US3156686A - Processes for preparing cycloalkylized - Google Patents
Processes for preparing cycloalkylized Download PDFInfo
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- US3156686A US3156686A US3156686DA US3156686A US 3156686 A US3156686 A US 3156686A US 3156686D A US3156686D A US 3156686DA US 3156686 A US3156686 A US 3156686A
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- Prior art keywords
- dihydro
- compounds
- cycloalkylized
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- 238000000034 method Methods 0.000 title claims description 16
- 150000001875 compounds Chemical class 0.000 claims description 16
- 230000000875 corresponding Effects 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 125000004432 carbon atoms Chemical group C* 0.000 description 12
- 238000002844 melting Methods 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 125000003545 alkoxy group Chemical group 0.000 description 10
- 230000017105 transposition Effects 0.000 description 10
- IOJUPLGTWVMSFF-UHFFFAOYSA-N Benzothiazole Chemical class C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 8
- 239000000155 melt Substances 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 6
- 238000000354 decomposition reaction Methods 0.000 description 6
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical class [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 150000003413 spiro compounds Chemical group 0.000 description 6
- VRVRGVPWCUEOGV-UHFFFAOYSA-N 2-aminobenzenethiol Chemical class NC1=CC=CC=C1S VRVRGVPWCUEOGV-UHFFFAOYSA-N 0.000 description 4
- YBBLSBDJIKMXNQ-UHFFFAOYSA-N 3,4-dihydro-2H-1,4-benzothiazine Chemical class C1=CC=C2NCCSC2=C1 YBBLSBDJIKMXNQ-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M NaHCO3 Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 125000004435 hydrogen atoms Chemical group [H]* 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 229940075930 picrate Drugs 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- SRXWLOLJJPXKDX-UHFFFAOYSA-N 10-[(1-methylpiperidin-2-yl)methyl]phenothiazine Chemical compound CN1CCCCC1CN1C2=CC=CC=C2SC2=CC=CC=C21 SRXWLOLJJPXKDX-UHFFFAOYSA-N 0.000 description 2
- ZTERZMMOIRJWIN-UHFFFAOYSA-N 2-aminobenzenethiol;sodium Chemical compound [Na].NC1=CC=CC=C1S ZTERZMMOIRJWIN-UHFFFAOYSA-N 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N Cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- OXNIZHLAWKMVMX-UHFFFAOYSA-N Picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 229910052736 halogen Chemical group 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 150000002367 halogens Chemical group 0.000 description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 239000011261 inert gas Substances 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 229940114148 picric acid Drugs 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- -1 tetramethylene 2,3 dihydro 6 chloro 1,4 benzthiazine Chemical compound 0.000 description 2
- 125000002769 thiazolinyl group Chemical group 0.000 description 2
- 229950002929 trinitrophenol Drugs 0.000 description 2
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
- C07D279/14—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems
- C07D279/18—[b, e]-condensed with two six-membered rings
- C07D279/20—[b, e]-condensed with two six-membered rings with hydrogen atoms directly attached to the ring nitrogen atom
Definitions
- the present invention relates to a process for the production of compounds of the following general formula:
- nn lagasifii a in which formula R, which may be at any desired positions of the aromatic ring, represents a hydrogen atom or a monovalent radical, particularly a halogen atom, for example chlorine, bromine, fluorine, or an alkyl or alkoxy group, Z represents an aliphatic bridge member connecting the carbon atoms 2 and 3 to form a ring, the said bridge member having from 3 to 6 carbon atoms, which in their turn can be substituted by other groups, for example alkyl or alkoxy.
- R which may be at any desired positions of the aromatic ring, represents a hydrogen atom or a monovalent radical, particularly a halogen atom, for example chlorine, bromine, fluorine, or an alkyl or alkoxy group
- Z represents an aliphatic bridge member connecting the carbon atoms 2 and 3 to form a ring, the said bridge member having from 3 to 6 carbon atoms, which in their turn can be substituted by other groups, for example alkyl or alkoxy
- R has the meaning indicated above, while A represents an aliphatic chain with 4 to 7 carbon atoms, which can be substituted, for example by alkyl or alkoxy groups.
- A forms, together with the carbon atom 2 of the thiazoline ring, a ring containing from to 8 carbon atoms.
- spiro compounds are the known 2,2-cycloalkylated benzthiazolines, which are, for example readily obtainable from o-aminothiophenols and ring ketones (see for example H. J. Teuber and H. Waider, Chem. Ber. 91, 234144 (1958)).
- 2,2-pentamethylene benzthiazoline which can for example be prepared in an almost quantitative yield by reaction of o-aminothiophenol with cyclohexanone, is transposed into 2,3-tetramethylene-2,3-dihydro-1,4-benzthiazine.
- the transposition can be carried out in the melt or also in the presence of suitable solvents, if necessary under pressure, by heating to relatively high temperature, more especially between 240 and 320 C. It is expedient in this case to work in an inert gas atmosphere, advanta- 3,156,686 Patented Nov. 10, 1964 geously under nitrogen, in order to avoid decomposition due to oxidation.
- the process can for example be carried out continuously in a throughflow heater. It is also possible to make use of the known process for the production of benzthiazoline compounds as starting products for the transposition by the benzthiazolines being transformed in situ in accordance with the data of the invention into the corresponding benzthiazoline compounds.
- reaction products can be isolated and purified in known manner.
- the cycloaikylated 2,3-dihydro-1,4-benzthiazines are bases which form salts with strong acids.
- the salts are however readily split hydrolytically.
- the picrates which are readily obtainable are especially suitable for characterisation purposes.
- the compounds which can be prepared by the new process can more especially be employed as anthelmintical agents.
- Example 1 250 g. of 2,2-pentamethylene benzthiazoline are heated for 6 hours in a stream of nitrogen to 260 C. The transposed product is allowed to cool to about 50 C., and it is taken up while still liquid in cc. of methanol. After a short time, 2,3-tetramethylene-2,3-dihydro-1,4- benzthiazine and also in some cases a little unreacted starting material is crystallised out. The suction-filtered product which is still moist with methanol is taken up, together with 175 g. of alcohol-moist picric acid, in such a quantity of alcohol that everything just dissolves at boiling temperature. 2,3-tetramethylene-2,3-dihydro-1,4- benzthiazine picrate immediately crystallises out from the solution. The melting point of the pure compound is at 168 to 168.5" C.
- the free base can be isolated from the picrate by stirring out with excess sodium bicarbonate in aqueous solution. By recrystallisation from methyl alcohol, pure 2,3- tetramethylene-2,3-dihydro-1,4-benzthiazine with the melt ing point 101 C., is obtained.
- the hydrochloride melts at 202 to 203 C.
- the purification of the crude product forming after the transposition can also be effected by distillation. 2,3-tetramethylene-2,3-dihydro-1,4-benzthiazine boils at 136 C./B.P.'
- Example 2 picrate is at C.
- 2,3-pentamethylene-2,3-dihydro-1,4- benzthiazine melts at 106 C.
- the melting point of the Example 3 20 g. of 2,2-pentamethylene-S-chloro-benzthiazoline of melting point 96 C. was heated in the molten state at 260 C., for four hours.
- the crude product was distilied in vacuum.
- the fraction distilling over between 160 and 190 C. yields after recrystallisation from alcohol pure 2,3 tetramethylene 2,3 dihydro 6 chloro 1,4 benzthiazine, melting point 168 C.
Description
United States Patent M 3,156,686 PROCESSES FR PREPARE JG CYCLQALKYMZED 2,3DEHYDRQ-d, l-BENZTll-HAZHNES Gerhard Haclrmack, Aurnuh'le, near Hamburg, and Walter Krastinat, Hamburg-Niendorf, Germany, assignnrs to Chernisehe Fabrik Promonta G.m.h.ll., Hamburg, Germany, a body corporate of Germany No Drawing. Filed Apr. 27, B61, er. No. 105,872 Claims priority, application Gzrmany, Apr. 28, 1%0,
21,31 3 Claims. (Cl. 260-243) The present invention relates to a process for the production of compounds of the following general formula:
nn lagasifii a in which formula R, which may be at any desired positions of the aromatic ring, represents a hydrogen atom or a monovalent radical, particularly a halogen atom, for example chlorine, bromine, fluorine, or an alkyl or alkoxy group, Z represents an aliphatic bridge member connecting the carbon atoms 2 and 3 to form a ring, the said bridge member having from 3 to 6 carbon atoms, which in their turn can be substituted by other groups, for example alkyl or alkoxy.
These compounds are prepared according to the invention by intramolecular transposition of spiro compounds of the following general formula:
In this formula, R has the meaning indicated above, while A represents an aliphatic chain with 4 to 7 carbon atoms, which can be substituted, for example by alkyl or alkoxy groups. A forms, together with the carbon atom 2 of the thiazoline ring, a ring containing from to 8 carbon atoms.
These spiro compounds are the known 2,2-cycloalkylated benzthiazolines, which are, for example readily obtainable from o-aminothiophenols and ring ketones (see for example H. J. Teuber and H. Waider, Chem. Ber. 91, 234144 (1958)). The melt without decomposition and some can also be distilled or sublimed, also Without decomposition. I
According to the invention, a peculiar and hitherto completely unknown transposition to the cycloalkylated 2,3-dihydro-1,4-benzthiazines takes place with these compounds at relatively high temperature.
I The underlying principle of this invention is illustrated by the following reaction scheme:
Thus, 2,2-pentamethylene benzthiazoline, which can for example be prepared in an almost quantitative yield by reaction of o-aminothiophenol with cyclohexanone, is transposed into 2,3-tetramethylene-2,3-dihydro-1,4-benzthiazine.
The transposition can be carried out in the melt or also in the presence of suitable solvents, if necessary under pressure, by heating to relatively high temperature, more especially between 240 and 320 C. It is expedient in this case to work in an inert gas atmosphere, advanta- 3,156,686 Patented Nov. 10, 1964 geously under nitrogen, in order to avoid decomposition due to oxidation. The process can for example be carried out continuously in a throughflow heater. It is also possible to make use of the known process for the production of benzthiazoline compounds as starting products for the transposition by the benzthiazolines being transformed in situ in accordance with the data of the invention into the corresponding benzthiazoline compounds.
The reaction products can be isolated and purified in known manner.
Among the cycloalkylated dihydrobenzthiazines readily obtainable in this manner, it is only the 2,3-tetramethylene-2,3-dihydro-1,4-benzthiazine, the hexahydrophanthiazine, which is already known in the literature. 0. Hrornatka, I. Augl, M. Vaculny and H. Petrousek (Mh. Chem. 89, 517 (1958)) were able for the first time to isolate hexahydrophenthiazine with the subsequent treatment of a reaction of sodium o-aminothiophenol with Z-chlorocyclohexanone, as described by K. Fujii (Yaku gaku Zasshi 77, 352 (1957); Chem. Abstr. '51 12l01f (1957)). A compound with the melting point 81 C., frequently designated as hexahydrophenthiazine in the literature prior to this Work has been identified by the Work of O. Hromatka, M. Vaculny, H. Petrousek and F. Grass (Mh. Chem. 88, 307 (1957)) and F. Asinger, M. Thiel and H. Kaltwasser (Ann. Chem. 606, 67 (1957)) as Z-hydroxy cyclohexyl-2-aminophenyl sulphide.
The cycloaikylated 2,3-dihydro-1,4-benzthiazines are bases which form salts with strong acids. The salts are however readily split hydrolytically. The picrates which are readily obtainable are especially suitable for characterisation purposes.
The compounds which can be prepared by the new process can more especially be employed as anthelmintical agents.
The invention is further illustrated by the following examples:
Example 1 250 g. of 2,2-pentamethylene benzthiazoline are heated for 6 hours in a stream of nitrogen to 260 C. The transposed product is allowed to cool to about 50 C., and it is taken up while still liquid in cc. of methanol. After a short time, 2,3-tetramethylene-2,3-dihydro-1,4- benzthiazine and also in some cases a little unreacted starting material is crystallised out. The suction-filtered product which is still moist with methanol is taken up, together with 175 g. of alcohol-moist picric acid, in such a quantity of alcohol that everything just dissolves at boiling temperature. 2,3-tetramethylene-2,3-dihydro-1,4- benzthiazine picrate immediately crystallises out from the solution. The melting point of the pure compound is at 168 to 168.5" C.
The free base can be isolated from the picrate by stirring out with excess sodium bicarbonate in aqueous solution. By recrystallisation from methyl alcohol, pure 2,3- tetramethylene-2,3-dihydro-1,4-benzthiazine with the melt ing point 101 C., is obtained. The hydrochloride melts at 202 to 203 C. The purification of the crude product forming after the transposition can also be effected by distillation. 2,3-tetramethylene-2,3-dihydro-1,4-benzthiazine boils at 136 C./B.P.'
Example 2 picrate is at C.
2,3-pentamethylene-2,3-dihydro-1,4- benzthiazine melts at 106 C. The melting point of the Example 3 20 g. of 2,2-pentamethylene-S-chloro-benzthiazoline of melting point 96 C., was heated in the molten state at 260 C., for four hours. The crude product was distilied in vacuum. The fraction distilling over between 160 and 190 C., yields after recrystallisation from alcohol pure 2,3 tetramethylene 2,3 dihydro 6 chloro 1,4 benzthiazine, melting point 168 C.
What We claim is:
1. A process for the production of compounds corresponding to the formula in which R is selected from the group consisting of hydrogen and halogens, and Z stands for hydrocarbon chain which connects the carbon atoms in the 2 and 3 position and is selected from the group consisting of and CH CH CH CH CH comprising heating spiro-compounds corresponding to the formula R I so A References Cited in the file of this patent UNITED STATES PATENTS Muth July 19, 1932 OTHER REFERENCES Hromatka et al.: I, Monatsh. Chem., vol. 88, pp. 307- 16 1957 Teuher et al.: Chem. Ber., Vol. 91, 2341-44 (1958).
Hroniatka et al.: II, Monatsh. Chem, vol. 89, pp. 517- 25 (1958).
Claims (1)
1. A PROCESS FOR THE PRODUCTION OF COMPOUNDS CORRESPONDING TO THE FORMULA
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3156686A true US3156686A (en) | 1964-11-10 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US3156686D Expired - Lifetime US3156686A (en) | Processes for preparing cycloalkylized |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US3156686A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1867863A (en) * | 1927-02-14 | 1932-07-19 | Gen Aniline Works Inc | Indophenol azine compounds |
-
0
- US US3156686D patent/US3156686A/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1867863A (en) * | 1927-02-14 | 1932-07-19 | Gen Aniline Works Inc | Indophenol azine compounds |
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