16052-40-7

Usage

Uses

Used in Organic Synthesis:
[1R-(1alpha,2beta,5alpha)]-2-(isopropyl)-5-methylcyclohexanecarboxylic acid is used as a building block in organic synthesis for the creation of more complex molecules. Its unique structure and reactivity make it a valuable component in the synthesis of pharmaceuticals, agrochemicals, and other specialty chemicals.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, [1R-(1alpha,2beta,5alpha)]-2-(isopropyl)-5-methylcyclohexanecarboxylic acid is used as an intermediate in the development of new drugs. Its chiral nature allows for the synthesis of enantiomerically pure compounds, which is crucial for ensuring the desired biological activity and minimizing potential side effects.
Used as a Flavoring Agent:
[1R-(1alpha,2beta,5alpha)]-2-(isopropyl)-5-methylcyclohexanecarboxylic acid is also used as a flavoring agent in the food and beverage industry. Its unique chemical structure may contribute to the development of novel flavors or enhance existing ones, providing a distinct taste profile to various products.

InChI:InChI=1/C11H20O2/c1-7(2)9-5-4-8(3)6-10(9)11(12)13/h7-10H,4-6H2,1-3H3,(H,12,13)

Upstream product

• 124-38-9 carbon dioxide 
• 15356-60-2 (1S,2R,5S)-(+)-menthol 
• 16052-42-9 (1R,2S,5R)-menthyl chloride 
• 1217664-77-1 C₁₁H₁₉N 
• 2216-51-5 (-)-menthol 
• 663218-94-8 menthylformic acid 
• 70985-58-9 (1S,2S,5R)-2-isopropyl-5-methylcyclohexane-1-carboxylic acid 
• 485843-44-5 menthyl 3-carboxaldehyde 
• 63474-24-8 (1R,2S,5R)-(-)menthylmagnesium chloride 
• 80434-59-9 (1R,2S,5R)-2-isopropyl-5-methylcyclohexanecarboxaldehyde 
• 4460-20-2 5-Pentyl-2-((1R)-3c-methyl-6t-isopropyl-cyclohexyl-(1r))-resorcin 
• 67-64-1 acetone 

Downstream Products

• 108340-97-2 meso-α,α,α,α-tetrakis<2-<(p-menth-3-ylcarbonyl)amino>phenyl>-porphyrin 
• 1221279-85-1 menthyl vinyl ketone 
• 70985-58-9 (1S,2S,5R)-2-isopropyl-5-methylcyclohexane-1-carboxylic acid 
• 1607820-38-1 (1R,1'R,2S,2'S,5R,5'R)-N,N'-[(2S,3S)-1,4-bis(benzyloxy)butane-2,3-diyl]bis(2-isopropyl-5-methylcyclohexanecarboxamide) 
• 223750-65-0 C₁₀H₂₁N 

Relevant academic research and scientific papers

Synthesis, characterization and hplc analysis of the (1S,2S,5R)-diastereomer and the enantiomer of the clinical candidate ar-15512

AR-15512 (formerly known as AVX-012 and WS-12) is a TRPM8 receptor agonist currently in phase 2b clinical trials for the treatment of dry eye. This bioactive compound with menthol-like cooling activity has three stereogenic centers, and its final structure and absolute configuration, (1R,2S,5R), have been previously solved by cryo-electron microscopy. The route of synthesis of AR-15512 has also been reported, revealing that epimerization processes at the C-1 can occur at specific stages of the synthesis. In order to confirm that the desired configuration of AR-15512 does not change throughout the process and to discard the presence of the enantiomer in the final product due to possible contamination of the initial starting material, both the enantiomer of AR-15512 and the diastereomer at the C-1 were synthesized and fully characterized. In addition, the absolute configuration of the (1S,2S,5R)-diastereomer was determined by X-ray crystallographic analysis, and new HPLC methods were designed and developed for the identification of the two stereoisomers and their comparison with the clinical candidate AR-15512.

Ester ammonolysis reaction catalyst composition and preparation method of L-menthane carboxamide

The invention discloses an ester ammonolysis reaction catalyst composition and a preparation method of L-menthane carboxamide. The ester ammonolysis reaction catalyst comprises a catalyst and a ligand, wherein the catalyst is cuprous salt CuX, the ligand is a (R)-N, N, N, N-tetraalkyl binaphthylamine compound shown as the specification, wherein R1, R2, R3 and R4 are independently selected from thegroups shown as the specification. Menthyl chloride is used as the starting raw material in the method to react with metal magnesium to prepare menthyl magnesium chloride, then reaction with chloroformate with different substituent groups is carried out to obtain menthyl formate, and then ammonolysis under the catalysis of an ester ammonolysis catalyst composition is conducted to obtain the L-menthane carboxamide. The yield is improved, the production cost is reduced, the optical purity is high, and environmental protection and no wastewater discharge are realized.

Method for preparing menthane carboxamide by taking L-menthol as raw material

The invention relates to a method for preparing menthane carboxamide by taking L-menthol as a raw material. The menthane carboxamide is prepared through the processes of chlorination, a Grignard reaction, acidification, acylating chlorination, amidation, distillation, recrystallization and the like in sequence. The process route is mature, has the advantages of operation management simplicity andsecurity risk reduction, during a chlorination process, lower-layer waste acid water is collected and reduced pressure distillation is carried out; H2O and HCl in the acid water are removed; recoveryof ZnCl2 is realized, reduced pressure distillation completion is realized, and a reagent, namely concentrated HCl, is added into the recovered ZnCl2; a ZnCl2/HCl saturated solution is prepared again,the L-menthol is added for chlorination reaction again, the steps are repeated, the waste acid water in the chlorination reaction can be repeatedly used, the production cost is saved, the wastewatertreatment cost is reduced, and the economic benefit is improved.

Stereochemistry of the Menthyl Grignard Reagent: Generation, Composition, Dynamics, and Reactions with Electrophiles

Menthyl Grignard reagent 1 from either menthyl chloride (2) or neomenthyl chloride (3) consists of menthylmagnesium chloride (1a), neomenthylmagnesium chloride (1b), trans-p-menthane (4), 2-menthene (8), 3-menthene (9), and Wurtz coupling products including symmetrical bimenthyl 13. The diastereomeric ratio 1a/1b was determined in situ by 13C NMR or after D2O quenching by 2H NMR analysis. Hydrolysis of the C-Mg bond proceeds with retention of configuration at C-1. The kinetic ratio 1a/1b from Grignard reagent generation (dr 59:41 at 50 °C in THF) is close to the thermodynamic ratio (56:44 at 50 °C in THF). Carboxylation of 1 at -78 °C separates diastereomers 1a/b to give the anion of menthanecarboxylic acid (19) from 1a, which combines with unreactive 1b to give neomenthylmagnesium menthanecarboxylate (1bI). The kinetics of epimerization for the menthyl/neomenthylmagnesium system was analyzed (ΔH? = 98.5 kJ/mol, ΔS? = -113 J/mol·K for 1bI → 1aI). Reactions of 1 with phosphorus electrophiles proceed stereoconvergently at C-1 of 1a/b to give predominantly menthyl-configured substitution products: PCl3 and 2 equiv of 1 give Men2PCl (6), which hydrolyzes to dimenthylphosphine P-oxide (7), whereas Ph2PCl with 1 equiv of 1 gave P-menthyldiphenylphosphine oxide (27) after workup in air.

Method for preparing menthol carboxamide intermediate peppermint acid

The invention discloses a method for preparing a menthol carboxamide intermediate peppermint acid. The method takes L-menthol as a starting raw material and comprises the following steps: enabling theL-menthol and p-toluene sulfonyl chloride to react to obtain menthyl toluenesulfinate; then enabling the menthyl toluenesulfinate to react with sodium cyanide to obtain cyano-peppermint; finally, hydrolyzing to obtain the peppermint acid. The synthesis method disclosed by the invention is simple and is suitable for industrial production; meanwhile, a lot of difficult-to-treat wastewater is avoided. The obtained peppermint acid has a good crystal form; the purity is greater than or equal to 97 percent, the yield is greater than or equal to 85 percent and ee is greater than or equal to 99.0 percent.

Method for preparing levorotatory menthyl formate

The invention provides a method for preparing levorotatory menthyl formate. In the method, ether compounds are used as a reaction solvent; the temperature of a system when carbon dioxide is introduced and the introducing rate are controlled in a process of preparing the levorotatory menthyl formate, so that the levorotatory menthyl formate with high purity and high stereo-selectivity is prepared at high yield.

Ni-Catalyzed Carboxylation of Unactivated Alkyl Chlorides with CO2

A catalytic carboxylation of unactivated primary, secondary, and tertiary alkyl chlorides with CO2 at atmospheric pressure is described. This protocol represents the first intermolecular cross-electrophile coupling of unactivated alkyl chlorides, thus leading to new knowledge in the cross-coupling arena.

INTERCONVERSION BETWEEN ISOMERIC P-MENTHANE-3-CARBOXYLIC ACIDS

A process for interconversion between WS-1 and neo-WS-1 by heating to a temperature in a range of from 60 degrees Celsius to 250 degrees Celsius. The heating can be done in the presence of an acid catalyst. Starting from practically pure (=98%) WS-1, or mixtures of WS-1 and neo-WS-1, practically pure (=98%) neo-WS-1 can be obtained. Starting from practically pure (=98%) neo-WS-1, or mixtures of WS-1 and neo-WS-1, practically pure (=98%) WS-1 can be obtained.

Process for making neo-enriched p-menthane compounds

A process for making neo-enriched p-menthane intermediates is disclosed. Lewis acid-catalyzed rearrangement of an oxaspiro compound provides an aldehyde mixture comprising normal (II) and neo (III) p-menthane-3-aldehydes: with the neo aldehyde (III) as the major product. The aldehyde mixture is readily oxidized to provide the corresponding carboxylic acids, and the acids are easily converted to a host of neo-enriched p-menthane esters or amides. The esters and amides are valuable as physiological coolants.

PROCESS FOR MAKING NEO-ENRICHED p-MENTHANE COMPOUNDS

A process for making neo-enriched p-menthane intermediates is disclosed. Lewis acid-catalyzed rearrangement of an oxaspiro compound provides an aldehyde mixture comprising normal (II) and neo (III) p-menthane-3-aldehydes: with the neo aldehyde (III) as the major product. The aldehyde mixture is readily oxidized to provide the corresponding carboxylic acids, and the acids are easily converted to a host of neo-enriched p-menthane esters or amides. The esters and amides are valuable as physiological coolants.