32175-02-3 cis-4-benzamino-1-methyl-cyclohexane 
• 59182-79-5 cis-N-(4-Methylcyclohexyl)-3,3-diphenylpropylamin 
• 1544664-54-1 3-((cis-4-methylcyclohexyl)amino)isoquinoline-7-carbaldehyde 
• 31946-74-4 2-(cis-4-methylcyclohexyl)-1H-isoindole-1,3(2H)-dione 
• 32175-04-5 trans-4-benzamino-1-methyl-cyclohexane 

Relevant articles and documents

Ceria supported Ru0-Ruδ+ clusters as efficient catalyst for arenes hydrogenation

Selective hydrogenation of aromatic amines, especially chemicals such as aniline and bis(4-aminocyclohexyl)methane for non-yellowing polyurethane, is of particular interests due to the extensive applications. To conquer the existing difficulties in selective hydrogenation, the Ru0-Ruδ+/CeO2 catalyst with solid frustrated Lewis pairs was developed for aromatic amines hydrogenation with excellent activity and selectivity under relative milder conditions. The morphology, electronic and chemical properties, especially the Ru0-Ruδ+ clusters and reducible ceria were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electronic microscopy (SEM), X-ray photoelectron spectroscopy (XPS), CO2 temperature programmed desorption (CO2-TPD), H2 temperature programmed reduction (H2-TPR), H2 diffuse reflectance Fourier transform infrared spectroscopy (H2-DRIFT), Raman, etc. The 2% Ru/CeO2 catalyst exhibited good conversion of 95% and selectivity greater than 99% toward cyclohexylamine. The volcano curve describing the activity and Ru state was found. Owning to the “acidic site isolation” by surrounding alkaline sites, condensation between the neighboring amine molecules could be effectively suppressed. The catalyst also showed good stability and applicability for other aromatic amines and heteroarenes containing different functional groups.

Application of Transaminases in a Disperse System for the Bioamination of Hydrophobic Substrates

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Preparation method of cis-4-methylcyclohexylamine

The invention discloses a preparation method of cis-4-methylcyclohexylamine, and belongs to the technical field of organic synthesis. According to the preparation method, 4-methyl phenyl boric acid/borate is taken as the raw material and is hydrogenated under the action of a rhodium-carbon catalyst to obtain a cis-/trans- mixture; then the mixture is subjected to recrystallization to obtain cis-4-methylcyclohexyl boric acid/borate; and finally sulfamic acid and an alkali water solution are added to carry out amine substitution reactions to obtain cis-4-methylcyclohexylamine. The operation of the preparation method is simple and convenient, the catalyst can be used for 7 times, the reaction yield is high, the purity of the cis- product can reach 99.5% or more, and the preparation method canbe applied to scale-up.