A continuous flow process for synthesis of organic azides
AssigneeIndian Institute of Science Education and Research, Pune (IISER Pune)
InventorsBoopathy Gnanaprakasam, Akanksha M. Pandey, Shankhajit Mondal
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Abstract
The present disclosure relates generally to the field of synthetic organic chemistry. More specifically, the disclosure is directed to a continuous flow process for synthesis of azides from alcohols and peroxides, wherein the process comprises azidation with trimethylsilyl azide and a catalyst Amberlyst-15. It is a non-hazardous, mild and controlled reaction giving good yields of azides. The azides can be further employed for synthesis of medicinally and industrially useful chemicals.
Claims8
A continuous flow process for synthesizing organic azides of formula (I), a stereoisomer, a tautomer, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof by direct azidation of alcohols of formula (II), wherein said process comprises the step of:
- reacting a compound of formula (II) with trimethylsilyl azide (TMSN3) in Amberlyst-15 catalyst loaded packed-bed reactor at room temperature;
- wherein:
- R1 is selected from substituted or unsubstituted (C6-16) aryl, or substituted or unsubstituted (C5-10) heterocycle;
- R2 and R3 are independently selected from H, substituted or unsubstituted (C6-16)aryl, substituted or unsubstituted (C1-6)alkyl, or substituted or unsubstituted —CH2—(C6-16)aryl;
- and
- the substituent is selected from one or more of halogen, (C1-6) alkyl, cyano, nitro, —NH2, (C1-6)alkoxy, —COOH, or combinations thereof,
- wherein, ratio of the formula (II) to trimethylsilyl azide is 1:3 M,
- wherein the Amberlyst-15 and the reactant compounds are present in a ratio of 1:1 w/w,
- wherein, flow rate of the reactant compound is 0.08 mL/min to 0.5 mL/min, and
- wherein, the process is carried out under a pressure of 0 to 1 bar.
A continuous flow process for synthesizing organic azides of formula (III), a stereoisomer, a tautomer, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof by direct azidation of alcohols of formula (IV), wherein said process comprises the step of:
- reacting a compound of Formula (IV) with trimethylsilyl azide and in Amberlyst-15 catalyst loaded packed-bed reactor at room temperature;
- wherein:
- R4, R5 and R6 are independently selected from one or more of H, halogen, —COOH, nitro, —NH2, (C1-6)alkoxy, substituted or unsubstituted (C6-16)aryl, substituted or unsubstituted (C1-6)alkyl;
- or substituted or unsubstituted —CH2—(C6-16)aryl;
- and the substituents is selected from one or more of halogen, (C1-6) alkyl, cyano, nitro, —NH2, —COOH, (C1-6)alkoxy, or combinations thereof,
- wherein, ratio of the formula (IV) to trimethylsilyl azide is 1:3 M,
- wherein the Amberlyst-15 and the reactant compounds are present in a ratio of 1:1 w/w,
- wherein, flow rate of the reactant compound is 0.08 mL/min to 0.5 mL/min, and
- wherein, the process is carried out under a pressure of 0 to 1 bar.
A continuous flow process for synthesizing azides of formula (V), a stereoisomer, a tautomer, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof by direct azidation of formula (VI), wherein said process comprises the step of:
- reacting a compound of formula (VI) with trimethylsilyl azide and in Amberlyst-15 catalyst loaded packed-bed reactor at room temperature;
- wherein:
- R7 is selected from H, (C1-6)alkyl, substituted or unsubstituted (C6-16)aryl;
- and substituted or unsubstituted —CH2—(C6-16)aryl;
- R8 and R9 is independently selected from one or more of H, halogen, (C1-6)alkyl, cyano, nitro, (C1-6)alkoxy, substituted or unsubstituted —CH2—(C6-16)aryl, and substituted or unsubstituted (C6-16)aryl;
- and the substituent is selected from one or more of halogen, (C1-6) alkyl, cyano, nitro, (C1-6)alkoxy, —COOH, and —NH2;
- and
- wherein Pr is a protecting group.
- wherein, ratio of the formula (VI) to trimethylsilyl azide is 1:3 M,
- wherein the Amberlyst-15 and the reactant compounds are present in a ratio of 1:1 w/w,
- wherein, flow rate of the reactant compound is 0.08 mL/min to 0.5 mL/min, and
- wherein, the process is carried out under a pressure of 0 to 1 bar.
A continuous flow process for synthesizing organic azides of formula (I′), a stereoisomer, a tautomer, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof by direct azidation of alcohols of formula (II′), wherein said process comprises the step of:
- reacting a compound of formula (II′) with trimethylsilyl azide and in Amberlyst-15 catalyst loaded packed-bed reactor at room temperature;
- wherein:
- Ar/R is selected 5 from group consisting of substituted or unsubstituted (C6-16)aryl, or substituted or unsubstituted (C5-10)heterocycle substituted or unsubstituted (C6-16)aryl, substituted or unsubstituted (C1-6)alkyl, or substituted or unsubstituted —CH2—(C6-16)aryl;
- and
- one or more of halogen, (C1-6)alkyl, cyano, nitro, —NH2, (C1-6)alkoxy, —COOH, or combinations thereof,
- wherein, ratio of the formula (II′) to trimethylsilyl azide is 1:3 M,
- wherein the Amberlyst-15 and the reactant compounds are present in a ratio of 1:1 w/w,
- wherein, flow rate of the reactant compound is 0.08 mL/min to 0.5 mL/min, and
- wherein, the process is carried out under a pressure of 0 to 1 bar.
Dependencies are inferred from the claim text.