# US 10,118,892 B2 · Compounds and their synthesis

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,118,892 B2
- Document ID: US10118892B2
- Status: Granted
- Kind: B2
- Application number: 14/435,046
- Filed: 2013-10-14
- Published: 2015-09-24
- Granted: 2018-11-06
- Earliest claimed: 2012-10-12
- Assignees: UCL Business PLC
- Applicants: Ucl Business PLC
- Inventors: Erik Arstad; Kerstin Sander; Thibault Gendron
- Web page: https://patentgrep.com/patent/US10118892B2

## CPC

- C07C 381/12: Sulfonium compounds
- B01D 15/08: Selective adsorption, e.g. chromatography
- B01J 20/22: comprising organic material
- C07B 59/001: {Acyclic or carbocyclic compounds}
- C07B 59/002: {Heterocyclic compounds}
- C07C 17/361: by reactions involving a decrease in the number of carbon atoms
- C07C 25/13: containing fluorine
- C07C 45/65: by splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups
- C07C 47/55: containing halogen
- C07C 49/807: all halogen atoms bound to the ring
- C07C 67/317: by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
- C07C 69/78: Benzoic acid esters
- C07D 207/46: with hetero atoms directly attached to the ring nitrogen atom
- C07D 211/20: with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D 211/22: by oxygen atoms
- C07D 211/32: by oxygen atoms
- C07D 211/70: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D 213/61: Halogen atoms or nitro radicals
- C07D 213/70: Sulfur atoms
- C07D 333/74: Naphthothiophenes
- C07D 333/76: Dibenzothiophenes
- C07D 401/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 403/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- B01D: SEPARATION (separating solids from solids by wet methods B03B, B03D; by pneumatic jigs or tables B03B; by other dry methods B07; magnetic or electrostatic separation of solid materials from solid materials or fluids, separation by high-voltage electric fields B03C; centrifuges, vortex apparatus B04; presses per se for squeezing-out liquid from liquid-containing material B30B9/02; treatment of water C02F, e.g. softening by ion-exchange C02F1/42; {arrangements of air intake cleaners in gas turbine plants F02C7/05} ; arrangements or mounting of filters in air-conditioning, air-humidification or ventilation F24F13/28)
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The present invention relates to sulfonium salts of formula (I): (I), their preparation, and utility as precursors for preparing functionalized organic compounds, wherein R1 and R2 are the same or different and each is independently selected from an optionally substituted aryl group, an optionally substituted alkynyl group, an optionally substituted alkenyl group, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkenyl group, an optionally substituted aralkyl group, an optionally substituted arylalkenyl group, an optionally substituted heteroaryl group, an optionally substituted heterocyclyl group, an optionally substituted amine, an optionally substituted alkoxy group, an optionally substituted thioether group, an optionally substituted phosphine group, an optionally substituted boron species, an optionally substituted carbene, an organometallic moiety, and a halide, or R1 and R2 are joined together to form an optionally substituted sulfur-containing ring; W is a bond, an optionally substituted alkynylene group, an optionally substituted alkenylene group, and optionally substituted alkylene group, an optionally substituted heterocyclyl group, an optionally substituted aryl group or an optionally substituted heteroaryl group; R3 is a moiety comprising at least one basic group, provided that when R3 does not contain any carbon atoms, W is not a bond; X is an anionic species; and n is an integer selected from 1 to 5.

## Claims

### Claim 1

A sulfonium salt according to formula (I):
wherein
R1 and R2 are joined together to form, together with the sulfur atom, an optionally substituted dibenzothiophene ring;
W is an optionally substituted aryl group or an optionally substituted heteroaryl group;
R3 is a moiety comprising at least one basic group, wherein the basic group of R3 is a Brønsted base and/or Lewis base and is selected from a primary amine, secondary amine, tertiary amine, amidine, guanidine, enamine, hydrazine, hydrazone, hydroxylamine, imine, an N-containing-heterocyclyl group, and an N-containing-heteroaryl group;
X is an anionic species; and
n is an integer selected from 1 to 5,
wherein W—R3 is a group capable of binding to a biological target and/or is a biologically active agent,
wherein the aryl group of the optionally substituted aryl group of W is a C6-C16 aryl group, and
wherein the heteroaryl group of the optionally substituted heteroaryl group of W is a 5-6 membered monocyclic or 8-16 membered fused bicyclic or tricyclic heteroaryl group.

### Claim 2 (depends on 1)

A sulfonium salt according to claim 1, wherein W is a C6-C14 aryl group.

### Claim 3 (depends on 1)

A sulfonium salt according to claim 1, wherein W—R3 is a fragment of a known pharmacologically active agent.

### Claim 4 (depends on 1)

A sulfonium salt according to claim 1, wherein X is selected from halide, triflate, mesylate, tosylate, tetrafluoroborate, and hexafluoroantimonate.

### Claim 5 (depends on 1)

A method of preparing a sulfonium salt according to claim 1, the method comprising
i) treating a thioether according to formula (II)
with an acidic compound so as to form an acid-base adduct by virtue of the basic group of R3;
ii) treating the adduct with a compound according to the formula [(R2)2I]m+Zm− or formula [(R1)(R2)I]m+Zm−, optionally in the presence of a catalyst,
or where R1 and R2 are joined together to form an optionally substituted sulfur-containing ring in formula (I), treating an adduct of formula (II) formed in step (i) in which R1 contains at least one unsaturated bond, with an acid or electrophilic species so as to cause formation of the optionally substituted sulfur-containing ring; and
iii) recovering the product sulfonium salt,
wherein R1, R2, W, and R3 are as defined in claim 1, Z is an anionic species, and m is an integer selected from 1 to 5.

### Claim 6 (depends on 5)

A method according to claim 5, wherein the acidic compound is a protic acid.

### Claim 7 (depends on 6)

A method according to claim 6, wherein the acidic compound is selected from sulfuric acid, fluorosulfuric acid, nitric acid, phosphoric acid, fluoroantimonic acid, fluoroboric acid, hexafluorophosphoric acid, chromic acid, boric acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, trifluoromethanesulfonic acid, trifluoroacetic acid, acetic acid, citric acid, formic acid, hydrogen chloride, hydrogen bromide, and hydrogen iodide.

### Claim 8 (depends on 5)

A method according to claim 5, wherein the catalyst is a transition metal coordination complex.

### Claim 9 (depends on 8)

A method according to claim 8, wherein the catalyst is a copper (II) complex.

### Claim 10 (depends on 1)

A method of preparing a compound according to formula (III):
the method comprising
i) treating a sulfonium salt according to claim 1 with a species capable of generating a nucleophile Y, optionally in the presence of a base and/or chelating agent; and
ii) recovering the compound according to formula (III),
wherein R3 and W are as defined in claim 1.

### Claim 11 (depends on 10)

A method according to claim 10, wherein the base is selected from sodium hydroxide, lithium hydroxide, potassium hydroxide, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium carbonate, potassium carbonate, and caesium carbonate.

### Claim 12 (depends on 10)

A method according to claim 10, wherein the chelating agent is a cryptand or a crown ether.

### Claim 13 (depends on 12)

A method according to claim 12, wherein the chelating agent is selected from 21-cryptand, 211-cryptand, 221-cryptand, 222-cryptand, 222B-cryptand, 12-crown-4, 15-crown-5, 18-crown-6, dibenzo-18-crown-6, and diaza-18-crown-6.

### Claim 14 (depends on 10)

A method according to claim 10, wherein the nucleophile is selected from a hydrocarbon species capable of forming a carbon anion, an amine, an amide, an alkoxy group, a phenolate, a thiolate, a thiophenolate, a cyanate, a thiocyanate, and a halide.

### Claim 15 (depends on 14)

A method according to claim 14, wherein the nucleophile is a halide.

### Claim 16 (depends on 10)

A method according to claim 10, wherein the sulfonium salt is linked to a surface of a solid phase adsorbent.

### Claim 17 (depends on 16)

A method according to claim 16, wherein the solid phase adsorbent is a reversed phase adsorbent.

### Claim 18 (depends on 16)

A method according to claim 16, wherein the solid phase adsorbent is presented in conjunction with a column or cartridge.

### Claim 19 (depends on 10)

A halogenated compound obtainable by the method of claim 10.

### Claim 20 (depends on 1)

A solid phase adsorbent comprising a sulfonium salt according to claim 1.

### Claim 21 (depends on 20)

A solid phase adsorbent according to claim 20, wherein the solid phase adsorbent is presented in conjunction with a column or cartridge.