JPH02214504A - Method for depositing crystal of compound having plural crystal forms - Google Patents
Method for depositing crystal of compound having plural crystal formsInfo
- Publication number
- JPH02214504A JPH02214504A JP3571389A JP3571389A JPH02214504A JP H02214504 A JPH02214504 A JP H02214504A JP 3571389 A JP3571389 A JP 3571389A JP 3571389 A JP3571389 A JP 3571389A JP H02214504 A JPH02214504 A JP H02214504A
- Authority
- JP
- Japan
- Prior art keywords
- crystals
- crystal
- compound
- compd
- melting point
- 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.)
- Granted
Links
- 239000013078 crystal Substances 0.000 title claims abstract description 80
- 238000000034 method Methods 0.000 title claims abstract description 14
- 150000001875 compounds Chemical class 0.000 title claims description 11
- 238000000151 deposition Methods 0.000 title abstract 6
- 239000002904 solvent Substances 0.000 claims abstract description 21
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 4
- 125000005843 halogen group Chemical group 0.000 claims abstract description 4
- 238000002425 crystallisation Methods 0.000 claims description 28
- 230000008025 crystallization Effects 0.000 claims description 20
- 150000002894 organic compounds Chemical class 0.000 claims description 15
- 239000000126 substance Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 5
- 229910052736 halogen Inorganic materials 0.000 abstract description 3
- 230000008021 deposition Effects 0.000 abstract 4
- 238000002844 melting Methods 0.000 description 25
- 230000008018 melting Effects 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 238000001035 drying Methods 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000002245 particle Substances 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 150000003252 quinoxalines Chemical class 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- -1 L-form quinoxaline compounds Chemical class 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-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
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 239000003849 aromatic solvent Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000013081 microcrystal Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N serine Chemical compound OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
Abstract
Description
【発明の詳細な説明】
（イ）産業上の利用分野
本発明は、結晶多形化合物の晶析法に関するものであり
、更に詳しくは複数の結晶形を有する有機化合物溶液よ
り所望の結晶形を有する有機化合物の晶析法に関するも
のである。Detailed Description of the Invention (a) Industrial Application Field The present invention relates to a method for crystallizing polymorphic compounds, and more specifically, the present invention relates to a method for crystallizing polymorphic compounds, and more specifically, a method for crystallizing a desired crystal form from an organic compound solution having a plurality of crystal forms. The present invention relates to a method for crystallizing organic compounds having the following properties.
（ロ）発明が解決しようとする課題
有機化合物の結晶はしばしば複数の結晶形を有すること
があり、これらの化合物を製造する際、条件によっては
工業的に操作が困難な結晶形を有する化合物が生成する
場合がある。(b) Problems to be Solved by the Invention Crystals of organic compounds often have multiple crystal forms, and depending on the conditions when producing these compounds, some compounds may have crystal forms that are difficult to manipulate industrially. may be generated.
又、これらの化合物を医薬品等として使用する場合、結
晶形により人体内への吸収速度が異なり薬効に大きく影
響する場合がある。Furthermore, when these compounds are used as medicines, the rate of absorption into the human body varies depending on the crystal form, which may greatly affect the drug efficacy.
従って、所望の結晶形を有する有機化合物を任意に晶析
する方法が待望されていた。Therefore, a method for arbitrarily crystallizing an organic compound having a desired crystal form has been desired.
（ハ）課題を解決するための手段
本発明者等は、上記問題点を解決すべく鋭意努力検討し
た結果、本発明を完成するに至った。(C) Means for Solving the Problems The inventors of the present invention have made diligent efforts to solve the above problems, and as a result, have completed the present invention.
即ち、本発明は複数の結晶形を有する有機化合物溶液の
温度を制御することを特徴とする所望の結晶形を有する
有機化合物の晶析法に関するものであり、特に複数の結
晶形を有する有機化合物溶液を、晶析温度に維持した溶
媒中へ添加し晶出させることを特徴とする所望の結晶形
を有する有機化合物の晶析法に関するものである。That is, the present invention relates to a method for crystallizing an organic compound having a desired crystal form, which is characterized by controlling the temperature of an organic compound solution having a plurality of crystal forms. The present invention relates to a method for crystallizing an organic compound having a desired crystal form, which is characterized by adding a solution to a solvent maintained at a crystallization temperature and causing crystallization.
本発明の複数の結晶形を有する有機化合物としては、例
えば
一般式（１）
（式中、Ｘはハロゲン原子、Ｒは低級アルキル基を示す
。）
で表される光学活性キノキサリン化合物が挙げられる。Examples of the organic compound of the present invention having multiple crystal forms include optically active quinoxaline compounds represented by the general formula (1) (wherein, X is a halogen atom and R is a lower alkyl group).
光学活性体にはＤ体及びＬ体のキノキサリン化合物が含
まれる。Optically active forms include D- and L-form quinoxaline compounds.
Ｘであるハロゲン原子としては、弗素、塩素、臭素、沃
素が挙げられる。Examples of the halogen atom that is X include fluorine, chlorine, bromine, and iodine.
Ｒである低級アルキル基としては、メチル基、エチルＬ
ｎ−プロピル基、ｉ−プロピル基、ｎブチル基、ｉ−
ブチル基、ｔ−ブチル基等が挙げられる。As the lower alkyl group R, methyl group, ethyl L
n-propyl group, i-propyl group, n-butyl group, i-
Examples include butyl group, t-butyl group, and the like.
一般式（１）の光学活性キノキサリン化合物のうち、Ｘ
が塩素原子、Ｒがエチル基の化合物が望ましく、更にＤ
体のＸが塩素原子、Ｒがエチル基の化合物が望ましい。Among the optically active quinoxaline compounds of general formula (1),
is a chlorine atom and R is an ethyl group, and further D
A compound in which X is a chlorine atom and R is an ethyl group is desirable.
その他、Ｌ−グルタミン酸、Ｄ、Ｌ−セリン等が挙げら
れる。Other examples include L-glutamic acid, D, L-serine, and the like.
上記溶媒及び複数の結晶形を有する有機化合物溶液を調
製する溶媒としては、メタノール、エタノール、イソプ
ロピルアルコール等のアルコール系溶媒、ベンゼン、ト
ルエン等の芳香族炭化水素系溶媒、ベンゼン、トルエン
等の芳香族炭化水素系溶媒とｎ−へキサン、ｎ−へブタ
ン等の脂肪族炭化水素系溶媒の混合溶媒、ジイソプロピ
ルエーテル、ジブチルエーテル等の脂肪族エーテル系溶
媒、ジクロロエタン、クロロホルム等の含ハロゲン系溶
媒、ジクロロエタン、クロロホルム等の含ハロゲン系溶
媒とｎ−ヘキサン、ｎ−へブタン等の脂肪族炭化水素系
溶媒の混合溶媒等が使用される。The above solvents and solvents for preparing organic compound solutions having multiple crystal forms include alcoholic solvents such as methanol, ethanol, and isopropyl alcohol, aromatic hydrocarbon solvents such as benzene and toluene, and aromatic solvents such as benzene and toluene. Mixed solvents of hydrocarbon solvents and aliphatic hydrocarbon solvents such as n-hexane and n-hebutane, aliphatic ether solvents such as diisopropyl ether and dibutyl ether, halogen-containing solvents such as dichloroethane and chloroform, dichloroethane A mixed solvent of a halogen-containing solvent such as , chloroform, and an aliphatic hydrocarbon solvent such as n-hexane or n-hebutane is used.
以下、本発明を一般式（１）の光学活性キノキサリン化
合物のうち、Ｄ体のＸが塩素原子、Ｒ’がエチル基の化
合物〔Ｄ−化合物（１）と略称する。〕を例にとり詳細
に説明する。Hereinafter, the present invention will be referred to as a compound of the optically active quinoxaline compound of general formula (1), in which X of the D form is a chlorine atom and R' is an ethyl group [abbreviated as D-compound (1)]. ] will be explained in detail using an example.
Ｄ−化合物（１）はＸ線回折測定により２つの結晶形を
有し、顕微鏡観察によって１つは微細な針状結晶形であ
り、他は板状の結晶形であることが確認された。D-Compound (1) was confirmed to have two crystal forms by X-ray diffraction measurement, and microscopic observation revealed that one was a fine needle-like crystal form and the other was a plate-like crystal form.
又、これら結晶形の差異は示差走査熱量測定により融点
の差異としても確認できた。Moreover, the difference between these crystal forms was also confirmed as a difference in melting point by differential scanning calorimetry.
２つの結晶形の特徴を下記に示す。The characteristics of the two crystal forms are shown below.
融点 結晶形
り一化合物（１）の所望の結晶形を有する結晶を晶析さ
せる因子としては、晶析温度が特に重要である。晶析温
度が低いと低融点型結晶が得られ、温度が高いと高融点
型結晶が得られる。その温度の境界は２０℃付近である
。Melting Point Crystal Form: Crystallization temperature is particularly important as a factor for crystallizing compound (1) having a desired crystal form. When the crystallization temperature is low, a low melting point type crystal is obtained, and when the crystallization temperature is high, a high melting point type crystal is obtained. The temperature boundary is around 20°C.
先ず、Ｄ−化合物（１）の低融点型結晶（板状）の晶析
法について述べる。First, a method for crystallizing low melting point crystals (plate-like) of D-Compound (1) will be described.
晶析法としては、Ｄ−化合物（１）１重量部を溶媒０．
６〜２重量部に溶解した溶液を、晶析温度に保った溶媒
２〜３゜５重量部中に滴下して晶析させるものである。As for the crystallization method, 1 part by weight of D-compound (1) is mixed with 0.0% of a solvent.
A solution dissolved in 6 to 2 parts by weight is dropped into 2 to 3.5 parts by weight of a solvent kept at the crystallization temperature to cause crystallization.
晶析温度は、結晶の大きさから通常５〜２０°Ｃ１好ま
しくは１５〜２０°Ｃがよい。The crystallization temperature is usually 5 to 20°C, preferably 15 to 20°C, depending on the size of the crystals.
又、Ｄ−化合物（１）溶液の滴下時間は、結晶の大きさ
から通常３０分〜１０時間、好ましくは３０分〜２時間
がよい。Further, the time for dropping the D-compound (1) solution is usually 30 minutes to 10 hours, preferably 30 minutes to 2 hours, depending on the size of the crystals.
晶出した結晶の乾燥温度は、通常７０°Ｃ未満、好まし
くは５０℃未満がよい。The drying temperature of the crystallized crystals is usually less than 70°C, preferably less than 50°C.
乾燥時間は、通常４〜２４時間、好ましくは６〜ＩＯ時
間がよい。The drying time is usually 4 to 24 hours, preferably 6 to IO hours.
晶出した結晶を７０°Ｃを越える温度で５時間以上乾燥
すると、低融点型結晶は高融点型結晶に変化する場合が
ある。If the crystallized crystals are dried at a temperature exceeding 70° C. for 5 hours or more, the low melting point crystals may change to high melting point crystals.
尚、大きな結晶を得る目的から、Ｄ−化合物（１）の純
度が高い程、Ｄ〜化合物（１）溶液の滴下時間を短くす
ることができる。In addition, for the purpose of obtaining large crystals, the higher the purity of D-compound (1), the shorter the dropping time of the D-compound (1) solution can be.
この晶析法により晶出したＤ−化合物（１）の結晶は低
融点型で結晶形が板状であり、その平均粒径はｌＯ〜３
５μである。The crystals of D-compound (1) crystallized by this crystallization method have a low melting point and a plate-like crystal shape, and the average particle size is 10~3
It is 5μ.
又、この低融点型結晶を含有する溶媒スラリーは移動、
晶出した結晶の濾過、乾燥を容易に行うことができる。In addition, the solvent slurry containing this low melting point crystal is moved,
The crystallized crystals can be easily filtered and dried.
尚、低融点型結晶を含有する溶媒スラリーは、低融点型
結晶が７０重量％以上存在すると濾過性等の操作性がよ
く、９０重量％以上存在すると濾過性等の操作性及び乾
燥特性がよい。In addition, the solvent slurry containing low melting point type crystals has good operability such as filterability when the low melting point type crystals are present in an amount of 70% by weight or more, and has good operability such as filterability and drying characteristics when the low melting point type crystals are present in an amount of 90% by weight or more. .
従って、低融点型結晶の含有量が７０重量％以上である
低融点型結晶と高融点型結晶の混合物が所望の場合の晶
析条件は次の通りである。Therefore, when a mixture of low melting point crystals and high melting point crystals in which the content of the low melting point crystals is 70% by weight or more is desired, the crystallization conditions are as follows.
晶析温度は、通常２０〜２５°Ｃが好ましい。The crystallization temperature is usually preferably 20 to 25°C.
又、Ｄ−化合物（１）溶液の滴下時間は、通常３０分〜
５時間、好ましくは１〜２時間がよい。Further, the dropping time of the D-compound (1) solution is usually 30 minutes to
5 hours, preferably 1 to 2 hours.
晶出した結晶の乾燥温度は、通常７０°Ｃ未満、好まし
くは５０°Ｃ未満がよい。The drying temperature of the crystallized crystals is usually less than 70°C, preferably less than 50°C.
乾燥時間は、通常４〜２４時間、好ましくは６〜１０時
間がよい。The drying time is usually 4 to 24 hours, preferably 6 to 10 hours.
又、Ｄ−化合物（１）の低融点型結晶（板状）を得る他
の晶析法としては、６０〜７０°Ｃに溶融したＤ−化合
物（１）１重量部に、５〜１０°Ｃに保った溶媒３〜１
０重量部を短時間（１〜５分間）で加え、晶析温度を１
５〜２０″Ｃとすれば、低融点型結晶を選択的に得るこ
とができる。In addition, as another crystallization method for obtaining low melting point crystals (plate-like) of D-Compound (1), 1 part by weight of D-Compound (1) melted at 60 to 70°C is mixed with 5 to 10°C. Solvent 3-1 kept at C
0 parts by weight was added in a short period of time (1 to 5 minutes), and the crystallization temperature was increased to 1.
If the temperature is 5 to 20''C, low melting point crystals can be selectively obtained.
しかし、この方法は溶媒の滴下を短時間で行う必要があ
り、晶析操作中に反応容器壁面に結晶が固着する場合が
ある。However, this method requires that the solvent be added dropwise in a short period of time, and crystals may adhere to the walls of the reaction vessel during the crystallization operation.
次に、Ｄ−化合物（１）の高融点型結晶（針状）の晶析
法について述べる。Next, a method for crystallizing high melting point type crystals (acicular) of D-Compound (1) will be described.
晶析法としては、Ｄ−化合物（１）１重量部を溶媒２〜
５重量部に溶解した溶液を、攪拌しながら徐冷して晶析
温度に保つものである。この方法により、容易に高融点
型結晶を９５％以上含有する結晶が得られる。As for the crystallization method, 1 part by weight of D-compound (1) is mixed with 2 to 2 parts by weight of solvent.
A solution containing 5 parts by weight is slowly cooled while stirring to maintain the crystallization temperature. By this method, crystals containing 95% or more of high melting point crystals can be easily obtained.
晶析温度は、通常３５°Ｃ以上、好ましくは３８°Ｃ以
上がよい。The crystallization temperature is usually 35°C or higher, preferably 38°C or higher.
又、Ｄ−化合物（１）溶液を晶析温度に維持する時間と
しては、通常３０分〜１０時間、好ましくは１〜２時間
がよい。Further, the time for maintaining the D-compound (1) solution at the crystallization temperature is usually 30 minutes to 10 hours, preferably 1 to 2 hours.
晶出した結晶の乾燥温度は、通常７０″Ｃ未満、好まし
くは５０°Ｃ未満がよい。The drying temperature of the crystallized crystals is usually less than 70''C, preferably less than 50°C.
乾燥時間は、通常４〜２４時間、好ましくは６〜１０時
間がよい。The drying time is usually 4 to 24 hours, preferably 6 to 10 hours.
この晶析法により晶出したＤ−化合物（１）の結晶は高
融点型で結晶形が針状であり、その平均粒径は１０μ程
度である。しかし、この結晶は顕微鏡観察により１μ以
下の微結晶が凝集したものであることが判明した。The crystals of D-Compound (1) crystallized by this crystallization method are of high melting point type, have a needle-like crystal shape, and have an average particle size of about 10 μm. However, microscopic observation revealed that this crystal was an agglomeration of microcrystals of 1 μm or less.
従って、この高融点型結晶を含有する溶媒スラリーの移
動、晶出した結晶の濾過、乾燥は困難な場合がある。Therefore, it may be difficult to move a solvent slurry containing these high melting point crystals, filter the crystals that have crystallized, and dry them.
（ニ）効果
本発明により、複数の結晶形を有する有機化合物のうち
、所望の結晶形を有する有機化合物を任意に晶析するこ
とができる。(D) Effects According to the present invention, it is possible to arbitrarily crystallize an organic compound having a desired crystal form among organic compounds having a plurality of crystal forms.
更に、本発明は光学活性キノキサリン化合物の晶析に有
効であり、特にＤ−化合物（１）の低融点型結晶、高融
点型結晶及びこれらの混合物を任意に晶析させることが
できる。Further, the present invention is effective for crystallizing optically active quinoxaline compounds, and in particular, low melting point crystals, high melting point crystals, and mixtures thereof of D-compound (1) can be arbitrarily crystallized.
（ホ）実施例
以下、実施例を挙げ本発明の詳細な説明するが、本発明
はこれらに限定されるものではない。(E) Examples Hereinafter, the present invention will be explained in detail with reference to Examples, but the present invention is not limited thereto.
実施例１
上記り一化合物（１）（純度９８％）１００ｇをエタノ
ールｌ１０ｇに６０〜７０℃で溶解した溶液を、１５°
Ｃの晶析温度に保ったエタノール３５０ｇ中に３０分間
で滴下した。Example 1 A solution prepared by dissolving 100 g of the above compound (1) (purity 98%) in 10 g of ethanol at 60 to 70°C was heated at 15°C.
The mixture was added dropwise over 30 minutes to 350 g of ethanol maintained at the crystallization temperature of C.
滴下終了後、冷却し０〜５°Ｃで１時間攪拌し、晶出し
た固体を濾過、乾燥し、Ｄ−化合物（１）９１ｇを得た
。得られた結晶は低融点型結晶（板状）１００％であり
、コールタ−カウンターを使用して測定した平均粒径は
３３μであった。After completion of the dropwise addition, the mixture was cooled and stirred at 0 to 5°C for 1 hour, and the crystallized solid was filtered and dried to obtain 91 g of D-Compound (1). The obtained crystals were 100% low melting point crystals (plate-like), and the average particle size measured using a Coulter counter was 33 μm.
実施例２
実施例１のＤ−化合物（１）（純度９８％）１００ｇを
エタノール１１０ｇに６０〜７０°Ｃで溶解した溶液に
ついて、滴下時間と晶析温度を変化させ次頁の結果を得
た。Example 2 Regarding a solution in which 100 g of D-compound (1) (purity 98%) of Example 1 was dissolved in 110 g of ethanol at 60 to 70°C, the dropwise addition time and crystallization temperature were varied to obtain the results on the next page. .
晶（針状）が９５％であり平均粒径は１０μであった。The crystals (acicular) accounted for 95% and the average particle size was 10 μm.
＊百分率は低融点型結晶（板状）の存在比、μは晶出し
た結晶の平均粒径を示す。*Percentage indicates the abundance ratio of low-melting point crystals (plate-like), and μ indicates the average particle size of crystals crystallized.
実施例３Example 3
Claims (3)
を制御することを特徴とする所望の結晶形を有する有機
化合物の晶析法。(1) A method for crystallizing an organic compound having a desired crystal form, which comprises controlling the crystallization temperature of an organic compound solution having a plurality of crystal forms.
度に維持した溶媒中へ添加し晶出させることを特徴とす
る請求項（１）記載の晶析法。(2) The crystallization method according to claim (1), characterized in that an organic compound solution having a plurality of crystal forms is added to a solvent maintained at a crystallization temperature for crystallization.
。） で表される光学活性キノキサリン化合物であることを特
徴とする請求項（２）記載の晶析法。(3) The organic compound is an optically active quinoxaline represented by the general formula [I] ▲Mathematical formula, chemical formula, table, etc.▼[I] (In the formula, X is a halogen atom and R is a lower alkyl group.) The crystallization method according to claim (2), wherein the crystallization method is a compound.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3571389A JPH02214504A (en) | 1989-02-15 | 1989-02-15 | Method for depositing crystal of compound having plural crystal forms |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3571389A JPH02214504A (en) | 1989-02-15 | 1989-02-15 | Method for depositing crystal of compound having plural crystal forms |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02214504A true JPH02214504A (en) | 1990-08-27 |
| JPH0476721B2 JPH0476721B2 (en) | 1992-12-04 |
Family
ID=12449503
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3571389A Granted JPH02214504A (en) | 1989-02-15 | 1989-02-15 | Method for depositing crystal of compound having plural crystal forms |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH02214504A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999002036A1 (en) * | 1997-07-11 | 1999-01-21 | Nissan Chemical Industries, Ltd. | Aqueous suspension-type pesticide composition |
| US6353104B1 (en) * | 1998-04-28 | 2002-03-05 | Nissan Chemical Industries, Ltd. | Method for producing high melting point crystals of phenoxypropionic acid derivative |
| US7750028B2 (en) | 1997-06-10 | 2010-07-06 | Novartis Ag | Crystal modifications of 1-(2,6-difluorobenzyl)-1H-1, 2,3-triazole-4-carboxamide |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003155214A (en) * | 2001-09-10 | 2003-05-27 | Lion Corp | Pearly brightener dispersion and method for producing the same |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5820283A (en) * | 1981-07-30 | 1983-02-05 | Ube Ind Ltd | Caking method for coal ash |
-
1989
- 1989-02-15 JP JP3571389A patent/JPH02214504A/en active Granted
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5820283A (en) * | 1981-07-30 | 1983-02-05 | Ube Ind Ltd | Caking method for coal ash |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7750028B2 (en) | 1997-06-10 | 2010-07-06 | Novartis Ag | Crystal modifications of 1-(2,6-difluorobenzyl)-1H-1, 2,3-triazole-4-carboxamide |
| US8076362B2 (en) | 1997-06-10 | 2011-12-13 | Novartis Ag | Crystal modification A of 1-(2,6-difluorobenzyI)-1 H-1,2,3-triazole-4-carboxamide and dosage forms and formulations thereof |
| WO1999002036A1 (en) * | 1997-07-11 | 1999-01-21 | Nissan Chemical Industries, Ltd. | Aqueous suspension-type pesticide composition |
| EP1000545A4 (en) * | 1997-07-11 | 2000-08-30 | Nissan Chemical Ind Ltd | Aqueous suspension-type pesticide composition |
| AU742672B2 (en) * | 1997-07-11 | 2002-01-10 | Nissan Chemical Industries Ltd. | Aqueous suspension-type pesticide composition |
| US7842648B2 (en) | 1997-07-11 | 2010-11-30 | Nissan Chemical Industries, Ltd. | Aqueous suspended agricultural chemical composition |
| US6353104B1 (en) * | 1998-04-28 | 2002-03-05 | Nissan Chemical Industries, Ltd. | Method for producing high melting point crystals of phenoxypropionic acid derivative |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0476721B2 (en) | 1992-12-04 |
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