Technology Category/Market
Chemical Engineering: Kinetics, Process design and
reaction engineering
Industry: Pharmaceutical, Reactor Design
Applications: Bio-medical, Flow Reactors,
Market: The global flow reactor market was valued at  USD 1.60 billion in 2022 and is expected to grow at a  CAGR of 11.2% over the forecast period.
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Problem Statement
- An infectious death causing disease Tuberculosis (TB) that primarily affects lungs is treatable and mendable but expensive treatment.
- FDA approved first line  anti TB drugs  include rifampicin, ethambutol, isoniazid, pyrazinamide.
- Though India is one of the largest producers of ethambutol, dl-2-amino-1-butanol; the key intermediate for synthesis of ethambutol is mostly  imported as there is no significant local production.
- Further, available batch processes for dl-2-amino-1-butanol synthesis suffer from bottlenecks/challenges including safe handling of  raw materials, excessive use of reagents and its  recovery, lack of reaction control, low , etc.
Hence there is a need to develop an improved method to overcome above-mentioned issues.
Technology
Process Flow
A continuous process for preparation of dl-2-nitro-1- butanol comprises of the following steps:
- Providing an aqueous solution of sodium hydroxide (A) and 1- nitro-propane (B) dissolved in an alcohol (methanol or ethanol);
- Pumping a predetermined first molar ratio of solution A and B to mix in a first tubular reactor for a first residence time to form intermediate product stream solution mixture;
- Pumping formaldehyde aqueous solution to react with the intermediate product stream at a second predetermined molar ratio in a second tubular reactor for a second residence time to form a product stream;
- Quenching the product stream in glacial acetic acid to obtain a quench liquor having dl-2-nitro-1- butanol, wherein the first and the second tubular reactors are maintained at temperature ≥ 35° C.
Reactor Design
The Continuous Flow Reactor comprises:
- A first reservoir configured to store a solution of 1-nitropropane (starting material) and connected to a first pump,
- A second reservoir for storing a solution of NaOH and connected to a second pump,
- Wherein the first pump and the second pump are connected with a tubing to join the first stream entering a first tubular reactor, and the first tubular reactor having a first length and is configured to output a mixture of solutions from first and second reservoir as intermediate product stream.
- A third reservoir is to store a solution of formaldehyde and connected to a third pump, wherein, the third pump is configured to pump the formaldehyde solution to join the intermediate product stream entering a second tubular reactor.
- Further, the second tubular reactor has a second length that is 3-8 times the first length and configured to output an end product having dl-2- nitro-1-butanol.
- The equipment is further provided with a quench reservoir having glacial acetic acid wherein the dl-2-nitro-1-butanol is extracted from the quench liquor using a solvent (dichloromethane) from being converted to other products.
The first & second tubular reactors are configured to be maintained at a temperature ≥ 35° C.
The process have a following properties:
- The process cycle is completed in ≥30 minutes;
- The predetermined first & second molar ratio= 1.
- The conversion to dl-2-nitro-1-butanol is ≤89%.
- The second residence time is 3-8 times the first residence time.
A continuous process for preparation of dl-2- nitro-1-butanol from 1-nitropropane is shown in FIG. 1 & a continuous flow reactor for producing dl-2-nitro-1-butanol from 1- nitropropane is shown in FIG. 2.
Key Features/Value Proposition
- Optimal use of reactants and reagents in flow reactor to produce dl-2-amino-1-butanol, making it a cost effective process.
- Facilitates reduction of reaction time using continuous flow process technology, grants better temperature control through high mass and heat  transfers.
- Over exposure of raw materials to reagents is avoided, thereby reducing the formation of undesired reaction products.
- The continuous flow process is amenable to online monitoring and control of reaction progress using spectroscopic techniques.
- Process design  and  reaction   engineering  are modifiable to any scale of production.
- The technology used capacitates optimization of operation conditions and study of intrinsic reaction kinetics.
Questions about this Technology?
Contact for Licensing
Research Lab
Prof: Sridharakumar Narasimhan
Department of Chemical Engineering
Dr. Shankar Narasimhan
Department of Chemical Engineering
Dr. Nirav Pravinbhai Bhatt
Department of Biotechnology
Intellectual Property
- IITM IDF Ref: 1921
- IN Patent No. 410884 (Granted)
- PCT Application No. PCT/IN2020/050683
Technology Readiness Level
TRL- 3/4
Proof of concept ready Stage
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