GB2087398A - Sulphur-containing pyridine derivatives - Google Patents
Sulphur-containing pyridine derivatives Download PDFInfo
- Publication number
- GB2087398A GB2087398A GB8201439A GB8201439A GB2087398A GB 2087398 A GB2087398 A GB 2087398A GB 8201439 A GB8201439 A GB 8201439A GB 8201439 A GB8201439 A GB 8201439A GB 2087398 A GB2087398 A GB 2087398A
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- United Kingdom
- Prior art keywords
- formula
- acid addition
- represents hydrogen
- hydrogen
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/32—Sulfur atoms
- C07D213/34—Sulfur atoms to which a second hetero atom is attached
Abstract
The invention relates to processes for preparing compounds of Formula I <IMAGE> and acid addition salts thereof wherein R represents hydrogen, lower alkyl, aryl or aralkyl, R<1> represents hydrogen or fluorine, R<2> represents hydrogen, fluorine, chlorine, or trifluoromethyl, and at least one of R, R<1> and R<2> is other than hydrogen, n is 1 or 2, by reacting a thiol compound of Formula II or an alkali- metal salt thereof, with a pyridine derivative of Formula III <IMAGE> wherein R, R<1>, R<2> and n are as defined above and Hal is a halogen atom, especially chlorine, bromine or iodine and if desired converting the product to an acid addition salt. The invention also concerns novel compounds of Formula I, namely the acid addition salts and the compounds of Formula I as defined above with the proviso that when n is 2 and one or more of R<2> is chlorine then at least one of R and R<1> is other than hydrogen.
Description
SPECIFICATION
Novel sulphur compounds
The invention relates to processes for preparing sulphur compounds which are intermediates for preparing the corresponding sulphoxides and to novel sulphur compounds.
The invention provides a process for preparing a compound of Formula I, or an acid addition salt thereof,
wherein R represents hydrogen, lower alkyl, aryl or aralkyl, R1 represents hydrogen or fluorine,
R2 represents hydrogen, fluorine, chlorine or trifluoromethyl, n is 1 or 2 and at least one of R,
R' and R2 is other than hydrogen which process comprises reacting a thiol compound compound of Formula 11, or an alkali-metal salt thereof.
wherein R1 and R2 are as defined above with a pyridine derivative of Formula Ill
wherein n is 1 or 2 and Hal is a halogen atom, especially chlorine, bromine or iodine and R is as defined above, and if desired converting the product to an acid addition salt.
The invention also provides the novel acid addition salts of the above compounds of Formula I and novel compounds of Formula I wherein R, R1, R2 and n are as defined above with the proviso that when n is 2, and one or more of R2 is chlorine then at least one of R and R' is other than hydrogen.
Preferably not more than two R2 groups are chlorine or trifluoromethyl.
In this specification a lower alkyl group has from 1 to 6 carbon atoms e.g. methyl, ethyl, npropyl, isopropyl, n-butyl, s-butyl, t-butyl, n-pentyl, and n-hexyl. A loweralkoxy substituent is alkoxy in which the alkyl portion is as defined for a lower alkyl group. Whenever the term lower alkyl is used as part of another radical, e.g. arylloweralkyl, the lower alkyl or lower alkoxy portion has 1 to 6 carbon atoms unless otherwide stated.
The aryl group R is preferably phenyl or substituted phenyl, substituents being halogen, lower alkyl, lower alkoxy and so on.
The acid addition salts of compounds of Formula I may be of an organic or inorganic acid, e.g. hydrochloric,, hydrobromic, phosphoric, sulphuric, nitric, citric, acetic, formic, fumaric, maleic, tartaric, embonic, methane sulphonic and p-toluene suiphonic acids.
The compounds prepared by the process of the invention may be oxidised to obtain corresponding sulphoxides which are described and claimed in our copending application 8104411.
The invention is illustrated by the following examples.
Example 1 2-(((4-Chlorophenyl)thio)methyl)pyridine 4-Chlorobenzenethiol (5g) in warm ethanol (5my) was added to a solution of sodium hydroxide (2.8g) in ethanol (50ml). To the solution was added a solution of 2-picolyl chloride, hydrochloride (5.7g) in ethanol (25ml) and the mixture was stirred at ambient temperature for 6 hours.
The mixture was filtered and evaporated and the residue was converted into the hydrochloride with ethereal HCI solution and this was recrystallised from ethanol-ether to give 2-(((4chlorophenyl)thio)methyl)pyridine, hydrochloride (8g) mp 196-8"C (Found: C,52.95; H,4.1; N,5. 15 C,2H10CINS-HCI requires C,53.1; H,4.2; N,4.9%).
Example 2 2-(((3, 4-Dichlorophenyl)thio)methyl)pyridine
3,4-Dichlorobenzenethiol (5g) was added to a solution of sodium hydroxide (2.25g) in ethanol (50ml) and the resulting solution was treated with 2-picolyl chloride, hydrochloride (4.6g) in ethanol (25ml). After stirring for 4 hours at ambient temperature the mixture was filtered and the solvent removed by evaporation. The residue was converted into the hydrochloride with ethereal HCI and this was recrystallised from ethanol/ether to give 2-(((3,4-dichlorophenyl)thio)methyl)pyridine, hydrochloride (5.5g)mp 213-4"C (Found: C,46.7; H,3.3; N,4.4 C,2HgCI2NS.HCI requires C.47.0; H,3.3; N,4.6%).
Example 3 2-(((4-Fluorophenyl)thio)methyl)pyridine 4-Fluorobenzenethiol (5g) was added to a solution of sodium hydroxide (3.1 4g) in ethanol (50ml) and the resulting solution was treated with 2-picolyl chloride, hydrochloride (6.4g) in ethanol (25ml) and the mixture was stirred for 6 hours at ambient temperature. The mixture was filtered, the solvent removed by evaporation and the residue was converted into the hydrochloride with ethereal HCI. Recrystallisation from ethanol-ether gave 2-(((4-fluorophenyl)thio)methyl)- pyridine, hydrochloride (7g) mp 190-2"C (Found: C,56.1; H,4.4; N,5.2 C,2H,0FNS.HCI requires C,56.4; H,4.3; N,5.4%).
Example 4 2-(((Penta fluorophen yl)th io)m eth yl)pyridin e
Pentafluorothiophenol (5g) was added to a solution of sodium hydroxide (2.0g) in ethanol (50ml) and the resulting solution was treated with a solution of 2-picolyl chloride, hydrochloride (4.1g) in ethanol (25ml). The mixture was stirred at ambient temperature for 4 hours, filtered through Kieselghur and the solvent removed by evaporation. The residue was converted into the hydrochloride with ethereal HCI solution and this was recrystallised from acetone-ether to give 2-(((pentafluorophenyl)thio)methyl)pyridine, hydrochloride (5.0g) mp 1 57-8"C (Found: C,44.0;
H,2.4; N,4.0; C,2H6F5NS.HCI requires C,44.0; H,2.15; N,4.3%).
Example 5 2-(((3-Trifluoromethylphenyl)thio)meth yl)pyridine m-Trifluoromethylbenzenethiol (5g) was added to a solution of NaOH (2.25g) in ethanol (50ml) and the resulting solution was treated with a solution of 2-picolyl chloride, hydrochloride (4.6g) in ethanol (25ml) and the mixture was stirred for 5 hours. The resulting suspension was filtered through kieselghur and the solvent was removed by evaporation. The residue was converted into the hydrochloride in ether with ethereal HCI and recrystallised from acetone-ether to give 2-(((3-trifluoromethylphenyl)thio)methylpyridine hydrochloride (4.8g) mp 1 45-6"C (Found: C,51.1; H,4.0; N,4.7; C,3H,oF3NS.HCI requires C,51.0; H,3.6; N,4.6%).
Example 6 2-Methyl- 6-((phen ylth io)m eth yl)p yridine Following the method of Example 1 thiophenol is reacted with 6-methyl-2-picolyl chloride hydrochloride in the presence of sodium ethoxide to give 2-methyl-6-((phenylthio)methyl)pyridine.
Claims (12)
1. A process for preparing a compound of Formula I or an acid addition salt thereof,
wherein R represents hydrogen, lower alkyl, aryl or aralkyl, R' represgnts hydrogen or fluorine,
R2 represents hydrogen, fluorine, chlorine or trifluoromethyl, n is 1 or 2 and at least one of R,
R' and R2 is other than hydrogen which process comprises reacting a thiol compound of
Formula II, or an alkali-metal salt thereof,
wherein R' and R2 are as defined above, with a pyridine derivative of Formula Ill
wherein n is 1 or 2 and the Hal is a halogen atom, especially chlorine, bromine or iodine and R is as defined above, and if desired converting the product to an acid addition salt.
2. A process as claimed in Claim 1, wherein n is 1.
3. A compound of Formula I
wherein R represents hydrogen, lower alkyl, aryl or aralkyl, R' represents hydrogen or fluorine,
R2 represents hydrogen, fluorine, chlorine or trifluoromethyl, n is 1 or 2 and at least one of R,
R' and R2 is other than hydrogen, with the proviso that when n is 2 and one or more of R' is chlorine then at least one of R and R' is other than hydrogen.
4. Acid addition salts of a compound of Formula I
wherein R represents hydrogen, lower alkyl, aryl or aralkyl, R' represents hydrogen or fluorine,
R2 represents hydrogen, fluorine, chlorine or trifluoromethyl, n is 1 or 2 and at least one of R,
R' and R2 is other than hydrogen.
5. 2-(((4-Chlorophenyl)thio)methyl)pyridine or a pharmaceutically acceptable acid addition salt thereof.
6. 2-(((3,4-Dichlorophenyl)thio)methyl)pyridine or a pharmaceutically acceptable acid addition salt thereof.
7. 2-(((4-Fluorophenyl)thio)methyl)pyridine or a pharmaceutically acceptable acid addition salt thereof.
8. 2-(((Pentafluorophenyi(thio)methyl)pyridine or a pharmaceutically acceptable acid addition salt thereof.
9. 2-(((3-Trifluoromethylphenyl)thio)methyl) pryidine or a pharmaceutically acceptable acid addition salt thereof.
1 0. A compound as claimed in 3 or 4 substantially as hereinbefore described in any one of
Examples 1, 2, 3, 4, 5 or 6.
11. A process as claimed in Claim 1, wherein the compound of Formula I which is prepared is a compound as claimed in any one of Claims 5 to 9.
1 2. A process as claimed in Claim 1, substantially as hereinbefore described in any one of
Examples 1, 2, 3, 4, 5 or 6.
1 3. A compound of Formula I, whenever prepared by a process as claimed in any one of
Claims 1,2, 11 or
12.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8005668 | 1980-02-20 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB2087398A true GB2087398A (en) | 1982-05-26 |
| GB2087398B GB2087398B (en) | 1984-03-21 |
Family
ID=10511513
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8201439A Expired GB2087398B (en) | 1980-02-20 | 1981-02-12 | Sulphur containing pyridine derivatives |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB2087398B (en) |
-
1981
- 1981-02-12 GB GB8201439A patent/GB2087398B/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| GB2087398B (en) | 1984-03-21 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PE20 | Patent expired after termination of 20 years |
Effective date: 20010211 |