JPH04117366A - Polyfluoroalkyl group-containing pyrimidine derivative and production thereof - Google Patents
Polyfluoroalkyl group-containing pyrimidine derivative and production thereofInfo
- Publication number
- JPH04117366A JPH04117366A JP2234570A JP23457090A JPH04117366A JP H04117366 A JPH04117366 A JP H04117366A JP 2234570 A JP2234570 A JP 2234570A JP 23457090 A JP23457090 A JP 23457090A JP H04117366 A JPH04117366 A JP H04117366A
- Authority
- JP
- Japan
- Prior art keywords
- pyrimidine
- pyrimidine derivative
- group
- formula
- perfluoro
- 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
- 150000003230 pyrimidines Chemical class 0.000 title claims abstract description 28
- 238000004519 manufacturing process Methods 0.000 title claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 12
- 150000002978 peroxides Chemical class 0.000 claims abstract description 12
- -1 diphenyl-tert-butylsilyl Chemical group 0.000 claims abstract description 10
- 125000004665 trialkylsilyl group Chemical group 0.000 claims abstract description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 abstract description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 8
- 150000001875 compounds Chemical class 0.000 abstract description 5
- 239000003921 oil Substances 0.000 abstract description 5
- 239000003905 agrochemical Substances 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 4
- 239000005871 repellent Substances 0.000 abstract description 4
- 230000002940 repellent Effects 0.000 abstract description 4
- 239000003443 antiviral agent Substances 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 3
- 230000003327 cancerostatic effect Effects 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 239000002904 solvent Substances 0.000 description 7
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- AJDIZQLSFPQPEY-UHFFFAOYSA-N 1,1,2-Trichlorotrifluoroethane Chemical compound FC(F)(Cl)C(F)(Cl)Cl AJDIZQLSFPQPEY-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 239000007809 chemical reaction catalyst Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 235000009518 sodium iodide Nutrition 0.000 description 2
- SLGOCMATMKJJCE-UHFFFAOYSA-N 1,1,1,2-tetrachloro-2,2-difluoroethane Chemical compound FC(F)(Cl)C(Cl)(Cl)Cl SLGOCMATMKJJCE-UHFFFAOYSA-N 0.000 description 1
- BOSAWIQFTJIYIS-UHFFFAOYSA-N 1,1,1-trichloro-2,2,2-trifluoroethane Chemical compound FC(F)(F)C(Cl)(Cl)Cl BOSAWIQFTJIYIS-UHFFFAOYSA-N 0.000 description 1
- HJRXHKBZNQULJQ-UHFFFAOYSA-N 1,1,1-trichloro-2,2,3,3,3-pentafluoropropane Chemical compound FC(F)(F)C(F)(F)C(Cl)(Cl)Cl HJRXHKBZNQULJQ-UHFFFAOYSA-N 0.000 description 1
- 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
- OVZATIUQXBLIQT-UHFFFAOYSA-N 1,2-dibromo-1-chloro-1,2,2-trifluoroethane Chemical compound FC(F)(Br)C(F)(Cl)Br OVZATIUQXBLIQT-UHFFFAOYSA-N 0.000 description 1
- 238000004293 19F NMR spectroscopy Methods 0.000 description 1
- ZPGMWBFCBUKITA-UHFFFAOYSA-N 2,2,3-trichloro-1,1,1,3,4,4,4-heptafluorobutane Chemical compound FC(F)(F)C(F)(Cl)C(Cl)(Cl)C(F)(F)F ZPGMWBFCBUKITA-UHFFFAOYSA-N 0.000 description 1
- QBXWGANCZVGATM-UHFFFAOYSA-N 2,4-dibutoxypyrimidine Chemical compound CCCCOC1=CC=NC(OCCCC)=N1 QBXWGANCZVGATM-UHFFFAOYSA-N 0.000 description 1
- KEVRHVMWBKFGLO-UHFFFAOYSA-N 2,4-dimethoxypyrimidine Chemical compound COC1=CC=NC(OC)=N1 KEVRHVMWBKFGLO-UHFFFAOYSA-N 0.000 description 1
- LJODWHMHKHLDLM-UHFFFAOYSA-N 2,4-dipropoxypyrimidine Chemical compound CCCOC1=CC=NC(OCCC)=N1 LJODWHMHKHLDLM-UHFFFAOYSA-N 0.000 description 1
- FSBNTQRWSOTNEW-UHFFFAOYSA-N Pyrimidine, 2,4- bis[(trimethylsilyl)oxy]- Chemical compound C[Si](C)(C)OC1=CC=NC(O[Si](C)(C)C)=N1 FSBNTQRWSOTNEW-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- UHASMEVRHWRZKF-UHFFFAOYSA-N [2,3,3,3-tetrafluoro-2-(1,1,2,2,3,3,3-heptafluoropropoxy)propanoyl] 2,3,3,3-tetrafluoro-2-(1,1,2,2,3,3,3-heptafluoropropoxy)propaneperoxoate Chemical compound FC(F)(F)C(F)(F)C(F)(F)OC(F)(C(F)(F)F)C(=O)OOC(=O)C(F)(C(F)(F)F)OC(F)(F)C(F)(F)C(F)(F)F UHASMEVRHWRZKF-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- KVBKAPANDHPRDG-UHFFFAOYSA-N dibromotetrafluoroethane Chemical compound FC(F)(Br)C(F)(F)Br KVBKAPANDHPRDG-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- KLABGSLRJVKZDX-UHFFFAOYSA-N triethyl-(2-triethylsilyloxypyrimidin-4-yl)oxysilane Chemical compound CC[Si](CC)(CC)OC1=CC=NC(O[Si](CC)(CC)CC)=N1 KLABGSLRJVKZDX-UHFFFAOYSA-N 0.000 description 1
- HZYRYIHXYMLGLI-UHFFFAOYSA-N trimethyl-(6-trimethylsilyloxypyrimidin-4-yl)oxysilane Chemical compound C[Si](C)(C)OC1=CC(O[Si](C)(C)C)=NC=N1 HZYRYIHXYMLGLI-UHFFFAOYSA-N 0.000 description 1
Abstract
Description
【発明の詳細な説明】
〈産業上の利用分野〉
本発明は、新規なポリフルオロアルキル基含有ピリミジ
ン誘導体及びその製造方法に関する。DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to a novel polyfluoroalkyl group-containing pyrimidine derivative and a method for producing the same.
〈従来の技術〉
有機化合物中に、ポリフルオロアルキル基を含有する化
合物は、耐熱性、撥水撥油性、生理活性等の有用な性質
を示すものとして注目を集めている。特にピリミジン化
合物中に、ポリフルオロアルキル基が導入されたポリフ
ルオロアルキル基含有ピリミジン誘導体は、医薬、農薬
、撥水撥油剤等として、特に制癌剤あるいは坑ウィルス
剤の合成中間体として有用であると考えられ注目されて
いる。しかしながら前記ポリフルオロアルキル−基含有
ピリミジン誘導体及びその製造方法については殆ど知ら
れていないのが現状である。<Prior Art> Among organic compounds, compounds containing polyfluoroalkyl groups are attracting attention as they exhibit useful properties such as heat resistance, water and oil repellency, and physiological activity. In particular, polyfluoroalkyl group-containing pyrimidine derivatives in which a polyfluoroalkyl group is introduced into a pyrimidine compound are considered to be useful as medicines, agricultural chemicals, water and oil repellents, etc., and especially as synthetic intermediates for anticancer agents and antiviral agents. It is attracting attention. However, at present, little is known about the polyfluoroalkyl-group-containing pyrimidine derivatives and their production methods.
〈発明が解決しようとする課題〉
本発明の目的は、医薬、農薬、撥水撥油剤等の合成中間
体として利用可能なポリフルオロアルキル基含有ピリミ
ジン誘導体及びその製造方法を提供することにある。<Problems to be Solved by the Invention> An object of the present invention is to provide a polyfluoroalkyl group-containing pyrimidine derivative that can be used as a synthetic intermediate for medicines, agricultural chemicals, water and oil repellents, etc., and a method for producing the same.
本発明の別の目的は、反応触媒及び特殊な装置を用いず
、高収率かつ容易にポリフルオロアルキル基含有ピリミ
ジン誘導体を製造する方法を提供することにある。Another object of the present invention is to provide a method for easily producing polyfluoroalkyl group-containing pyrimidine derivatives in high yield without using a reaction catalyst or special equipment.
く課題を解決するための手段〉
本発明によれば、下記一般式（Ｉ）
（式中Ｒ０は、水素原子又は炭素数１〜４のアルキル基
を示す。またｎは０〜８の整数を示す）で表わされるポ
リフルオロアルキル基含有ピリミジン誘導体が提供され
る。According to the present invention, the following general formula (I) (wherein R0 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and n represents an integer of 0 to 8) A polyfluoroalkyl group-containing pyrimidine derivative represented by the following is provided.
また本発明によれば、下記一般式（ｎ）（式中ｎは０〜
８の整数を示す）で表わされる過酸化ポリフルオロアル
カノイルと、
下記一般式（ｎｌ）
（式中Ｒ２は、
炭素数１〜４のアルキル基、
トリ
アルキルシリル基又はジフェニル−ｔ−ブチルシリル基
を示す）で表わされるピリミジン類とを反応させること
を特徴とする前記一般式（［）で表わされるポリフルオ
ロアルキル基含有ピリミジン誘導体の製造方法が提供さ
れる。Further, according to the present invention, the following general formula (n) (where n is 0 to
polyfluoroalkanoyl peroxide represented by the following general formula (nl) (in which R2 represents an alkyl group having 1 to 4 carbon atoms, a trialkylsilyl group, or a diphenyl-t-butylsilyl group) ) There is provided a method for producing a polyfluoroalkyl group-containing pyrimidine derivative represented by the general formula ([), which comprises reacting the pyrimidine derivative represented by the formula ([)] with a pyrimidine derivative represented by the formula ([)].
以下本発明を更に詳細に説明する。The present invention will be explained in more detail below.
本発明のポリフルオロアルキル基含有ピリミジン誘導体
は、下記一般式（Ｉ）で表わすことができ、
式中Ｒ□は、水素原子又は炭素数１〜４のアルキル基を
示す。またｎは０〜８の整数を示す。この際Ｒ１が炭素
数５以上のアルキル基の場合には製造が困難であり、前
記ｎが９以上の場合には、溶媒に対する溶解性が低下す
るので使用できない。The polyfluoroalkyl group-containing pyrimidine derivative of the present invention can be represented by the following general formula (I), where R□ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. Moreover, n represents an integer of 0 to 8. In this case, when R1 is an alkyl group having 5 or more carbon atoms, production is difficult, and when n is 9 or more, the solubility in the solvent decreases, so that it cannot be used.
前記一般式（Ｉ）で表わされるポリフルオロアルキル基
含有ピリミジン誘導体としては、例えば、２．４−ジメ
トキシ−５−（ペルフルオロ−１１−メチル−２′オキ
サペンチル）ピリミジン、２゜４−ジメトキシ−５−く
ペルフルオロ−１′４′−ジメチル−２’ 、５’ −
ジオキサオクチル）ピリミジン、２，４−ジメトキシ−
５−（ペルフルオロ−１’ 、４’ 、７’ −トリメ
チル−２′５’ 、８’−トリオキサウンデシル）ピリ
ミジン、２．４−ジメトキシ−５−くペルフルオロ−１
′４’ ７’ １０’ −テトラメチル−２’
、５’８’ １１’−テトラオキサテトラデシル
）ピリミジン、２，４−ジメトキシ−５−（ペルフルオ
ロ−１’、４’、７’ １０’、１３’ −ペンタ
メチル−２’ 、５’ 、８’ 、１１’ 、１４’
−ペンタオキサヘプタデシル）ピリミジン、２，４−ジ
ヒドロキシ−５−（ペルフルオロ−１′−メチル−２′
オキサペンチル）ピリミジン、２，４−ジヒドロキシ−
５−（ペルフルオロ−１’ 、４’−ジメチル−２’
、５’−ジオキサオクチル）ピリミジン、２，４−ジヒ
ドロキシ−５−（ペルフルオロ−１’ 、４’ 、７’
−）−リメチル−２′５’ 、８’−トリオキサウン
デシル）ピリミジン、２，４−ジヒドロキシ−５−くペ
ルフルオロ−１’ 、４’ 、７’ 、１０’ −テト
ラメチル−２′５’ 、８’ 、１１’ −テトラオキ
サテトラデシル）ピリミジン、２，４−ジヒドロキシ−
５−（ペルフルオロ−１’ 、４’ 、７’ 、１０’
、１３’ペンタメチル−２’ 、５’ 、８’ 、１
１’１４′−ペンタオキサヘプタデシル）ピリミジン等
を好ましく挙げることができる。Examples of the polyfluoroalkyl group-containing pyrimidine derivative represented by the general formula (I) include 2,4-dimethoxy-5-(perfluoro-11-methyl-2'oxapentyl)pyrimidine, 2°4-dimethoxy-5 -perfluoro-1'4'-dimethyl-2',5'-
dioxaoctyl)pyrimidine, 2,4-dimethoxy-
5-(perfluoro-1',4',7'-trimethyl-2'5',8'-trioxaundecyl)pyrimidine, 2,4-dimethoxy-5-perfluoro-1
'4'7'10'-tetramethyl-2'
, 5'8'11'-tetraoxatetradecyl)pyrimidine,2,4-dimethoxy-5-(perfluoro-1',4',7'10',13'-pentamethyl-2',5',8' , 11', 14'
-pentaoxaheptadecyl)pyrimidine, 2,4-dihydroxy-5-(perfluoro-1'-methyl-2'
oxapentyl)pyrimidine, 2,4-dihydroxy-
5-(perfluoro-1', 4'-dimethyl-2'
, 5'-dioxaoctyl)pyrimidine, 2,4-dihydroxy-5-(perfluoro-1', 4', 7')
-)-limethyl-2'5', 8'-trioxaundecyl)pyrimidine, 2,4-dihydroxy-5-perfluoro-1', 4', 7', 10'-tetramethyl-2'5' , 8', 11'-tetraoxatetradecyl)pyrimidine, 2,4-dihydroxy-
5-(perfluoro-1', 4', 7', 10'
, 13'pentamethyl-2', 5', 8', 1
Preferred examples include pyrimidine (1'14'-pentaoxaheptadecyl).
本発明におけるポリフルオロアルキル基含有ピリミジン
誘導体の製造方法は、特定の過酸化ポリフルオロアルカ
ノイルと特定のピリミジン類とを反応させることを特徴
とする。The method for producing a polyfluoroalkyl group-containing pyrimidine derivative in the present invention is characterized by reacting a specific polyfluoroalkanoyl peroxide with a specific pyrimidine.
本発明の製造方法において原料成分として用いる過酸化
ポリフルオロアルカノイルは下記一般式％式％
式中ｎはＯ〜８の整数を示す。この際ｎが９以上の場合
には、溶媒の存在下において反応させる際に前記過酸化
ポリフルオロアルカノイルの溶解性に問題が生じるので
使用できない。前記一般式（ＩＩ）で表わされる過酸化
ポリフルオロアルカノイル中の
としては、具体的には
である。The polyfluoroalkanoyl peroxide used as a raw material component in the production method of the present invention has the following general formula % where n represents an integer of O to 8. In this case, if n is 9 or more, it cannot be used because a problem arises in the solubility of the polyfluoroalkanoyl peroxide when reacting in the presence of a solvent. Specifically, the peroxide polyfluoroalkanoyl represented by the general formula (II) is as follows.
本発明の製造方法において、前記過酸化ポリフルオロア
ルカノイルと反応させるピリミジン類は、下記一般式（
ＩＩＩ）で表わすことができ、式中Ｒ２は、炭素数１〜
４のアルキル基、トリアルキルシリル基、ジフェニル−
ｔ−ブチルシリル基を示す。この際Ｒ２が、炭素数５以
上のアルキル基もしくは炭素数５以上のアルキル基を有
するトリアルキルシリル基の場合には製造が困難である
。前記一般式（ＩＩＩ）で表わされるピリミジン類とし
ては、例えば２，４−ジメトキシピリミジン、２．４−
ジェトキシピリミジン、２，４−ジプロポキシピリミジ
ン、２，４−ジブトキシピリミジン、２，４−ビス（ジ
フェニル−ｔ−ブチルシロキシ）ピリミジン、２，４−
ビス（トリメチルシロキシ）ピリミジン、２，４−ビス
（トリエチルシロキシ）ピリミジン、２，４−ビス（ト
リプロピルシロキシ）ピリミジン、２，４−ビス（トリ
ブチルシロキシ）ピリミジン等を好ましく挙げることが
できる。In the production method of the present invention, the pyrimidine to be reacted with the polyfluoroalkanoyl peroxide has the following general formula (
III), where R2 has 1 to 1 carbon atoms.
4 alkyl group, trialkylsilyl group, diphenyl-
Indicates a t-butylsilyl group. In this case, production is difficult when R2 is an alkyl group having 5 or more carbon atoms or a trialkylsilyl group having an alkyl group having 5 or more carbon atoms. Examples of the pyrimidines represented by the general formula (III) include 2,4-dimethoxypyrimidine, 2,4-
Jetoxypyrimidine, 2,4-dipropoxypyrimidine, 2,4-dibutoxypyrimidine, 2,4-bis(diphenyl-t-butylsiloxy)pyrimidine, 2,4-
Preferred examples include bis(trimethylsiloxy)pyrimidine, 2,4-bis(triethylsiloxy)pyrimidine, 2,4-bis(tripropylsiloxy)pyrimidine, and 2,4-bis(tributylsiloxy)pyrimidine.
本発明の製造方法において、前記過酸化ポリフルオロア
ルカノイルと前記ピリミジン類との仕込みモル比は、１
：０．２〜１０が好ましく、特に１：０．５〜５である
ことが好ましい。前記ピリミジン類の仕込みモル比が０
．２未満の場合には、生成するポリフルオロアルキル基
含有ピリミジン誘導体の収率が低下し、また１０を超え
る場合には反応終了後において未反応のピリミジン類が
多量に残存し、目的とする生成物の単離が困難となるの
で好ましくない。また、反応は常圧で行なうことが可能
であり、且つ反応温度は一１０〜１５０℃の範囲が好ま
しく、０〜１００℃の範囲が特に好ましい。前記反応温
度が一１０℃未満の場合には反応時間に長時間を要し、
１５０℃を超えると反応時の圧力が高くなり、反応操作
が困難であるので好ましくない。更に反応時間は３０分
〜２０時間の範囲が好ましく、工業的には３〜１０時間
の範囲とするのが特に好ましい。In the production method of the present invention, the charging molar ratio of the polyfluoroalkanoyl peroxide and the pyrimidine is 1
: preferably 0.2 to 10, particularly preferably 1:0.5 to 5. The molar ratio of the pyrimidines charged is 0.
．． If it is less than 2, the yield of the polyfluoroalkyl group-containing pyrimidine derivative to be produced will decrease, and if it is more than 10, a large amount of unreacted pyrimidines will remain after the reaction is completed, and the desired product will not be produced. This is not preferred because it makes isolation difficult. Further, the reaction can be carried out at normal pressure, and the reaction temperature is preferably in the range of -10 to 150°C, particularly preferably in the range of 0 to 100°C. When the reaction temperature is less than 110°C, the reaction time takes a long time,
If the temperature exceeds 150°C, the pressure during the reaction will be high and the reaction operation will be difficult, which is not preferable. Further, the reaction time is preferably in the range of 30 minutes to 20 hours, and industrially particularly preferably in the range of 3 to 10 hours.
本発明の製造方法では、前記種々の反応条件下においで
、前記過酸化ポリフルオロアルカノイルと前記ピリミジ
ン類とを反応させる二とにより、目的とするポリフルオ
ロアルキル基含有ピリミジン誘導体を製造することがで
きるが、前記過酸化ポリフルオロアルカノイルの取扱い
及び反応をより円滑に行なうために溶媒を用いて反応さ
せるのが好ましい。前記溶媒としてはハロゲン化脂肪族
溶媒、具体的には例えば、２−クロロ−１，２−ジブロ
モ−１，１，２−トリフルオロエタン、１゜２−ジブロ
モへキサフルオロプロパン、１，２−ジブロモテトラフ
ルオロエタン、１，１−ジフルオロテトラクロロエタン
、１，２−ジフルオロテトラクロロエタン、フルオロト
リクロロメタン、ヘプタフルオロ−２，３，３−トリク
ロロブタン、１．１，１．３−テトラクロロテトラフル
オロプロパン、１，１．１−トリクロロペンタフルオロ
プロパン、１，１．２−トリクロロトリフルオロエタン
等を好ましく挙げることができ、特に工業的には、１，
１．２−トリクロロトリフルオロエタンが好ましい。ま
た前記溶媒の仕込み量は、前記ポリフルオロアルカノイ
ルの濃度が前記溶媒に対して１〜３０重量％の範囲とな
るように調整するのが望ましい。In the production method of the present invention, the desired polyfluoroalkyl group-containing pyrimidine derivative can be produced by reacting the polyfluoroalkanoyl peroxide and the pyrimidine under the various reaction conditions. However, in order to more smoothly handle and react the polyfluoroalkanoyl peroxide, it is preferable to carry out the reaction using a solvent. The solvent is a halogenated aliphatic solvent, specifically, for example, 2-chloro-1,2-dibromo-1,1,2-trifluoroethane, 1°2-dibromohexafluoropropane, 1,2- Dibromotetrafluoroethane, 1,1-difluorotetrachloroethane, 1,2-difluorotetrachloroethane, fluorotrichloromethane, heptafluoro-2,3,3-trichlorobutane, 1.1,1,3-tetrachlorotetrafluoropropane , 1,1.1-trichloropentafluoropropane, 1,1.2-trichlorotrifluoroethane, etc., and particularly industrially, 1,
1.2-Trichlorotrifluoroethane is preferred. Further, the amount of the solvent charged is desirably adjusted so that the concentration of the polyfluoroalkanoyl is in the range of 1 to 30% by weight based on the solvent.
また、前記一般式（Ｉ）で表わされるポリフルオロアル
キル基含有ピリミジン誘導体において、Ｒ□が水素原子
のものは、前記製造方法の他、前記製造方法により得ら
れたＲ１がアルキル基であるポリフルオロアルキル基含
有ピリミジン誘導体をヨウ化ナトリウムの存在下、氷酢
酸などの酸性条件下にて処理することによっても得るこ
とができる。Furthermore, in the polyfluoroalkyl group-containing pyrimidine derivative represented by the general formula (I), those in which R□ is a hydrogen atom can be used in addition to the above-mentioned production method. It can also be obtained by treating an alkyl group-containing pyrimidine derivative under acidic conditions such as glacial acetic acid in the presence of sodium iodide.
本発明の製造法により得られる反応生成物は蒸留、カラ
ムクロマトグラフィー等の公知の方法で精製することが
可能である。The reaction product obtained by the production method of the present invention can be purified by known methods such as distillation and column chromatography.
〈発明の効果〉
本発明のポリフルオロアルキル基含有ピリミジン誘導体
は、新規な化合物であり、医薬、農薬、撥水撥油剤等と
して、特に制癌剤及び坑ウィルス剤の合成中間体として
有用である。また本発明の製造方法においては、短時間
で高収率かつ容易に、しかも反応触媒及び特殊な装置を
使用せずにポリフルオロアルキル基含有ピリミジン誘導
体を製造することができる。<Effects of the Invention> The polyfluoroalkyl group-containing pyrimidine derivative of the present invention is a novel compound, and is useful as a medicine, an agrochemical, a water/oil repellent, etc., and particularly as a synthetic intermediate for anticancer agents and antiviral agents. Further, in the production method of the present invention, a polyfluoroalkyl group-containing pyrimidine derivative can be produced easily in a short time with high yield and without using a reaction catalyst or special equipment.
〈実施例〉
以下本発明を実施例により更に詳しく説明するが、本発
明はこれらに限定されるものではない。<Examples> The present invention will be explained in more detail below with reference to Examples, but the present invention is not limited thereto.
笑凰夙よ
窒素雰囲気下にて、２，４−ビス（トリメチルシロキシ
）ピリミジン１．２８ｇを１．１．２−トリクロロトリ
フルオロエタン２０ｍＱに溶解した。1.28 g of 2,4-bis(trimethylsiloxy)pyrimidine was dissolved in 20 mQ of 1.1.2-trichlorotrifluoroethane under a nitrogen atmosphere.
次いで得られた溶液の温度を３０℃に保ちながら、過酸
化ペルフルオロ−２−メチル−３−オキサヘキサノイル
１．６０ｇ（ピリミジン類に対して０．５倍当量）を含
む１，１．２−トリクロロトリフルオロエタン溶液２１
．６ ｇを滴下漏斗より約１分間かけて滴下した。次い
で同温度にて３時間撹拌を行なった後、２時間還流を行
なった。反応終了後、反応混合物を室温まで冷却し、水
１０〇−を加えて、２時間撹拌した。次いで酢酸エチル
１５０ｍＱを加えて抽出を行ない、有機層を飽和炭酸水
素ナトリウム水溶液及び水で洗浄した後、硫酸ナトリウ
ムを用いて乾燥した。最終に、カラムクロマトグラフィ
ーにより精製を行ない、２，４−ジヒドロキシ−５−（
ペルフルオロ−１′−メチル−２′−オキサペンチル）
ピリミジンを収率６８％で得た。得られた化合物の各種
分析結果について以下に示す。Next, while maintaining the temperature of the obtained solution at 30°C, 1,1.2- containing 1.60 g of perfluoro-2-methyl-3-oxahexanoyl peroxide (0.5 times equivalent to pyrimidines) was added. Trichlorotrifluoroethane solution 21
．． 6 g was added dropwise from the dropping funnel over about 1 minute. Next, the mixture was stirred at the same temperature for 3 hours, and then refluxed for 2 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, 100 ml of water was added, and the mixture was stirred for 2 hours. Next, 150 mQ of ethyl acetate was added to perform extraction, and the organic layer was washed with a saturated aqueous sodium bicarbonate solution and water, and then dried using sodium sulfate. Finally, purification was performed by column chromatography, and 2,4-dihydroxy-5-(
perfluoro-1'-methyl-2'-oxapentyl)
Pyrimidine was obtained with a yield of 68%. Various analysis results of the obtained compound are shown below.
ＭＳ ｍＨｚ ３９６
Ｅｘａｃｔ ＭＡＳＳ ｍＨｚ ３９５．９９６８
（実測値）ＣＳＨ，Ｆ、、０．Ｎ、： ３９５．９９７
０（理論値）ＩＲ（ａｍ−”）３１６０（ＮＨ）、１６
８０．１７５０（Ｃ−０）。MS mHz 396 Exact MASS mHz 395.9968
(Actual measurement value) CSH,F,,0. N: 395.997
0 (theoretical value) IR (am-”) 3160 (NH), 16
80.1750 (C-0).
１３２０．１３４０（ＣＦ、）、１２３０（ＣＦ２）１
）１−ＮＭＲ（ｄ’ −ＤＭＳＯ） ６７．９７（ｓ、
ＬＨ）”Ｆ−ＮＭＲ（ｄ’−ＤＭＳＯ；ｅｘｔ、ＣＦ、
Ｃ００Ｈ）δ−２，０〜−８，５（８Ｆ） 、−５１，
８（ＩＦ） 、−５４，７（２Ｆ）去１１」炎
過酸化ペルフルオロ−２−メチル−３−オキサヘキサノ
イルを過酸化ペルフルオロ−２，５−ジメチル−３，６
−シオキサノナノイルに代えた以外は、実施例１と同様
にして反応及び精製を行ない、２，４−ジヒドロキシ−
５−くペルフルオロ−１’ 、４’ −ジメチル−２′
、５′−ジオキサオクチル）ピリミジンを収率６６％で
得た。分析結果を以下に示す。1320.1340 (CF, ), 1230 (CF2)1
)1-NMR(d'-DMSO) 67.97(s,
LH)"F-NMR (d'-DMSO; ext, CF,
C00H) δ-2,0 to -8,5 (8F), -51,
8(IF), -54,7(2F)
The reaction and purification were carried out in the same manner as in Example 1 except that 2,4-dihydroxy-
5-perfluoro-1', 4'-dimethyl-2'
, 5'-dioxaoctyl)pyrimidine was obtained in a yield of 66%. The analysis results are shown below.
ＭＳ ｍＨｚ ５４６（Ｍ”）
Ｅｘａｃｔ ＭＡＳＳ ｍＨｚ ５４５．９８７７
（実測値）Ｃ１□Ｈ，Ｆ、□Ｏ，Ｎ２； ５４５．９８
７４（理論値）ＩＲ（ｃｍ−１）３２４０（ＮＨ）、１
６７０．１７６０（Ｃ＝Ｏ）、１３２０（ＣＦ、）、１
３４０（ＣＦ３）、１２２５（ＣＦ２）” Ｈ−ＮＭＲ
（ｄ’−ＤＭＳＯ）δ７，９５（ｓ、ＩＨ）１’ Ｆ−
ＮＭＲ（ｄ’ −ＤＭＳＯ；ｅｘ ｔ −ＣＦ３ Ｃｏ
ｏｌ ）δ−３，５〜−９，４（Ｉ３Ｆ） 、−５４，
１（２Ｆ） 、−５６，４（ＩＦ）、−７０，１（ＩＦ
）
去】１」ジ
過酸化ペルフルオロ−２−メチル−３−オキサヘキサノ
イルを、過酸化ペルフルオロ−２，５゜８−トリメチル
−３，６，９−トリオキサドデカメイルに代えた以外は
、実施例１と同様にして反応及び精製を行ない、２，４
−ジヒドロキシ−５−くペルフルオロ−１’ 、４’
−ジメチル−２′５′−ジオキサオクチル）ピリミジン
を収率７１％で得た。分析結果を以下に示す。MS mHz 546 (M”) Exact MASS mHz 545.9877
(Actual measurement value) C1□H,F,□O,N2; 545.98
74 (theoretical value) IR (cm-1) 3240 (NH), 1
670.1760 (C=O), 1320 (CF, ), 1
340 (CF3), 1225 (CF2)” H-NMR
(d'-DMSO) δ7,95 (s, IH) 1' F-
NMR(d'-DMSO; ex t-CF3Co
ol) δ-3,5 to -9,4(I3F), -54,
1 (2F), -56,4 (IF), -70,1 (IF
) 1'' The same procedure was carried out except that perfluoro-2-methyl-3-oxahexanoyl diperoxide was replaced with perfluoro-2,5゜8-trimethyl-3,6,9-trioxadodecayl peroxide. Reaction and purification were carried out in the same manner as in Example 1, and 2,4
-dihydroxy-5-perfluoro-1',4'
-dimethyl-2'5'-dioxaoctyl)pyrimidine was obtained in a yield of 71%. The analysis results are shown below.
ＭＳ ｍＨｚ ７２８
Ｅｘａｃｔ ＭＡＳＳ ｍＨｚ ７２７．９６７３
（実測値）Ｃ，ｓＨ，Ｆ、３０．Ｎ２； ７２７．９６
７６（理論値）ＩＲ（ｃｍ−１）３２４０（ＮＨ）、１
６７０．１７５０（Ｃ＝０）、１３２０（ＣＦ、）、１
３４０（ＣＦ３）、１２２５（ＣＦ、）１）１−ＮＭＲ
（ｄ’ −ＤＭＳＯ） δ７．９４（ｓ、１）１）”Ｆ
−ＮＭＲ（ｄ’−ＤＭＳＯ；ｅｘｔ、ｃＦ３ＣＯＯＨ）
δ−２，１〜−９，９（Ｉ８Ｆ） 、−５３，９（２Ｆ
） 、−５６，０（ＩＦ）、−６９，９（２Ｆ）
去】１」支
２．４−ビス（トリメチルシロキシ）ピリミジンを２，
４−ジメトキシピリミジンに代えた以外は、実施例１と
同様にして反応及び精製を行ない、２．４−ジメトキシ
−５−（ペルフルオロ−１′−メチル−２′−オキサペ
ンチル）ピリミジンを収率８４％で得た。分析結果を以
下に示す。MS mHz 728 Exact MASS mHz 727.9673
(Actual measurement value) C, sH, F, 30. N2; 727.96
76 (theoretical value) IR (cm-1) 3240 (NH), 1
670.1750 (C=0), 1320 (CF, ), 1
340(CF3), 1225(CF,)1)1-NMR
(d' -DMSO) δ7.94(s,1)1)”F
-NMR (d'-DMSO; ext, cF3COOH)
δ-2,1 to -9,9 (I8F), -53,9 (2F
), -56,0 (IF), -69,9 (2F)
The reaction and purification were carried out in the same manner as in Example 1, except that 4-dimethoxypyrimidine was used, and 2,4-dimethoxy-5-(perfluoro-1'-methyl-2'-oxapentyl)pyrimidine was obtained in a yield of 84. Obtained in %. The analysis results are shown below.
阿Ｓ ｍＨｚ ４２６（Ｍ”）
Ｅｘａｃｔ ＭＡＳＳ ｍＨｚ ４２６．０４３８
（実測値）Ｃ１□Ｈ，Ｆ、□Ｏ，Ｎ２； ４２６．０４
３５（理論値）ＩＲ（ｃｍ−１） １３２０ （ＣＦ３
） 、１３４０ （ＣＦ３ ） 、１２２５ （ＣＦ
２ ）１Ｈ−ＮＭＲ（ｄ’ −ＤＭＳＯ） δ４．０
３（３Ｈ，ｓ）、４．０５（３）１．ｓ） 。Exact MASS mHz 426.0438
(Actual measurement value) C1□H,F,□O,N2; 426.04
35 (theoretical value) IR (cm-1) 1320 (CF3
), 1340 (CF3), 1225 (CF
2) 1H-NMR (d'-DMSO) δ4.0
3 (3H, s), 4.05 (3) 1. s).
７．９４（ｓ、ＩＨ）
１９Ｆ−ＮＭＲ（ｄ’−ＤＭＳＯ；ｅｘｔ、ＣＦ３ＣＯ
０■）δ−２，９〜−９，５（８Ｆ）、−５１，０（Ｉ
Ｆ） 、−５４，５（２Ｆ）去】１」ｉ
実施例４で得られた２、４−ジメトキシ−５−（ペルフ
ルオロ−１１−メチル−２′−オキサペンチル）プロピ
ルピリミジン０．５０ｇを氷酢酸２０ｍＱに添加し、更
にヨウ化ナトリウム１．３４ｇ［２ｐ４−ジメトキシ−
５−（ペルフルオロ−１′−メチル−２′−オキサペン
チル）ピリミジンに対して５倍モル量］を加えて、１０
０℃にて５時間反応を行なった。反応終了後、酢酸を除
去し、得られた生成物をベンゼンで洗浄した後、温水中
に溶解させた。次いでチオ硫酸ナトリウムを加えた後水
溶液を冷却して、２，４−ジヒドロキシ−５−（ペルフ
ルオロ−１′−メチル−２′オキサペンチル）ピリミジ
ンを収率８８％で得た。7.94 (s, IH) 19F-NMR (d'-DMSO; ext, CF3CO
0 ■) δ-2,9 to -9,5 (8F), -51,0 (I
F) , -54,5(2F) [1''i] 0.50 g of 2,4-dimethoxy-5-(perfluoro-11-methyl-2'-oxapentyl)propylpyrimidine obtained in Example 4 was added to ice. Added to 20 mQ of acetic acid, and further added 1.34 g of sodium iodide [2p4-dimethoxy-
5 times the molar amount of 5-(perfluoro-1'-methyl-2'-oxapentyl)pyrimidine] to make 10
The reaction was carried out at 0°C for 5 hours. After the reaction was completed, acetic acid was removed, the resulting product was washed with benzene, and then dissolved in warm water. Next, sodium thiosulfate was added and the aqueous solution was cooled to obtain 2,4-dihydroxy-5-(perfluoro-1'-methyl-2'oxapentyl)pyrimidine in a yield of 88%.
Claims (1)
基を示す。またｎは０〜８の整数を示す）で表わされる
ポリフルオロアルキル基含有ピリミジン誘導体。 ２）下記一般式（II） ▲数式、化学式、表等があります▼・・・（II） （式中ｎは０〜８の整数を示す）で表わされる過酸化ポ
リフルオロアルカノイルと、 下記一般式（III） ▲数式、化学式、表等があります▼・・・（III） （式中Ｒ＿２は、炭素数１〜４のアルキル基、トリアル
キルシリル基又はジフェニル−ｔ−ブチルシリル基を示
す）で表わされるピリミジン類とを反応させることを特
徴とする請求項１記載のポリフルオロアルキル基含有ピ
リミジン誘導体の製造方法。[Claims] 1) The following general formula (I) ▲ Numerical formulas, chemical formulas, tables, etc. are included ▼... (I) (In the formula, R_1 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. and a polyfluoroalkyl group-containing pyrimidine derivative represented by (n represents an integer of 0 to 8). 2) The following general formula (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼...(II) (In the formula, n represents an integer from 0 to 8) Polyfluoroalkanoyl peroxide and the following general formula (III) ▲There are mathematical formulas, chemical formulas, tables, etc.▼...(III) (In the formula, R_2 represents an alkyl group having 1 to 4 carbon atoms, a trialkylsilyl group, or a diphenyl-t-butylsilyl group) 2. The method for producing a polyfluoroalkyl group-containing pyrimidine derivative according to claim 1, which comprises reacting the pyrimidine derivative with a polyfluoroalkyl group-containing pyrimidine derivative.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2234570A JPH04117366A (en) | 1990-09-06 | 1990-09-06 | Polyfluoroalkyl group-containing pyrimidine derivative and production thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2234570A JPH04117366A (en) | 1990-09-06 | 1990-09-06 | Polyfluoroalkyl group-containing pyrimidine derivative and production thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH04117366A true JPH04117366A (en) | 1992-04-17 |
Family
ID=16973088
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2234570A Pending JPH04117366A (en) | 1990-09-06 | 1990-09-06 | Polyfluoroalkyl group-containing pyrimidine derivative and production thereof |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH04117366A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014510743A (en) * | 2011-03-31 | 2014-05-01 | シェファー、コンスタンツェ | Perfluorinated compounds for non-viral introduction of nucleic acids |
-
1990
- 1990-09-06 JP JP2234570A patent/JPH04117366A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014510743A (en) * | 2011-03-31 | 2014-05-01 | シェファー、コンスタンツェ | Perfluorinated compounds for non-viral introduction of nucleic acids |
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