CN101768093A - Preparation method of 2-carbomethoxy-5-iodobenzene sulfamide - Google Patents
Preparation method of 2-carbomethoxy-5-iodobenzene sulfamide Download PDFInfo
- Publication number
- CN101768093A CN101768093A CN201010300776A CN201010300776A CN101768093A CN 101768093 A CN101768093 A CN 101768093A CN 201010300776 A CN201010300776 A CN 201010300776A CN 201010300776 A CN201010300776 A CN 201010300776A CN 101768093 A CN101768093 A CN 101768093A
- Authority
- CN
- China
- Prior art keywords
- methoxycarbonyl
- sulfamide
- iodobenzene
- preparation
- temperature
- 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
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of 2-carbomethoxy-5-iodobenzene sulfamide. The preparation method comprises the following steps of: (1) reacting p-nitro o-sulpho benzoic acid with an acyl chlorinating agent to generate p-nitro o-chlorosulfony benzoic acid, and then reacting the p-nitro o-chlorosulfony benzoic acid with methanol to obtain 2-chlorosulfonyl-4-nitrobenzoic acid methyl ester; (2) reacting the 2-chlorosulfonyl-4-nitrobenzoic acid methyl ester with ammonia gas to obtain 2-carbomethoxy-5-nitrobenzene sulfamide; (3) reacting the 2-carbomethoxy-5-nitrobenzene sulfamide with hydrogen under a Pb/C catalyst to obtain 2-carbomethoxy-5aminobenzene sulfamide; (4) reacting the 2-carbomethoxy-5aminobenzene sulfamide with a sodium nitrite solution; and then reacting an obtained diazonium salt with an iodizating agent to obtain the 2-carbomethoxy-5-iodobenzene sulfamide. The method has simple reaction and operation, wide resource of the raw material p-nitro o-sulpho benzoic acid, low price and lower production cost and is suitable for industrial production.
Description
Technical field
The present invention relates to a kind of organic chemical industry's intermediates preparation, particularly relate to the preparation method of a kind of 2-methoxycarbonyl-5-iodobenzene sulfamide.
Background technology
Iodosulfuron methyl sodium is the cornfield herbicidal of the high-efficiency low-toxicity developed in recent years, and 2-methoxycarbonyl-5-iodobenzene sulfamide is the important intermediate of synthetic iodosulfuron methyl sodium.
It is starting raw material with 2-acetamido-4-iodo-methyl benzoate that U.S. Pat 5463081 discloses a kind of, obtains the method for 2-methoxycarbonyl-5-iodobenzene sulfamide through 4 step reaction such as decarboxylation, diazotization curing, sulfonating chlorinating, amination.The starting raw material 2-acetamido of this method-4-iodo-methyl benzoate costs an arm and a leg, and overall raw materials cost height is difficult to suitability for industrialized production.
Summary of the invention
The objective of the invention is to overcome the problems referred to above, provide a kind of raw material cheap and easy to get, operation is simple, and cost is lower and be suitable for the preparation method of the 2-methoxycarbonyl-5-iodobenzene sulfamide of suitability for industrialized production.
Realize that technical scheme steps of the present invention is as follows: the preparation method of a kind of 2-methoxycarbonyl-5-iodobenzene sulfamide, have following steps: 1. will in the DMF organic solvent, generate the benzoic acyl chloride reaction of the adjacent sulfuryl chlorio of nitro, and under 0 ℃～50 ℃ temperature, carry out esterification with methyl alcohol again and obtain 2-chlorosulfonyl-4-nitrobenzoic acid methyl esters to nitro o-sulfobenzoic acid and acyl chlorinating agent; Described acyl chlorinating agent is sulfur oxychloride, phosphorus trichloride or phosphorus oxychloride; 2. 2-chlorosulfonyl-4-nitrobenzoic acid methyl esters that 1. step is obtained and ammonia react under 10 ℃～15 ℃ temperature in organic solvent and obtain 2-methoxycarbonyl-5-nitrobenzene sulfonamide; Described organic solvent is methylene dichloride, chloroform or tetracol phenixin; 3. the 2-methoxycarbonyl-5-nitrobenzene sulfonamide that 2. step is obtained under the Pd/C catalyzer with hydrogen in organic solvent under 15 ℃～25 ℃ temperature reaction obtain 2-methoxycarbonyl-5 aminobenzene sulfonamide; Described organic solvent is methyl alcohol, dehydrated alcohol or Virahol; 4. 2-methoxycarbonyl-5 aminobenzene sulfonamide that 3. step is obtained carries out diazotization reaction with sodium nitrite solution under 0 ℃～15 ℃ temperature in acidic medium, more resulting diazonium salt and iodinating agent are carried out iodide reaction under 50 ℃～80 ℃ temperature and obtain 2-methoxycarbonyl-5-iodobenzene sulfamide; Described acidic medium is the mixing acid of hydrochloric acid, sulfuric acid, acetic acid or acetic acid and hydrochloric acid; Described iodinating agent is potassiumiodide or sodium iodide.
The acyl chlorinating agent of above-mentioned steps described in 1. is sulfur oxychloride.
The esterification reaction temperature of above-mentioned steps described in 1. is 18 ℃～22 ℃.
The organic solvent of above-mentioned steps described in 2. is methylene dichloride.
The temperature of reaction of above-mentioned steps described in 2. is 0 ℃～5 ℃.
The content of Pd is 9wt%～11wt% in the Pd/C catalyzer of above-mentioned steps described in 3..
The organic solvent of above-mentioned steps described in 3. is dehydrated alcohol.
The acidic medium of above-mentioned steps described in 4. is hydrochloric acid.
The diazotization temperature of above-mentioned steps described in 4. is 0 ℃～5 ℃.
The iodinating agent of above-mentioned steps described in 4. is potassiumiodide.
Reaction process of the present invention is:
The positively effect that the present invention has is: method operation of the present invention is simple, and raw material is to nitro o-sulfobenzoic acid wide material sources, and cheap, production cost is lower, is suitable for suitability for industrialized production.
Embodiment
(embodiment 1)
The preparation method of the 2-methoxycarbonyl-5-iodobenzene sulfamide of present embodiment has following steps:
1. the acyl chlorinating agent sulfur oxychloride that in the four-hole boiling flask of 500mL, adds 240mL, stir, be chilled to 5 ℃ with ice-water bath, gradation add 64g purity be 94% to the nitro o-sulfobenzoic acid, after adding, splash into the organic solvent DMF (dimethyl formamide) of 5mL, remove ice bath then, heat temperature raising to 25 ℃, slowly heat temperature raising refluxes to beginning again, and backflow 4h takes place to generate to the benzoic acyl chloride reaction of the adjacent sulfuryl chlorio of nitro.Reaction finishes the back underpressure distillation and reclaims unreacted excessive sulfur oxychloride, thereby the esterification that the methyl alcohol generation of dropping 100mL generates 2-chlorosulfonyl-4-nitrobenzoic acid methyl esters in leftover materials after dripping off, stirs under 20 ℃ temperature and spends the night.Then, ice bath crystallization, vacuum filtration; oven dry gets 60g light yellow solid 2-chlorosulfonyl-4-nitrobenzoic acid methyl esters, and fusing point is 88 ℃～90 ℃; yield is 83%, and the measured purity of high performance liquid chromatography (HPLC) instrument is 93% (being simplified shown as HPLC 93%).
2. the organic solvent dichloromethane that in the four-hole boiling flask of 500mL, adds 250mL; add purity that 1. the 60g step make again and be 2-chlorosulfonyl-4-nitrobenzoic acid methyl esters of 93%; stirring and dissolving; ice-water bath is cooled to 0 ℃～5 ℃, feeds the ammonia of 60g and generates the reaction of 2-methoxycarbonyl-5-nitrobenzene sulfonamide.React the end post-heating and evaporate organic solvent dichloromethane and recovery, the washing leftover materials, suction filtration, the dry 2-methoxycarbonyl-5-nitrobenzene sulfonamide (HPLC 95%) that gets 50g, fusing point is 196 ℃～198 ℃, MS (m/z) mass-to-charge ratio: 261 (M
+), yield is 91%.
3. in the four-hole boiling flask of 500mL, add the organic solvent dehydrated alcohol of 400mL, purity that 2. the 25g step makes and be 95% 2-methoxycarbonyl-5-nitrobenzene sulfonamide and the 10%Pd/C catalyzer of 2g, under 20 ℃ temperature, stir and feed the reaction that excessive hydrogen 8h generates 2-methoxycarbonyl-5-aminobenzene sulfonamide.The reaction after-filtration, filtrate concentrates, the dry faint yellow solid 2-methoxycarbonyl-5-aminobenzene sulfonamide (HPLC 95%) that gets 20g, fusing point is 168 ℃～170 ℃, MS (m/z): 231 (M
+), yield is 91%.
4. in the four-hole boiling flask of 500mL, add the acidic medium concentrated hydrochloric acid of 44g and the water of 200mL, stir, add 2-methoxycarbonyl-5-aminobenzene sulfonamide that 3. the 68g step makes then, stir 1h, cooling bath is cooled to 0 ℃～5 ℃, drip the sodium nitrite in aqueous solution (Sodium Nitrite that contains 25g) of 60g and the diazotization reaction of diazonium salt takes place to generate, after 0.5h drips off, continue diazotization reaction 0.5h.Then drip the iodinating agent potassium iodide aqueous solution (potassiumiodide that contains 46g) of 80g again and take place to generate the iodide reaction of 2-methoxycarbonyl-5-iodobenzene sulfamide with diazonium salt, 1h drips off, and heat temperature raising to 65 ℃ reacts 1h again.After reaction finishes, be chilled to 0 ℃ and separate out 2-methoxycarbonyl-5-iodobenzene sulfamide crystal, suction filtration with ice-water bath, solid is collected in washing, the dry 2-methoxycarbonyl-5-iodobenzene sulfamide (HPLC 95%) that gets 87g, fusing point is 176 ℃～177 ℃, MS (m/z): 342 (M
+), yield is 87%.
(embodiment 2～embodiment 5)
The preparation method of embodiment 2～embodiment 5 is substantially the same manner as Example 1, and difference is: acyl chlorinating agent or esterification temperature difference that step is adopted in 1. specifically see Table 1.
Table 1
| Acyl chlorinating agent | Esterification temperature | The weight of 2-chlorosulfonyl-4-nitrobenzoic acid methyl esters | Yield | |
| Embodiment 1 | Sulfur oxychloride | ??20℃ | 60g | ??83％ |
| Embodiment 2 | Sulfur oxychloride | ??0℃ | 57.5g | ??80％ |
| Embodiment 3 | Sulfur oxychloride | ??50℃ | 50.5g | ??70％ |
| Embodiment 4 | Phosphorus trichloride | ??20℃ | 52.5g | ??73％ |
| Embodiment 5 | Phosphorus oxychloride | ??20℃ | 54g | ??75％ |
As can be seen from Table 1, esterification temperature is too high on the one hand, and side reaction is easily taken place the adjacent sulfuryl chlorio phenylformic acid of nitro, causes reaction yield to reduce, therefore 20 ℃ esterification temperature optimum.Acyl chlorinating agent difference on the other hand, reaction effect are also different, adopt the yield of sulfur oxychloride the highest.
(embodiment 6～embodiment 9)
The preparation method of embodiment 6～embodiment 9 is substantially the same manner as Example 1, and difference is: organic solvent or temperature of reaction difference that step is adopted in 2. specifically see Table 2.
Table 2
| Organic solvent | Temperature of reaction | The weight of 2-methoxycarbonyl-5-nitrobenzene sulfonamide | Yield | |
| Embodiment 1 | Methylene dichloride | 0℃～5℃ | 50g | ??91％ |
| Embodiment 6 | Methylene dichloride | -10℃～0℃ | 48.5g | ??88％ |
| Embodiment 7 | Methylene dichloride | 5℃～15℃ | 46g | ??84％ |
| Embodiment 8 | Chloroform | 0℃～5℃ | 46.5g | ??85％ |
| Embodiment 9 | Tetracol phenixin | 0℃～5℃ | 47g | ??86％ |
As can be seen from Table 2, temperature of reaction is too high on the one hand, and reaction yield slightly reduces, therefore 0 ℃～5 ℃ temperature of reaction optimum.Organic solvent difference on the other hand, reaction effect are also different, adopt the yield of methylene dichloride the highest.
(embodiment 10～embodiment 12)
The preparation method of embodiment 12～embodiment 14 is substantially the same manner as Example 1, and difference is: organic solvent or catalyzer difference that step is adopted in 3. specifically see Table 3.
Table 3
| Organic solvent | Catalyzer | The weight of 2-methoxycarbonyl-5-aminobenzene sulfonamide | Yield | |
| Embodiment 1 | Dehydrated alcohol | ??10％Pd/C | 20g | ??91??％ |
| Embodiment 10 | Methyl alcohol | ??10％Pd/C | 19g | ??87??％ |
| Embodiment 11 | Virahol | ??10％Pd/C | 18.5g | ??85??％ |
| Embodiment 12 | Dehydrated alcohol | ??5％Pd/C | 18g | ??83??％ |
As can be seen from Table 3, the catalysis efficiency of 10%Pd/C is more better than 5%Pd/C on the one hand.Organic solvent difference on the other hand, yield are slightly different, adopt the yield of dehydrated alcohol the highest.
(embodiment 13～embodiment 17)
The preparation method of embodiment 13～embodiment 17 is substantially the same manner as Example 1, and difference is: acidic medium, diazotization temperature or iodinating agent difference that step is adopted in 4. specifically see Table 4.
Table 4
| Acidic medium | The diazotization temperature | Iodinating agent | The weight of 2-methoxycarbonyl-5-iodobenzene sulfamide | Yield | |
| Embodiment 1 | Hydrochloric acid | ??0℃～5℃ | Potassiumiodide | 87g | ??87％ |
| Embodiment 13 | Sulfuric acid | ??0℃～5℃ | Potassiumiodide | 80g | ??80％ |
| Embodiment 14 | Hydrochloric acid and acetic acid | ??0℃～5℃ | Potassiumiodide | 82g | ??82％ |
| Embodiment 15 | Hydrochloric acid | ??5℃～10℃ | Potassiumiodide | 84g | ??84％ |
| Embodiment 16 | Hydrochloric acid | ??10℃～15℃ | Potassiumiodide | 78g | ??78％ |
| Embodiment 17 | Hydrochloric acid | ??0℃～5℃ | Sodium iodide | 85g | ??85％ |
As can be seen from Table 4, adopt acetate and hydrochloride mixing acid and adopt hydrochloric acid as reaction medium, poor yields is few, and sulfuric acid is low slightly as medium, mainly is because the diazonium salt of this arylamine is comparatively stable.But adopt the operation of acetate and hydrochloride mixing acid cumbersome, solvent consumption is big, reclaims difficulty, and therefore, it is reaction medium the best that diazotization reaction adopts hydrochloric acid.The diazotization reaction temperature is too high, and diazonium salt may decompose, and also influences reaction yield, therefore 0 ℃～5 ℃ optimums.And adopting potassiumiodide or sodium iodide as iodinating agent, weak effect is few, but potassiumiodide is widely used more easily buying.
Claims (10)
1. the preparation method of 2-methoxycarbonyl-5-iodobenzene sulfamide is characterized in that having following steps:
1. will in organic solvent DMF, generate the benzoic acyl chloride reaction of the adjacent sulfuryl chlorio of nitro nitro o-sulfobenzoic acid and acyl chlorinating agent, and under 0 ℃～50 ℃ temperature, carry out esterification with methyl alcohol again and obtain 2-chlorosulfonyl-4-nitrobenzoic acid methyl esters; Described acyl chlorinating agent is sulfur oxychloride, phosphorus trichloride or phosphorus oxychloride;
2. 2-chlorosulfonyl-4-nitrobenzoic acid methyl esters that 1. step is obtained and ammonia react under-10 ℃～15 ℃ temperature in organic solvent and obtain 2-methoxycarbonyl-5-nitrobenzene sulfonamide; Described organic solvent is methylene dichloride, chloroform or tetracol phenixin;
3. the 2-methoxycarbonyl-5-nitrobenzene sulfonamide that 2. step is obtained under the Pd/C catalyzer with hydrogen in organic solvent under 15 ℃～25 ℃ temperature reaction obtain 2-methoxycarbonyl-5 aminobenzene sulfonamide; Described organic solvent is methyl alcohol, dehydrated alcohol or Virahol;
4. 2-methoxycarbonyl-5 aminobenzene sulfonamide that 3. step is obtained carries out diazotization reaction with sodium nitrite solution under 0 ℃～15 ℃ temperature in acidic medium, more resulting diazonium salt and iodinating agent are carried out iodide reaction under 50 ℃～80 ℃ temperature and obtain 2-methoxycarbonyl-5-iodobenzene sulfamide; Described acidic medium is the mixing acid of hydrochloric acid, sulfuric acid, acetic acid or acetic acid and hydrochloric acid; Described iodinating agent is potassiumiodide or sodium iodide.
2. according to the preparation method of claims 1 described 2-methoxycarbonyl-5-iodobenzene sulfamide, it is characterized in that: the acyl chlorinating agent of step described in 1. is sulfur oxychloride.
3. according to the preparation method of claims 1 described 2-methoxycarbonyl-5-iodobenzene sulfamide, it is characterized in that: the esterification reaction temperature of step described in 1. is 18 ℃～22 ℃.
4. according to the preparation method of claims 1 described 2-methoxycarbonyl-5-iodobenzene sulfamide, it is characterized in that: the organic solvent of step described in 2. is methylene dichloride.
5. according to the preparation method of claims 1 described 2-methoxycarbonyl-5-iodobenzene sulfamide, it is characterized in that: the temperature of reaction of step described in 2. is 0 ℃～5 ℃.
6. according to the preparation method of claims 1 described 2-methoxycarbonyl-5-iodobenzene sulfamide, it is characterized in that: the content of Pd is 9wt%～11wt% in the Pd/C catalyzer of step described in 3..
7. according to the preparation method of claims 1 described 2-methoxycarbonyl-5-iodobenzene sulfamide, it is characterized in that: the organic solvent of step described in 3. is dehydrated alcohol.
8. according to the preparation method of claims 1 described 2-methoxycarbonyl-5-iodobenzene sulfamide, it is characterized in that: the acidic medium of step described in 4. is hydrochloric acid.
9. according to the preparation method of claims 1 described 2-methoxycarbonyl-5-iodobenzene sulfamide, it is characterized in that: the diazotization temperature of step described in 4. is 0 ℃～5 ℃.
10. according to the preparation method of claims 1 described 2-methoxycarbonyl-5-iodobenzene sulfamide, it is characterized in that: the iodinating agent of step described in 4. is potassiumiodide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010300776A CN101768093A (en) | 2010-01-27 | 2010-01-27 | Preparation method of 2-carbomethoxy-5-iodobenzene sulfamide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010300776A CN101768093A (en) | 2010-01-27 | 2010-01-27 | Preparation method of 2-carbomethoxy-5-iodobenzene sulfamide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101768093A true CN101768093A (en) | 2010-07-07 |
Family
ID=42501216
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201010300776A Pending CN101768093A (en) | 2010-01-27 | 2010-01-27 | Preparation method of 2-carbomethoxy-5-iodobenzene sulfamide |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101768093A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105622358A (en) * | 2016-02-02 | 2016-06-01 | 天津城建大学 | 1,3-dichloro-5-ethoxy-2-iodobenzene preparation method |
| WO2017071410A1 (en) * | 2015-10-29 | 2017-05-04 | Rotam Agrochem International Company Limited | Process for preparing novel crystalline form of iodosulfuron-methyl-sodium and use |
-
2010
- 2010-01-27 CN CN201010300776A patent/CN101768093A/en active Pending
Non-Patent Citations (1)
| Title |
|---|
| 薛红艳等: "《有机化学简明教程（第2版）》", 28 February 2006, 化学工业出版社 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017071410A1 (en) * | 2015-10-29 | 2017-05-04 | Rotam Agrochem International Company Limited | Process for preparing novel crystalline form of iodosulfuron-methyl-sodium and use |
| GB2555344A (en) * | 2015-10-29 | 2018-04-25 | Jiangsu Rotam Chemistry Co Ltd | Process for preparing novel crystalline form of iodosulfuron-methyl-sodium and use |
| GB2555344B (en) * | 2015-10-29 | 2020-07-15 | Jiangsu Rotam Chemistry Co Ltd | A process for preparing a novel crystalline form of iodosulfuron-methyl-sodium and use the same |
| CN105622358A (en) * | 2016-02-02 | 2016-06-01 | 天津城建大学 | 1,3-dichloro-5-ethoxy-2-iodobenzene preparation method |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101572187B (en) | Preparation method of electrolyte of medium-high voltage aluminum electrolytic capacitor | |
| CN104045637B (en) | A kind of preparation method of Eliquis | |
| KR101771997B1 (en) | Method for producing a methylene disulfonate compound | |
| CN104496917B (en) | A kind of synthetic method of Favipiravir | |
| US20100267949A1 (en) | Method of Synthesizing 6,7-Substituted 4-Anilino Quinazoline | |
| CN103965201A (en) | Method for synthesizing intermediate 4-amino-3-(4-phenoxy-phenyl)-1H-pyrazolo[3,4-d]pyrimidine of Ibrutinib | |
| ES2535702T3 (en) | Process for the preparation of an alkyl methanesulfonate solution | |
| CN101830866B (en) | Method for preparing bentazone | |
| CN103282355A (en) | Method for producing alpha -mino-gamma-butyrolactone | |
| CN101768093A (en) | Preparation method of 2-carbomethoxy-5-iodobenzene sulfamide | |
| CN103058872A (en) | Processes of phase-transfer catalyzed synthesis of salicylic acid benzyl esters | |
| CN101735167B (en) | Preparation method of 6-nitrosaccharin | |
| CN116836077A (en) | Preparation method of N- (8- [ 2-hydroxybenzoyl ] -amino) sodium octoate | |
| BR112014015512B1 (en) | process for the preparation of compounds including nitrile functions | |
| CN108383718A (en) | The preparation method of one kind 2,4,5- trifluoro benzene acetic acids | |
| CN101239932B (en) | Preparation of 3,5-di(2-cyano-isopropyl)-toluene | |
| CN103193666B (en) | The preparation method of 2-amino-3-chloro benzoic ether | |
| CN103073606B (en) | Synthetic and the preparation method of 5 '-S-(4,4 '-dimethoxytrityl)-2 '-deoxyinosine | |
| Melnyk et al. | STUDY OF THE PENTYL ACETATE AND ETHANOLAMINE CATALYTIC AND NON-CATALYTIC INTERACTION. | |
| JP5432605B2 (en) | Method for producing aromatic carboxylic dianhydride having ester group | |
| US9006486B2 (en) | Synthesis of N1,N3-bis(2,3-dihydroxypropyl)-5-nitroisophthalamide | |
| CN103232344B (en) | A kind of method of synthesizing S-2-methyl chloropropionate | |
| US20060167292A1 (en) | Process for preparing enantiomerically enriched 2-fluorocarboxylic esters | |
| CN101139311A (en) | Method for mass preparation of formamide phenol compound | |
| CN105073722A (en) | Process for producing glycidyl (meth)acrylate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20100707 |