JPH0249304B2 - - Google Patents
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- Publication number
- JPH0249304B2 JPH0249304B2 JP57156335A JP15633582A JPH0249304B2 JP H0249304 B2 JPH0249304 B2 JP H0249304B2 JP 57156335 A JP57156335 A JP 57156335A JP 15633582 A JP15633582 A JP 15633582A JP H0249304 B2 JPH0249304 B2 JP H0249304B2
- Authority
- JP
- Japan
- Prior art keywords
- reaction
- acid
- trichloromethylpyridine
- melting point
- hours
- 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.)
- Expired - Lifetime
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- 238000000034 method Methods 0.000 claims description 12
- -1 trichloromethylpyridine compound Chemical class 0.000 claims description 8
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims 1
- 229910052782 aluminium Inorganic materials 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 20
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 19
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 16
- 238000002844 melting Methods 0.000 description 12
- 230000008018 melting Effects 0.000 description 12
- 239000007795 chemical reaction product Substances 0.000 description 8
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
- 230000035484 reaction time Effects 0.000 description 8
- 238000006460 hydrolysis reaction Methods 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 230000007062 hydrolysis Effects 0.000 description 6
- 239000005457 ice water Substances 0.000 description 6
- VLJIVLGVKMTBOD-UHFFFAOYSA-N 2-chloro-5-(trichloromethyl)pyridine Chemical compound ClC1=CC=C(C(Cl)(Cl)Cl)C=N1 VLJIVLGVKMTBOD-UHFFFAOYSA-N 0.000 description 4
- IBRSSZOHCGUTHI-UHFFFAOYSA-N 2-chloropyridine-3-carboxylic acid Chemical class OC(=O)C1=CC=CN=C1Cl IBRSSZOHCGUTHI-UHFFFAOYSA-N 0.000 description 4
- 238000005660 chlorination reaction Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- RELMFMZEBKVZJC-UHFFFAOYSA-N 1,2,3-trichlorobenzene Chemical compound ClC1=CC=CC(Cl)=C1Cl RELMFMZEBKVZJC-UHFFFAOYSA-N 0.000 description 2
- RXATZPCCMYMPME-UHFFFAOYSA-N 2-chloro-3-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=CN=C1Cl RXATZPCCMYMPME-UHFFFAOYSA-N 0.000 description 2
- JFZJMSDDOOAOIV-UHFFFAOYSA-N 2-chloro-5-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=C(Cl)N=C1 JFZJMSDDOOAOIV-UHFFFAOYSA-N 0.000 description 2
- RXTRRIFWCJEMEL-UHFFFAOYSA-N 2-chloropyridine-3-carbonyl chloride Chemical compound ClC(=O)C1=CC=CN=C1Cl RXTRRIFWCJEMEL-UHFFFAOYSA-N 0.000 description 2
- UAWMVMPAYRWUFX-UHFFFAOYSA-N 6-Chloronicotinic acid Chemical compound OC(=O)C1=CC=C(Cl)N=C1 UAWMVMPAYRWUFX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- UGCSPKPEHQEOSR-UHFFFAOYSA-N 1,1,2,2-tetrachloro-1,2-difluoroethane Chemical compound FC(Cl)(Cl)C(F)(Cl)Cl UGCSPKPEHQEOSR-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
- WOOVSQCALYYUDO-UHFFFAOYSA-N 1-oxidopyridin-1-ium-3-carbonitrile Chemical compound [O-][N+]1=CC=CC(C#N)=C1 WOOVSQCALYYUDO-UHFFFAOYSA-N 0.000 description 1
- ULRPBTXNKBYTSK-UHFFFAOYSA-N 2,3,6-trichloro-5-(trichloromethyl)pyridine Chemical compound ClC1=CC(C(Cl)(Cl)Cl)=C(Cl)N=C1Cl ULRPBTXNKBYTSK-UHFFFAOYSA-N 0.000 description 1
- ZJNBCPFIEDYDFH-UHFFFAOYSA-N 2,3,6-trichloro-5-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC(Cl)=C(Cl)N=C1Cl ZJNBCPFIEDYDFH-UHFFFAOYSA-N 0.000 description 1
- ABNQGNFVSFKJGI-UHFFFAOYSA-N 2,3-dichloro-5-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CN=C(Cl)C(Cl)=C1 ABNQGNFVSFKJGI-UHFFFAOYSA-N 0.000 description 1
- XMJRZCYSCMZVJQ-UHFFFAOYSA-N 2,5,6-trichloropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC(Cl)=C(Cl)N=C1Cl XMJRZCYSCMZVJQ-UHFFFAOYSA-N 0.000 description 1
- LWYLTZLBKBQGNL-UHFFFAOYSA-N 2,5-dichloro-3-(trichloromethyl)pyridine Chemical compound ClC1=CN=C(Cl)C(C(Cl)(Cl)Cl)=C1 LWYLTZLBKBQGNL-UHFFFAOYSA-N 0.000 description 1
- CZVBTOGZRGRJSC-UHFFFAOYSA-N 2,5-dichloro-3-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC(Cl)=CN=C1Cl CZVBTOGZRGRJSC-UHFFFAOYSA-N 0.000 description 1
- SXQSMLIMBNMUNB-UHFFFAOYSA-N 2,5-dichloropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC(Cl)=CN=C1Cl SXQSMLIMBNMUNB-UHFFFAOYSA-N 0.000 description 1
- XLZHJPALXIYDGU-UHFFFAOYSA-N 2,6-dichloro-3-(trichloromethyl)pyridine Chemical compound ClC1=CC=C(C(Cl)(Cl)Cl)C(Cl)=N1 XLZHJPALXIYDGU-UHFFFAOYSA-N 0.000 description 1
- UPWAAFFFSGQECJ-UHFFFAOYSA-N 2,6-dichloro-3-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=C(Cl)N=C1Cl UPWAAFFFSGQECJ-UHFFFAOYSA-N 0.000 description 1
- AJPKQSSFYHPYMH-UHFFFAOYSA-N 2,6-dichloropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=C(Cl)N=C1Cl AJPKQSSFYHPYMH-UHFFFAOYSA-N 0.000 description 1
- UEYQJQVBUVAELZ-UHFFFAOYSA-N 2-Hydroxynicotinic acid Chemical compound OC(=O)C1=CC=CN=C1O UEYQJQVBUVAELZ-UHFFFAOYSA-N 0.000 description 1
- TZKVGCQBQQFWOV-UHFFFAOYSA-N 2-chloro-3-(trichloromethyl)pyridine Chemical compound ClC1=NC=CC=C1C(Cl)(Cl)Cl TZKVGCQBQQFWOV-UHFFFAOYSA-N 0.000 description 1
- JAUPUQRPBNDMDT-UHFFFAOYSA-N 2-chloropyridine-3-carbonitrile Chemical compound ClC1=NC=CC=C1C#N JAUPUQRPBNDMDT-UHFFFAOYSA-N 0.000 description 1
- GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 description 1
- RNRLTTNKVLFZJS-UHFFFAOYSA-N 5,6-dichloropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=C(Cl)C(Cl)=C1 RNRLTTNKVLFZJS-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229940117389 dichlorobenzene Drugs 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 125000006575 electron-withdrawing group Chemical group 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- FJCFFCXMEXZEIM-UHFFFAOYSA-N oxiniacic acid Chemical compound OC(=O)C1=CC=C[N+]([O-])=C1 FJCFFCXMEXZEIM-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Description
本発明は、クロロ ニコチン酸系化合物（以下
CNAと略称）の製造方法に関する。
従来、CNAの製造方法としては、種々のもの
が提案されている。例えば、２−クロロ ニコチ
ン酸の製造方法として、
(1) ニコチン酸Ｎ−オキシドとオキシ塩化リン及
びトリエチルアミンとを反応させ、反応混合物
から２−クロロ ニコチン酸クロリドを留出さ
せ、この留出物を加水分解する方法（特開昭52
−122377号）
(2) ３−シアノピリジンＮ−オキシドとオキシ塩
化リンとを反応させて２−クロロ−３−シアノ
ピリジンを生成、次いでこれを加水分解する方
法（特開昭56−169672号）などが提案されてい
る。
しかしながら、これらの方法は種々の欠点を有
している。すなわち、(1)の方法は塩素化剤として
刺激性のあるオキシ塩化リンを用いる必要がある
こと、塩素化の際、異性体が生成すること、かつ
２−クロロ ニコチン酸クロリドが不安定な化合
物であるため、加水分解の前に精製を必要とし、
更にその取扱いに慎重を要することなどの欠点を
有する。また(2)の方法は３−シアノピリジンが高
価であり、オキシ塩化リンも取扱い難いこと、塩
素化の際、異性体が生成すること、並びにアルカ
リによる加水分解後、酸を添加して目的物を分離
するという煩雑な操作を必要とすることなどの欠
点を有する。
本発明者達はCNAの製造方法について検討し
たところ、トリフルオロメチルピリジン系化合物
（以下TFPと略称）と塩化アルミニウムとを反応
させるとTFP中のトリフルオロメチル基がトリ
クロロメチル基に変り、対応するトリクロロメチ
ルピリジン系化合物（以下TCPと略称）が生成、
このTCPを硫酸の存在下に加水分解すると目的
のCNAが生成するという知見を得、本発明を完
成した。
すなわち、本発明は〔〕
一般式（）
（式中X1、X2及びX3は水素原子或は塩素原子で
あり、X1或はX3の少くともいずれか一方は塩素
原子である。）で表わされるトリフルオロメチル
ピリジン系化合物と塩化アルミニウムとを反応さ
せて、一般式（）
（式中X1、X2及びX3は前述の通りである）で表
わされるトリクロロメチルピリジン系化合物を
得、次いで前記トリクロロメチルピリジン系化合
物を硫酸の存在下に加水分解して、一般式（）
（式中X1、X2及びX3は前述の通りである）で表
わされるクロロ ニコチン酸系化合物を製造する
ことを特徴とする、クロロ ニコチン酸系化合物
の製造方法である。
本発明方法によれば下記の利点が得られる。
(1) 原料物質である前記一般式（）で表わされ
るTFPは、すでに工業的に製造されているも
のであつて、経済的に入手できるものである。
(2) 本方法では余り副反応が発生せず、また中間
物のTCPも安定しているため、高収率でかつ
高純度で目的物が得られる。
(3) 反応が簡便で、かつ反応時間も短かい。
塩素化工程；
本発明方法によれば、TFPと塩化アルミニウ
ムとを溶媒を存在させずに反応させることができ
るが、工業的には溶媒中で反応させる方が望まし
い。本発明方法に用いられるTFPとしては、２
−クロロ−３−トリフルオロメチルピリジン（融
点39.1℃）、６−クロロ−３−トリフルオロメチ
ルピリジン（融点30.2℃）、２，５ジクロロ−３
−トリフルオロメチルピリジン（沸点119〜121
℃／90mmHg）、２，６−ジクロロ−３−トリフル
オロメチルピリジン（融点6.0〜6.5℃）、５，６
−ジクロロ−３−トリフルオロメチルピリジン
（融点９〜10℃）及び２，５，６−トリクロロ−
３−トリフルオロメチルピリジン（融点48〜50
℃）が挙げられ、溶媒としては、例えば塩化メチ
レン、クロロホルム、Ｆ−112（CFCl2・CFCl2）、
エチレンクロライドなどのハロゲン化炭化水素、
モノクロロベンゼン、ジクロロベンゼン、トリク
ロロベンゼン、ニトロベンゼンなどの電子吸引性
基を有する芳香族炭化水素などが挙げられる。塩
化アルミニウムの使用量は、TFP1モルに対して
普通0.5〜５モル、望ましくは１〜1.5モルであ
り、塩化アルミニウムを一括添加してもよいが、
分括して数回に分けて添加する方が均一な反応を
進める上で有利である。反応温度は一概に規定で
きないが通常30〜180℃、望ましくは50〜130℃で
ある。反応時間は一般的に0.5〜10時間である。
上記反応で得られた反応物を冷却後氷水中に投
入した後、通常の溶媒抽出、蒸留によつてTCP
を得ることができるが、上記反応物を水中に投入
し、分液して塩化アルミニウムを除去した後、次
の反応に供するとより工業的に有利である。
TCPとしては、２−クロロ−３−トリクロロメ
チルピリジン、６−クロロ−３−トリクロロメチ
ルピリジン、２，５−ジクロロ−３−トリクロロ
メチルピリジン、２，６−ジクロロ−３−トリク
ロロメチルピリジン、５，６−ジクロロ−３−ト
リクロロメチルピリジン及び２，５，６−トリク
ロロ−３−トリクロロメチルピリジンが挙げられ
る。
加水分解工程；
次いで、TCPを硫酸の存在下に加水分解して、
CNAを得る。CNAとしては、２−クロロ ニコ
チン酸（融点196〜198℃）、６−クロロ ニコチ
ン酸（融点199〜201℃）、２，５−ジクロロニコ
チン酸（融点152〜155℃）、２，６−ジクロロニ
コチン酸（融点148〜150℃）、５，６−ジクロロ
ニコチン酸（融点166〜168℃）、及び２，５，６
−トリクロロニコチン酸（融点150〜154℃）が挙
げられる。硫酸の使用量は、TCP1モルに対して
一般的に１〜100モル、望ましくは２〜30モルで
あり、この硫酸の濃度は通常１〜100％、望まし
くは30〜100％、さらに望ましくは40〜100％であ
り、また、加水分解の反応温度は50〜150℃、望
ましくは80〜130℃であり、反応時間は一般に0.5
〜30時間である。本発明方法の実施に際しては、
これら反応条件の中から適切なものを選択する必
要がある。すなわちこの加水分解の反応において
は濃度の薄い硫酸を用いたり、反応温度を高くし
たり、或は反応時間を長くしたりすると、一旦生
成した目的のCNAが、そのα位の塩素原子を水
酸基によつて置換された副生物、例えば２−ヒド
ロキシニコチン酸に誘導されるので留意する必要
がある。できるだけこの副反応を避けるために
は、例えば50％硫酸を用いて100℃で反応させる
場合反応時間を約２時間とし、60％硫酸を用いて
100℃で反応させる場合反応時間を約７〜８時間
とし、更に100％硫酸を用いて110〜120℃で反応
させる場合反応時間を約２時間とするのがよい。
上記反応で得られた反応物を冷却した後、通常
の過、洗浄、精製などのの操作によつて高純度
のCNAを得ることができる。
次に本発明の実施例を記載する。
例 １〜５
塩素化工程；
２−クロロ−５−トリフルオロメチルピリジン
18.2ｇに塩化アルミニウム20ｇを２時間にわたつ
て添加し、所定の反応条件で反応させた。反応終
了後、反応物を冷却した後氷水中に投入し、油層
を分液した。溶媒を溜去して、２−クロロ−５−
トリクロロメチルピリジンを得た。
The present invention relates to chloronicotinic acid compounds (hereinafter referred to as
Regarding the manufacturing method of CNA (abbreviated as CNA). Conventionally, various methods for producing CNA have been proposed. For example, as a method for producing 2-chloronicotinic acid, (1) nicotinic acid N-oxide is reacted with phosphorus oxychloride and triethylamine, 2-chloronicotinic acid chloride is distilled from the reaction mixture, and this distillate is Method of hydrolysis (Japanese Unexamined Patent Publication No. 52
-122377) (2) A method of reacting 3-cyanopyridine N-oxide with phosphorus oxychloride to produce 2-chloro-3-cyanopyridine, which is then hydrolyzed (JP-A-56-169672) etc. have been proposed. However, these methods have various drawbacks. Specifically, method (1) requires the use of irritating phosphorus oxychloride as a chlorinating agent, isomers are generated during chlorination, and 2-chloronicotinic acid chloride is an unstable compound. Therefore, it requires purification before hydrolysis,
Furthermore, it has drawbacks such as the need for careful handling. In addition, in method (2), 3-cyanopyridine is expensive, phosphorus oxychloride is difficult to handle, isomers are generated during chlorination, and after hydrolysis with an alkali, an acid is added to obtain the desired product. It has the disadvantage that it requires a complicated operation of separating the . The present inventors studied the method for producing CNA and found that when a trifluoromethylpyridine compound (hereinafter abbreviated as TFP) and aluminum chloride are reacted, the trifluoromethyl group in TFP changes to a trichloromethyl group. Trichloromethylpyridine compound (hereinafter abbreviated as TCP) is generated,
The present invention was completed based on the finding that the desired CNA is produced when this TCP is hydrolyzed in the presence of sulfuric acid. That is, the present invention [] General formula () (In the formula, X 1 , X 2 and X 3 are hydrogen atoms or chlorine atoms, and at least one of X 1 or X 3 is a chlorine atom.) By reacting with aluminum chloride, the general formula () A trichloromethylpyridine compound represented by the formula (wherein X 1 , X 2 and ) A method for producing a chloronicotinic acid compound represented by the formula (wherein X 1 , X 2 and X 3 are as described above). The method of the present invention provides the following advantages. (1) The TFP represented by the above general formula (), which is a raw material, has already been produced industrially and is economically available. (2) This method does not generate many side reactions, and the intermediate TCP is also stable, so the target product can be obtained in high yield and with high purity. (3) The reaction is simple and the reaction time is short. Chlorination Step: According to the method of the present invention, TFP and aluminum chloride can be reacted without the presence of a solvent, but industrially it is preferable to react in a solvent. The TFP used in the method of the present invention includes 2
-Chloro-3-trifluoromethylpyridine (melting point 39.1°C), 6-chloro-3-trifluoromethylpyridine (melting point 30.2°C), 2,5dichloro-3
- trifluoromethylpyridine (boiling point 119-121
℃/90mmHg), 2,6-dichloro-3-trifluoromethylpyridine (melting point 6.0-6.5℃), 5,6
-dichloro-3-trifluoromethylpyridine (melting point 9-10°C) and 2,5,6-trichloro-
3-Trifluoromethylpyridine (melting point 48-50
℃), and examples of the solvent include methylene chloride, chloroform, F-112 (CFCl 2 CFCl 2 ),
halogenated hydrocarbons such as ethylene chloride,
Examples include aromatic hydrocarbons having an electron-withdrawing group such as monochlorobenzene, dichlorobenzene, trichlorobenzene, and nitrobenzene. The amount of aluminum chloride used is usually 0.5 to 5 mol, preferably 1 to 1.5 mol, per 1 mol of TFP, and aluminum chloride may be added all at once.
It is advantageous to add the mixture in several batches in order to proceed with a uniform reaction. Although the reaction temperature cannot be absolutely defined, it is usually 30 to 180°C, preferably 50 to 130°C. Reaction times are generally 0.5 to 10 hours. After cooling the reaction product obtained in the above reaction and putting it into ice water, TCP was extracted by ordinary solvent extraction and distillation.
However, it is more industrially advantageous to pour the above reaction product into water, separate the layers to remove aluminum chloride, and then subject it to the next reaction.
TCP includes 2-chloro-3-trichloromethylpyridine, 6-chloro-3-trichloromethylpyridine, 2,5-dichloro-3-trichloromethylpyridine, 2,6-dichloro-3-trichloromethylpyridine, 5, Mention may be made of 6-dichloro-3-trichloromethylpyridine and 2,5,6-trichloro-3-trichloromethylpyridine. Hydrolysis step; Next, TCP is hydrolyzed in the presence of sulfuric acid,
Get a CNA. Examples of CNA include 2-chloronicotinic acid (melting point 196-198°C), 6-chloronicotinic acid (melting point 199-201°C), 2,5-dichloronicotinic acid (melting point 152-155°C), and 2,6-dichloronicotinic acid (melting point 152-155°C). Nicotinic acid (melting point 148-150°C), 5,6-dichloronicotinic acid (melting point 166-168°C), and 2,5,6
- trichloronicotinic acid (melting point 150-154°C). The amount of sulfuric acid used is generally 1 to 100 mol, preferably 2 to 30 mol, per 1 mol of TCP, and the concentration of sulfuric acid is usually 1 to 100%, preferably 30 to 100%, more preferably 40 mol. ~100%, and the reaction temperature for hydrolysis is 50~150℃, preferably 80~130℃, and the reaction time is generally 0.5~100%.
~30 hours. When carrying out the method of the present invention,
It is necessary to select appropriate reaction conditions from among these reaction conditions. In other words, in this hydrolysis reaction, if diluted sulfuric acid is used, the reaction temperature is raised, or the reaction time is lengthened, the target CNA once generated will convert its α-position chlorine atom into a hydroxyl group. Care must be taken as this leads to substituted by-products, such as 2-hydroxynicotinic acid. In order to avoid this side reaction as much as possible, for example, when using 50% sulfuric acid at 100℃, the reaction time should be about 2 hours, and when using 60% sulfuric acid, the reaction time should be about 2 hours.
When the reaction is carried out at 100°C, the reaction time is preferably about 7 to 8 hours, and when the reaction is carried out using 100% sulfuric acid at 110 to 120°C, the reaction time is preferably about 2 hours. After cooling the reaction product obtained in the above reaction, high-purity CNA can be obtained by conventional operations such as filtration, washing, and purification. Next, examples of the present invention will be described. Examples 1-5 Chlorination step; 2-chloro-5-trifluoromethylpyridine
20 g of aluminum chloride was added to 18.2 g over 2 hours and reacted under predetermined reaction conditions. After the reaction was completed, the reaction product was cooled and then placed in ice water to separate the oil layer. The solvent was distilled off and 2-chloro-5-
Trichloromethylpyridine was obtained.
【表】
加水分解工程；
２−クロロ−５−トリクロロメチルピリジン20
ｇに鉱酸を加え、充分撹拌しながら反応させ、反
応終了後反応物を氷水中に投入し、析出した結晶
物を過、洗浄し、更に水とアセトニトリルとの
混合溶媒（混合比、１：１）にて精製して下記第
２表に示す結果を得た。[Table] Hydrolysis step; 2-chloro-5-trichloromethylpyridine 20
Add mineral acid to g and react with sufficient stirring. After the reaction, the reaction product was poured into ice water, the precipitated crystals were filtered and washed, and a mixed solvent of water and acetonitrile (mixing ratio, 1: 1) to obtain the results shown in Table 2 below.
【表】
例 ６
２−クロロ−５−トリクロロメチルピリジン５
ｇを濃硫酸30ｇに溶解させ、110℃に加熱すると
激しく塩酸ガスが発生し、110〜120℃で２時間反
応させた。反応終了後、反応物を氷水中に投入す
ると白色結晶が析出し、これを過、洗浄、乾燥
して、６−クロロニコチン酸3.2ｇ（収率94％）
を得た。
例 ７
２−クロロ−３−トリフルオロメチルピリジン
18.2ｇをトリクロロベンゼン30mlに溶解させ、
100℃で塩化アルミニウム20ｇを2.5時間にわたつ
て添加し、４時間反応させた。反応終了後、反応
物を冷却した後氷水中に投入し、油層を分液し
た。この油層に60％硫酸120mlを加え、100℃で８
時間撹拌しながら反応させた。反応終了後、反応
物を氷水中に投入し、析出した結晶物を過洗浄
し、更に水とアセトニトリルとの混合溶媒（混合
比、１：１）にて精製して、２−クロロニコチン
酸8.5ｇ（収率54％）を得た。[Table] Example 6 2-chloro-5-trichloromethylpyridine 5
When this solution was dissolved in 30 g of concentrated sulfuric acid and heated to 110°C, hydrochloric acid gas was violently generated, and the reaction was continued at 110 to 120°C for 2 hours. After the reaction, the reaction product was poured into ice water, white crystals precipitated, which were filtered, washed, and dried to give 3.2 g of 6-chloronicotinic acid (yield 94%).
I got it. Example 7 2-chloro-3-trifluoromethylpyridine
Dissolve 18.2g in 30ml of trichlorobenzene,
20 g of aluminum chloride was added over 2.5 hours at 100° C. and reacted for 4 hours. After the reaction was completed, the reaction product was cooled and then placed in ice water to separate the oil layer. Add 120ml of 60% sulfuric acid to this oil layer, and
The reaction was allowed to take place while stirring for hours. After the reaction, the reaction product was poured into ice water, the precipitated crystals were washed, and further purified using a mixed solvent of water and acetonitrile (mixing ratio, 1:1) to obtain 2-chloronicotinic acid (8.5%). g (yield 54%) was obtained.
Claims (1)
あり、X1或はX3の少くともいずれか一方は塩素
原子である）で表わされるトリフルオロメチルピ
リジン系化合物と塩化アルミニウムとを反応させ
て、一般式 （式中X1、X2及びX3は前述の通りである）で表
わされるトリクロロメチルピリジン系化合物を
得、次いで前記トリクロロメチルピリジン系化合
物を硫酸の存在下に加水分解して、一般式 （式中X1、X2及びX3は前述の通りである）で表
わされるクロロニコチン酸系化合物を製造するこ
とを特徴とする、クロロニコチン酸系化合物の製
造方法。[Claims] 1. General formula (In the formula, X 1 , X 2 and X 3 are hydrogen atoms or chlorine atoms, and at least one of X 1 or X 3 is a chlorine atom) and chloride By reacting with aluminum, the general formula A trichloromethylpyridine compound represented by the formula (wherein X 1 , X 2 and A method for producing a chloronicotinic acid compound, the method comprising producing a chloronicotinic acid compound represented by the formula (wherein X 1 , X 2 and X 3 are as described above).
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15633582A JPS5946271A (en) | 1982-09-08 | 1982-09-08 | Preparation of chloronicotinic acid compound |
| US06/482,535 US4504665A (en) | 1982-04-12 | 1983-04-06 | Process for producing chloronicotinic acid compounds |
| EP83103409A EP0092117B1 (en) | 1982-04-12 | 1983-04-07 | Process for producing chloronicotinic acid compounds |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15633582A JPS5946271A (en) | 1982-09-08 | 1982-09-08 | Preparation of chloronicotinic acid compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5946271A JPS5946271A (en) | 1984-03-15 |
| JPH0249304B2 true JPH0249304B2 (en) | 1990-10-29 |
Family
ID=15625521
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP15633582A Granted JPS5946271A (en) | 1982-04-12 | 1982-09-08 | Preparation of chloronicotinic acid compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5946271A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0421114U (en) * | 1990-06-15 | 1992-02-21 |
-
1982
- 1982-09-08 JP JP15633582A patent/JPS5946271A/en active Granted
Non-Patent Citations (1)
| Title |
|---|
| PYPIDINE AND ITS DERIVATIVES PART THREE * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0421114U (en) * | 1990-06-15 | 1992-02-21 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5946271A (en) | 1984-03-15 |
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