GB1585168A - 6,7,8,9-tetrahydro-4h-naphthopyran-2-carboxylic acid derivatives and a process for their production - Google Patents
6,7,8,9-tetrahydro-4h-naphthopyran-2-carboxylic acid derivatives and a process for their production Download PDFInfo
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- GB1585168A GB1585168A GB4183776A GB4183776A GB1585168A GB 1585168 A GB1585168 A GB 1585168A GB 4183776 A GB4183776 A GB 4183776A GB 4183776 A GB4183776 A GB 4183776A GB 1585168 A GB1585168 A GB 1585168A
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- tetrahydro
- process according
- oxo
- naphtho
- pyran
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/78—Ring systems having three or more relevant rings
- C07D311/92—Naphthopyrans; Hydrogenated naphthopyrans
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- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
(54) 6,7 ,8 ,9-TETRAHYDRO-4H-NAPHTHOPYRAN-2-CARBOXYLI(: ACID DERIVATIVES AND A PROCESS FOR THEIR PRODUCTION
(71) We, FISONS LIMITED, a British Company of Fison House, 9 Grosvenor Street,
London W1X OAH, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed to be particularly described in and by the following statement:
According to the invention there is provided a process for the production of 5-amino-6,7,S,9-tetrahydro-4-oXo-10-propyl-4H-naphthoL2,3-b]pyran-2-carboxylic acid of tormula I,
or an ester thereof, which comprises the catalytic hydrogenation of 6,7,8,9-tetrahydro-5 nitro-4-oxo-10-propyl-4H-naphtho[2,3-b pyran-2-carboxylic acid of formula II,
or an ester thereof, using a precious metal catalyst other than palladium.
We prefer to produce an ester of 5-amino-6,7,8,9-tetrahydro-4-oxo-10-propyl-4H- naphtho[2,3-b]pyran-2-carboxylic acid from an ester of 6,7,8,9-tetrahydro-5-nitro-4-oxo-10 propyl4R-naphtho[2,3-b]-pyran-2-carboxylic acid.
The hydrogenation may be carried out at a temperature of from 20 to 100" and preferably 30 to 50"C.
The hydrogenation may be carried out in a solvent which is inert under the reaction conditions, e.g. a lower alkanol such as methanol, propanol, butanol or preferably ethanol; a lower alkyl ketone such as acetone or methyl ethyl ketone; an organic acid, e.g. a lower alkanoic acid such as acetic acid; or an ester, e.g. a lower alkyl ester such as ethyl acetate or propyl acetate. The solvent is preferably water miscible. A mixture of solvents may also be used. We prefer to use ethanol. The concentration of 6,7,8,9-tetrahydro-5-nitro-4-oxo-10 propyl-4H-naphtho[2,3-b]pyran-2-carboxylic acid, or the ester thereof, in the solvent is preferably not greater than 20% w/v.
The proportion of precious metal in the catalyst to the 6,7,8,9-tetrahydro-5-nitro-4-oxo- 10-propyl-4H-naptho[2,3-b]-pyran-2-carboxylic acid, or the ester thereof, may be in the range 0.1 to 5:100, preferably 0.1 to 1:100, e.g. 0.25.100 w/w.
The hydrogenation reaction is preferably carried out for the minimum time necessary to convert more than 95%, and preferably more than 98% of the starting material to a corresponding amino compound.
The hydrogenation reaction may be carried out at pressures of from 0 to 60, and preferably from 10 to 30 psig.
It is desirable that the hydrogenation reaction be carried out as rapidly as possible and we therefore prefer the reaction mixture to be vigourously agitated, e.g. by shaking or more preferably by stirring.
The catalyst may be a conventional precious metal hydrogenation catalyst other than a palladium catalyst. The catalyst, and the conditions under which it is used, are preferably such as to produce the optimum yield of the desired product and to avoid, in so far as is possible, the production of undesirable bi-products and in particular the chromanone analogue of 5-amino-6,7,8,9-tetrahydro-4-oxo-10-propyl-4H-naphtho[2,3-b]pyran-2- carboxylic acid (or of the ester thereof).
The catalyst may be supported on a suitable support,.e.g. carbon, alumina, barium sulphate or calcium carbonate.
In particular we have found that a platinum, e.g. a platinum on carbon catalyst is suitable, but other catalysts, and the optimum conditions under which they can be used, can be found by routine experimentation. Catalysts which may be mentioned include
5% Platinum on Carbon
5% Platinum on Carbon. 50% Moisture. Sulfided.
1% Platinum on Carbon. 50% Moisture
5% Platinum on Alumina
5% Rhodium on Carbon
5% Ruthenium on Alumina
5% Ruthenium on Carbon.
We prefer catalysts containing 1% or more of precious metal. The catalyst may if desired contain water. The catalyst may be improved by the addition of a small quantity of a strong acid, e.g. hydrochloric acid thereto.
Where the product is an ester of 5-amino-6,7,8,9-tetrahydro-4-oxo-10-propyl-4H- naphtho[2,3-b]pyran-2-carboxylic acid the ester may, if desired, be treated with acid and isolated as an acid addition salt thereof.
The acid with which the product 5-amino-6,7,8,9-tetrahydro-4-oxo-10-propyl-4H- naphtho[2,3-b]pyran-2-carboxylic acid ester is treated may be any strong acid which is not deleterious to the product compound and with which the product compound forms a salt, e.g. hydrochloric acid. The acid, when it is used, is preferably used in the proportion of at least one mole per mole of the 6,7,8,9-tetrahydro-5-nitro-4-oxo-10-propyl-4H-naphtho- [2,3-b]pyran-2-carboxylic acid ester used inthe reaction. We have surprisingly found that new compounds, i.e. the half acid addition salts, and notably the half hydrochloride, of the esters of the 5-amino-6,7,8,9-tetrahydro-4-oxo-10-propyl-4H-naphtho[2,3-b]-pyran-2- carboxylic acid may be produced by the process of the invention.
We have found that during the hydrogenation of an ester of the 6,7,8,9-tetrahydro-5 nitro-4-oXo-10-propyl-4H-naphtho[2,3-b]pyran-2-carboxylic acid to an ester of 5-amino 6,7 ,8,9-tetrahydro-4-oxo- 10-propyl-4R-naphtho[2,3-b]pyran-2-carboxylic acid a certain amount of the chromanone corresponding to the ester of the 5-amino-6,7,8,9-tetrahydro-4 oXo-10-propyl-4H-naphtho[2,3-b]pyran-2-carboxylic acid is produced. The ester of this corresponding chromanone does not form acid addition salts, and in particular does not form an acid addition salt with hydrochloric acid. When using a platinum catalyst the proportion of the chromanone produced can be minimised.
According to a further feature of the invention therefore we provide a method of separating a mixture of an ester of 5-amino-6,7,8,9-tetrahydro-4-oxo-10-propyl-4H- naphtho[2,3-b]pyran-2-carboxylic acid and a corresponding chromanone (in either free acid or ester form), which comprises treating the mixture with an acid, preferably a strong acid and more preferably hydrochloric acid, and isolating the ester of the 5-amino-6,7,8,9 tetrahydro-4-oxo-10-propyl-4H-naphtho[2 ,3-b]pyran-2-carboxylic acid as an acid addition salt thereof.
The isolation of the acid addition salt may be effected by recrystallisation and/or slurrying, e.g. from, or in, ethanol.
The hydrogenation may be carried out in apparatus conventionally used for catalytic hydrogenations, e.g. comprising a stirred reactor, but we prefer to carry out the hydrogenation in an apparatus comprising a self priming mixture jet. In such an apparatus the major part of the reaction takes place in the mixing jet and, because of the high shear forces prevailing, a higher rate of reaction occurs than in conventional stirred reactors. The reaction mixture is continuously circulated through the mixing jet. The apparatus is also provided with heat exchange units to ensure control of the temperature of the reaction
mixture. One form of suitable apparatus is available from Buss, AG, Basel, Switzerland.
The process of the invention is advantageous in that greater yields, less loss of expensive
catalyst, or less production of unwanted bi-products can be achieved.
In this specification and in the claims the term 'lower' is used to mean a group containing up to and including 6 carbon atoms.
The invention is illustrated, but in no way limited by the following Examples.
EXAMPLE 1
Ethyl 5-amino-6, 7, 8, 9-tetrahydro-4-oxo-10-propyl-4H-naphtho- (2,3-b)pyran-2-carboxylate, half hydrochloride
1% Platinum/Carbon catalyst (50 g) was added to a suspension of ethyl 6,7,8,9 tetrahydro-5-nitro-4-oXo-10-propyl-4H-naphtho(2,3-b)pyran-2-carboxylate (100 g) in ethanol (1 litre). The mixture was stirred with hydrogen at an overpressure of 20 psi at 35-45"C.
Reaction was complete after 2.5 hours. The catalyst was removed by filtration, and the filtrate concentrated to 0.5 litre. Concentrated hydrochloric acid (24 ml) was added and the solution cooled. An orange solid precipitated from the solution. It was filtered off, washed with ethanol and dried to give the title compound 56g (58%). A sample (20g) was twice recrystallised from ethanol and dried, to yield the title product mp 152-154"C. (lug).
EXAMPLE 2
Ethyl-5-amino-6, 7, 8, 9-tetrahydro-4-oxo-1 O-propyl-4H-naphtho (2, 3-b) -pyran-2-carboxylate
1% Platinum on carbon catalyst (as a 50% paste) (0.825g dry weight) was added to a suspension of ethyl 5-nitro-6,78,9-tetrahydro-4-oxo-10-propyl-4H-naphtho(2,3-b)pyran-2- carboxylate (30g) (0.0835 mole) in ethanol (300 ml). The mixture was stirred with hydrogen at an overpressure of 20 psi at 45-550C. Reaction was complete after 4 hours. The catalyst was removed by filtration and the filtrate concentrated to 100 ml. then treated with water (115 ml) and cooled to 0 C. The solid which crystallised was filtered off, washed with aqueous ethanol and dried to give the title compound as orange crystals, mp 79-82"C (25.lg).
WHAT WE CLAIM IS:
1. A process for the production of 5-amino-6.7.8,9-tetrahydro-4-oxo-10-propyl-411 naphtho[2,3-b]pyran-2-carboxylic acid of formula I.
or an ester thereof, which comprises the catalytic hydrogenation of 6.7,8.9-tetrahydro-5- nitro-4-oxo-l0-propyI-4H-naphtho[2,~7-b] 2-carboxylic acid of formula II,
or an ester thereof, using a precious metal catalyst other than palladium.
2. A process according to Claim 1. wherein there is produced an ester of 5-amino 6,7.8 ,9-tetrahydro-4-oxo- 10-propyl-4H-naphtho[2 ,3-bjpyran-2-carboxylic acid from an ester of 6.7,8,9-tetrahydro-5-nitro-4-oxo- 1 0-propyl-4H-naphtho[2,3-b]pyran-2-carboxylic acid.
3. A process according to Claim 1 or Claim 2. wherein the hydrogenation is carried out at a temperature of from 20 to 100"C.
4. A process according to Claim 3, wherein the hydrogenation is carried out at a temperature of from 30 to 50"C.
5. A process according to any one of the preceding claims, wherein the hvdrogenation reaction is carried out in a solvent which is water miscible.
6. A process according to Claim 5 wherein the solvent is a lower alkanol.
7. A process according to Claim 6. wherein the solvent is ethanol.
8. A process according to any one of Claims 5 to 7. wherein the concentration of 6,7 ,8,9-tetrahydro-5-nitro-4-oxo- i0propyl-4H-naphtho[2,3-b]pyran-2-carboxylic acid. or the ester thereof. in the solvent is not greater than 20% w/v.
9. A process according to any one of the preceding claims. wherein the proportion of
**WARNING** end of DESC field may overlap start of CLMS **.
Claims (27)
1. A process for the production of 5-amino-6.7.8,9-tetrahydro-4-oxo-10-propyl-411 naphtho[2,3-b]pyran-2-carboxylic acid of formula I.
or an ester thereof, which comprises the catalytic hydrogenation of 6.7,8.9-tetrahydro-5- nitro-4-oxo-l0-propyI-4H-naphtho[2,~7-b] 2-carboxylic acid of formula II,
or an ester thereof, using a precious metal catalyst other than palladium.
2. A process according to Claim 1. wherein there is produced an ester of 5-amino 6,7.8 ,9-tetrahydro-4-oxo- 10-propyl-4H-naphtho[2 ,3-bjpyran-2-carboxylic acid from an ester of 6.7,8,9-tetrahydro-5-nitro-4-oxo- 1 0-propyl-4H-naphtho[2,3-b]pyran-2-carboxylic acid.
3. A process according to Claim 1 or Claim 2. wherein the hydrogenation is carried out at a temperature of from 20 to 100"C.
4. A process according to Claim 3, wherein the hydrogenation is carried out at a temperature of from 30 to 50"C.
5. A process according to any one of the preceding claims, wherein the hvdrogenation reaction is carried out in a solvent which is water miscible.
6. A process according to Claim 5 wherein the solvent is a lower alkanol.
7. A process according to Claim 6. wherein the solvent is ethanol.
8. A process according to any one of Claims 5 to 7. wherein the concentration of 6,7 ,8,9-tetrahydro-5-nitro-4-oxo- i0propyl-4H-naphtho[2,3-b]pyran-2-carboxylic acid. or the ester thereof. in the solvent is not greater than 20% w/v.
9. A process according to any one of the preceding claims. wherein the proportion of
precious metal in the catalyst to the 6,7,8 ,9-tetrahydro-5-nitro-4-oxo-10-propyl-4H- naphtho[2,3-b]-pyran-2-carboxylic acid, or the ester thereof, is in the range 0.1 to 5:100 w/w.
10. A process according to Claim 9, wherein the proportion is in the range 0.1 to 1:100 w/w.
11. A process according to Claim 10, wherein the proportion is 0.25:100 w/w.
12. A process according to any one of the preceding claims wherein the hydrogenation reaction is carried out at a pressure of from 0 to 60 psig.
13. A process according to Claim 12, wherein the reaction is carried out at from 10 to 30 psig.
14. A process according to any one of the preceding claims wherein the reaction mixture is vigourously agitated.
15. A process according to any one of the preceding claims, wherein the catalyst is supported on carbon, alumina, barium sulphate or calcium carbonate.
16. A process according to any one of the preceding claims, wherein the catalyst is a platinum catalyst.
17. A process according to any one of the preceding claims, wherein the catalyst contains water.
18. A process according to any one of the preceding claims, wherein the catalyst is treated by addition of a small quantity of strong acid.
19. A process according to any one of the preceding claims, wherein the product is an ester of 5-amino-6,7 ,8,9-tetrahydro-4-oxo-10-propyl-4H-naphtho[2 ,3-b]pyran-2-carboxylic acid and the ester is treated with acid and isolated as an acid addition salt thereof.
20. A process according to Claim 19, wherein the acid is hydrochloric acid.
21. A method of separating a mixture of an ester of 5-amino-6,7,8,9-tetrahydro-4-oxo 10-propyl-4H-naphtho[2,3-b]pyran-2-carboxylic acid and a corresponding chromanone (in either free acid or ester form), which comprises treating the mixture with an acid and isolating the ester of the 5-amino-6,7,8,9-tetrahydro-4-oxo-10-propyl-4H-naphtho[2,3- b]pyran-2-carboxylic acid as the acid addition salt thereof.
22. A method according to Claim 21, wherein the isolation of the acid addition salt is effected by recrystallisation from, or slurrying in, ethanol.
23. A process according to Claim 1 and substantially as hereinbefore described in either of the Examples.
24. A method according to Claim 21 and substantially as hereinbefore described in
Example 1.
25. Half acid addition salts of an ester of 5-amino-6,7,8,9-tetrahydro-4-oxo-10-propyl- 4H-naphtho[2,3-b]pyran-2-carboxylic acid.
26. Ethyl 5-amino-6,7,8.9-tetrahydro-4-oxo-10-propyl-4H-naphtho(2,3-b)pyran-2- carboxylate, half hydrochloride.
27. 5-amino-6 7,8 ,9-tetrahydro-4-oxo- 10-propyl-4H-naphtho[2,3-b]-pyran-2-carboxylic acid, or an ester thereof, whenever prepared by a process accordng to any one of Claim 1 to 20 or by a method according to either one of Claims 21 or 22.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB4183776A GB1585168A (en) | 1977-10-05 | 1977-10-05 | 6,7,8,9-tetrahydro-4h-naphthopyran-2-carboxylic acid derivatives and a process for their production |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB4183776A GB1585168A (en) | 1977-10-05 | 1977-10-05 | 6,7,8,9-tetrahydro-4h-naphthopyran-2-carboxylic acid derivatives and a process for their production |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB1585168A true GB1585168A (en) | 1981-02-25 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB4183776A Expired GB1585168A (en) | 1977-10-05 | 1977-10-05 | 6,7,8,9-tetrahydro-4h-naphthopyran-2-carboxylic acid derivatives and a process for their production |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB1585168A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003080555A1 (en) * | 2002-02-28 | 2003-10-02 | Sumitomo Chemical Company, Limited | Process for producing chromone compound |
-
1977
- 1977-10-05 GB GB4183776A patent/GB1585168A/en not_active Expired
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003080555A1 (en) * | 2002-02-28 | 2003-10-02 | Sumitomo Chemical Company, Limited | Process for producing chromone compound |
| US7094914B2 (en) | 2002-02-28 | 2006-08-22 | Sumitomo Chemical Company, Limited | Process for producing chromone compound |
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| Date | Code | Title | Description |
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| CSNS | Application of which complete specification have been accepted and published, but patent is not sealed |