CN104292179A - Preparation method of 2-chlorobenzo[d]oxazole-5-formaldehyde - Google Patents
Preparation method of 2-chlorobenzo[d]oxazole-5-formaldehyde Download PDFInfo
- Publication number
- CN104292179A CN104292179A CN201410561635.9A CN201410561635A CN104292179A CN 104292179 A CN104292179 A CN 104292179A CN 201410561635 A CN201410561635 A CN 201410561635A CN 104292179 A CN104292179 A CN 104292179A
- Authority
- CN
- China
- Prior art keywords
- compound
- temperature
- solvent
- reaction
- xylol
- 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.)
- Pending
Links
- SSWZUOXLFTXIEZ-UHFFFAOYSA-N Cc(cc1)cc(N2)c1OC2=S Chemical compound Cc(cc1)cc(N2)c1OC2=S SSWZUOXLFTXIEZ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
Abstract
The invention discloses a preparation method of 2-chlorobenzo[d]oxazole-5-formaldehyde. According to the preparation method, 2-nitro-4-methylphenol serving as a raw material is subjected to reduction, cyclization, chloration and oxidation to obtain the target product 2-chlorobenzo[d]oxazole-5-formaldehyde which is an important medicine immediate.
Description
Technical field
The present invention relates to a kind of novel processing step of medicine intermediate, particularly the preparation method of a kind of 2-chlorobenzene also [d] oxazole-5-formaldehyde.
Technical background
Compound 2-chlorobenzene is [d] oxazole-5-formaldehyde also, and structural formula is:
This compound 2-chlorobenzene also [d] oxazole-5-formaldehyde and relevant derivative has widespread use in pharmaceutical chemistry and organic synthesis.The synthesis of current 2-chlorobenzene also [d] oxazole-5-formaldehyde is comparatively difficult.Therefore, need exploitation raw material to be easy to get, easy to operate, reaction is easy to control, the synthetic method that overall yield is suitable.
Summary of the invention
The invention discloses the method that one prepares 2-chlorobenzene also [d] oxazole-5-formaldehyde, with 2-nitro-4-methyl phenol for starting raw material, obtain target product 5 through reduction, Guan Huan, chlorination, oxidation, synthetic route as shown in Figure 1.Synthesis step is as follows:
(1) with 2-nitro-4-methyl phenol for starting raw material, obtain 2 through reduction reaction;
(2) carry out ring closure reaction 2, obtain 3;
(3) carry out chlorination reaction 3 and obtain 4;
(4) carry out oxidizing reaction 4 and obtain 5;
One preferred embodiment in, the reductive agent that described reduction reaction prepares compound 2 used is selected from hydrogen; The reagent that described ring closure reaction prepares compound 3 used is selected from potassium ethyl xanthonate; The alkali that described chlorination reaction prepares compound 4 used is selected from sulfur oxychloride; The oxygenant that described oxidizing reaction prepares compound 5 used is selected from tin anhydride.
One preferred embodiment in, described reduction reaction prepares compound 2 solvent selected from methanol used; The solvent that described ring closure reaction prepares compound 3 used is selected from pyridine; The solvent that the described standby compound 4 of chlorination counter is used is selected from sulfur oxychloride; The solvent that described oxidizing reaction prepares compound 5 used is selected from methylene dichloride.
One preferred embodiment in, it is room temperature that described reduction reaction prepares compound 2 temperature of reaction used; Described ring closure reaction prepares the reflux temperature that compound 3 temperature used is solvent; Described chlorination reaction prepares the backflow that compound 4 temperature used is solvent; It is room temperature that described oxidizing reaction prepares compound 5 temperature used.
The present invention relates to the preparation method of a kind of 2-chlorobenzene also [d] oxazole-5-formaldehyde, there is no other Patents bibliographical informations at present.
Accompanying drawing explanation
Fig. 1 is the synthetic route chart of compound 2-chlorobenzene also [d] oxazole-5-formaldehyde.
The present invention is further described by the following embodiment, and these descriptions are not be further limited content of the present invention.One skilled in the art will understand that the equivalent replacement that technical characteristic of the present invention is done, or improve accordingly, still belong within protection scope of the present invention.
Specific embodiment mode
Embodiment 1
(1) synthesis of 2-amido-4-methylphenol
15g 2-nitro-4-methyl phenol and 1g 10% palladium carbon are joined in 120ml methyl alcohol, passes into hydrogen, stirring at room temperature 8 hours, filter, collect filtrate, concentrated, obtain 13g 2-amido-4-methylphenol.
(2) synthesis of 5-methyl benzo [d] oxazole-2-(3H)-thiophene ketone
12g 2-amido-4-methylphenol and 18g potassium ethyl xanthonate are joined in 180ml pyridine, reflux stirs 3 hours, be cooled to room temperature, add 10% hydrochloric acid, then add ethyl acetate, extraction separatory, collect organic phase, drying, concentrated, on residuum, silicagel column is separated and obtains 9g 5-methyl benzo [d] oxazole-2-(3H)-thiophene ketone.
(3) synthesis of 2-chloro-5-methyl benzo [d] oxazole
8g 5-methyl benzo [d] oxazole-2-(3H)-thiophene ketone is joined in 70ml sulfur oxychloride, and reflux stirs 22 hours, cooling, concentrated, obtains 7.2g 5-ethyl oxazole-4-ethyl formate.
(4) synthesis of 2-chlorobenzene also [d] oxazole-5-formaldehyde
6g 5-ethyl oxazole-4-ethyl formate is joined in 130ml methylene dichloride, then adds 15g tin anhydride, stirring at room temperature 12 hours, add water, extraction, separatory, collect organic phase, dry, concentrated, on residuum, silicagel column is separated to obtain 2.9g 2-chlorobenzene also [d] oxazole-5-formaldehyde.
Claims (6)
1. prepare a preparation method for 2-chlorobenzene also [d] oxazole-5-formaldehyde, with 2-nitro-4-methyl phenol for starting raw material, obtain target product 5 through reduction, Guan Huan, chlorination, oxidation, synthetic route is as follows.
2. method according to claim 1, it is characterized by 4 described step reactions is,
(1) with 2-nitro-4-methyl phenol for starting raw material, obtain 2 through reduction reaction;
(2) carry out ring closure reaction 2, obtain 3;
(3) carry out chlorination reaction 3 and obtain 4;
(4) carry out oxidizing reaction 4 and obtain 5;
3. according to the method for claim 1-2, it is characterized in that, described reduction reaction is prepared compound 2 reductive agent used and is selected from the mixture of one or more in iron powder, zinc powder, hydrogen, sodium borohydride, POTASSIUM BOROHYDRIDE, lithium borohydride, sodium cyanoborohydride, lithium aluminium hydride, borine; The reagent that described ring closure reaction prepares compound 3 used is selected from potassium ethyl xanthonate; Described chlorination reaction is prepared compound 4 alkali used and is selected from the mixture of one or more in phosphorus oxychloride, phosphorus trichloride, phosphorus pentachloride, chlorine, hydrogenchloride, sulfur oxychloride; Described oxidizing reaction is prepared compound 5 oxygenant used and is selected from one or both mixture in Manganse Dioxide, chromium trioxide, pyridinium chloro-chromate, Pyridinium dichromate, 2-iodoxybenzoic acid, Dai Si-Martin's oxygenant, tin anhydride.
4. according to the method for claim 1-2, it is characterized in that, described reduction reaction prepares compound 2 solvent selected from methanol used, ethanol, n-propyl alcohol, Virahol, tetrahydrofuran (THF), methylene dichloride, toluene, o-Xylol, p-Xylol, m-xylene, N, the mixture of one or more in dinethylformamide, N,N-dimethylacetamide, triethylamine; Described ring closure reaction prepares compound 3 solvent selected from methanol used, ethanol, n-propyl alcohol, Virahol, tetrahydrofuran (THF), methylene dichloride, toluene, o-Xylol, p-Xylol, m-xylene, N, the mixture of one or more in dinethylformamide, N,N-dimethylacetamide, pyridine; Solvent selected from methanol, ethanol, n-propyl alcohol, Virahol, tetrahydrofuran (THF), methylene dichloride, toluene, o-Xylol, p-Xylol, m-xylene, N that the described standby compound 4 of chlorination counter is used, the mixture of one or more in dinethylformamide, N,N-dimethylacetamide, phosphorus oxychloride, sulfur oxychloride, pyridine; Described oxidizing reaction prepares compound 5 solvent selected from methanol used, ethanol, n-propyl alcohol, Virahol, tetrahydrofuran (THF), methylene dichloride, toluene, o-Xylol, p-Xylol, m-xylene, N, the mixture of one or more in dinethylformamide, N,N-dimethylacetamide.
5. according to the method for claim 1-2, it is characterized in that, described reduction reaction prepares the reflux temperature that compound 2 temperature of reaction used is 0 DEG C ~ solvent; Described ring closure reaction prepares the reflux temperature that compound 3 temperature used is 0 DEG C ~ solvent; Described chlorination reaction prepares the reflux temperature that compound 4 temperature used is 0 DEG C ~ solvent; Described oxidizing reaction prepares the reflux temperature that compound 5 temperature used is 0 DEG C ~ solvent.
6. according to the method for claim 1-2, it is characterized in that, it is room temperature that described reduction reaction prepares compound 2 temperature of reaction used; Described ring closure reaction prepares the reflux temperature that compound 3 temperature used is solvent; Described chlorination reaction prepares the backflow that compound 4 temperature used is solvent; It is room temperature that described oxidizing reaction prepares compound 5 temperature used.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410561635.9A CN104292179A (en) | 2014-10-19 | 2014-10-19 | Preparation method of 2-chlorobenzo[d]oxazole-5-formaldehyde |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410561635.9A CN104292179A (en) | 2014-10-19 | 2014-10-19 | Preparation method of 2-chlorobenzo[d]oxazole-5-formaldehyde |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104292179A true CN104292179A (en) | 2015-01-21 |
Family
ID=52312168
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410561635.9A Pending CN104292179A (en) | 2014-10-19 | 2014-10-19 | Preparation method of 2-chlorobenzo[d]oxazole-5-formaldehyde |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104292179A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106810543A (en) * | 2017-01-09 | 2017-06-09 | 湖南华腾制药有限公司 | It is a kind of（The base of thiazole 5）The preparation method of benzo [d] oxazole |
| CN107011283A (en) * | 2017-05-31 | 2017-08-04 | 湖南华腾制药有限公司 | A kind of methyl mercapto replaces the preparation method of benzo [d] oxazole derivatives |
| CN107266387A (en) * | 2016-04-07 | 2017-10-20 | 湖南华腾制药有限公司 | A kind of preparation method of 2- bromobenzenes simultaneously [d] oxazole -5- formaldehyde |
| CN107400098A (en) * | 2016-05-19 | 2017-11-28 | 湖南华腾制药有限公司 | A kind of preparation method of 2- chlorobenzenes simultaneously [d] oxazole -5- formic acid |
| CN107513043A (en) * | 2016-06-18 | 2017-12-26 | 湖南华腾制药有限公司 | A kind of preparation method of bromine substitution benzoxazoles derivative |
| CN107698534A (en) * | 2016-08-08 | 2018-02-16 | 湖南华腾制药有限公司 | A kind of preparation method of polysubstituted benzo oxazoline compound |
| CN108129413A (en) * | 2016-12-01 | 2018-06-08 | 湖南华腾制药有限公司 | A kind of preparation method of benzo [d] oxazole derivatives |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101041623A (en) * | 2007-04-26 | 2007-09-26 | 上海华谊丙烯酸有限公司 | Method for preparation of (substituted radical containted) aminophenol by catalytic hydrogenation of (substituted radical containted) nitrophenol |
| WO2008035956A1 (en) * | 2006-09-22 | 2008-03-27 | Ewha University - Industry Collaboration Foundation | New benzoxazole derivative, process for the preparation thereof and pharmaceutical composition comprising the same |
| CN102046622A (en) * | 2008-04-15 | 2011-05-04 | 因特蒙公司 | Novel macrocyclic inhibitors of hepatitis C virus replication |
| CN103209980A (en) * | 2010-11-23 | 2013-07-17 | 皮埃尔法布雷医药公司 | Derivatives of heteroarylsulfonamides, their preparation and their application in human therapy |
| WO2014130869A1 (en) * | 2013-02-22 | 2014-08-28 | Samumed, Llc | Gamma-diketones as wnt/beta -catenin signaling pathway activators |
-
2014
- 2014-10-19 CN CN201410561635.9A patent/CN104292179A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008035956A1 (en) * | 2006-09-22 | 2008-03-27 | Ewha University - Industry Collaboration Foundation | New benzoxazole derivative, process for the preparation thereof and pharmaceutical composition comprising the same |
| CN101041623A (en) * | 2007-04-26 | 2007-09-26 | 上海华谊丙烯酸有限公司 | Method for preparation of (substituted radical containted) aminophenol by catalytic hydrogenation of (substituted radical containted) nitrophenol |
| CN102046622A (en) * | 2008-04-15 | 2011-05-04 | 因特蒙公司 | Novel macrocyclic inhibitors of hepatitis C virus replication |
| CN103209980A (en) * | 2010-11-23 | 2013-07-17 | 皮埃尔法布雷医药公司 | Derivatives of heteroarylsulfonamides, their preparation and their application in human therapy |
| WO2014130869A1 (en) * | 2013-02-22 | 2014-08-28 | Samumed, Llc | Gamma-diketones as wnt/beta -catenin signaling pathway activators |
Non-Patent Citations (3)
| Title |
|---|
| FORTUNA HAVIV ET AL.: "3-[1-(2-Benzoxazolyl)hydrazino]propanenitrile Derivatives: Inhibitors of Immune Complex Induced Inflammation", 《JOURNAL OF MEDICINAL CHEMISTRY》 * |
| YUKIYOSHI YAMAZAKI ET AL.: "Design and synthesis of highly potent and selective human peroxisome proliferator-activated receptor a agonists", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 》 * |
| 王永梅 等: "《有机化学提要与习题精解》", 31 January 2013, 南开大学出版社 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107266387A (en) * | 2016-04-07 | 2017-10-20 | 湖南华腾制药有限公司 | A kind of preparation method of 2- bromobenzenes simultaneously [d] oxazole -5- formaldehyde |
| CN107400098A (en) * | 2016-05-19 | 2017-11-28 | 湖南华腾制药有限公司 | A kind of preparation method of 2- chlorobenzenes simultaneously [d] oxazole -5- formic acid |
| CN107513043A (en) * | 2016-06-18 | 2017-12-26 | 湖南华腾制药有限公司 | A kind of preparation method of bromine substitution benzoxazoles derivative |
| CN107698534A (en) * | 2016-08-08 | 2018-02-16 | 湖南华腾制药有限公司 | A kind of preparation method of polysubstituted benzo oxazoline compound |
| CN108129413A (en) * | 2016-12-01 | 2018-06-08 | 湖南华腾制药有限公司 | A kind of preparation method of benzo [d] oxazole derivatives |
| CN106810543A (en) * | 2017-01-09 | 2017-06-09 | 湖南华腾制药有限公司 | It is a kind of（The base of thiazole 5）The preparation method of benzo [d] oxazole |
| CN107011283A (en) * | 2017-05-31 | 2017-08-04 | 湖南华腾制药有限公司 | A kind of methyl mercapto replaces the preparation method of benzo [d] oxazole derivatives |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104292179A (en) | Preparation method of 2-chlorobenzo[d]oxazole-5-formaldehyde | |
| CN104230853B (en) | A kind of preparation method of (p-methylphenyl) methylamine-N-ethylmorpholine hydrochloride | |
| CN104292145A (en) | Preparation method of 6-bromoindole derivative | |
| CN104262257A (en) | Preparation method of pyrazole derivative | |
| CN104926775A (en) | Preparation method of fluorine-containing pyran derivative | |
| CN104277042A (en) | Preparation method of imidazopyridine derivative | |
| CN104387367A (en) | Method for preparing disubstituted benzimidazole derivative | |
| CN104829581A (en) | Preparation method of 6-bromo pyran derivative | |
| CN104311544A (en) | Preparation method of benzoxazole derivative | |
| CN104860910A (en) | Preparation method of 8-fluoropyran derivative | |
| CN104829574A (en) | 8-bromo pyran derivative preparation method | |
| CN104829576A (en) | Preparation method of 7-fluoropyran derivatives | |
| CN104844549A (en) | Preparation method of 7 - bromine pyran derivatives | |
| CN104829575A (en) | Preparation method of 6-fluoropyran derivative | |
| CN104326977A (en) | Preparation method of 6,7-diethyl-4-hydroxyquinoline | |
| CN104292143A (en) | 2-(4-bromine benzyl) pyrrolidine preparation method | |
| CN104402880A (en) | Preparation method of imidazopyridine derivative | |
| CN105001117A (en) | Method for synthesizing chlorine-containing azide compound | |
| CN104262265B (en) | A kind of preparation method of tetrahydro quinazoline derivative | |
| CN108129413A (en) | A kind of preparation method of benzo [d] oxazole derivatives | |
| CN104072495B (en) | The preparation method of natural product alkaloid A aptamine | |
| CN107698534A (en) | A kind of preparation method of polysubstituted benzo oxazoline compound | |
| CN104370835A (en) | Preparation method of triazole derivative | |
| CN107513043A (en) | A kind of preparation method of bromine substitution benzoxazoles derivative | |
| CN105061253A (en) | Preparation method of bromine-containing azide |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20150121 |