Azole Intermediate Production via Lower-Cost Oxirane Synthesis

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Solution Overview

Problem

The production of azole derivatives is costly due to the use of expensive reagents like trimethylsulfoxonium bromide (TMSOB), iodine, and iodomethane in existing methods.

Innovation Solution

A method using dimethyl sulfide and/or dimethyl sulfoxide, along with a methyl-LG leaving group, in the presence of an inorganic base, to convert a ketoester derivative into an oxirane derivative, bypassing the need for TMSOB, iodine, and iodomethane.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If trimethylsulfoxonium bromide (TMSOB), iodine, and iodomethane are used for oxiranation and substitution, then the reaction can proceed effectively, but the production cost increases significantly

Engineering Contradiction:

Improvereaction effectivenessVSAvoidproduction cost

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent replaces expensive reagents (TMSOB, iodine, iodomethane) with cheaper alternatives (dimethyl sulfide, dimethyl sulfoxide, methyl-LG). These cheaper reagents achieve the same chemical transformation (oxiranation of ketoester to produce oxirane intermediate) without the high cost burden, directly resolving the contradiction between reaction effectiveness and production cost.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent changes the chemical parameters of the reagents used in the oxiranation reaction. Instead of using TMSOB (a sulfonium salt), the invention uses dimethyl sulfide and dimethyl sulfoxide with a methyl-LG (leaving group). This parameter change in reagent selection maintains the reaction's effectiveness while dramatically reducing the cost of materials.

Inventive Principle:

Principle #35Parameter changes

2Productivity

If expensive reagents are used to ensure high reaction yield and efficiency, then the intermediate product can be produced reliably, but the overall manufacturing cost increases

Engineering Contradiction:

Improvereaction yieldVSAvoidmanufacturing cost

Core Design Contradiction:

ProductivityVSEase of manufacture

Solution Approach 1:

The patent employs inexpensive reagents (dimethyl sulfide, dimethyl sulfoxide, methyl-LG) that can be readily obtained and used to achieve high reaction yields. The cheaper reagents do not compromise the productivity or yield of the intermediate product, thereby resolving the contradiction between maintaining high reaction yield and reducing manufacturing cost.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

3Adaptability or versatility

If conventional reagents (TMSOB, iodine, iodomethane) are employed, then the established reaction pathway can be followed, but the production process becomes more costly

Engineering Contradiction:

Improvereaction pathway compatibilityVSAvoidproduction cost

Core Design Contradiction:

Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The patent modifies the reaction parameters by changing the reagent system from TMSOB-based to dimethyl sulfide/dimethyl sulfoxide-based chemistry. This parameter change maintains compatibility with the overall reaction pathway (oxiranation followed by substitution to form azole derivatives) while eliminating the cost disadvantage of using expensive conventional reagents.

Inventive Principle:

Principle #35Parameter changes

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 method reduces production costs by eliminating the use of expensive reagents, leading to a more cost-effective synthesis of azole derivatives.

Implementation Method 1

converting a compound represented by General Formula (II) into the compound represented by General Formula (IV) using: (a) dimethyl sulfide and/or dimethyl sulfoxide, and (b) a methyl-LG (an LG is a nucleophilically substitutable leaving group)

Methodology Applied

Scientific EffectNucleophilic substitution: Chemical Bonding

Implementation Method 2

Methodology Applied

Scientific EffectBase-catalyzed reaction: Chemical Bonding

Data Source

PatentUS12428387B2Method for producing compound

Publication Date: 2025.09.30 KUREHA CORPORATION

AI summary

A method by which an intermediate product of an azole derivative can be produced at a lower cost than known production methods is provided. A method for producing a compound represented by General Formula (IV) includes converting a compound represented by General Formula (II) into the compound represented by General Formula (IV) using (a) dimethyl sulfide and/or dimethyl sulfoxide, and (b) a methyl-LG (an LG is a nucleophilically substitutable leaving group and is selected from the group consisting of a halogen group, an alkoxysulfonyloxy group, an aryloxysulfonyloxy group, an alkylsulfonyloxy group, a haloalkylsulfonyloxy group, and an arylsulfonyloxy group) in the presence of an inorganic base.