JPH02188589A - Production of tri-lower alkanoyloxyboron - Google Patents
Production of tri-lower alkanoyloxyboronInfo
- Publication number
- JPH02188589A JPH02188589A JP923489A JP923489A JPH02188589A JP H02188589 A JPH02188589 A JP H02188589A JP 923489 A JP923489 A JP 923489A JP 923489 A JP923489 A JP 923489A JP H02188589 A JPH02188589 A JP H02188589A
- Authority
- JP
- Japan
- Prior art keywords
- anhydride
- acid
- lower alkanoic
- compound
- reaction
- 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
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 5
- 239000002253 acid Substances 0.000 claims abstract description 16
- JKWMSGQKBLHBQQ-UHFFFAOYSA-N diboron trioxide Chemical compound O=BOB=O JKWMSGQKBLHBQQ-UHFFFAOYSA-N 0.000 claims abstract description 10
- 150000008064 anhydrides Chemical class 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 abstract description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 abstract description 15
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 abstract description 15
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 abstract description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 abstract description 4
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 abstract description 4
- 230000002194 synthesizing effect Effects 0.000 abstract description 3
- PGZVFRAEAAXREB-UHFFFAOYSA-N 2,2-dimethylpropanoyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC(=O)C(C)(C)C PGZVFRAEAAXREB-UHFFFAOYSA-N 0.000 abstract description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 abstract description 2
- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 abstract description 2
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 abstract description 2
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 2
- PKHMTIRCAFTBDS-UHFFFAOYSA-N hexanoyl hexanoate Chemical compound CCCCCC(=O)OC(=O)CCCCC PKHMTIRCAFTBDS-UHFFFAOYSA-N 0.000 abstract description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 abstract description 2
- DUCKXCGALKOSJF-UHFFFAOYSA-N pentanoyl pentanoate Chemical compound CCCCC(=O)OC(=O)CCCC DUCKXCGALKOSJF-UHFFFAOYSA-N 0.000 abstract description 2
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 abstract description 2
- 235000019260 propionic acid Nutrition 0.000 abstract description 2
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 abstract description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 abstract description 2
- 229940005605 valeric acid Drugs 0.000 abstract description 2
- 150000008065 acid anhydrides Chemical class 0.000 abstract 2
- 239000004599 antimicrobial Substances 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 17
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000000034 method Methods 0.000 description 10
- 125000000217 alkyl group Chemical group 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- -1 cyclohexane Chemical compound 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 125000004423 acyloxy group Chemical group 0.000 description 3
- 150000007514 bases Chemical class 0.000 description 3
- 239000013522 chelant Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 238000004880 explosion Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000012456 homogeneous solution Substances 0.000 description 2
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 239000011736 potassium bicarbonate Substances 0.000 description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 235000011181 potassium carbonates Nutrition 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- XYHKNCXZYYTLRG-UHFFFAOYSA-N 1h-imidazole-2-carbaldehyde Chemical compound O=CC1=NC=CN1 XYHKNCXZYYTLRG-UHFFFAOYSA-N 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-M 3-Methylbutanoic acid Natural products CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 1
- FREZLSIGWNCSOQ-UHFFFAOYSA-N 3-methylbutanoyl 3-methylbutanoate Chemical compound CC(C)CC(=O)OC(=O)CC(C)C FREZLSIGWNCSOQ-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 101100295738 Gallus gallus COR3 gene Proteins 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 229910001508 alkali metal halide Inorganic materials 0.000 description 1
- 150000008045 alkali metal halides Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N beta-methyl-butyric acid Natural products CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- KWZWNVAHEQHCTQ-UHFFFAOYSA-N diacetyloxyboranyl acetate Chemical compound CC(=O)OB(OC(C)=O)OC(C)=O KWZWNVAHEQHCTQ-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000020169 heat generation Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052806 inorganic carbonate Inorganic materials 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- LSACYLWPPQLVSM-UHFFFAOYSA-N isobutyric acid anhydride Chemical compound CC(C)C(=O)OC(=O)C(C)C LSACYLWPPQLVSM-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 235000011118 potassium hydroxide Nutrition 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-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、トリ低級アルカノイルオキシホウ素の製造法
に関する。DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to a process for producing tri-lower alkanoyloxyboron.
従来の技術及びその問題点
従来トリ低級アルカノイルオキシホウ素は、ホウ酸と無
水低級アルカン酸とを反応させることにより製造されて
いる［Ａ、Ｐｌｃｔｅｔ ａｎｄ Ａ、Ｇｅ１ｅｚｎｏ
ｆｆ。BACKGROUND ART AND PROBLEMS Conventionally, tri-lower alkanoyloxyboron is produced by reacting boric acid with lower alkanoic anhydride [A, Plctet and A, Ge1ezno
ff.
Ｂｅｒ、、３８．２２１９（１９０３） 、 Ｉａ＋ｐ
ｅｒｉａｌ ＣｈｅｍｉｃａｌＩｎｄｕｓｔｒｉｅｓ
Ｌｔｄ、Ｂｒ１ｔ、、１３５７９５５（１９７４）参照
］。Ber, 38.2219 (1903), Ia+p
erial Chemical Industries
Ltd, Brlt, 1357955 (1974)].
しかしながら、この方法によれば、急激な発熱を伴い爆
発の危険性があり［Ｌｅｏｎ Ｍ、Ｌｅｒｎｅｒ、Ｃｈ
ｅｍ。However, this method involves the risk of explosion due to rapid heat generation [Leon M., Lerner, Ch.
em.
Ｅｎｇ、Ｎｅｗｓ、１９７３．５１（３４）］ 、また
反応時間も長い等操作が煩雑で、大量合成を行ない得す
、従って工業的製法として不適当であるという欠点を有
している。Eng, News, 1973.51 (34)], and the process is complicated, such as requiring a long reaction time, and requires large-scale synthesis, making it unsuitable as an industrial production process.
一方、無水ホウ酸と無水低級アルカン酸とを反応させる
ことによりトリ低級アルカノイルオキシホウ素を得る方
法も知られている［Ａ、Ｐｉｃｔｅｔ ａｎｄＡ、Ｇｅ
１ｅｚｎｏｆｆ、Ｂｅｒ、、 ３６．２２１９（１９０
３）参照］。On the other hand, a method for obtaining tri-lower alkanoyloxyboron by reacting boric anhydride and lower alkanoic anhydride is also known [A, Pictet and A, Ge
1eznoff, Ber,, 36.2219 (190
See 3)].
しかしながらミこの方法によれば、反応が非常に不活性
であり、長時間の加熱を必要とし、これにより目的物を
高収率、高純度で製造し難いという欠点を有している。However, this method has the disadvantage that the reaction is very inert and requires long heating times, making it difficult to produce the desired product in high yield and purity.
問題点を解決するための手段
本発明は、上記欠点を有しないトリ低級アルカノイルオ
キシホウ素の製造法を提供するものである。Means for Solving the Problems The present invention provides a process for producing tri-lower alkanoyloxyboron which does not have the above-mentioned disadvantages.
即ち、本発明は、低級アルカン酸の存在下に無水ホウ酸
と無水低級アルカン酸とを反応させることを特徴とする
トリ低級アルカノイルオキシホウ素の製造法に係る。That is, the present invention relates to a method for producing tri-lower alkanoyloxyboron, which is characterized by reacting boric anhydride and lower alkanoic anhydride in the presence of a lower alkanoic acid.
本発明で得られるトリ低級アルカノイルオキシホウ素は
、抗菌剤を合成するための中間体として有用な一般式
［式中Ｒ１は低級アルキル基、Ｘ及びＸＩはそれぞれハ
ロゲン原子を示す。Ｒ２は基
１０ ＣＯＲ３（Ｒ３及びＲ４はそれぞれ低−Ｂ−〇Ｃ
ＯＲ’
級アルキル基）を示す。］
で表わされるベンゾヘテロ環化合物及びその塩を製造す
る際の有用な試薬である。例えば上記一般式（１）のベ
ンゾヘテロ環化合物は、下記反応式に従い製造される。The tri-lower alkanoyloxyboron obtained in the present invention has the general formula [wherein R1 is a lower alkyl group, and X and XI each represent a halogen atom], which is useful as an intermediate for synthesizing antibacterial agents. R2 is a group 10 COR3 (R3 and R4 are each a low-B-○C
OR' class alkyl group). ] It is a useful reagent in producing the benzoheterocyclic compound and its salt. For example, the benzoheterocyclic compound of the above general formula (1) is produced according to the following reaction formula.
［反応式−１コ
［式中Ｒ１、Ｒ２、Ｒ３、Ｒ４、Ｘ及びＸｌは前記に同
じ。Ｒ５は低級アルキル基を示す。Ｒ６は水素原子又は
低級アルキル基を示す。］一般般式１ａ）の化合物と本
発明の一般式（２）の化合物の反応は、適当な溶媒中に
て行なわれる。[Reaction formula-1] [In the formula, R1, R2, R3, R4, X and Xl are the same as above. R5 represents a lower alkyl group. R6 represents a hydrogen atom or a lower alkyl group. ] The reaction between the compound of general formula 1a) and the compound of general formula (2) of the present invention is carried out in a suitable solvent.
ここで使用される溶媒としては、例えばジエチルエーテ
ル、ジオキサン、テトラヒドロフラン、モノグライム、
ジグライム等のエーテル類、ベンゼン、トルエン、キシ
レン等の芳香族炭化水素類、ｎ−へキサン、ヘプタン、
シクロヘキサン等の脂肪族炭化水素類、無水酢酸等の無
水低級アルカン酸類、ジメチルホルムアミド（ＤＭＦ）
、ジメチルスルホキシド（ＤＭＳＯ） 、＞キサメチ
ルリン酸トリアミド（Ｉ（ＭＰＡ） 、アセトニトリル
、Ｎ−メチルビロリドン等の非プロトン性極性溶媒等が
挙げられる。該反応は、通常室温〜２００℃程度、好ま
しくは室温〜１５０℃付近にて進行し、一般に１０分〜
５時間程度にて終了する。一般式（２）の化合物の使用
量は、一般式（１ａ）の化合物に対して少なくとも等モ
ル程度、好ましくは等モル−１０倍モルとするのがよい
。Examples of the solvent used here include diethyl ether, dioxane, tetrahydrofuran, monoglyme,
Ethers such as diglyme, aromatic hydrocarbons such as benzene, toluene, xylene, n-hexane, heptane,
Aliphatic hydrocarbons such as cyclohexane, lower alkanoic anhydrides such as acetic anhydride, dimethylformamide (DMF)
, dimethylsulfoxide (DMSO), >xamethylphosphoric acid triamide (I (MPA)), acetonitrile, N-methylpyrrolidone, and other aprotic polar solvents.The reaction is usually carried out at room temperature to about 200°C, preferably room temperature to 150°C Proceeds around ℃, generally 10 minutes ~
It will be completed in about 5 hours. The amount of the compound of general formula (2) to be used is at least equimolar to the compound of general formula (1a), preferably equimolar to 10 times the molar amount.
ここで、一般式（１）の化合物は、例えば抗菌剤として
有用な一般式
［式中Ｒ１及びＸは前記に同じ。Ｒ７は基−Ａ
−Ｎ Ｎ−Ｒ８（Ｒ８は水素原子又は低級アル℃−１
素原子、硫黄原子又はメチレン基を示す。ｍは′１又は
２を示す。Ｒ９は水素原子、低級アルキル基、低級アル
コキシ基、水酸基、フェニル低級アルキル基、低級アル
カノイルオキシ基、置換基として低級アルキル基又は低
級アルカノイル基を有することのあるアミノ基、オキソ
基又はカルバモイル基を示す。）を示す。］で表わされ
るベンゾヘテロ環化合物を合成するための中間体として
有用である。Here, the compound of general formula (1) is, for example, a compound of the general formula [wherein R1 and X are the same as above] useful as an antibacterial agent. R7 represents a group -A-N N-R8 (R8 represents a hydrogen atom, a lower alkyl atom, a sulfur atom, or a methylene group; m represents '1 or 2; R9 represents a hydrogen atom, a lower alkyl group, Indicates a lower alkoxy group, a hydroxyl group, a phenyl lower alkyl group, a lower alkanoyloxy group, an amino group, an oxo group, or a carbamoyl group that may have a lower alkyl group or a lower alkanoyl group as a substituent. ] It is useful as an intermediate for synthesizing the benzoheterocyclic compound represented by
一般式（１）の化合物を合成中間体として用いると、一
般式（Ａ）のベンゾヘテロ環化合物を緩和な条件下、短
時間で、高収率、高純度にてしかも工業的規模にて製造
することができる。When the compound of general formula (1) is used as a synthetic intermediate, the benzoheterocyclic compound of general formula (A) can be produced in a short time under mild conditions, in high yield, and with high purity, and on an industrial scale. be able to.
また一般式（Ａ）の化合物は、上記一般式（１）の化合
物と一般式Ｒ７Ｈ（Ｒ７は前記と同じ）で表わされる化
合物とから、下記に示す方法によっても製造され得る。Further, the compound of general formula (A) can also be produced by the method shown below from the compound of general formula (1) above and a compound represented by general formula R7H (R7 is the same as above).
［反応式−２］
（１） （Ａ’ ）［式中
Ｒ１、Ｒ２、Ｒ７、ＸＩ及びＸは前記に同じ。］
一般式（１）の化合物と一般式（３）の化合物との反応
において、両者の使用割合は特に限定がなく広い範囲か
ら適宜選択できるが、通常前者に対して後者を少なくと
も等モル程度、好ましくは等モル−５倍モル程度使用す
るのがよい。該反応は不活性溶媒、具体的には水、メタ
ノール、エタノール、イソプロパツール、ブタノール、
アミルアルコール、イソアミルアルコール等のアルコー
ル類、ベンゼン、トルエン、キシレン等の芳香族炭化水
素類、テトラヒドロフラン、ジオキサン、ジグライム等
のエーテル類、ジメチルアセタミド、ＤＭＦＳＤＭＳＯ
ｌＨＭＰＡ、アセトニトリル、Ｎ−メチルピロリドン等
又はこれらの混合溶媒中で行なわれる。これらのうちＤ
ＭＦ、ＤＭＳＯ。[Reaction Formula-2] (1) (A') [In the formula, R1, R2, R7, XI and X are the same as above. ] In the reaction between the compound of general formula (1) and the compound of general formula (3), the ratio of the two used is not particularly limited and can be appropriately selected from a wide range, but usually the latter is at least equimolar to the former, Preferably, it is used in an equimolar amount to about 5 times the molar amount. The reaction is carried out in an inert solvent, specifically water, methanol, ethanol, isopropanol, butanol,
Alcohols such as amyl alcohol and isoamyl alcohol, aromatic hydrocarbons such as benzene, toluene and xylene, ethers such as tetrahydrofuran, dioxane and diglyme, dimethylacetamide, DMFSDMSO
The reaction is carried out in a solvent such as lHMPA, acetonitrile, N-methylpyrrolidone, etc. or a mixed solvent thereof. Among these, D
MF, DMSO.
ＨＭＰＡ１アセトニトリル及びＮ−メチルピロリドンが
好ましい。また該反応は脱酸剤、具体的には炭酸ナトリ
ウム、炭酸カリウム、炭酸水素ナトリウム、炭酸水素カ
リウム、水素化ナトリウム等の無機炭酸塩類、ピリジン
、キノリン、トリエチルアミン等の有機塩基類等の存在
下に行なうこともできる。また弗化カリウム等のアルカ
リ金属ハロゲン化物を添加してもよい。反応は通常１〜
２０気圧、好ましくは１〜１０気圧の圧力下、室温〜２
５０℃程度、好ましくは室温〜２００°Ｃの温度下に行
なわれ、一般に１０分〜３０時間程度で終了する。HMPA1 acetonitrile and N-methylpyrrolidone are preferred. The reaction is carried out in the presence of a deoxidizing agent, specifically inorganic carbonates such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, and sodium hydride, and organic bases such as pyridine, quinoline, and triethylamine. You can also do it. Further, an alkali metal halide such as potassium fluoride may be added. The reaction is usually 1~
Under a pressure of 20 atm, preferably 1 to 10 atm, room temperature to 2
The process is carried out at a temperature of about 50°C, preferably room temperature to 200°C, and is generally completed in about 10 minutes to 30 hours.
上記で製造された一般式（Ａ′）の化合物を酸又は塩基
性化合物で処理することによりキレートを分解させ、対
応するＲ２が水素原子である化合物（Ａ）に導くことが
できる。ここで使用される酸としては、塩酸、硫酸等の
鉱酸、酢酸、ｐ−）ルエンスルホン酸等の有機酸が挙げ
られる。塩基性化合物としては、水酸化ナトリウム、水
酸化カリウム、炭酸水素ナトリウム、炭酸水素カリウム
、炭酸カリウム等の無機塩基、トリエチルアミン等の有
機塩基が挙げられる。該反応は、０〜１５０℃程度、好
ましくは０〜１００″Ｃ付近にて好適に進行する。酸又
は塩基性化合物の使用量しては、原料化合物に対して通
常少なくとも等モル程度、好ましくは１〜１０倍量使用
するのがよい。By treating the compound of general formula (A') produced above with an acid or basic compound, the chelate can be decomposed, leading to the corresponding compound (A) in which R2 is a hydrogen atom. Examples of acids used here include mineral acids such as hydrochloric acid and sulfuric acid, and organic acids such as acetic acid and p-)luenesulfonic acid. Examples of the basic compound include inorganic bases such as sodium hydroxide, potassium hydroxide, sodium hydrogen carbonate, potassium hydrogen carbonate, and potassium carbonate, and organic bases such as triethylamine. The reaction proceeds suitably at about 0 to 150°C, preferably around 0 to 100"C. The amount of the acid or basic compound to be used is usually at least about equimolar, preferably at least equimolar to the starting material compound. It is best to use 1 to 10 times the amount.
本発明の方法は、低級アルカン酸の存在下、無水ホウ酸
と無水低級アルカン酸とを反応させることにより実施さ
れる。The method of the present invention is carried out by reacting boric anhydride and lower alkanoic anhydride in the presence of a lower alkanoic acid.
本明細書において、低級アルカノイルオキシ基としては
、例えばアセチルオキシ、プロピオニルオキシ、ブチリ
ルオキシ、イソブチリルオキシ、ペンタノイルオキシ、
ｔｅｒｔ−ブチルカルボニルオキシ、ヘキサノイルオキ
シ基等の炭素数２〜６の直鎖又は分枝鎖状アルカノイル
オキシ基が挙げられる。In this specification, examples of the lower alkanoyloxy group include acetyloxy, propionyloxy, butyryloxy, isobutyryloxy, pentanoyloxy,
Examples include straight-chain or branched alkanoyloxy groups having 2 to 6 carbon atoms, such as tert-butylcarbonyloxy and hexanoyloxy groups.
無水低級アルカン酸としては、例えば無水酢酸、無水プ
ロピオン酸、無水酪酸、無水イソ酪酸、無水吉草酸、無
水イソ吉草酸、無水ピバリン酸、無水ヘキサン酸等の炭
素数２〜６の直鎖又は分枝鎖状無水アルカン酸を挙げる
ことができる。Examples of lower alkanoic anhydrides include linear or branched carbon atoms having 2 to 6 carbon atoms, such as acetic anhydride, propionic anhydride, butyric anhydride, isobutyric anhydride, valeric anhydride, isovaleric anhydride, pivalic anhydride, and hexanoic anhydride. Mention may be made of branched alkanoic anhydrides.
低級アルカン酸としては、例えば酢酸、プロピオン酸、
酪酸、イン酪酸、吉草酸、イソ吉草酸、ピバリン酸、ヘ
キサン酸等の炭素数２〜６の直鎖又は分枝鎖状アルカン
酸を挙げることができる。Examples of lower alkanoic acids include acetic acid, propionic acid,
Examples include straight-chain or branched alkanoic acids having 2 to 6 carbon atoms, such as butyric acid, inbutyric acid, valeric acid, isovaleric acid, pivalic acid, and hexanoic acid.
本発明の反応は、通常室温〜２００ ”Ｃ１好まし−く
は室温〜１５０℃付近にて行なわれ、一般に０．５〜２
時間程度で終了する。The reaction of the present invention is usually carried out at room temperature to 200°C, preferably around room temperature to 150°C, and generally at 0.5 to 200°C.
It will finish in about an hour.
本−発明において、無水低級アルカン酸は、無水ホウ酸
に対して通常大過剰量、好ましくは３〜２０倍モル量使
用するのがよい。また低級アルカン酸の使用量としては
、特に限定されず、通常無水ホウ酸に対して１〜５０倍
重量使用するのがよい。In the present invention, the lower alkanoic anhydride is usually used in a large excess amount, preferably 3 to 20 times the molar amount, relative to the boric anhydride. The amount of the lower alkanoic acid to be used is not particularly limited, but it is usually 1 to 50 times the weight of boric anhydride.
斯くして得られる本発明の目的化合物は、通常の分離手
段により容易に単離、精製できる。該分離手段としては
、例えば溶媒抽出法、希釈法、再結晶法、カラムクロマ
トグラフィー、プレパラティブ薄層クロマトグラフィー
等が挙げられる。The target compound of the present invention thus obtained can be easily isolated and purified by conventional separation means. Examples of the separation means include solvent extraction, dilution, recrystallization, column chromatography, and preparative thin layer chromatography.
発明の効果
本発明による製造法は、従来の方法に比し、反応時間が
短く、爆発の危険性もな（、また反応操作は極めて簡便
であり、高収率、高純度にて大量合成も容易であり、従
って工業的に極めて有利な方法である。Effects of the Invention Compared to conventional methods, the production method according to the present invention has a shorter reaction time and no risk of explosion (also, the reaction operation is extremely simple, and large-scale synthesis is possible with high yield and high purity). This method is easy and therefore industrially extremely advantageous.
実 施 例
以下に実施例及び参考例を掲げて本発明をより一層明ら
かにする。EXAMPLES Examples and reference examples are given below to further clarify the present invention.
実施例１
無水ホウ酸０．５６ｇ、無水酢酸９．２ｇ及び酢酸２．
９ｇを混合し、均一溶液になるまで約１時間加熱還流す
る。反応終了後、反応液を濃縮し、得られた残渣に石油
エーテルを加え、析出する結晶を枦取し、これを乾燥さ
せてトリアセチルオキシホウ素３．０ｇ（収率９８．５
％）を得る。Example 1 0.56 g of boric anhydride, 9.2 g of acetic anhydride, and 2.0 g of acetic acid.
Mix 9 g and heat under reflux for about 1 hour until a homogeneous solution is obtained. After the reaction was completed, the reaction solution was concentrated, petroleum ether was added to the resulting residue, the precipitated crystals were collected and dried to give 3.0 g of triacetyloxyboron (yield: 98.5).
%).
融点１２１℃、白色結晶
元素分析（Ｃｓ Ｈ９０６Ｂとして）
ＣＨ
計算値（％） ３８，３４ ４．８３実測値（％）
３８．５６ ４．９５参考例１
８．９−ジフルオロ−５−メチル−６，７−シヒドロー
１−オキソ−ＩＨ，５Ｈ−ベンゾ［ｉｊ］キノリジン−
２−カルボン酸
−Ｂ （ＯＣＯＣＨ３）２キレート０．８１ｇ、４−ヒ
ドロキシピペリジン０．８１ｇ及びアセトニトリル２．
８１１１１２を混合し、５０〜８０℃にて３０分〜４時
間攪拌する。反応混合物に濃塩酸８．１鯨を加え、１０
分間加熱還流後冷却し、析出晶を枦取する。５０％エタ
ノールより再結晶して０．５０ｇの９−フルオロ−８−
（４−ヒドロキシ−１−ピペリジニル）−５−メチル−
６，７−シヒドロー１−オキソ−ＩＨ，５Ｈ−ベンゾ［
ｉｊｌキノリジン−２−カルボン酸を得る。Melting point 121°C, white crystal Elemental analysis (as Cs H906B) CH Calculated value (%) 38,34 4.83 Actual value (%)
38.56 4.95 Reference Example 1 8.9-difluoro-5-methyl-6,7-sihydro-1-oxo-IH,5H-benzo[ij]quinolidine-
2-carboxylic acid-B (OCOCH3) 2 chelate 0.81 g, 4-hydroxypiperidine 0.81 g and acetonitrile 2.
811112 and stirred at 50 to 80°C for 30 minutes to 4 hours. Concentrated hydrochloric acid 8.1 was added to the reaction mixture, and 10
After heating under reflux for a minute, the mixture is cooled and the precipitated crystals are collected. Recrystallized from 50% ethanol to obtain 0.50 g of 9-fluoro-8-
(4-hydroxy-1-piperidinyl)-5-methyl-
6,7-Sihydro-1-oxo-IH,5H-benzo[
ijl quinolidine-2-carboxylic acid is obtained.
融点２４７℃（分解）、白色結晶
参考例２
８．９−ジフルオロ−５−メチル−６，７−シヒドロー
１−オキソ−ＩＨ，５Ｈ−ベンゾ［ｉｊｌキノリジン−
２−カルボン酸
−Ｂ （ＯＣＯＣＨａ ）２キレ−）３．４６ｇを用い
、参考例２と同様にして９−フルオロ−８−（４−メチ
ル−１−ピペラジニル）−５−メチル−６，７−シヒド
ロー１−オキソ−ＩＨ，５Ｈ−ベンゾ［ｉｊ］キノリジ
ン−２−カルボン酸を２７．４８ｇ得る。Melting point: 247°C (decomposed), white crystals Reference Example 2 8.9-difluoro-5-methyl-6,7-sihydro-1-oxo-IH,5H-benzo[ijlquinolidine-
9-Fluoro-8-(4-methyl-1-piperazinyl)-5-methyl-6,7- was prepared in the same manner as in Reference Example 2 using 3.46 g of 2-carboxylic acid-B (OCOCHa) 27.48 g of sihydro-1-oxo-IH,5H-benzo[ij]quinolidine-2-carboxylic acid are obtained.
融点２６１℃（分解）、白色結晶
参考例３
無水ホウ酸２４．８ｇ、無水酢酸４０７脱及び酢酸１２
３脱を混合し、均一溶液になるまで約１時間加熱還流す
る。得られたトリアセチルオキ・シホウ素は、単離する
ことなく、上記反応液に８゜９−ジフルオロ−５−メチ
ル−６，７−シヒドロー１−オキソ−ＩＨ，５Ｈ−ベン
ゾ［ｉｊ］キノリジン−２−カルボン酸１８２ｇを加え
、更に１時間加熱還流する。その後溶媒を濃縮後、更に
トルエン共沸を繰り返した後、トルエンを留去する。Melting point 261°C (decomposition), white crystals Reference example 3 Boric anhydride 24.8g, acetic anhydride 407 removed and acetic acid 12
Mix the three solutions and heat to reflux for about 1 hour until a homogeneous solution is obtained. The obtained triacetyloxy cyboron was added to the above reaction solution without isolation. Add 182 g of 2-carboxylic acid and heat under reflux for an additional hour. Thereafter, after concentrating the solvent, toluene azeotropy is repeated, and then toluene is distilled off.
２６５．３７ｇの８，９−ジフルオロ−５−メチル−６
，７−シヒドロー１−オキソ−ＩＨ，５Ｈ−ベンゾ［ｉ
ｊ］キノリジン−２−カルボン酸−Ｂ （ＯＣＯＣＨａ
）２キレートを得る。265.37 g of 8,9-difluoro-5-methyl-6
,7-sihydro-1-oxo-IH,5H-benzo[i
j] Quinolidine-2-carboxylic acid-B (OCOCHa
)2 chelates are obtained.
融点２０５℃（分解）、白色結晶
参考例４
参考例３と同様にして適当な出発原料を用いて以下の化
合物を得る。Melting point: 205°C (decomposed), white crystals Reference Example 4 The following compound was obtained in the same manner as in Reference Example 3 using appropriate starting materials.
８−ブロモ−９−フルオロ−５−メチル−６゜７−シヒ
ドロー１−オキソ−ＩＨ，５Ｈ−ベンゾＣＬ ｊ］キノ
リジン−２−カルボン酸−Ｂ（ＯＣＯＣＨ３）ｚキレー
ト
融点２１５℃（分解）、白色結晶
（以 上）8-bromo-9-fluoro-5-methyl-6゜7-sihydro-1-oxo-IH,5H-benzoCL j]quinolidine-2-carboxylic acid-B (OCOCH3) z Chelate melting point 215 °C (decomposition), white Crystal (and above)
Claims (1)
アルカン酸とを反応させることを特徴とするトリ低級ア
ルカノイルオキシホウ素の製造法。(1) A method for producing tri-lower alkanoyloxyboron, which comprises reacting boric anhydride and lower alkanoic anhydride in the presence of a lower alkanoic acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP923489A JP2731853B2 (en) | 1989-01-17 | 1989-01-17 | Method for producing tri-lower alkanoyloxyboron |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP923489A JP2731853B2 (en) | 1989-01-17 | 1989-01-17 | Method for producing tri-lower alkanoyloxyboron |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02188589A true JPH02188589A (en) | 1990-07-24 |
| JP2731853B2 JP2731853B2 (en) | 1998-03-25 |
Family
ID=11714715
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP923489A Expired - Lifetime JP2731853B2 (en) | 1989-01-17 | 1989-01-17 | Method for producing tri-lower alkanoyloxyboron |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2731853B2 (en) |
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|---|---|---|---|---|
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| US6608078B2 (en) | 2000-05-08 | 2003-08-19 | Wockhardt Limited | Antibacterial chiral 8-(substituted piperidino)-benzo [i,j] quinolizines, processes, compositions and methods of treatment |
| US6664267B1 (en) | 2002-05-28 | 2003-12-16 | Wockhardt Limited | Crystalline fluoroquinolone arginine salt form |
| US6750224B1 (en) | 1999-05-07 | 2004-06-15 | Wockhardt Limited | Antibacterial optically pure benzoquinolizine carboxylic acids, processes, compositions and methods of treatment |
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1989
- 1989-01-17 JP JP923489A patent/JP2731853B2/en not_active Expired - Lifetime
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|---|---|---|---|---|
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| US6750224B1 (en) | 1999-05-07 | 2004-06-15 | Wockhardt Limited | Antibacterial optically pure benzoquinolizine carboxylic acids, processes, compositions and methods of treatment |
| US6753333B2 (en) | 1999-12-14 | 2004-06-22 | Wockhardt Limited | Chiral fluoroquinolone arginine salt forms |
| US6608078B2 (en) | 2000-05-08 | 2003-08-19 | Wockhardt Limited | Antibacterial chiral 8-(substituted piperidino)-benzo [i,j] quinolizines, processes, compositions and methods of treatment |
| US7098219B2 (en) | 2000-08-01 | 2006-08-29 | Wockhart Limited | Inhibitors of cellular efflux pumps of microbes |
| US6514986B2 (en) | 2000-11-22 | 2003-02-04 | Wockhardt Limited | Chiral fluoroquinolone arginine salt forms |
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| US7132541B2 (en) | 2002-05-28 | 2006-11-07 | Wockhardt Limited | Crystalline fluoroquinolone arginine salt form |
| US6664267B1 (en) | 2002-05-28 | 2003-12-16 | Wockhardt Limited | Crystalline fluoroquinolone arginine salt form |
| US7164023B2 (en) | 2003-09-04 | 2007-01-16 | Wockhardt Limited | Benzoquinolizine-2-carboxylic acid arginine salt tetrahydrate |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2731853B2 (en) | 1998-03-25 |
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