Microfluidic process for the general electrochemical synthesis of geminal dipseudohalide or halide-pseudohalide compounds

Patent metadata

Field	Value
Publication number	US-11926911-B2
Application number	US-202318153683-A
Country	US
Kind code	B2
Filing date	Jan 12, 2023
Priority date	Feb 7, 2022
Publication date	Mar 12, 2024
Grant date	Mar 12, 2024

Abstract

A process for the microfluidic electrochemical synthesis of geminal dipseudohalide or halide-pseudohalide compounds comprising the steps of
pumping a solution comprising a compound of Formula I

into a microfluidic electrochemical reactor in the presence of a base, one of a halide or pseudohalide salt (MY), and a mediator;
applying an electrical current through the microfluidic electrochemical reactor; and
performing oxidative addition to create a geminal dipseudohalide or halide-pseudohalide compound of the general Formula II

First claim

What is claimed is:

1. A process for the microfluidic electrochemical synthesis of geminal dipseudohalide or halide-pseudohalide compounds comprising the steps of:
pumping a solution comprising a compound of Formula I

wherein for Formula I, R 1 and R 2 are any combination of H, methyl (—CH 3 ), ethyl (—CH 2 CH 3 ), propyl (—CH 2 CH 2 CH 3 ), hydroxy (—OH), methoxy (—CH 2 OH), ethoxy (—CH 2 CH 2 OH), methyl ester (—CH 2 COOCH 3 ), propyl methyl ester (—CH 2 CH 2 COOCH 3 ), cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azetidine, oxetane, 2,2-dimethyl-1,3,dioxane, and phenyl, and X is a pseudohalide moiety selected from the group consisting of nitro (—NO 2 ), cyano (—CN), cyanate (—CNO), thiocyanoate (—SCN), and thioisocyanato (—NCS)
through a continuous flow microfluidic electrochemical reactor in the presence of a base, one of a halide salt or pseudohalide salt (MY), and a mediator;
applying an electrical current through the continuous flow microfluidic electrochemical reactor; and
performing a single pass oxidative addition to create a geminal dipseudohalide or halide-pseudohalide compound of the general Formula II

wherein for Formula II, R 1 and R 2 are any combination of H, methyl (—CH 3 ), ethyl (—CH 2 CH 3 ), propyl (—CH 2 CH 2 CH 3 ), hydroxy (—OH), methoxy (—CH 2 OH), ethoxy (—CH 2 CH 2 OH), methyl ester (—CH 2 COOCH 3 ), propyl methyl ester (—CH 2 CH 2 COOCH 3 ), cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azetidine, oxetane, 2,2-dimethyl-1,3,dioxane, and phenyl, and X is a pseudohalide moiety selected from the group consisting of nitro (—NO 2 ), cyano (—CN), cyanate (—CNO), thiocyanoate (—SCN), and thioisocyanato (—NCS) and Y is a nitro (—NO), cyano (—CN), cyanate (—CNO), thiocyanate (—SCN), thioisocyanate (—NCS), azido (—N 3 ), chloro (—Cl), or bromo (—Br) functional group.

2. The process of claim 1 , wherein the compound of Formula I has the structure of R 1 R 2 CHX and R 1 and R 2 are any combination of H, methyl (—CH 3 ), ethyl (—CH 2 CH 3 ), propyl (—CH 2 CH 2 CH 3 ), hydroxy (—OH), methoxy (—CH 2 OH), ethoxy (—CH 2 CH 2 OH), methyl ester (—CH 2 COOCH 3 ), propyl methyl ester (—CH 2 CH 2 COOCH 3 ), cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azetidine, oxetane, 2,2-dimethyl-1,3,dioxane, and phenyl, and X is a pseudohalide moiety selected from the group consisting of nitro (—NO 2 ), cyano (—CN), cyanate (—CNO), thiocyanoate (—SCN), and thioisocyanato (—NCS).

3. The process of claim 1 , wherein the base comprises at least one hydroxide, carbonate, or phosphate and a cation selected from the group consisting of [Li]+, [Na]+, [K]+, [Cs]+, [Rb]+, and [NH 4 ]+.

4. The process of claim 1 , wherein the base comprises at least one of lithium hydroxide (LiOH), sodium hydroxide (NaOH), potassium hydroxide (KOH), cesium hydroxide (CsOH), rubidium hydroxide (RbOH), ammonium hydroxide (NH 4 OH), lithium carbonate (Li 2 CO 3 ), sodium carbonate (Na 2 CO 3 ), potassium carbonate (K 2 CO 3 ), cesium carbonate (Cs 2 CO 3 ), rubidium carbonate (Rb 2 CO 3 ), lithium phosphate (Li 2 PO 4 ), sodium phosphate (Na 3 PO 4 ), sodium phosphate dibasic (Na 2 HPO 4 ), potassium phosphate (K 3 PO 4 ), potassium phosphate dibasic (K 2 HPO 4 ), or ammonium phosphate dibasic ((NH 4 ) 2 PO 4 ).

5. The process of claim 1 , wherein the pseudohalide salt (MY) is selected from the group consisting of [Li]+, [Na]+, [K]+, [Cs]+, [Rb]+, and [NH 4 ]+ salts of nitrite (NO 2 − ), azide (N 3 − ), cyanide (CN − ), cyanate (OCN − ), thiocyanate (SCN − ), and isothiocyanate (NCS − ).

6. The process of claim 1 , wherein the pseudohalide salt (MY) is selected from the group consisting of sodium nitrite (NaNO 2 ), potassium nitrite (KNO 2 ), sodium cyanide (NaCN), potassium cyanide (KCN), sodium cyanate (NaCNO), potassium cyanate (KCNO), sodium thiocyanate (NaSCN), potassium thiocyanate (KSCN), sodium thioisocyanate (NaNCS), potassium thioisocyanate (KNCS), sodium azide (NaN 3 ), and potassium azide (KN 3 ).

7. The process of claim 1 , wherein a halide salt (MY) source is selected from the group consisting of [Li]+, [Na]+, [K]+, [Cs]+, [Rb]+ and [NH 4 ]+ salts of chloride (Cl − ) and bromide (Br − ).

8. The process of claim 1 , wherein the halide salt (MY) is selected from the group consisting of lithium chloride (LiCl), potassium chloride (KCl), sodium chloride (NaCl), cesium chloride (CsCl), rubidium chloride (RbCl), ammonium chloride (NH 4 Cl), lithium bromide (LiBr), potassium bromide (KBr), sodium bromide (NaBr), cesium bromide (CsBr), rubidium bromide (RbBr), and ammonium bromide (NH 4 Br).

9. The process of claim 1 , wherein the mediator is selected from the group consisting of potassium ferricyanide (K 3 Fe(CN) 6 ), potassium ferrocyanide (K 4 Fe(CN) 6 ), benzoquinone, 2,2-azino-bis(2-ethylbenzothiazoline-6-sulfonic acid), 1,1-dimethyl-ferrocene, ferrocene monocarboxylic acid, sodium ferricyanide, 2,6-dichlorophenol-indophenol, hexaammineruthenium (III) chloride, 1,4-napthoquinone, and Os(im)(dm-bpy) 2 Cl.

10. The process of claim 1 , further comprising controlling the oxidative addition of said halide salt or said pseudohalide salt (MY) to the compound of Formula I through one of potentiostatic (controlled potential) or galvanostatic (controlled current) operating conditions.

11. The process of claim 1 , wherein the microfluidic electrochemical reactor comprises electrodes comprising an element selected from the group consisting of iron, nickel, platinum, copper, cobalt, titanium, lead dioxide, mixed metal oxides, gold, palladium, rhodium, iridium, ruthenium, silver, graphite, carbon black, glassy carbon, carbonaceous materials and mixtures thereof.

12. The process of claim 11 , wherein the microfluidic electrochemical reactor is an undivided (single compartment) microfluidic electrochemical cell.

13. The process of claim 1 , wherein an oxidative addition reaction is conducted in an anode compartment in a two-phase plug-flow, the two-phase plug flow comprising said solution and an organic solvent, to continually extract the compound of Formula II.

14. The process of claim 13 , wherein the organic solvent is immiscible with water, and is selected from the group consisting of chloroform, dichloromethane, 1,2-dichloroethane, carbon tetrachloride, cyclohexane, diethyl ether, dioxane, ethyl acetate, heptane, hexane, methyl ethyl ketone, methyl tert-butyl ether, pentane, toluene, and xylene.

Assignees

• Us Gov Air Force
• Us Air Force

Inventors

• Schroer Thorsten G
• Lecroy Gregory E
• Aguila Miguel
• Rodriguez Mayra R
• Downard Tyler J
• Macleod Brianna L

Classifications

• C25B3/11 Primary

  Halogen containing compounds · CPC title

• C25B9/19

  with diaphragms · CPC title

• C25B11/091

  consisting of at least one catalytic element and at least one catalytic compound; consisting of two or more catalytic elements or catalytic compounds · CPC title

• C25B3/29

  Coupling reactions · CPC title

• C25B3/23

  Oxidation (halogenation C25B3/27) · CPC title