32175-00-1

Basic information

• Product Name: trans-4-Methycyclohexyl isocyanate
• Synonyms: trans-4-methycyclohexyl isocyanate;TRANS-4-METHYL CYCLO HEXANE ISOCYANATE;TRANS-4-METHYL CYCLOHEXYL ISOCYANATE;trans-1-Isocyanato-4-methyl-cyclohexane;isocyanic acid trans-4-methylcyclohexyl ester;t-4 Me Cyclohexyl Isocyanate;Isocyanic;trans-4-Methulcyclohexyl
• CAS NO: 32175-00-1
• Molecular Formula: C₈H₁₃NO
• Molecular Weight: 139.19
• EINECS: 1312995-182-4
• Product Categories: PHARMACEUTICAL INTERMEDIATES
• Mol File: 32175-00-1.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 182°C
• Flash Point: 60°C
• Appearance: clear colourless liquid
• Density: 1.04
• Vapor Pressure: 0.818mmHg at 25°C
• Refractive Index: 1.518
• CAS DataBase Reference: trans-4-Methycyclohexyl isocyanate(CAS DataBase Reference)
• NIST Chemistry Reference: trans-4-Methycyclohexyl isocyanate(32175-00-1)
• EPA Substance Registry System: trans-4-Methycyclohexyl isocyanate(32175-00-1)

Safety Data

• Hazardous Substances Data: 32175-00-1(Hazardous Substances Data)

Usage

General Description

Trans-4-Methycyclohexyl isocyanate is a chemical compound with the molecular formula C8H13NO that is used primarily in the production of polyurethane foams and coatings. It is classified as a highly hazardous chemical due to its potential to cause respiratory irritation and sensitization. Exposure to trans-4-Methycyclohexyl isocyanate can result in skin and eye irritation, as well as respiratory tract irritation and allergic reactions. Due to its reactivity and potential health hazards, careful handling and proper personal protective equipment are necessary when working with this chemical. Additionally, it is important to follow strict safety protocols and regulations to minimize the risks associated with trans-4-Methycyclohexyl isocyanate exposure.

InChI:InChI=1/C8H13NO/c1-7-2-4-8(5-3-7)9-6-10/h7-8H,2-5H2,1H3/t7-,8-

Synthetic route

phosgene (75-44-5) + trans-4-methylcyclohexanamine (2523-55-9) → (1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1)

C8H14FNO → (1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1)

Conditions	Yield
In 5,5-dimethyl-1,3-cyclohexadiene at 140℃; under 760.051 Torr; for 3h; Concentration;

(1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) + N-{2-[4-(aminosulfonyl)phenyl]ethyl}-3-ethyl-4-methyl-2-oxo-2,5-dihydro-1H-pyrrole-1-carboxamide (119018-29-0) → glimepiride (93479-97-1)

Conditions	Yield
In tert-butyl methyl ether; cyclohexanone at 30℃; for 10h; Temperature;	94.5%
Stage #1: N-{2-[4-(aminosulfonyl)phenyl]ethyl}-3-ethyl-4-methyl-2-oxo-2,5-dihydro-1H-pyrrole-1-carboxamide With potassium carbonate In acetone; butanone for 0.5h; Inert atmosphere; Reflux; Stage #2: (1R,4R)-1-isocyanato-4-methylcyclohexane In acetone; butanone Inert atmosphere; Reflux;	90%
Stage #1: N-{2-[4-(aminosulfonyl)phenyl]ethyl}-3-ethyl-4-methyl-2-oxo-2,5-dihydro-1H-pyrrole-1-carboxamide With potassium carbonate at 55 - 60℃; for 1h; Heating / reflux; Stage #2: (1R,4R)-1-isocyanato-4-methylcyclohexane In toluene for 12h; Heating / reflux;	86.3%

Chloroiodomethane (593-71-5) + (1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) → trans-2-chloro-N-(4-methylcyclohexyl)acetamide (31715-94-3)

Conditions	Yield
With methyllithium; lithium bromide In diethyl ether at -78℃; for 1h; chemoselective reaction;	91%

(1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) → N-(4-methylcyclohexyl)formamide (26003-39-4)

Conditions	Yield
With zirconocene dichloride; lithium tri-t-butoxyaluminum hydride In tetrahydrofuran; 2-methyltetrahydrofuran at 0 - 20℃; for 1h; Inert atmosphere; chemoselective reaction;	87%

(1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) + methyl 2-(methylamino)-5-oxo-5H-thieno[3,2-b]pyran-6-carboxylate → methyl 2-(1-methyl-3-((1r,4r)-4-methylcyclohexyl)ureido)-5-oxo-5H-thieno[3,2-b]pyran-6-carboxylate

Conditions	Yield
In tetrahydrofuran at 90 - 100℃; for 16h;	32.37%

5-fluorouracil (51-21-8) + (1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) → 5-Fluoro-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-carboxylic acid (4-methyl-cyclohexyl)-amide

Conditions	Yield
With pyridine 1.) 90 deg C, 2 h, 2.) RT, overnight;	31%

(1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) + N-[2-(4-Sulfamoyl-phenyl)-butyl]-benzamide (25199-66-0) → C25H33N3O4S

Conditions	Yield
With sodium hydroxide In acetone

(1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) + 3-Methyl-N-[2-(4-sulfamoyl-phenyl)-butyl]-benzamide (54198-69-5) → C26H35N3O4S

Conditions	Yield
With sodium hydroxide In acetone

(1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) + 4-Chloro-N-methyl-N-(4-sulfamoyl-benzyl)-benzamide (25200-70-8) → C23H28ClN3O4S

Conditions	Yield
With sodium hydroxide In acetone

(1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) + 3,N-Dimethyl-N-[2-(4-sulfamoyl-phenyl)-ethyl]-benzamide (25200-65-1) → C25H33N3O4S

Conditions	Yield
With sodium hydroxide In acetone

(1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) + 4-Chloro-N-[2-(4-sulfamoyl-phenyl)-butyl]-benzamide (25199-68-2) → C25H32ClN3O4S (25257-24-3)

Conditions	Yield
With sodium hydroxide In acetone

(1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) + N-[2-Methyl-2-(4-sulfamoyl-phenyl)-propyl]-benzamide (25199-70-6) → C25H33N3O4S (25257-26-5)

Conditions	Yield
With sodium hydroxide In acetone

(1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) + 3-Chloro-N-methyl-N-[2-(4-sulfamoyl-phenyl)-ethyl]-benzamide (54198-67-3) → C24H30ClN3O4S

Conditions	Yield
With sodium hydroxide In acetone

(1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) + N-[2-(2,4,6-Trimethyl-3-sulfamoyl-phenyl)-ethyl]-benzamide (25196-93-4) → C26H35N3O4S

Conditions	Yield
With sodium hydroxide In acetone

(1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) + 2-(3,4-Dichloro-phenyl)-N-[2-(4-sulfamoyl-phenyl)-ethyl]-acetamide (25199-42-2) → C24H29Cl2N3O4S

Conditions	Yield
With sodium hydroxide In acetone

(1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) + 3-Methyl-3-phenyl-N-[2-(4-sulfamoyl-phenyl)-ethyl]-butyramide (25199-60-4) → C27H37N3O4S

Conditions	Yield
(i) K2CO3, acetone, (ii) /BRN= 2080824/; Multistep reaction;

(1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) + (E)-3-(3,4-Dichloro-phenyl)-N-[2-(4-sulfamoyl-phenyl)-ethyl]-acrylamide (25199-46-6) → C25H29Cl2N3O4S

Conditions	Yield
With sodium hydroxide In acetone

(1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) + 2-Benzyl-N-[2-(4-sulfamoyl-phenyl)-ethyl]-butyramide (25199-53-5) → C27H37N3O4S

Conditions	Yield
With sodium hydroxide In acetone

(1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) + 3-Methyl-2-phenyl-N-[2-(4-sulfamoyl-phenyl)-ethyl]-butyramide (25199-63-7) → C27H37N3O4S

Conditions	Yield
(i) K2CO3, acetone, (ii) /BRN= 2080824/; Multistep reaction;

(1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) + 2-(3,5-Dimethyl-phenoxy)-N-[2-(4-sulfamoyl-phenyl)-ethyl]-acetamide (25199-34-2) → C26H35N3O5S

Conditions	Yield
With sodium hydroxide In acetone

(1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) + 2-(3,4-Dimethyl-phenoxy)-N-[2-(4-sulfamoyl-phenyl)-ethyl]-acetamide (25199-36-4) → C26H35N3O5S

Conditions	Yield
With sodium hydroxide In acetone

(1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) + 2-Ethyl-2-phenyl-N-(4-sulfamoyl-benzyl)-butyramide (25199-55-7) → C27H37N3O4S

Conditions	Yield
With sodium hydroxide In acetone

(1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) + 3-Phenethyloxy-N-[2-(4-sulfamoyl-phenyl)-ethyl]-propionamide (53446-60-9) → C27H37N3O5S

Conditions	Yield
With sodium hydroxide In acetone

(1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) + 2-(3,4-Dimethoxy-phenyl)-N-[2-(4-sulfamoyl-phenyl)-ethyl]-acetamide (25199-44-4) → C26H35N3O6S

Conditions	Yield
With sodium hydroxide In acetone

(1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) + 2-(2,4-Dichloro-phenoxy)-N-[2-(4-sulfamoyl-phenyl)-ethyl]-acetamide (25199-38-6) → C24H29Cl2N3O5S

Conditions	Yield
With sodium hydroxide In acetone

(1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) + 2-(4-Chloro-phenyl)-2-ethyl-N-[2-(4-sulfamoyl-phenyl)-ethyl]-butyramide (25311-80-2) → C28H38ClN3O4S

Conditions	Yield
With sodium hydroxide In acetone

(1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) + 2-(2,4-Dichloro-6-methyl-phenoxy)-N-[2-(4-sulfamoyl-phenyl)-ethyl]-acetamide (25199-40-0) → C25H31Cl2N3O5S

Conditions	Yield
With sodium hydroxide In acetone

(1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) + N-(2-Chloro-5-sulfamoyl-benzyl)-benzamide → C22H26ClN3O4S

Conditions	Yield
With sodium hydroxide In acetone

(1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) + 2-methyl-N-(4-sulfamoylphenethyl)benzamide → C24H31N3O4S

Conditions	Yield
With sodium hydroxide In acetone

(1R,4R)-1-isocyanato-4-methylcyclohexane (32175-00-1) + N-[2-(2-Chloro-5-sulfamoyl-phenyl)-ethyl]-benzamide (25196-89-8) → C23H28ClN3O4S

Conditions	Yield
With sodium hydroxide In acetone

Upstream product

• 75-44-5 phosgene 
• 2523-55-9 trans-4-methylcyclohexanamine 

Downstream Products

• 25257-24-3 C₂₅H₃₂ClN₃O₄S 
• 25257-26-5 C₂₅H₃₃N₃O₄S 

Relevant articles and documents

Method for preparing isocyanate by using amine and carbonyl fluoride

The invention discloses an efficient synthesis method for preparing corresponding isocyanate by enabling carbonyl fluoride to directly react with amine. The efficient synthesis method mainly comprises the following two steps: carrying out acylation reaction on the amine and the carbonyl fluoride according to a preferable proportion in an anhydrous inertial organic solvent under a sealed environment and a proper reaction condition, thus generating an intermediate-carbamyl fluoride; (2) carrying out dehydrofluorination on the intermediate-carbamyl fluoride under normal pressure and the proper reaction condition, thus obtaining the target isocyanate. During a reaction process, addition of a catalyst is not needed, the reaction conditions are mild, excessive carbonyl fluoride and a used solvent during the reaction process can be efficiently recycled and reused, and a by-product HF can be commercially sold after being collected and refined.