WO1998002408A1 - Procede de nitrosation d'un compose phenolique substitue par un groupememt electro-attracteur et son utilisation - Google Patents
Procede de nitrosation d'un compose phenolique substitue par un groupememt electro-attracteur et son utilisation Download PDFInfo
- Publication number
- WO1998002408A1 WO1998002408A1 PCT/FR1997/001292 FR9701292W WO9802408A1 WO 1998002408 A1 WO1998002408 A1 WO 1998002408A1 FR 9701292 W FR9701292 W FR 9701292W WO 9802408 A1 WO9802408 A1 WO 9802408A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- group
- phenolic compound
- sulfuric acid
- substituted
- acid
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B43/00—Formation or introduction of functional groups containing nitrogen
- C07B43/02—Formation or introduction of functional groups containing nitrogen of nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
Definitions
- the present invention relates to a process for the nitrosation of a phenolic compound substituted by an electron-withdrawing group.
- the invention relates more particularly to the nitrosation of a phenolic compound substituted by a carbonyl group and / or a carboxylic group and derivative.
- the invention also relates to the use of the nitrosene phenolic compound obtained as an intermediate product in the preparation of a nitrated phenolic compound and of its derivatives, in particular, amines.
- the invention applies preferably to the preparation of nitro compounds which results from the nitrosation and oxidation of salicylic acid with a view to obtaining 5-nitrosalicylic acid and salicylic aldehyde to 5-nitrosalicylic aldehyde .
- a variant of the process of the invention is to carry out the preparation of the nitroso intermediate compounds which can also be separated.
- the basis of the invention is to carry out the preparation under certain conditions of a nitrosed phenolic compound which is then oxidized to a nitrated phenolic compound.
- a first object of the invention is a process for nitrosation of a phenolic compound substituted by an electro-attractor group characterized in that it consists in carrying out the nitrosation of said compound in the presence of acid sulfuric; the concentration of sulfuric acid being at least 60% by weight, then optionally carrying out the separation of the nitrosed phenolic compound obtained.
- Another object of the invention is a process for the nitration of a phenolic compound substituted by an electron-withdrawing group, characterized in that it consists:
- a first step to carry out the nitrosation of said compound in the presence of sulfuric acid; the concentration of sulfuric acid being at least 60% by weight, and in the second step, oxidizing the p-nitrosed phenolic compound obtained with nitric acid; the sulfuric acid concentration then being at most equal to 80% which makes it possible to precipitate the substituted p-nitrophenolic compound which is then separated.
- the Applicant has found, unexpectedly, that the nitrosed intermediate compound is soluble under the conditions defined by the invention, which is entirely surprising because, unlike phenol, the phenolic compound substituted by an electron-attracting group in particular by a group. carboxylic (salicylic acid) is not soluble in the starting sulfuric acid solution.
- carboxylic salicylic acid
- the nitrosed compound obtained can be either separated or used directly in the nitration step.
- nitrosation process of the invention possibly associated with an oxidation step applies to any substituted phenolic compound.
- compound substituted phenolic means any aromatic compound carrying a hydroxyl group and an electron-withdrawing group and having a hydrogen atom in the para position of the OH group.
- electro-attracting group is understood to mean a group as defined by H.C. BROWN in the work of Jerry MARCH - Advanced Organic Chemistry, chapter 9, pages 243 and 244 (1985).
- They are preferably carbonyl and / or carboxylic and derivative groups.
- represents an alkyl radical, a cycloalkyl, phenyte, aralkyl radical
- R 2 represents an alkyl or cycloalkyl radical
- R 3 represents an alkyl or cycloalkyl radical
- X represents a chlorine or bromine atom
- R- represents an alkyl radical, a cycloalkyl, phenyl, aralkyl radical,
- a group -CON (R 3 ) 2 in which R3, identical or different, represent a hydrogen atom or a radical R-
- the present invention does not exclude the presence of other substituents on the aromatic ring insofar as they do not interfere with the reactions of the process of the invention. Mention may in particular be made of alkyl radicals having preferably 1 to 4 carbon atoms or halogen atoms, preferably chlorine or bromine.
- the ring carries a group of the type -SOR-], said group can be transformed during the reaction, into group - S0 2 R-). If the ring carries a group of the type -S0 2 N (R 3 ), -S0 3 R 3 , the said group can be transformed into the group - SO3H.
- an alkyl radical linear or branched, having from 1 to 12 carbon atoms, preferably from 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl,.
- a cycloalkyl radical having 3 to 8 carbon atoms, preferably a cyclopentyl or cyclohexyl radical
- radicals R-) and R 3 also represent, in a preferred manner:
- a phenyl radical a phenylalkyl radical having from 7 to 12 carbon atoms, preferably a benzyl radical.
- the present invention preferably applies to the compounds of formula (I) in which n is equal to 1 and Z represents a group -COY in which Y represents a hydroxyl group, a hydrogen atom; or a group -COR-), in which R- ⁇ represents a linear or branched alkyl radical having from 1 to 12 carbon atoms, preferably 1 to 4 carbon atoms, a cyclopentyl or cyclohexyl radical; or a group -COOR 2 , in which R 2 represents an alkyl radical having from 1 to 4 carbon atoms; or a CO-NH group.
- the compounds of formula (I) have a substituent on the ring such as a group -S0 2 R 1 ( -SOR ⁇ -S0 2 N (R 3 ) 2 , -S0 3 R 3 , R-
- the first step is the nitrosation of the substituted phenolic compound, in the presence of sulfuric acid.
- the quantity of sulfuric acid used is particularly critical.
- the concentration of sulfuric acid in the reaction medium is at least equal to 60% by weight.
- the sulfuric acid concentration is between 60% and 90%. It is preferably chosen between 65% and 80%.
- the nitrosating agent is any source of NO +.
- nitrogen dioxide N0 2 nitrogen anhydride N2O3, nitrogen peroxide N2O4, nitrogen oxide NO associated with an oxidizing agent such as, for example, nitric acid. , nitrogen dioxide or oxygen.
- an oxidizing agent such as, for example, nitric acid. , nitrogen dioxide or oxygen.
- the nitrosating agent is gaseous under the reaction conditions, it is bubbled in the medium.
- Nitrous acid nitrosyl or nitrosed sulphate or a nitrous salt, preferably an alkali metal salt, and even more preferably sodium, can also be used.
- the amount of nitrosating agent used can vary widely. When it is expressed by the molar ratio of substituted phenolic compound / nitrosating agent defined in NO + , it is at least equal to the stoichiometric amount but it is preferable that it be used in an excess which can reach 500% of the stoichiometric quantity, and preferably between 150% and 300%. As regards the concentration of the substituted phenolic compound substrate in the reaction medium, it is preferably between 2% and 20% by weight and even more preferably between 5 and 10%.
- the substituted phenolic compound is introduced in solid form or in liquid form. It can therefore either be introduced in the molten state, or as a mixture with water or the sulfuric acid solution. In the latter case, mixtures comprising from 60% to 90% of substituted phenolic compound are very suitable. It should be ensured that the water content in the reaction medium is such that the concentration of sulfuric acid is respected. At the end of this nitrosation step, it is possible to remove the starting substrate which has not reacted and which is in insoluble form. To this end, a conventional solid / liquid separation technique is used, and more preferably filtration.
- the phenolic compound is obtained carrying an electron-withdrawing group, essentially nitrosed in the para position and which corresponds to the following formula:
- Z and n have the meaning given above. It is possible according to the invention to directly engage the nitrosed compound obtained in the nitration step, without separation of the intermediate product.
- Another variant of the process of the invention consists in separating the intermediate product which can be used for purposes other than those of the invention.
- the nitrosed compound obtained can be separated by precipitation.
- a preferred method of precipitation consists in diluting the reaction medium so that the concentration of sulfuric acid in the reaction medium, expressed by the weight ratio sulfuric acid / sulfuric acid + water, is less than 60% by weight, preferably , between 20 and 50%.
- the phenolic compound carrying the electro-attracting and nitrosed group precipitates.
- It can be separated according to conventional solid / liquid separation techniques, preferably by filtration.
- the nitrosed product is oxidized without separation of the intermediate product.
- nitric acid such as for example nitrogen peroxide
- a precursor of nitric acid such as for example nitrogen peroxide
- Use is made of an aqueous nitric acid solution having an indifferent concentration which can vary between 30% and 100%. However, a concentration of between 60% and 100% is preferred.
- Another source of nitric acid can be a sulfonitric mixture. We mean a mixture of concentrated sulfuric acid and nitric acid. There are several types of sulfonitric mixtures on the market which vary according to the proportion of nitric acid relative to sulfuric acid. Examples include mixtures containing 1 mole of nitric acid per 2 moles of sulfuric acid or 1 mole of nitric acid per 5 moles of sulfuric acid.
- the amount of nitric acid expressed by the molar ratio of substituted phenolic compound / nitric acid generally varies between 0.9 and 1.2, preferably between 0.95 and 1.05.
- account should be taken of the quantity of nitric acid which is likely to be consumed by the oxidation reactions of the groups possibly carried by the cycle, such as than the groups -SOR-
- the quantity of sulfuric acid used must be particularly controlled in this step.
- the sulfuric acid concentration is less than or equal to 80%.
- the lower limit is not critical. It is advantageously between 50% and 80%, and preferably between 65% and 75%.
- the process of the invention is advantageously carried out at a temperature between 0 and 60 ° C. It is preferably chosen to be greater than or equal to 30 ° C and more particularly between 30 ° C and 50 ° C.
- the process of the invention is generally carried out under atmospheric pressure but can also be carried out under slightly reduced pressure of, for example, between 500 and 760 mm of mercury [66500 and 101080 Pa] or under conditions of overpressure which may reach , for example, 5 bars.
- the nitrosation step is carried out under a controlled atmosphere of inert gases.
- a controlled atmosphere of inert gases One can establish an atmosphere of rare gases, preferably argon, but it is more economical to use nitrogen.
- the method of the invention is easy to implement since it does not require the use of specific apparatus.
- the method of the invention can be implemented in the manner described below.
- reaction mixture The various constituents of the reaction mixture are loaded into the chosen apparatus. Many modes of implementation can be envisaged insofar as the reagents used make it possible to respect the concentration of sulfuric acid defined in the nitrosation and possibly oxidation step.
- a first variant consists in first loading the sulfuric acid solution and then in adding the substituted phenolic compound and the nitrosating agent in parallel.
- the sulfuric acid solution and the nitrosating agent are introduced and then the substituted phenolic compound is added, preferably in portions or continuously by casting.
- Another variant resides in the fact of introducing in parallel, on a base stock, the substituted phenolic compound on one side and the sulfuric acid and the nitrosating agent on the other.
- the reaction mixture After using the reagents, the reaction mixture is kept in the aforementioned temperature zone. It may be appropriate to cool the reaction mixture.
- nitric acid is then introduced into the reaction medium comprising the intermediate nitrosed compound. It can be added all at once or gradually in portions or continuously, by casting. It is also possible to introduce nitric acid from the start, for example in parallel with the addition of the substituted phenolic compound.
- the temperature of the reaction mixture is maintained in the aforementioned temperature zone.
- nitric acid in situ from nitrogen peroxide which serves both as a nitrosating agent in the first stage and as an acid precursor.
- nitrogen peroxide which serves both as a nitrosating agent in the first stage and as an acid precursor.
- the nitrogen peroxide is introduced from the start and in the second stage, is heated to a temperature between 20 ° C and 60 ° C.
- the substituted phenolic compound which is nitrated in the para position precipitates.
- the precipitate obtained is separated according to conventional solid / liquid separation techniques, preferably by filtration.
- the precipitate obtained can be washed, preferably, with a sulfuric acid solution having the same concentration as that defined in the oxidation step.
- the process of the invention makes it possible essentially to obtain the para isomer because the quantity of isomer nitrated in ortho is generally low (most often less than 2%).
- the para isomer preferentially precipitates with respect to the ortho isomer and the dinitric phenolic compounds obtained as impurities.
- the process of the invention makes it possible to obtain, inter alia, 5-nitrosalicylic acid which is widely used in the pharmaceutical field.
- the nitrated phenolic compounds obtained in particular corresponding to formula (III) can be used to prepare the corresponding amino phenolic compounds by reduction, preferably, with hydrogen in the presence of conventional catalysts for reduction of NO 2 groups, for example palladium on black carbon or Raney nickel.
- 5-nitrosa! Icylic acid is thus reduced to 5-aminosalicylic acid.
- the reaction mixture is then maintained for 15 min at 37 ° C, and then cooled to 20 ° C.
- the medium is heterogeneous: there is salicylic acid not consumed in suspension.
- reaction medium is then filtered to remove this residual salicylic acid.
- the filtrate is returned to the three-necked flask and then poured onto this new filtered reaction mixture 4.2 g of fuming nitric acid at 68% (0.0453 mol) in 15 min.
- the reaction medium is then left for 5 min at 20 ° C. and then the reaction mixture is filtered.
- the cake is washed with three times 20 ml of water.
- the product is then dried under vacuum at room temperature. 4.95 g of a light brown product are collected.
- reaction mixture is heated to 40 ° C in 10 min, then 46 g of salicylic acid (0.333 mol) are charged in half an hour in 4.5 g fractions every 3 min.
- reaction medium is then filtered and the cake washed with 43 g of 70% sulfuric acid. This cake after dosing contains 3.58 g of residual salicylic acid.
- the medium is then left under stirring for 10 min.
- the reaction mixture is filtered.
- the reactor and the cake are washed with twice 130 g of 70% sulfuric acid, then 2 times with 100 g of water.
- the different products are then dosed.
- the yield compared to the initial salicylic acid (RR) is 78% and compared to the transformed salicylic acid (RT) 85%.
- the reaction is carried out in a perfectly stirred and standardized 100 ml reactor equipped with mechanical stirring (turbine with 4 inclined blades), a condenser surmounted by a bubbler, a bulb with addition of solid, a bromine bulb, nitrogen inlet.
- the reactor is initially degassed with nitrogen, the reaction is carried out under an inert atmosphere.
- the solid contains 90.3% 5-nitrosalicylic acid, which corresponds to a yield of 73% based on the isolated product.
- Methyl salicylate (3.9462 g) is introduced through the dropping funnel over a period of 35 min.
- the reaction mixture is kept under vigorous stirring for 3 h 10 at 37 ° C.
- the reaction mixture is transferred to a second 500 ml reactor cooled by an ice bath.
- the internal temperature stabilizes at around 10 ° C.
- 220 ml of ice water are added over a period of 35 min, controlling the flow rate of the pouring so that the internal temperature is close to 10 ° C.
- This reaction mixture is embedded in a water / ice solution containing sulfamic acid.
- the total volume is brought to 1 liter and assayed by high performance liquid chromatography. 1.2 g of 5-nitrososalicylic acid are measured, ie a yield of 82%.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP97933724A EP0922025A1 (fr) | 1996-07-12 | 1997-07-11 | Procede de nitrosation d'un compose phenolique substitue par un groupememt electro-attracteur et son utilisation |
JP50568398A JP2001508763A (ja) | 1996-07-12 | 1997-07-11 | 電子求引性基で置換されたフェノール性化合物のニトロソ化方法及びその使用 |
AU36975/97A AU3697597A (en) | 1996-07-12 | 1997-07-11 | Nitrosation method of a phenolic composition substituted by an electro-attracting group and use thereof |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR9608725A FR2750986B1 (fr) | 1996-07-12 | 1996-07-12 | Procede de nitration d'un compose phenolique substitue par un groupement electro-attracteur |
FR9608725 | 1996-07-12 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1998002408A1 true WO1998002408A1 (fr) | 1998-01-22 |
Family
ID=9493982
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/FR1997/001292 WO1998002408A1 (fr) | 1996-07-12 | 1997-07-11 | Procede de nitrosation d'un compose phenolique substitue par un groupememt electro-attracteur et son utilisation |
Country Status (8)
Country | Link |
---|---|
EP (1) | EP0922025A1 (fr) |
JP (1) | JP2001508763A (fr) |
CN (1) | CN1116273C (fr) |
AU (1) | AU3697597A (fr) |
CA (1) | CA2259931A1 (fr) |
FR (1) | FR2750986B1 (fr) |
WO (1) | WO1998002408A1 (fr) |
ZA (1) | ZA976212B (fr) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113620763A (zh) * | 2021-09-13 | 2021-11-09 | 江南大学 | 一种酰基保护的邻位亚硝化芳胺衍生物的合成方法 |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN100334063C (zh) * | 2002-06-04 | 2007-08-29 | 高俊 | 一种水杨酸或其甲酯或乙酯的硝化反应生产工艺 |
CN1850334B (zh) * | 2006-05-26 | 2012-03-28 | 中国科学院上海有机化学研究所 | 含锆物质在催化水杨酸类化合物的清洁硝化方法中的应用 |
CN105541785B (zh) * | 2016-03-09 | 2017-12-22 | 西安近代化学研究所 | 2,2‑二甲基‑5‑硝基‑5‑亚硝基‑1,3‑二氧环己烷的后处理方法 |
CN106083623B (zh) * | 2016-06-08 | 2018-05-15 | 黑龙江鑫创生物科技开发有限公司 | 一种5-氨基水杨酸的制备方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US1502849A (en) * | 1922-03-11 | 1924-07-29 | Verona Chemical Co | Process for the production of nitroso-meta-cresol and its application to the separation of meta-cresol and para-cresol |
GB1165637A (en) * | 1967-07-19 | 1969-10-01 | Coalite Chem Prod Ltd | Production of Nitrophenols. |
EP0626366A1 (fr) * | 1993-05-26 | 1994-11-30 | Rhone-Poulenc Chimie | Procédé de préparation de nitrophénols |
-
1996
- 1996-07-12 FR FR9608725A patent/FR2750986B1/fr not_active Expired - Fee Related
-
1997
- 1997-07-11 WO PCT/FR1997/001292 patent/WO1998002408A1/fr not_active Application Discontinuation
- 1997-07-11 CA CA002259931A patent/CA2259931A1/fr not_active Abandoned
- 1997-07-11 CN CN97198055A patent/CN1116273C/zh not_active Expired - Fee Related
- 1997-07-11 AU AU36975/97A patent/AU3697597A/en not_active Abandoned
- 1997-07-11 EP EP97933724A patent/EP0922025A1/fr not_active Withdrawn
- 1997-07-11 JP JP50568398A patent/JP2001508763A/ja active Pending
- 1997-07-14 ZA ZA9706212A patent/ZA976212B/xx unknown
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US1502849A (en) * | 1922-03-11 | 1924-07-29 | Verona Chemical Co | Process for the production of nitroso-meta-cresol and its application to the separation of meta-cresol and para-cresol |
GB1165637A (en) * | 1967-07-19 | 1969-10-01 | Coalite Chem Prod Ltd | Production of Nitrophenols. |
EP0626366A1 (fr) * | 1993-05-26 | 1994-11-30 | Rhone-Poulenc Chimie | Procédé de préparation de nitrophénols |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113620763A (zh) * | 2021-09-13 | 2021-11-09 | 江南大学 | 一种酰基保护的邻位亚硝化芳胺衍生物的合成方法 |
Also Published As
Publication number | Publication date |
---|---|
EP0922025A1 (fr) | 1999-06-16 |
CN1262672A (zh) | 2000-08-09 |
CN1116273C (zh) | 2003-07-30 |
CA2259931A1 (fr) | 1998-01-22 |
JP2001508763A (ja) | 2001-07-03 |
FR2750986A1 (fr) | 1998-01-16 |
FR2750986B1 (fr) | 1998-10-16 |
AU3697597A (en) | 1998-02-09 |
ZA976212B (en) | 1998-03-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP1222181B1 (fr) | Procede de preparation d'un compose de type benzofurane ou benzothiophene | |
FR2800067A1 (fr) | Intermediaires de fabrication d'un derive de type benzofurane ou benzothiophene nitre en position 5 et leurs utilisations | |
EP0922025A1 (fr) | Procede de nitrosation d'un compose phenolique substitue par un groupememt electro-attracteur et son utilisation | |
EP0877726A1 (fr) | Procede d'acylation d'un compose aromatique | |
EP0091385B1 (fr) | Procédé de préparation de p-hydroxybenzylnitriles ou p-hydroxybenzylamines | |
EP2417092B1 (fr) | Procede d'hydroxylation de phenols et d'ethers de phenols | |
EP0626366B1 (fr) | Procédé de préparation de nitrophénols | |
EP0780366B1 (fr) | Procédé d'obtention d'hydroxylamine N-monosubstituée | |
EP0709361A1 (fr) | Procédé de préparation d'isovanilline | |
EP0279716B1 (fr) | Procédé de n-omega-trifluoroacetylation des alpha,omega diaminoacides monocarboxyliques aliphatiques saturés | |
EP0211775B1 (fr) | Procédé de nitration de composés phénoliques | |
EP0779883B1 (fr) | Procede de preparation d'un 4-hydroxybenzaldehyde substitue | |
FR2809397A1 (fr) | Procede de preparation d'un compose de type benzofuranne ou benzothiophene | |
EP3539955B1 (fr) | Procédé de préparation de tétrazines | |
EP1144357A1 (fr) | Procede de fabrication de solutions aqueuses de sels insatures d'ammonium quaternaire | |
FR2787787A1 (fr) | Procede de preparation de thioethers aromatiques de type diphenyle | |
EP1259521B1 (fr) | Procede de preparation du tris-trifluoromethanesulfonate de bismuth | |
FR2784986A1 (fr) | Procede de preparation d'un compose de type indanone ou thioindanone | |
BE875594A (fr) | Procede de preparation de cetazines, et produits ainsi obtenus | |
EP0102909A1 (fr) | Procédé de préparation d'hydroxy-triazoles utilisables comme intermédiaires pour les herbicides | |
EP0927153A1 (fr) | Procede de carboxylation d'un aminonaphtol | |
FR2774685A1 (fr) | Procede d'hydrogenation d'acides nitrosalicyliques | |
WO2000043342A1 (fr) | Procede de preparation d'un compose de type indanone ou thioindanone | |
BE862711A (fr) | Procede de preparation d'amino-phenyl-urees et d'amino-carbanylates |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 97198055.1 Country of ref document: CN |
|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AL AM AU AZ BA BB BG BR BY CA CN CU CZ EE GE GH HU IL IS JP KE KG KP KR KZ LC LK LR LS LT LV MD MG MK MN MW MX NO NZ PL RO RU SD SG SI SK TJ TM TR TT UA UG US UZ VN YU AM AZ BY KG KZ MD RU TJ TM |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH KE LS MW SD SZ UG ZW AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 1997933724 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref document number: 2259931 Country of ref document: CA Ref document number: 2259931 Country of ref document: CA Kind code of ref document: A |
|
ENP | Entry into the national phase |
Ref document number: 1998 505683 Country of ref document: JP Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 09230214 Country of ref document: US |
|
WWP | Wipo information: published in national office |
Ref document number: 1997933724 Country of ref document: EP |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 1997933724 Country of ref document: EP |