JPH115765A - Production of 3-acetoxy-2-methylbenzoic acid - Google Patents
Production of 3-acetoxy-2-methylbenzoic acidInfo
- Publication number
- JPH115765A JPH115765A JP9158320A JP15832097A JPH115765A JP H115765 A JPH115765 A JP H115765A JP 9158320 A JP9158320 A JP 9158320A JP 15832097 A JP15832097 A JP 15832097A JP H115765 A JPH115765 A JP H115765A
- Authority
- JP
- Japan
- Prior art keywords
- mol
- reaction
- acid
- amba
- yield
- 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
- LHVJUPHCLWIPLZ-UHFFFAOYSA-N 3-acetyloxy-2-methylbenzoic acid Chemical compound CC(=O)OC1=CC=CC(C(O)=O)=C1C LHVJUPHCLWIPLZ-UHFFFAOYSA-N 0.000 title claims abstract description 33
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims abstract description 48
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 34
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 17
- RIERSGULWXEJKL-UHFFFAOYSA-N 3-hydroxy-2-methylbenzoic acid Chemical compound CC1=C(O)C=CC=C1C(O)=O RIERSGULWXEJKL-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000003054 catalyst Substances 0.000 claims abstract description 6
- 230000000397 acetylating effect Effects 0.000 claims abstract description 5
- 239000012442 inert solvent Substances 0.000 claims abstract description 5
- 238000000034 method Methods 0.000 claims description 10
- 150000008065 acid anhydrides Chemical class 0.000 abstract description 18
- 239000006227 byproduct Substances 0.000 abstract description 12
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- 150000001875 compounds Chemical class 0.000 abstract description 2
- 239000002253 acid Substances 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 40
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000002994 raw material Substances 0.000 description 17
- 230000000052 comparative effect Effects 0.000 description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 230000035484 reaction time Effects 0.000 description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 238000006640 acetylation reaction Methods 0.000 description 6
- ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluic acid Chemical compound CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical class N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 2
- HCJMNOSIAGSZBM-UHFFFAOYSA-N 6-methylsalicylic acid Chemical compound CC1=CC=CC(O)=C1C(O)=O HCJMNOSIAGSZBM-UHFFFAOYSA-N 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 239000012345 acetylating agent Substances 0.000 description 2
- 230000021736 acetylation Effects 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- SMUQFGGVLNAIOZ-UHFFFAOYSA-N quinaldine Chemical compound C1=CC=CC2=NC(C)=CC=C21 SMUQFGGVLNAIOZ-UHFFFAOYSA-N 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- YPQAFWHSMWWPLX-UHFFFAOYSA-N 1975-50-4 Chemical compound CC1=C(C(O)=O)C=CC=C1[N+]([O-])=O YPQAFWHSMWWPLX-UHFFFAOYSA-N 0.000 description 1
- PBAFFKDGFHOMBF-UHFFFAOYSA-N 2-(acetyloxymethyl)benzoic acid Chemical compound CC(=O)OCC1=CC=CC=C1C(O)=O PBAFFKDGFHOMBF-UHFFFAOYSA-N 0.000 description 1
- MGMNPSAERQZUIM-UHFFFAOYSA-N 2-(hydroxymethyl)benzoic acid Chemical compound OCC1=CC=CC=C1C(O)=O MGMNPSAERQZUIM-UHFFFAOYSA-N 0.000 description 1
- AWFYPPSBLUWMFQ-UHFFFAOYSA-N 2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]-1-(1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NN=C(O1)CC(=O)N1CC2=C(CC1)NN=C2 AWFYPPSBLUWMFQ-UHFFFAOYSA-N 0.000 description 1
- TYAIGNOSODVIHJ-UHFFFAOYSA-N 2-acetyloxy-4-methylbenzoic acid Chemical compound CC(=O)OC1=CC(C)=CC=C1C(O)=O TYAIGNOSODVIHJ-UHFFFAOYSA-N 0.000 description 1
- OSRBGUCAZNZFMF-UHFFFAOYSA-N 2-acetyloxy-6-methylbenzoic acid Chemical compound CC(=O)OC1=CC=CC(C)=C1C(O)=O OSRBGUCAZNZFMF-UHFFFAOYSA-N 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- MTJGVAJYTOXFJH-UHFFFAOYSA-N 3-aminonaphthalene-1,5-disulfonic acid Chemical compound C1=CC=C(S(O)(=O)=O)C2=CC(N)=CC(S(O)(=O)=O)=C21 MTJGVAJYTOXFJH-UHFFFAOYSA-N 0.000 description 1
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
- NJESAXZANHETJV-UHFFFAOYSA-N 4-methylsalicylic acid Chemical compound CC1=CC=C(C(O)=O)C(O)=C1 NJESAXZANHETJV-UHFFFAOYSA-N 0.000 description 1
- XRBMKGUDDJPAMH-UHFFFAOYSA-N CRESOPYRINE Chemical compound CC(=O)OC1=C(C)C=CC=C1C(O)=O XRBMKGUDDJPAMH-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- -1 chlorobenzene Chemical class 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000004030 hiv protease inhibitor Substances 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、３−アセトキシ−
２−メチル安息香酸の製造方法に関する。更に詳しく
は、３−ヒドロキシ−２−メチル安息香酸を原料とし、
副反応を抑制して、３−アセトキシ−２−メチル安息香
酸を収率よく製造する方法に関する。The present invention relates to 3-acetoxy-
The present invention relates to a method for producing 2-methylbenzoic acid. More specifically, using 3-hydroxy-2-methylbenzoic acid as a raw material,
The present invention relates to a method for producing 3-acetoxy-2-methylbenzoic acid with good yield by suppressing side reactions.
【０００２】[0002]
【従来の技術】３−アセトキシ−２−メチル安息香酸
（以下ＡＭＢＡという）は、米国特許５４８４９２６に
記載されているように、例えばＨＩＶプロテアーゼ阻害
剤等の医薬品の中間体として有用な化合物である。ＡＭ
ＢＡの製造法として、３−ヒドロキシ−２−メチル安息
香酸（以下ＨＭＢＡという）を原料とし、硫酸を触媒と
して、無水酢酸でアセチル化する方法が知られている
（米国特許５４８４９２６実施例８１）。この方法は収
率が３１％と低く、ＡＭＢＡを安価に製造することは困
難である。2. Description of the Related Art As described in U.S. Pat. No. 5,484,926, 3-acetoxy-2-methylbenzoic acid (AMBA) is a compound useful as an intermediate of pharmaceuticals such as HIV protease inhibitors. AM
As a method for producing BA, there is known a method in which 3-hydroxy-2-methylbenzoic acid (hereinafter, referred to as HMBA) is used as a raw material, and acetylation is performed with acetic anhydride using sulfuric acid as a catalyst (US Pat. No. 5,484,926, Example 81). This method has a low yield of 31%, and it is difficult to produce AMBA at low cost.
【０００３】一方、ＡＭＢＡの異性体についても、対応
するヒドロキシメチル安息香酸を種々のアセチル化剤で
アセチル化する事により、アセトキシメチル安息香酸が
得られることが知られている。例えば、２−アセトキシ
−３−メチル安息香酸は対応する２−ヒドロキシ−３−
メチル安息香酸を、 ベンゼン溶媒中で塩化アセチルで処理することによっ
て製造する方法（Ａｃｔａ Ｃｒｙｓｔ．，Ｂ３７，１
６２３（１９８１））、 無水酢酸と濃硫酸で処理することにより製造する方法
（収率７５％、Ｔｅｔｒａｈｅｄｒｏｎ，３４，１２２
１（１９５３））等がある。On the other hand, it is known that acetoxymethyl benzoic acid can be obtained by acetylating the corresponding hydroxymethyl benzoic acid with various acetylating agents also for the isomer of AMBA. For example, 2-acetoxy-3-methylbenzoic acid has the corresponding 2-hydroxy-3-
A method for producing methylbenzoic acid by treating it with acetyl chloride in a benzene solvent (Acta Cryst., B37, 1).
623 (1981)), a method of producing by treating with acetic anhydride and concentrated sulfuric acid (75% yield, Tetrahedron, 34, 122).
1 (1953)).
【０００４】又、２−アセトキシ−６−メチル安息香酸
は、対応する２−ヒドロキシ−６−メチル安息香酸を、 無水酢酸とピリジンで処理する方法（薬学雑誌，９
１，２５７（１９７１）・・・収率７４％）、 無水酢酸と濃硫酸で処理する方法（Ｊ．Ｏｒｇ．Ｃｈ
ｅｍ．，１８，１６７９（１９５３）・・・収率８１
％）。 が知られている。[0004] 2-acetoxy-6-methylbenzoic acid is prepared by treating the corresponding 2-hydroxy-6-methylbenzoic acid with acetic anhydride and pyridine (Pharmaceutical Magazine, 9).
1,257 (1971): yield of 74%), a method of treating with acetic anhydride and concentrated sulfuric acid (J. Org. Ch.
em. , 18, 1679 (1953) ... yield 81
%). It has been known.
【０００５】又、２−アセトキシ−４−メチル安息香酸
は、対応する２−ヒドロキシ−４−メチル安息香酸を、
無水酢酸とピリジンで処理することにより収率６１．８
％で得られる（Ｊｏｕｒｎａｌ ｏｆ Ｃｏｌｌｏｉｄ
ａｎｄ Ｉｎｔｅｒｆａｃｅ Ｓｃｉｅｎｃｅ，Ｖｏ
ｌ．８３，１４６（１９８１））。[0005] 2-acetoxy-4-methylbenzoic acid is the corresponding 2-hydroxy-4-methylbenzoic acid,
Yield 61.8 by treatment with acetic anhydride and pyridine.
% (Journal of Colloid)
and Interface Science, Vo
l. 83, 146 (1981)).
【０００６】上記の各方法のうち、無水酢酸とピリジン
で処理する方法では、比較的高収率でアセトキシ−２−
メチル安息香酸が得られているが、これらの方法を本発
明の目的とするＡＭＢＡを得るため、ＨＭＢＡを原料と
する反応に適用しても副反応が起こりやすく、目的物Ａ
ＭＢＡの収率は極めて低い。[0006] Among the above methods, the method of treating with acetic anhydride and pyridine has a relatively high yield in acetoxy-2-.
Although methyl benzoic acid is obtained, these methods are liable to cause side reactions even when applied to a reaction using HMBA as a raw material in order to obtain AMBA which is the object of the present invention.
The yield of MBA is very low.
【０００７】[0007]
【発明が解決しようとする課題】本発明者らは、ピリジ
ン触媒を用い、無水酢酸によりアセチル化する方法をＨ
ＭＢＡにそのまま適用できない原因について検討した。
その結果、アセトキシ−メチル安息香酸はその２分子が
脱水縮合した無水物を生成しやすいが、無水物の生成は
異性体の種類により異なり、特にカルボキシル基の近傍
の置換基の大きさ等により大きく影響を受け、ＡＭＢＡ
は他の異性体と異なり、アセチル化反応中に容易に酸無
水物を形成することが判明した。SUMMARY OF THE INVENTION The present inventors have proposed a method of acetylating with acetic anhydride using a pyridine catalyst.
The cause which cannot be directly applied to MBA was examined.
As a result, acetoxy-methylbenzoic acid easily produces an anhydride in which two molecules are dehydrated and condensed, but the formation of the anhydride differs depending on the type of isomer, and is particularly large due to the size of the substituent near the carboxyl group. Affected, AMBA
Was found to form acid anhydrides easily during the acetylation reaction, unlike the other isomers.
【０００８】従って、前記従来技術を単にＨＭＢＡに適
用したのでは、酸無水物の生成が顕著で、目的とするＡ
ＭＢＡを収率よく製造することは困難であり、他の異性
体の場合よりも反応条件を厳密にコントロールしなけれ
ばならないことを知った。そこで本発明者らは、この問
題点を解決すべく鋭意検討を重ねた結果、ＨＭＢＡに対
して特定量の無水酢酸を用いて、特定の温度範囲でアセ
チル化することにより、酸無水物の生成反応を抑制し、
ＡＭＢＡが収率よく得られることを見出し本発明に到達
した。[0008] Therefore, when the above-mentioned prior art is simply applied to HMBA, the formation of an acid anhydride is remarkable, and the desired A
It has been found that it is difficult to produce MBA in good yield, and that the reaction conditions must be more strictly controlled than in the case of other isomers. The present inventors have conducted intensive studies to solve this problem, and as a result, HMBA was acetylated using a specific amount of acetic anhydride in a specific temperature range to thereby form an acid anhydride. Suppress the reaction,
The present inventors have found that AMBA can be obtained in good yield, and have reached the present invention.
【０００９】[0009]
【課題を解決するための手段】即ち、本発明は３−ヒド
ロキシ−２−メチル安息香酸を、不活性溶媒中でピリジ
ン類を触媒とし、３−ヒドロキシ−２−メチル安息香酸
１モルに対して１．０〜１．５モルの無水酢酸により、
５０〜１００℃の温度でアセチル化することを特徴とす
る３−アセトキシ−２−メチル安息香酸の製造方法であ
る。That is, the present invention relates to 3-hydroxy-2-methylbenzoic acid, which is obtained by reacting 3-hydroxy-2-methylbenzoic acid with 1 mole of 3-hydroxy-2-methylbenzoic acid in an inert solvent using pyridine as a catalyst. With 1.0-1.5 moles of acetic anhydride,
A method for producing 3-acetoxy-2-methylbenzoic acid, which comprises acetylating at a temperature of 50 to 100 ° C.
【００１０】[0010]
【発明の実施の形態】本発明においては、出発原料とし
て使用するＨＭＢＡは、３−ニトロ−ο−トルイル酸の
還元−ジアゾ化・加水分解、７−アミノ−１，５−ナフ
タレンジスルホン酸のアルカリ分解等によって製造する
ことが出来る。ただし、本発明で用いるＨＭＢＡは、前
記の製造法で得られたものに限定されるものではなく、
何れの製造法によって得られたものであっても使用でき
る。BEST MODE FOR CARRYING OUT THE INVENTION In the present invention, HMBA used as a starting material is obtained by reducing-diazotizing / hydrolyzing 3-nitro-o-toluic acid, alkali-forming 7-amino-1,5-naphthalenedisulfonic acid. It can be manufactured by decomposition or the like. However, the HMBA used in the present invention is not limited to those obtained by the above-mentioned production method,
What was obtained by any manufacturing method can be used.
【００１１】本発明において使用する不活性溶媒とは、
反応に不活性な溶媒であれば何れも使用出来る。かかる
溶媒としては、ベンゼン、トルエン、キシレン等の芳香
族炭化水素、クロロベンゼン等のハロゲン化芳香族炭化
水素、酢酸エチル等の低級脂肪族カルボン酸エステル及
びこれらの混合物である。好ましくは、トルエン、酢酸
エチルである。The inert solvent used in the present invention is
Any solvent which is inert to the reaction can be used. Examples of the solvent include aromatic hydrocarbons such as benzene, toluene and xylene, halogenated aromatic hydrocarbons such as chlorobenzene, lower aliphatic carboxylic acid esters such as ethyl acetate, and mixtures thereof. Preferably, toluene and ethyl acetate are used.
【００１２】溶媒の使用量は、アセチル化反応終了後生
成したＡＭＢＡがハンドリング出来ればよく特に制限は
ないが、通常原料であるＨＭＢＡに対して１〜５０重量
倍使用する。The amount of the solvent used is not particularly limited as long as the AMBA produced after the acetylation reaction is completed, and is not particularly limited, but is usually used in an amount of 1 to 50 times by weight based on the raw material HMBA.
【００１３】本発明で触媒として使用するピリジン類の
使用量は、原料であるＨＭＢＡ１モルに対して、０．０
５〜０．５モル、好ましくは０．１〜０．３モルの範囲
である。使用量はこの範囲より多くとも反応成績に影響
しないが必要以上の使用は経済的でない。又、この範囲
より少ない場合は反応時間が長時間必要となり、好まし
くない。The amount of pyridine used as a catalyst in the present invention is 0.0 to 1 mol of HMBA as a raw material.
The range is 5 to 0.5 mol, preferably 0.1 to 0.3 mol. Use of more than this range does not affect the reaction results, but use beyond necessity is not economical. On the other hand, when the amount is less than this range, a long reaction time is required, which is not preferable.
【００１４】ピリジン類とは、ピリジン、ピコリン、ル
チジン等のアルキルピリジン、ｐ−ジメチルアミノピリ
ジン、及びキノリン、イソキノリン、キナルジン等のベ
ンゾピリジン類であり、好ましくはピリジンである。The pyridines are alkylpyridines such as pyridine, picoline and lutidine, p-dimethylaminopyridine, and benzopyridines such as quinoline, isoquinoline and quinaldine, and are preferably pyridine.
【００１５】本発明においては、アセチル化剤として使
用する無水酢酸の使用量が重要であり、原料であるＨＭ
ＢＡ１モルに対して１．０ 〜１．５モル、好ましくは
１．０〜１．３モルの範囲とする。使用量がこの範囲よ
り多いと酸無水物の生成が多くなり、ＡＭＢＡの選択性
が低下するため好ましくない。又、この範囲より少ない
場合は反応が完結せず目的物の収率が低下する。In the present invention, the amount of acetic anhydride used as an acetylating agent is important,
The range is 1.0 to 1.5 mol, preferably 1.0 to 1.3 mol, per 1 mol of BA. If the amount is more than this range, the production of acid anhydride increases, and the selectivity of AMBA decreases, which is not preferable. On the other hand, if it is less than this range, the reaction is not completed and the yield of the desired product is reduced.
【００１６】本発明においては反応温度もまた重要であ
り、５０℃〜１００℃、好ましくは６０℃〜９０℃とす
る。反応温度が上記範囲より高くなると酸無水物の生成
が多くなり、目的物の選択性が著しく低下するため好ま
しくない。又、この範囲より低い場合は反応時間が長時
間となり、工業的でない。In the present invention, the reaction temperature is also important, and is set to 50 ° C. to 100 ° C., preferably 60 ° C. to 90 ° C. If the reaction temperature is higher than the above range, the production of acid anhydride increases and the selectivity of the target product is remarkably reduced, which is not preferable. On the other hand, when it is lower than this range, the reaction time becomes long, and it is not industrial.
【００１７】反応時間は、一般的に０．５時間〜３．０
時間、好ましくは１時間である。この範囲より長時間で
も反応成績に影響しないが、工業的に不利である。又、
この範囲より短時間では反応が充分進行せず、収率が低
下する。The reaction time is generally 0.5 hours to 3.0.
Time, preferably one hour. A reaction time longer than this range does not affect the reaction results, but is industrially disadvantageous. or,
If the time is shorter than this range, the reaction does not proceed sufficiently, and the yield decreases.
【００１８】アセチル化反応終了後、アセチル化反応液
を冷却し固液分離すれば反応生成物としてＡＭＢＡが得
られる。これはさらに有機溶媒で洗浄すれば容易に純度
を向上させることも可能である。After completion of the acetylation reaction, the acetylation reaction solution is cooled and solid-liquid separated to obtain AMBA as a reaction product. This can be easily improved in purity by further washing with an organic solvent.
【００１９】[0019]
【実施例】以下、実施例で本発明を具体的に説明する
が、本発明はこれら実施例に限定されるものではない。
尚、生成物は液体クロマトグラフィーで分析した。EXAMPLES The present invention will be described below in more detail with reference to examples, but the present invention is not limited to these examples.
The product was analyzed by liquid chromatography.
【００２０】［実施例１］攪拌機及び還流冷却器、温度
計を備えた０．１Ｌガラス製反応器に原料ＨＭＢＡ（純
度７７．４％）４．２１ｇ及び不活性溶媒としてトルエ
ン１５ｍＬ（１３．５ｇ）、ピリジン０．４５ｇ、無水
酢酸２．４７ｇ（対ＨＭＢＡモル比１．１）を仕込み、
攪拌して温度を９０℃に昇温した。９０℃で１時間反応
した後、反応生成物を室温まで冷却し、吸引濾過して得
た粗結晶を少量のトルエンで洗浄したのち乾燥してＡＭ
ＢＡを得た。これを粗結晶を濾別した反応母液及びトル
エン洗浄液中に含まれるＡＭＢＡと合わせると、原料Ｈ
ＭＢＡ基準で転化率１００モル％、ＡＭＢＡ収率９７モ
ル％、酸無水物の副生は１モル％であった。結果を他の
実施例、比較例の結果とともに表１に示す。Example 1 4.21 g of raw material HMBA (purity: 77.4%) and 15 mL (13.5 g) of toluene as an inert solvent were placed in a 0.1 L glass reactor equipped with a stirrer, a reflux condenser and a thermometer. ), 0.45 g of pyridine and 2.47 g of acetic anhydride (molar ratio to HMBA 1.1).
With stirring, the temperature was raised to 90 ° C. After reacting at 90 ° C. for 1 hour, the reaction product was cooled to room temperature, and the crude crystals obtained by suction filtration were washed with a small amount of toluene, dried and dried.
BA was obtained. When this was combined with the AMBA contained in the reaction mother liquor from which the crude crystals were filtered off and the toluene washing solution, the raw material H
The conversion was 100 mol% based on MBA, the AMBA yield was 97 mol%, and the by-product of the acid anhydride was 1 mol%. The results are shown in Table 1 together with the results of other examples and comparative examples.
【００２１】［実施例２］実施例１において、反応温度
を６０℃とした以外は実施例１と同様に反応を行い、Ａ
ＭＢＡを得た。その結果、原料ＨＭＢＡ基準で転化率１
００モル％、ＡＭＢＡ収率９５モル％、酸無水物の副生
は０．５モル％であった。Example 2 A reaction was carried out in the same manner as in Example 1 except that the reaction temperature was changed to 60 ° C.
MBA was obtained. As a result, the conversion rate was 1 based on the raw material HMBA.
00 mol%, the AMBA yield was 95 mol%, and the by-product of the acid anhydride was 0.5 mol%.
【００２２】［実施例３］実施例１において反応溶媒を
酢酸エチルに変え、反応温度を６０℃とした以外は実施
例１と同様に反応を行い、ＡＭＢＡを得た。その結果、
原料ＨＭＢＡ基準で転化率１００モル％、ＡＭＢＡ収率
９４モル％、酸無水物の副生は０．５モル％であった。Example 3 The reaction was carried out in the same manner as in Example 1 except that the reaction solvent was changed to ethyl acetate, and the reaction temperature was changed to 60 ° C., to obtain AMBA. as a result,
The conversion was 100 mol%, the AMBA yield was 94 mol%, and the by-product of the acid anhydride was 0.5 mol% based on the raw material HMBA.
【００２３】［比較例１］原料ＨＭＢＡを２．０ｇ、ピ
リジン６．５ｇ、無水酢酸３．６ｇ（対ＨＭＢＡモル比
３．５）仕込み、２５℃で１２時間反応を行い、ＡＭＢ
Ａを得た。反応液を分析した結果、原料ＨＭＢＡ基準
で、転化率１００モル％、ＡＭＢＡ収率は従来技術の２
−ヒドロキシ−６−メチル安息香酸を反応した場合の反
応収率と同様、７４モル％の値を示したが、酸無水物の
副生は１５モル％であった。Comparative Example 1 A starting material HMBA (2.0 g), pyridine (6.5 g) and acetic anhydride (3.6 g, molar ratio to HMBA: 3.5) were charged and reacted at 25 ° C. for 12 hours to obtain an AMB.
A was obtained. As a result of analyzing the reaction solution, the conversion rate was 100 mol% and the AMBA yield was 2
As in the case of the reaction yield when -hydroxy-6-methylbenzoic acid was reacted, the value was 74 mol%, but the by-product of the acid anhydride was 15 mol%.
【００２４】［比較例２］５０ｍｌの反応容器に原料Ｈ
ＭＢＡを２．０ｇ、ピリジン０．２９ｇ、無水酢酸４．
３ｇ（対ＨＭＢＡモル比４．１）を仕込み、１３０℃で
１時間反応を行った。反応液を分析した結果、原料ＨＭ
ＢＡ基準で、転化率１００モル％、ＡＭＢＡ収率７５モ
ル％であったが、酸無水物の副生は１５モル％であっ
た。Comparative Example 2 Raw material H was placed in a 50 ml reaction vessel.
3. 2.0 g of MBA, 0.29 g of pyridine, acetic anhydride
3 g (mol ratio to HMBA 4.1) was charged and reacted at 130 ° C. for 1 hour. As a result of analyzing the reaction solution, the raw material HM
The conversion was 100 mol% and the AMBA yield was 75 mol% based on BA, but the by-product of the acid anhydride was 15 mol%.
【００２５】［比較例３］実施例１において、ピリジン
を仕込まず、反応時間を７時間とした以外は実施例１と
同様に反応を行った。その結果、ＡＭＢＡの収率は、原
料ＨＭＢＡ基準で転化率８５モル％、ＡＭＢＡ収率８０
モル％、酸無水物の副生は４モル％であった。Comparative Example 3 A reaction was carried out in the same manner as in Example 1 except that pyridine was not charged and the reaction time was changed to 7 hours. As a result, the yield of AMBA was 85 mol% based on the raw material HMBA and the AMBA yield was 80 mol%.
Mol%, and the by-product of the acid anhydride was 4 mol%.
【００２６】［比較例４］実施例１において、ピリジン
を仕込まず、溶媒を酢酸に変え、反応時間を７時間とし
た以外は実施例１と同様に反応を行った。その結果、原
料ＨＭＢＡ基準で転化率８４モル％、ＡＭＢＡ収率７９
モル％、酸無水物の副生は５モル％であった。Comparative Example 4 A reaction was carried out in the same manner as in Example 1 except that pyridine was not used, the solvent was changed to acetic acid, and the reaction time was changed to 7 hours. As a result, the conversion was 84 mol% and the AMBA yield was 79 based on the raw material HMBA.
Mol%, and the by-product of the acid anhydride was 5 mol%.
【００２７】［比較例５］比較例４において反応温度を
１２５℃とし、反応時間を３．５時間とした以外は比較
例４と同様に反応を行った。その結果、原料ＨＭＢＡ基
準で転化率１００モル％、ＡＭＢＡ収率８９モル％であ
ったが、酸無水物の副生は１０モル％であった。Comparative Example 5 A reaction was carried out in the same manner as in Comparative Example 4, except that the reaction temperature was 125 ° C. and the reaction time was 3.5 hours. As a result, the conversion was 100 mol% and the AMBA yield was 89 mol% based on the raw material HMBA, but the by-product of the acid anhydride was 10 mol%.
【００２８】［比較例６］実施例１と同様の反応器に純
度９９．９％のＨＭＢＡ１０ｇ及び塩化アセチル５．２
ｇ、ピリジン５．８ｇ、ジイソプロピルエーテル３０ｍ
ｌ（２１．７ｇ）を仕込み、反応温度２２℃で６．５時
間、実施例１と同様に反応した。 その結果、原料ＨＭ
ＢＡ基準で転化率８９モル％、ＡＭＢＡ収率４０モル
％、酸無水物の副生は３６モル％であった。Comparative Example 6 10 g of HMBA having a purity of 99.9% and 5.2 of acetyl chloride were placed in the same reactor as in Example 1.
g, pyridine 5.8 g, diisopropyl ether 30 m
1 (21.7 g), and reacted at a reaction temperature of 22 ° C. for 6.5 hours in the same manner as in Example 1. As a result, the raw material HM
The conversion was 89 mol% based on BA, the AMBA yield was 40 mol%, and the by-product of the acid anhydride was 36 mol%.
【００２９】［比較例７］ピリジンを使用せず、溶媒を
トルエンに変え、反応温度８７℃、反応時間７時間とし
た以外は比較例６と同様に反応を行った。その結果、酸
無水物の副生は１モル％であったが、原料ＨＭＢＡ基準
で転化率４３モル％、ＡＭＢＡ収率３７モル％であっ
た。Comparative Example 7 A reaction was carried out in the same manner as in Comparative Example 6, except that pyridine was not used, the solvent was changed to toluene, and the reaction temperature was 87 ° C. and the reaction time was 7 hours. As a result, the by-product of the acid anhydride was 1 mol%, but the conversion was 43 mol% and the AMBA yield was 37 mol% based on the raw material HMBA.
【００３０】［比較例８］実施例１において、反応温度
を１１０℃とした以外は実施例１と同様に反応を行い、
ＡＭＢＡを得た。その結果、原料ＨＭＢＡ基準で転化率
１００モル％、ＡＭＢＡ収率８８モル％であったが酸無
水物の副生は８モル％であった。Comparative Example 8 A reaction was carried out in the same manner as in Example 1 except that the reaction temperature was changed to 110 ° C.
AMBA was obtained. As a result, the conversion was 100 mol% based on the raw material HMBA and the AMBA yield was 88 mol%, but the by-product of the acid anhydride was 8 mol%.
【００３１】[0031]
【表１】 [Table 1]
【００３２】[0032]
【発明の効果】本発明方法は、ＨＭＢＡに対する無水酢
酸の添加量及び反応温度を特定の範囲にコントロールし
てアセチル化することにより、酸無水物の生成反応を抑
制し、ＡＭＢＡが収率よく得られ、ＡＭＢＡの工業的製
造法として有用である。According to the method of the present invention, the amount of acetic anhydride added to HMBA and the reaction temperature are controlled within specific ranges to effect acetylation, thereby suppressing the reaction of the formation of acid anhydride and obtaining AMBA in good yield. It is useful as an industrial method for producing AMBA.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 横田 圭一 茨城県鹿嶋市大字光３番地 住金化工株式 会社開発研究所内 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Keiichi Yokota, Inventor Keiichi Yokota 3, Oaza Hikari, Kashima City, Ibaraki Pref.
Claims (1)
を、不活性溶媒中でピリジン類を触媒とし、３−ヒドロ
キシ−２−メチル安息香酸１モルに対して１．０〜１．
５モルの無水酢酸により、５０〜１００℃の温度でアセ
チル化することを特徴とする３−アセトキシ−２−メチ
ル安息香酸の製造方法。1. A method according to claim 1, wherein 3-hydroxy-2-methylbenzoic acid is used in an inert solvent with pyridine as a catalyst, and 1.0 to 1.
A method for producing 3-acetoxy-2-methylbenzoic acid, which comprises acetylating with 5 mol of acetic anhydride at a temperature of 50 to 100 ° C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9158320A JPH115765A (en) | 1997-06-16 | 1997-06-16 | Production of 3-acetoxy-2-methylbenzoic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9158320A JPH115765A (en) | 1997-06-16 | 1997-06-16 | Production of 3-acetoxy-2-methylbenzoic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH115765A true JPH115765A (en) | 1999-01-12 |
Family
ID=15669068
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9158320A Pending JPH115765A (en) | 1997-06-16 | 1997-06-16 | Production of 3-acetoxy-2-methylbenzoic acid |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH115765A (en) |
-
1997
- 1997-06-16 JP JP9158320A patent/JPH115765A/en active Pending
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