JP2000154171A - Production of cyanobenzoic acid compound - Google Patents
Production of cyanobenzoic acid compoundInfo
- Publication number
- JP2000154171A JP2000154171A JP10328171A JP32817198A JP2000154171A JP 2000154171 A JP2000154171 A JP 2000154171A JP 10328171 A JP10328171 A JP 10328171A JP 32817198 A JP32817198 A JP 32817198A JP 2000154171 A JP2000154171 A JP 2000154171A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- cyanobenzamide
- cyanobenzoic acid
- reaction
- formula
- 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
- -1 cyanobenzoic acid compound Chemical class 0.000 title claims abstract description 48
- 238000004519 manufacturing process Methods 0.000 title claims description 10
- 238000006243 chemical reaction Methods 0.000 claims abstract description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000003960 organic solvent Substances 0.000 claims abstract description 10
- FUKWTMJZHKZKFA-UHFFFAOYSA-N 4-cyanobenzamide Chemical compound NC(=O)C1=CC=C(C#N)C=C1 FUKWTMJZHKZKFA-UHFFFAOYSA-N 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 7
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 6
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 6
- 125000001424 substituent group Chemical group 0.000 claims abstract description 5
- PAQVSWFCADWSLB-UHFFFAOYSA-N 3-cyanobenzamide Chemical compound NC(=O)C1=CC=CC(C#N)=C1 PAQVSWFCADWSLB-UHFFFAOYSA-N 0.000 claims abstract description 4
- GYLKKXHEIIFTJH-UHFFFAOYSA-N 3-cyanobenzoic acid Chemical compound OC(=O)C1=CC=CC(C#N)=C1 GYLKKXHEIIFTJH-UHFFFAOYSA-N 0.000 claims abstract description 4
- 230000002378 acidificating effect Effects 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims 2
- 239000005711 Benzoic acid Substances 0.000 claims 1
- 235000010233 benzoic acid Nutrition 0.000 claims 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 abstract description 18
- ADCUEPOHPCPMCE-UHFFFAOYSA-N 4-cyanobenzoic acid Chemical compound OC(=O)C1=CC=C(C#N)C=C1 ADCUEPOHPCPMCE-UHFFFAOYSA-N 0.000 abstract description 8
- 239000002994 raw material Substances 0.000 abstract description 5
- 239000003905 agrochemical Substances 0.000 abstract description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 abstract 2
- 229940079593 drug Drugs 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- DTNSDCJFTHMDAK-UHFFFAOYSA-N 2-cyanobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1C#N DTNSDCJFTHMDAK-UHFFFAOYSA-N 0.000 description 6
- BHXFKXOIODIUJO-UHFFFAOYSA-N benzene-1,4-dicarbonitrile Chemical compound N#CC1=CC=C(C#N)C=C1 BHXFKXOIODIUJO-UHFFFAOYSA-N 0.000 description 5
- 125000002560 nitrile group Chemical group 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- LAQPNDIUHRHNCV-UHFFFAOYSA-N isophthalonitrile Chemical compound N#CC1=CC=CC(C#N)=C1 LAQPNDIUHRHNCV-UHFFFAOYSA-N 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- STQPCKPKAIRSEL-UHFFFAOYSA-N 2-cyanobenzamide Chemical class NC(=O)C1=CC=CC=C1C#N STQPCKPKAIRSEL-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- TXRVDQMSXQKAPG-UHFFFAOYSA-N 2,3,5,6-tetrachlorobenzene-1,4-dicarbonitrile Chemical compound ClC1=C(Cl)C(C#N)=C(Cl)C(Cl)=C1C#N TXRVDQMSXQKAPG-UHFFFAOYSA-N 0.000 description 2
- PCRSJGWFEMHHEW-UHFFFAOYSA-N 2,3,5,6-tetrafluorobenzene-1,4-dicarbonitrile Chemical compound FC1=C(F)C(C#N)=C(F)C(F)=C1C#N PCRSJGWFEMHHEW-UHFFFAOYSA-N 0.000 description 2
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- CRQQGFGUEAVUIL-UHFFFAOYSA-N chlorothalonil Chemical compound ClC1=C(Cl)C(C#N)=C(Cl)C(C#N)=C1Cl CRQQGFGUEAVUIL-UHFFFAOYSA-N 0.000 description 2
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 2
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000012847 fine chemical Substances 0.000 description 2
- 229920001002 functional polymer Polymers 0.000 description 2
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 2
- 229910001385 heavy metal Inorganic materials 0.000 description 2
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 239000004973 liquid crystal related substance Substances 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- XTFCOCGBWMNRKW-UHFFFAOYSA-N 2,3,4,6-tetrachloro-5-cyanobenzamide Chemical compound NC(=O)C1=C(Cl)C(Cl)=C(Cl)C(C#N)=C1Cl XTFCOCGBWMNRKW-UHFFFAOYSA-N 0.000 description 1
- NFJYPRIMFBREAR-UHFFFAOYSA-N 2,3,5,6-tetrachloro-4-cyanobenzamide Chemical compound NC(=O)C1=C(Cl)C(Cl)=C(C#N)C(Cl)=C1Cl NFJYPRIMFBREAR-UHFFFAOYSA-N 0.000 description 1
- WVHMPQKZPHOCRD-UHFFFAOYSA-N 2,4,5,6-tetrafluorobenzene-1,3-dicarbonitrile Chemical compound FC1=C(F)C(C#N)=C(F)C(C#N)=C1F WVHMPQKZPHOCRD-UHFFFAOYSA-N 0.000 description 1
- NHWQMJMIYICNBP-UHFFFAOYSA-N 2-chlorobenzonitrile Chemical compound ClC1=CC=CC=C1C#N NHWQMJMIYICNBP-UHFFFAOYSA-N 0.000 description 1
- NWPNXBQSRGKSJB-UHFFFAOYSA-N 2-methylbenzonitrile Chemical compound CC1=CC=CC=C1C#N NWPNXBQSRGKSJB-UHFFFAOYSA-N 0.000 description 1
- WMNNILBXIBTXNM-UHFFFAOYSA-N 3-cyano-2,4,5,6-tetrafluorobenzamide Chemical compound NC(=O)C1=C(F)C(F)=C(F)C(C#N)=C1F WMNNILBXIBTXNM-UHFFFAOYSA-N 0.000 description 1
- SVGNVFMKAIBMOW-UHFFFAOYSA-N 4-cyano-2,3,5,6-tetrafluorobenzamide Chemical compound NC(=O)C1=C(F)C(F)=C(C#N)C(F)=C1F SVGNVFMKAIBMOW-UHFFFAOYSA-N 0.000 description 1
- RXQNKKRGJJRMKD-UHFFFAOYSA-N 5-bromo-2-methylaniline Chemical compound CC1=CC=C(Br)C=C1N RXQNKKRGJJRMKD-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 102100024522 Bladder cancer-associated protein Human genes 0.000 description 1
- 101150110835 Blcap gene Proteins 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 101100010166 Mus musculus Dok3 gene Proteins 0.000 description 1
- KEJOCWOXCDWNID-UHFFFAOYSA-N Nitrilooxonium Chemical class [O+]#N KEJOCWOXCDWNID-UHFFFAOYSA-N 0.000 description 1
- 101100493740 Oryza sativa subsp. japonica BC10 gene Proteins 0.000 description 1
- 238000000297 Sandmeyer reaction Methods 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229960004050 aminobenzoic acid Drugs 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 150000008359 benzonitriles Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical class O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000010814 metallic waste Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- WCZAXBXVDLKQGV-UHFFFAOYSA-N n,n-dimethyl-2-(7-oxobenzo[c]fluoren-5-yl)oxyethanamine oxide Chemical compound C12=CC=CC=C2C(OCC[N+](C)([O-])C)=CC2=C1C1=CC=CC=C1C2=O WCZAXBXVDLKQGV-UHFFFAOYSA-N 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- ILGQIWVECKRNLJ-UHFFFAOYSA-N nitroso hydrogen sulfate;sulfuric acid Chemical compound OS(O)(=O)=O.OS(=O)(=O)ON=O ILGQIWVECKRNLJ-UHFFFAOYSA-N 0.000 description 1
- VPCDQGACGWYTMC-UHFFFAOYSA-N nitrosyl chloride Chemical compound ClN=O VPCDQGACGWYTMC-UHFFFAOYSA-N 0.000 description 1
- 235000019392 nitrosyl chloride Nutrition 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229920006391 phthalonitrile polymer Polymers 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は医・農薬及び液晶、
機能性高分子モノマー等の各種ファインケミカルズの原
料または中間体として有用な、シアノ安息香酸またはそ
の塩素またはフッ素原子による核置換体の製造法に関す
る。TECHNICAL FIELD The present invention relates to medical and agricultural chemicals and liquid crystals,
The present invention relates to a method for producing a cyanobenzoic acid or a nucleus-substituted product thereof with a chlorine or fluorine atom, which is useful as a raw material or an intermediate of various fine chemicals such as functional polymer monomers.
【０００２】[0002]
【従来の技術】シアノ安息香酸の製造方法としては、古
くからｐ−アミノ安息香酸をジアゾ化した後シアン化銅
を反応させるサンドマイヤー反応［Lucas et al.,J.Am.
Chem.Soc.,51(1929)2718］が知られている。また、トル
ニトリルをクロム酸や過マンガン酸などの強力な試薬酸
化剤で酸化し合成する方法［Levine et al.,J.Org.Che
m.,24(1959)115 ］、［Kattwinkel et al.,Chem.Ber.,3
7(1904)3226］が知られている。しかしサンドマイヤー
法は危険なシアン化銅を必要とし、シアン化水素の遊離
する酸性条件下でのｐ−シアノ安息香酸の単離精製は困
難である。クロム酸や過マンガン酸などの試薬酸化剤を
用いた場合は、有毒な重金属廃棄物が化学量論量以上生
成し、有毒な重金属を含む廃液が大量に出て環境に対す
る問題が多い。最近では、クロロベンゾニトリルのよう
に、ハロゲンが置換されたベンゾニトリルを触媒を用い
て一酸化炭素と反応させてｐ−シアノ安息香酸を合成す
る方法［特開昭64-47 公報、Dokl.Akad.Nauk.SSSR,312,
5,1129,(1990) 、J.Organomet.Chem.,358,1-3,563,(198
8)］、テレフタロニトリルの片側ニトリル基をモノニト
ラーゼ等を用いて酵素的に加水分解してｐ−シアノ安息
香酸を合成する方法［特開昭61-85194公報］等が報告さ
れている。さらに、本発明に関連のある先行技術とし
て、テレフタロニトリルを加圧下アンモニア水でニトリ
ル基を加水分解する方法［Arkhipova et al.,J.Gen.Che
m.USSR,33(1963)631］がある。著者らによれば、テレフ
タロニトリルの片側水和で生じるｐ−シアノベンズアミ
ドのアミド基が加水分解を受け、ｐ−シアノ安息香酸が
できるとしている。しかし上記方法では、原料の入手が
難しく価格が高かったり、また合成が煩雑で過酷な条件
が必要であったり、いずれも工業的に安価で有利な方法
としては未だ充分なものではなかった。2. Description of the Related Art As a method for producing cyanobenzoic acid, a sand Meyer reaction in which p-aminobenzoic acid is diazotized and then reacted with copper cyanide [Lucas et al., J. Am.
Chem. Soc., 51 (1929) 2718] is known. In addition, a method of oxidizing tolunitrile with a strong reagent oxidizing agent such as chromic acid or permanganic acid to synthesize it [Levine et al., J. Org.
m., 24 (1959) 115], [Kattwinkel et al., Chem. Ber., 3
7 (1904) 3226]. However, the Sandmeyer method requires dangerous copper cyanide, and it is difficult to isolate and purify p-cyanobenzoic acid under acidic conditions under which hydrogen cyanide is released. When a reagent oxidizing agent such as chromic acid or permanganic acid is used, toxic heavy metal waste is generated in a stoichiometric amount or more, and a large amount of waste liquid containing toxic heavy metal is generated, which is a problem for the environment. Recently, a method of synthesizing p-cyanobenzoic acid by reacting a halogen-substituted benzonitrile such as chlorobenzonitrile with carbon monoxide using a catalyst [Japanese Patent Laid-Open No. 64-47, Dokl. Akad. .Nauk.SSSR, 312,
5,1129, (1990), J. Organomet.Chem., 358, 1-3, 563, (198
8)], and a method of synthesizing p-cyanobenzoic acid by enzymatically hydrolyzing a nitrile group on one side of terephthalonitrile using mononitrase or the like [Japanese Patent Laid-Open No. 61-85194] has been reported. Further, as a prior art related to the present invention, a method of hydrolyzing a terephthalonitrile with aqueous ammonia under pressure to a nitrile group [Arkhipova et al., J. Gen. Che.
m.USSR, 33 (1963) 631]. According to the authors, the amide group of p-cyanobenzamide generated by one-sided hydration of terephthalonitrile undergoes hydrolysis to form p-cyanobenzoic acid. However, in the above-mentioned methods, raw materials are difficult to obtain and the price is high, and the synthesis is complicated and severe conditions are required. In any case, the methods are still insufficient as industrially inexpensive and advantageous methods.
【０００３】[0003]
【発明が解決しようとする課題】本発明は、かかる状況
に鑑みてなされたものであり、比較的容易に入手可能な
シアノベンズアミド化合物から、温和な条件でシアノ安
息香酸化合物を高純度且つ高収率で得る、工業的に有利
な製造法を提供するものである。DISCLOSURE OF THE INVENTION The present invention has been made in view of the above circumstances, and is intended to obtain a cyanobenzoic acid compound from a relatively easily available cyanobenzamide compound under mild conditions with high purity and high yield. The present invention provides an industrially advantageous production method which can be obtained at a high rate.
【０００４】[0004]
【課題を解決するための手段】本発明者らは、上記課題
を達成すべく種々検討した結果、シアノベンズアミド化
合物を出発原料として、ベンゼン環上のシアノ基を損な
うことなくアミド基（−ＣＯＮＨ2 ）をカルボキシル基
（−ＣＯＯＨ）に変換することにより、シアノ安息香酸
化合物を合成する方法を見いだし、本発明を完成するに
至った。すなわち本発明は、次の事項に関する。 （１）下記一般式（Ｉ）Means for Solving the Problems The present inventors have conducted various studies in order to achieve the above object, and as a result, using a cyanobenzamide compound as a starting material, without damaging a cyano group on a benzene ring (-CONH 2). ) Was converted to a carboxyl group (-COOH) to find a method for synthesizing a cyanobenzoic acid compound, thereby completing the present invention. That is, the present invention relates to the following matters. (1) The following general formula (I)
【化３】 （式中、−ＣＯＮＨ2 と−Ｘｎはベンゼン環上の置換基
を表わし、−ＣＯＮＨ2は−ＣＮのｍ位あるいはｐ位で
あり、Ｘは塩素原子またはフッ素原子を表わし、ｎは０
〜４の整数を表わす。ただし、ｎが２以上の場合、Ｘは
同一であっても異なっていてもよい。）で示されるシア
ノベンズアミド化合物とニトロソニウム塩化合物を酸性
条件下で反応させることを特徴とする下記一般式（Ｉ
Ｉ）Embedded image (Wherein -CONH 2 and -Xn represent a substituent on a benzene ring, -CONH 2 is at the m or p position of -CN, X represents a chlorine atom or a fluorine atom, and n is 0
Represents an integer of ４4. However, when n is 2 or more, X may be the same or different. ) And a nitrosonium salt compound are reacted under acidic conditions.
I)
【化４】 （式中、−ＣＯＯＨと−Ｘｎはベンゼン環上の置換基を
表わし、−ＣＯＯＨは−ＣＮのｍ位あるいはｐ位であ
り、Ｘは塩素原子またはフッ素原子を表わし、ｎは０〜
４の整数を表わす。ただし、ｎが２以上の場合、Ｘは同
一であっても異なっていてもよい。）で示されるシアノ
安息香酸化合物の製造法。 （２）反応を実質的に水を含まない有機溶媒で行う上記
（１）に記載のシアノ安息香酸化合物の製造法。 （３）一般式（Ｉ）のシアノベンズアミド化合物が、ｍ
−シアノベンズアミドまたはｐ−シアノベンズアミドで
あり、一般式（ＩＩ）のシアノ安息香酸化合物が対応す
るｍ−シアノ安息香酸またはｐ−シアノ安息香酸である
上記（１）または（２）に記載のシアノ安息香酸化合物
の製造法。Embedded image (Wherein -COOH and -Xn represent a substituent on a benzene ring, -COOH is at the m-position or p-position of -CN, X represents a chlorine atom or a fluorine atom, and n represents 0 to 0.
Represents an integer of 4. However, when n is 2 or more, X may be the same or different. The method for producing a cyanobenzoic acid compound represented by the formula: (2) The method for producing a cyanobenzoic acid compound according to the above (1), wherein the reaction is carried out in an organic solvent substantially free of water. (3) the cyanobenzamide compound of the general formula (I)
The cyanobenzoic acid according to the above (1) or (2), which is -cyanobenzamide or p-cyanobenzamide, and wherein the cyanobenzoic acid compound of the general formula (II) is a corresponding m-cyanobenzoic acid or p-cyanobenzoic acid. A method for producing an acid compound.
【０００５】[0005]
【発明の実施の形態】本発明のシアノ安息香酸化合物の
製造法における反応は、シアノベンズアミド化合物、ニ
トロソニウム塩化合物を有機溶媒の存在下、撹拌下に所
定の温度で、所定の時間まで攪拌することにより行われ
る。反応原材料の仕込みおよび反応は、特に制限はない
が、一般に大気圧下で行うことができる。用いる反応器
としては、ガラス、耐強酸金属容器が適する。BEST MODE FOR CARRYING OUT THE INVENTION In the reaction of the present invention for producing a cyanobenzoic acid compound, a cyanobenzamide compound and a nitrosonium salt compound are stirred under a predetermined temperature at a predetermined temperature for a predetermined time in the presence of an organic solvent. This is done by: The charging and reaction of the reaction raw materials are not particularly limited, but generally can be performed under atmospheric pressure. As a reactor to be used, glass and a strong acid-resistant metal container are suitable.
【０００６】本反応で用いられるシアノベンズアミド化
合物は無置換またはハロゲンで置換されたシアノベンズ
アミドである。無置換のシアノベンズアミド化合物はｐ
−シアノベンズアミド、ｍ−シアノベンズアミドであ
り、それぞれテレフタロニトリルおよびイソフタロニト
リルの片側ニトリル基の加水分解反応[Berther et al.,
Chem.Ber.,92(1959)2616] で容易に合成できる。次にハ
ロゲンで置換されたシアノベンズアミド化合物について
説明する。４−シアノ−２，３，５，６−テトラクロロ
ベンズアミド、３−シアノ−２，４，５，６−テトラク
ロロベンズアミドなどの塩素化シアノベンズアミド化合
物はテレフタロニトリルおよびイソフタロニトリルの塩
素化により得られるテトラクロロテレフタロニトリルな
どの塩素化テレフタロニトリル化合物およびテトラクロ
ロイソフタロニトリルなどの塩素化イソフタロニトリル
化合物の片側ニトリル基の加水分解反応で容易に合成で
きる。４−シアノ−２，３，５，６−テトラフルオロベ
ンズアミド、３−シアノ−２，４，５，６−テトラフル
オロベンズアミドなどのフッ素化シアノベンズアミド化
合物はテトラクロロテレフタロニトリルなどの塩素化テ
レフタロニトリル化合物およびテトラクロロイソフタロ
ニトリルなどの塩素化イソフタロニトリル化合物のフッ
素化反応で得られるテトラフルオロテレフタロニトリル
などのフッ素テレフタロニトリル化合物およびテトラフ
ルオロイソフタロニトリルなどのフッ素化イソフタロニ
トリル化合物の片側ニトリル基の加水分解反応で容易に
合成できる。The cyanobenzamide compound used in this reaction is unsubstituted or halogen-substituted cyanobenzamide. Unsubstituted cyanobenzamide compounds have p
-Cyanobenzamide and m-cyanobenzamide, respectively, a hydrolysis reaction of one side nitrile group of terephthalonitrile and isophthalonitrile [Berther et al.,
Chem. Ber., 92 (1959) 2616]. Next, a halogenated cyanobenzamide compound will be described. Chlorinated cyanobenzamide compounds such as 4-cyano-2,3,5,6-tetrachlorobenzamide and 3-cyano-2,4,5,6-tetrachlorobenzamide can be obtained by chlorinating terephthalonitrile and isophthalonitrile. The chlorinated terephthalonitrile compound such as tetrachloroterephthalonitrile and the chlorinated isophthalonitrile compound such as tetrachloroisophthalonitrile can be easily synthesized by a hydrolysis reaction of one side nitrile group. Fluorinated cyanobenamide compounds such as 4-cyano-2,3,5,6-tetrafluorobenzamide and 3-cyano-2,4,5,6-tetrafluorobenzamide are chlorinated terephthalolines such as tetrachloroterephthalonitrile. Of fluorinated isophthalonitrile compounds such as tetrafluoroterephthalonitrile and tetrafluoroisophthalonitrile such as tetrafluoroterephthalonitrile obtained by a fluorination reaction of chlorinated isophthalonitrile compounds such as nitrile compounds and tetrachloroisophthalonitrile It can be easily synthesized by a hydrolysis reaction of one side nitrile group.
【０００７】本発明においては、シアノベンズアミド化
合物にニトロソニウム塩化合物を反応させる。ニトロソ
ニウム塩化合物は、一般式ＮＯ+ Ｘ- （Ｘは一価のカチ
オン）で示され、主にイオン性の結晶固体である。本反
応で用いるニトロソニウム塩化合物としては、ＮＯＣｌ
Ｏ4 、ＮＯＳＯ3 Ｆ、ＮＯＨＳＯ4 、ＮＯＳＣＮ、ＮＯ
ＢＦ4 、ＮＯＰＦ4 、ＮＯＡｓＦ4 、ＮＯＳｂＦ4 、Ｎ
ＯＦｅＣｌ4 、ＮＯＭｏＦ6 などが挙げられる。好まし
くは、ＮＯＨＳＯ4 、ＮＯＢＦ4 を用いるのがよい。ニ
トロソニウム塩化合物は別途合成して用いてもよく、反
応系内で用事調製して用いてもよい。用いるニトロソニ
ウム塩化合物の量は、シアノベンズアミド化合物に対し
てモル比で１〜５が好ましい。In the present invention, a nitrosonium salt compound is reacted with a cyanobenzamide compound. Nitrosonium salt compound of the general formula NO + X - (X is a monovalent cation) is indicated by a predominantly ionic crystalline solid. The nitrosonium salt compound used in this reaction is NOCl
O 4 , NOSO 3 F, NOHSO 4 , NOSCN, NO
BF 4 , NOPF 4 , NOAsF 4 , NOSbF 4 , N
OFeCl 4 , NOMoF 6 and the like. Preferably, NOHSO 4 or NOBF 4 is used. The nitrosonium salt compound may be separately synthesized and used, or prepared and used in the reaction system. The amount of the nitrosonium salt compound to be used is preferably 1 to 5 in a molar ratio with respect to the cyanobenzamide compound.
【０００８】本反応は好適には実質的に水を含まない有
機溶媒中で行うのがよい。用いることができる有機溶媒
としては、ホルムアミド、ジメチルホルムアミドなどの
極性アミド系、ジメチルスルホキシド、スルホランなど
の含イオウ系、１，３−ジメチル−２−イミダゾリジオ
ンなどのイミダゾリドン系、ジオキサン、１，２−ジメ
トキシエタン、ジグライムなどのエーテル系、ジクロロ
メタン、クロロホルム、１，２−ジクロロエタンなどの
ハロゲン系、ベンゼン、トルエンなどの芳香族炭化水素
系、無水酢酸、無水プロピオン酸などの酸無水物系、ア
セトニトリル、プロピオニトリルなどのニトリル系など
が好ましく用いられる。より好ましくは各種ニトロソニ
ウム塩化合物の溶解性の高いアセトニトリルが用いられ
る。これらの有機溶媒は単独、もしくは２種以上を混合
して使用してもよい。また、有機溶媒の代わりに水を用
いることもできるが、ニトロソニウム塩化合物は水で速
やかに加水分解をうけるので、ＮＯ+ ＨＳＯ4 -と濃硫酸
の反応系などに限られる。本反応における溶媒量は、シ
アノベンズアミド化合物の重量に対し５〜１００倍が好
適である。This reaction is preferably carried out in an organic solvent substantially free of water. Examples of the organic solvent that can be used include polar amides such as formamide and dimethylformamide; sulfur-containing systems such as dimethylsulfoxide and sulfolane; imidazolidones such as 1,3-dimethyl-2-imidazolidione; dioxane; -Dimethoxyethane, ethers such as diglyme, dichloromethane, chloroform, halogens such as 1,2-dichloroethane, aromatic hydrocarbons such as benzene and toluene, acetic anhydride, acid anhydrides such as propionic anhydride, acetonitrile, Nitriles such as propionitrile are preferably used. More preferably, acetonitrile having high solubility of various nitrosonium salt compounds is used. These organic solvents may be used alone or in combination of two or more. In addition, water can be used instead of the organic solvent. However, since the nitrosonium salt compound is rapidly hydrolyzed with water, it is limited to a reaction system of NO + HSO 4 − and concentrated sulfuric acid. The amount of the solvent in this reaction is preferably 5 to 100 times the weight of the cyanobenzamide compound.
【０００９】本発明における反応温度は、−３０〜１０
０℃が好ましく、−１０〜５０℃がより好ましい。反応
温度が高すぎるとニトロソニウム塩化合物が分解し、低
すぎるとシアノベンズアミド化合物の溶解度が低く反応
しにくいので、ニトロソニウム塩の安定性とシアノベン
ズアミド化合物の溶解度の加減により反応温度を選択す
る。本反応における反応時間は、溶媒の組成により異な
るが概ね１０分〜１０時間が好適である。The reaction temperature in the present invention is -30 to 10
0 ° C is preferred, and -10 to 50 ° C is more preferred. If the reaction temperature is too high, the nitrosonium salt compound is decomposed, and if the reaction temperature is too low, the solubility of the cyanobenzamide compound is low and the reaction is difficult. The reaction time in this reaction varies depending on the composition of the solvent, but is preferably about 10 minutes to 10 hours.
【００１０】シアノ安息香酸化合物の単離精製について
説明する。本反応では通常有機溶媒を用いる。反応終了
後、溶媒によりシアノ安息香酸化合物は析出したり、溶
解したままでいる。析出した場合は、ろ過し、水洗し、
乾燥するだけで単離精製できる。シアノ安息香酸化合物
が溶解している場合は、減圧下低温で溶媒を留去し、残
査に水を加え、シアノ安息香酸を析出させる。以下同様
である。有機溶媒を用いた場合にも、シアノ安息香酸の
純度は用いたシアノベンズアミド化合物の純度を反映す
る。The isolation and purification of a cyanobenzoic acid compound will be described. In this reaction, an organic solvent is usually used. After completion of the reaction, the cyanobenzoic acid compound is precipitated or remains dissolved by the solvent. If precipitated, filter, wash with water,
It can be isolated and purified only by drying. When the cyanobenzoic acid compound is dissolved, the solvent is distilled off under reduced pressure and low temperature, and water is added to the residue to precipitate cyanobenzoic acid. The same applies hereinafter. Even when an organic solvent is used, the purity of cyanobenzoic acid reflects the purity of the cyanobenzamide compound used.
【００１１】[0011]
【実施例】以下に実施例を挙げ本発明をさらに詳細に説
明するが、本発明はこれらの実施例によりなんら限定さ
れるものではない。なお、液体クロマトグラフィーの測
定条件は以下の通りである。 カラム：Ｓｈｏｄｅｘ（登録商標：昭和電工株式会社）
ＤＥ−５１３Ｌ、プレカラム カラム温度：４０℃、 溶離液流速：１ｍｌ／ｍｉｎ、 溶離液：水／アセトニトリル／酢酸＝２２５０／７５０
／１５（ｍｌ）１−オクタンスルホン酸ナトリウム６．
４５ｇ 検出器：ＵＶ２５４ｎｍ、EXAMPLES The present invention will be described in more detail with reference to the following Examples, which by no means limit the present invention. The measurement conditions of the liquid chromatography are as follows. Column: Shodex (registered trademark: Showa Denko KK)
DE-513L, precolumn Column temperature: 40 ° C, Eluent flow rate: 1 ml / min, Eluent: water / acetonitrile / acetic acid = 2250/750
/ 15 (ml) sodium 1-octanesulfonate6.
45 g detector: UV 254 nm,
【００１２】（実施例１）氷浴下、１００ｍｌの三口フ
ラスコにアセトニトリル２０ｍｌとｐ−シアノベンズア
ミド２．９２ｇを加え溶液とし、十分冷却後、ニトロソ
ニウムテトラフルオロボレート２．５７ｇのアセトニト
リル２０ｍｌ溶液を攪拌しながら５分かけて滴下した。
滴下終了後、ガスの発生が止むまでさらに攪拌を続け
た。溶液を減圧下留去し、残査に水１０ｍｌを加えた。
析出した結晶をろ取し、水洗後乾燥してｐ−シアノ安息
香酸２．７７ｇ（収率９５％）を得た。高速液体クロマ
トグラフィーの分析により得られたｐ−シアノ安息香酸
の純度は９９％以上であった。Example 1 In a 100 ml three-necked flask, 20 ml of acetonitrile and 2.92 g of p-cyanobenzamide were added to form a solution in an ice bath, and after cooling sufficiently, a solution of 2.57 g of nitrosonium tetrafluoroborate in 20 ml of acetonitrile was stirred. While dropping over 5 minutes.
After the completion of the dropwise addition, the stirring was further continued until the generation of gas stopped. The solution was distilled off under reduced pressure, and 10 ml of water was added to the residue.
The precipitated crystals were collected by filtration, washed with water and dried to obtain 2.77 g (yield 95%) of p-cyanobenzoic acid. The purity of p-cyanobenzoic acid obtained by high performance liquid chromatography analysis was 99% or more.
【００１３】（実施例２）２００ｍｌの三口フラスコに
７０％重量濃度の硫酸水溶液１００ｍｌとｍ−シアノベ
ンズアミド２．９２ｇを加え攪拌させた。次に硫酸５ｇ
にニトロシル硫酸５ｇを溶解させた、５０％重量濃度ニ
トロシル硫酸の硫酸溶液１０ｇを滴下し、滴下終了後３
０分間室温で反応させた。析出した結晶をろ取し、水洗
後乾燥してｍ−シアノ安息香酸２．６８ｇ（収率９２
％）を得た。純度は９８％以上であった。Example 2 A 200 ml three-necked flask was charged with 100 ml of a 70% strength by weight aqueous sulfuric acid solution and 2.92 g of m-cyanobenzamide and stirred. Next, 5g of sulfuric acid
10 g of a 50% by weight nitrosyl sulfuric acid sulfuric acid solution in which 5 g of nitrosyl sulfuric acid were dissolved was added dropwise.
The reaction was allowed to proceed for 0 minutes at room temperature. The precipitated crystals were collected by filtration, washed with water, and dried to obtain 2.68 g of m-cyanobenzoic acid (yield 92).
%). Purity was over 98%.
【００１４】[0014]
【発明の効果】本発明により、フタロニトリル化合物か
ら容易に得られるシアノベンズアミド化合物と安価なニ
トロソニウム塩から簡便にシアノ安息香酸化合物を収
率、純度よく製造することができるため、医・農薬及び
液晶、機能性高分子モノマー等各種ファインケミカルズ
の原料または中間体としてのシアノ安息香酸又は核塩素
又はフッ素置換体の製造に有用である。According to the present invention, a cyanobenzoic acid compound can be easily produced with high yield and purity from a cyanobenzamide compound easily obtained from a phthalonitrile compound and an inexpensive nitrosonium salt. It is useful for the production of cyanobenzoic acid or a chlorinated or fluorine-substituted product as a raw material or intermediate of various fine chemicals such as liquid crystals and functional polymer monomers.
───────────────────────────────────────────────────── フロントページの続き Ｆターム(参考） 4H006 AA02 AC46 BB12 BB15 BB17 BB20 BB21 BB22 BB24 BC10 BC19 BC31 BE02 BJ50 BM71 BM72 BS30 FC50 FE74 FE75 QN30 ──────────────────────────────────────────────────続 き Continued on the front page F term (reference) 4H006 AA02 AC46 BB12 BB15 BB17 BB20 BB21 BB22 BB24 BC10 BC19 BC31 BE02 BJ50 BM71 BM72 BS30 FC50 FE74 FE75 QN30
Claims (3)
を表わし、−ＣＯＮＨ2は−ＣＮのｍ位あるいはｐ位で
あり、Ｘは塩素原子またはフッ素原子を表わし、ｎは０
〜４の整数を表わす。ただし、ｎが２以上の場合、Ｘは
同一であっても異なっていてもよい。）で示されるシア
ノベンズアミド化合物とニトロソニウム塩化合物を酸性
条件下で反応させることを特徴とする下記一般式（Ｉ
Ｉ） 【化２】 （式中、−ＣＯＯＨと−Ｘｎはベンゼン環上の置換基を
表わし、−ＣＯＯＨは−ＣＮのｍ位あるいはｐ位であ
り、Ｘは塩素原子またはフッ素原子を表わし、ｎは０〜
４の整数を表わす。ただし、ｎが２以上の場合、Ｘは同
一であっても異なっていてもよい。）で示されるシアノ
安息香酸化合物の製造法。1. A compound represented by the following general formula (I) (Wherein -CONH 2 and -Xn represent a substituent on a benzene ring, -CONH 2 is at the m or p position of -CN, X represents a chlorine atom or a fluorine atom, and n is 0
Represents an integer of ４4. However, when n is 2 or more, X may be the same or different. ) And a nitrosonium salt compound are reacted under acidic conditions.
I) (Wherein -COOH and -Xn represent a substituent on a benzene ring, -COOH is at the m-position or p-position of -CN, X represents a chlorine atom or a fluorine atom, and n represents 0 to 0.
Represents an integer of 4. However, when n is 2 or more, X may be the same or different. The method for producing a cyanobenzoic acid compound represented by the formula:
行う請求項１記載のシアノ安息香酸化合物の製造法。2. The process for producing a cyanobenzoic acid compound according to claim 1, wherein the reaction is carried out in an organic solvent substantially free of water.
物が、ｍ−シアノベンズアミドまたはｐ−シアノベンズ
アミドであり、一般式（ＩＩ）のシアノ安息香酸化合物
が対応するｍ−シアノ安息香酸またはｐ−シアノ安息香
酸である請求項１または請求項２に記載のシアノ安息香
酸化合物の製造法。3. The cyanobenzamide compound of the general formula (I) is m-cyanobenzamide or p-cyanobenzamide, and the cyanobenzoic acid compound of the general formula (II) corresponds to the corresponding m-cyanobenzoic acid or p-cyanobenzamide. The method for producing a cyanobenzoic acid compound according to claim 1 or 2, which is benzoic acid.
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10328171A JP2000154171A (en) | 1998-11-18 | 1998-11-18 | Production of cyanobenzoic acid compound |
| EP99118800A EP0989115A3 (en) | 1998-09-24 | 1999-09-23 | Process for producing cyanobenzoic acid derivatives |
| EP04022599A EP1514866B1 (en) | 1998-09-24 | 1999-09-23 | Process for producing cyanobenzoic acid derivatives |
| DE69934033T DE69934033T2 (en) | 1998-09-24 | 1999-09-23 | Process for the preparation of derivatives of cyanobenzoic acid |
| AT04022599T ATE345325T1 (en) | 1998-09-24 | 1999-09-23 | METHOD FOR PRODUCING CYANOBENZOIC ACID DERIVATIVES |
| EP04022598A EP1508567B1 (en) | 1998-09-24 | 1999-09-23 | Process for producing cyanobenzoic acid derivatives |
| DE69934034T DE69934034T2 (en) | 1998-09-24 | 1999-09-23 | Process for the preparation of derivatives of cyanobenzoic acid |
| AT04022598T ATE345324T1 (en) | 1998-09-24 | 1999-09-23 | METHOD FOR PRODUCING CYANOBENZOIC ACID DERIVATIVES |
| US09/404,362 US6433211B1 (en) | 1998-09-24 | 1999-09-24 | Process for producing cyanobenzoic acid derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10328171A JP2000154171A (en) | 1998-11-18 | 1998-11-18 | Production of cyanobenzoic acid compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2000154171A true JP2000154171A (en) | 2000-06-06 |
Family
ID=18207284
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10328171A Pending JP2000154171A (en) | 1998-09-24 | 1998-11-18 | Production of cyanobenzoic acid compound |
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| Country | Link |
|---|---|
| JP (1) | JP2000154171A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011516448A (en) * | 2008-04-04 | 2011-05-26 | エフ．ホフマン−ラ ロシュ アーゲー | Novel process for the production of cyclohexanecarboxylic acid derivatives via the corresponding cyclohexanecarboxamide derivatives |
-
1998
- 1998-11-18 JP JP10328171A patent/JP2000154171A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011516448A (en) * | 2008-04-04 | 2011-05-26 | エフ．ホフマン−ラ ロシュ アーゲー | Novel process for the production of cyclohexanecarboxylic acid derivatives via the corresponding cyclohexanecarboxamide derivatives |
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