Quinazoline Synthesis via Thiourea Cyclization
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Solution Overview
Problem
There is a need for a general, simple, and direct method for the preparation of quinazoline derivatives with a carbon-attached substituent at position 4 of the quinazoline ring, which may also contain other functional groups at positions 5, 6, and 7, and for the synthesis of perimidine-based heterocycles, as existing methods often involve complex processes or attachment of functional groups at position 2, making it difficult to remove additional functional groups.
Innovation Solution
A method involving the reaction between thiourea and a 2-aminobenzophenone or 2-aminoaryl aryl ketone in a solvent of high boiling point, allowing for the formation of quinazolines with a substituent at position 4 and potentially other functional groups, as well as the synthesis of perimidines, anthrapyrimidin-7-ones, and benzo[e]pyrimido[4,5,6-gh]pyrimidines.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If existing synthetic methods are used to prepare quinazoline derivatives with functional groups at position 4, then the methods often involve complex processes or require attachment of functional groups at position 2, but this makes it difficult to remove additional functional groups and reduces manufacturing simplicity
Solution Approach 1:
The patent applies preliminary action by using 2-aminobenzophenone or 2-aminoaryl aryl ketone as starting materials that already contain the amino group at the ortho position, which is pre-configured for direct cyclization to form the quinazoline ring with the substituent at position 4. This eliminates the need for subsequent functional group attachment or removal steps, simplifying the overall synthesis process.
Solution Approach 2:
The patent extracts the amino group from the starting material (2-aminobenzophenone or 2-aminoaryl aryl ketone) and utilizes it directly in the cyclization reaction to form the quinazoline ring system. By taking out the amino group as a reactive functional group in the starting material, the method avoids complex multi-step processes and achieves direct formation of the target compound with the substituent at position 4.
2Productivity
If conventional methods are used to attach functional groups at position 4 of quinazoline, then the processes become complex and yield reduction occurs, but this reduces productivity and increases loss of substance
Solution Approach 1:
The patent merges the cyclization reaction and the formation of the quinazoline ring system into a single step. By reacting 2-aminobenzophenone or 2-aminoaryl aryl ketone with appropriate reagents in one operation, the method simultaneously forms the quinazoline core and establishes the substituent at position 4, eliminating the need for multiple separate steps and reducing overall substance loss.
Solution Approach 2:
The patent utilizes parameter changes by employing specific reaction conditions (such as using thiourea or other carbon sources with 2-aminobenzophenone derivatives) that enable direct cyclization to the quinazoline ring system. By changing the reaction parameters and starting material structure, the method achieves high yield and minimizes loss of starting material and intermediates.
3Manufacturing precision
If existing methods are used to synthesize quinazoline derivatives with specific functional groups at desired positions, then the processes are complex and time-consuming, but this increases loss of time and reduces productivity
Solution Approach 1:
The patent applies preliminary action by preparing 2-aminobenzophenone or 2-aminoaryl aryl ketone starting materials with the amino group already positioned at the ortho location. This pre-positioning allows direct cyclization to form the quinazoline ring with the substituent at position 4 in a single step, achieving position specificity without time-consuming multi-step processes.
Solution Approach 2:
The patent uses 2-aminobenzophenone or 2-aminoaryl aryl ketone as an intermediary starting material that contains the necessary functional groups and structural framework. This intermediary compound facilitates direct cyclization to the quinazoline ring system, achieving precise positioning of functional groups at desired locations while minimizing synthesis time.
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
This method provides a straightforward and efficient synthesis of quinazoline and perimidine derivatives with high yields, allowing for the production of compounds with specific functional groups at desired positions, which are applicable in pharmaceutical and dye industries.
Implementation Method 1
The reaction between thiourea and a 2-aminobenzophenone or 2-aminoaryl aryl ketone in a solvent of high boiling point, allowing for the formation of quinazolines with a substituent at position 4
Implementation Method 2
in a solvent of high boiling point
Data Source
AI summary
A straightforward single step method for the preparation and/or production of substituted quinazolines is disclosed, wherein said quinazolines preferably contain one substituent at position 4, and may contain other functional groups at various positions, such as 5, 6, 7, and/or 8 of quinazolines. In addition, the extension of this new method leads to the formation of different type of heterocyclic aromatic compounds, that include but are not limited to perimidines, anthrapyrimidin-7-ones (also known as anthrapyrimidinones), anthra[1,9:5,10]dipyrimidines (also known as quinazoline[5,4-ef]perimidines) and benzo[e]-pyrimido[4,5,6-gh]pyrimidines.