Cyclohexane Coolant Synthesis via Copper-Catalyzed Coupling
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Solution Overview
Problem
Current coolant compounds used in consumer products, such as menthol and its derivatives, have low potency and short-lasting cooling effects, requiring high concentrations and being expensive to produce, leading to increased costs in formulations.
Innovation Solution
Development of alternative synthetic routes for preparing high-potency cyclohexane-based coolants like menthyl esters and menthanecarboxamide derivatives using less expensive raw materials, with specific isomers like G-180 and its neoisomer, which exhibit intense and long-lasting cooling effects through copper-catalyzed coupling reactions with aryl halides in the presence of potassium phosphate and water.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current coolant compounds (menthol and derivatives) are used, then cooling effect is provided, but potency is low and duration is short, requiring high concentrations which increase cost
Solution Approach 1:
The patent modifies the chemical structure of menthol derivatives by introducing specific substituents at the amide nitrogen position (such as aryl groups with electron-withdrawing substituents like cyano, nitro, or carbonyl groups). These parameter changes in molecular structure enhance the cooling potency and duration without requiring higher concentrations
Solution Approach 2:
The invention creates composite coolant molecules by combining the menthol core structure with various functional groups (carboxamide, ester, ether) and additional substituents at the nitrogen position. This composite approach produces molecules with synergistic effects that increase cooling potency while reducing required concentration
2Duration of action of moving object
If current coolant compounds are used, then cooling effect is provided, but duration of action is short
Solution Approach 1:
The patent extends cooling duration by modifying molecular parameters including introducing bulky aryl substituents at the amide nitrogen that increase molecular stability and binding affinity to TRPM8 receptors. The electron-withdrawing groups on these aryl rings further enhance duration by optimizing the interaction with the receptor site
3Reliability
If high concentrations of coolant compounds are used to achieve desired effect, then cooling potency is sufficient, but production cost and formulation cost increase
Solution Approach 1:
The patent achieves high cooling potency at low concentrations through parameter changes in molecular structure, specifically adding aryl groups with electron-withdrawing substituents at the amide nitrogen. This increases the coolant's intrinsic activity, allowing effective use at lower concentrations and reducing both production and formulation costs
4Reliability
If certain coolant compounds are used, then cooling effect is provided, but unpleasant sensory effects like burning sensations occur
Solution Approach 1:
The patent eliminates burning sensations by introducing specific electron-withdrawing substituents (cyano, nitro, carbonyl groups) at the amide nitrogen position. These local structural modifications change the molecular properties to reduce irritation while preserving the desired cooling effect, creating a differentiated local quality in the coolant molecule
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The new synthetic routes provide cyclohexane-based coolants with high cooling potency and long-lasting sensory effects, reducing the need for high concentrations and production costs, while minimizing unpleasant sensory effects like 'burning' sensations.
Implementation Method 1
a copper catalyzed coupling of a primary menthanecarboxamide with an aryl halide
Implementation Method 2
coolants or compounds that have a physiological cooling effect particularly on oral and other mucosal surfaces and skin
Data Source
AI summary
The present invention provides synthetic routes for preparing various isomers of cyclohexane-based coolants, such as menthyl esters and menthanecarboxamide derivatives, in particular those substituted at the amide nitrogen, for example with an aromatic ring or aryl moiety. Such structures have high cooling potency and long lasting sensory effect, which make them useful in a wide variety of consumer products. One synthetic route involves a copper catalyzed coupling of a primary menthanecarboxamide with an aryl halide, such reaction working best in the presence of potassium phosphate and water. Using this synthetic route, specific isomers can be prepared including the menthanecarboxamide isomer having the same configuration as l-menthol and new isomers such as a neoisomer having opposite stereochemistry at the carboxamide (C-1) position. The neoisomer unexpectedly has potent and long lasting cooling effect. Preparation schemes for neoisomers of other menthyl derivatives which are useful as coolants, including esters, ethers, carboxy esters and other N-substituted carboxamides are also provided.