JPH01110676A - Production of quinazolinone compound - Google Patents
Production of quinazolinone compoundInfo
- Publication number
- JPH01110676A JPH01110676A JP62266490A JP26649087A JPH01110676A JP H01110676 A JPH01110676 A JP H01110676A JP 62266490 A JP62266490 A JP 62266490A JP 26649087 A JP26649087 A JP 26649087A JP H01110676 A JPH01110676 A JP H01110676A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- aryl
- expressed
- dimethoxybenzaldehyde
- 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 description 6
- -1 quinazolinone compound Chemical class 0.000 title abstract description 10
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims abstract description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 10
- WJUFSDZVCOTFON-UHFFFAOYSA-N veratraldehyde Chemical compound COC1=CC=C(C=O)C=C1OC WJUFSDZVCOTFON-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000003054 catalyst Substances 0.000 claims abstract description 8
- 238000009833 condensation Methods 0.000 claims abstract description 7
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 6
- 230000005494 condensation Effects 0.000 claims abstract description 6
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 6
- 229940098779 methanesulfonic acid Drugs 0.000 claims abstract description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000005843 halogen group Chemical group 0.000 claims abstract 3
- 230000018044 dehydration Effects 0.000 claims description 9
- 238000006297 dehydration reaction Methods 0.000 claims description 9
- 230000002378 acidificating effect Effects 0.000 claims description 6
- AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical compound C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims 3
- 125000005489 p-toluenesulfonic acid group Chemical group 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 6
- 239000002904 solvent Substances 0.000 abstract description 5
- 238000006482 condensation reaction Methods 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 4
- 239000006227 byproduct Substances 0.000 abstract description 3
- 239000004599 antimicrobial Substances 0.000 abstract 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 13
- 239000008096 xylene Substances 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 10
- 238000000034 method Methods 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 230000000844 anti-bacterial effect Effects 0.000 description 4
- 238000000921 elemental analysis Methods 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 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
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000002367 halogens Chemical group 0.000 description 3
- NZHGWWWHIYHZNX-UHFFFAOYSA-N 2-((3-(3,4-dimethoxyphenyl)-1-oxo-2-propenyl)amino)benzoic acid Chemical compound C1=C(OC)C(OC)=CC=C1C=CC(=O)NC1=CC=CC=C1C(O)=O NZHGWWWHIYHZNX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 150000004982 aromatic amines Chemical class 0.000 description 2
- 238000010533 azeotropic distillation Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- RWGFKTVRMDUZSP-UHFFFAOYSA-N cumene Chemical compound CC(C)C1=CC=CC=C1 RWGFKTVRMDUZSP-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 101100275487 Paracoccus denitrificans ctaH gene Proteins 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000005427 anthranyl group Chemical group 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003849 aromatic solvent Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229910052801 chlorine Inorganic materials 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
- XPPKVPWEQAFLFU-UHFFFAOYSA-N diphosphoric acid Chemical compound OP(O)(=O)OP(O)(O)=O XPPKVPWEQAFLFU-UHFFFAOYSA-N 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- VYFOAVADNIHPTR-UHFFFAOYSA-N isatoic anhydride Chemical compound NC1=CC=CC=C1CO VYFOAVADNIHPTR-UHFFFAOYSA-N 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- REUAIENZNFYKFJ-UHFFFAOYSA-N n-phenylanthracene-1-carboxamide Chemical class C=1C=CC2=CC3=CC=CC=C3C=C2C=1C(=O)NC1=CC=CC=C1 REUAIENZNFYKFJ-UHFFFAOYSA-N 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 229940005657 pyrophosphoric acid Drugs 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000005979 thermal decomposition reaction Methods 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C45/00—Injection moulding, i.e. forcing the required volume of moulding material through a nozzle into a closed mould; Apparatus therefor
- B29C45/0017—Injection moulding, i.e. forcing the required volume of moulding material through a nozzle into a closed mould; Apparatus therefor moulding interconnected elements which are movable with respect to one another, e.g. chains or hinges
Landscapes
- Engineering & Computer Science (AREA)
- Manufacturing & Machinery (AREA)
- Mechanical Engineering (AREA)
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は、キナゾリノン化合物の製造方法に関する。本
発明により製造されるキナゾリノン化合物は、優れた抗
菌活性を持ち、抗菌剤として極めて有用な化合物である
。また、アレルギーに起因する疾患の治療剤Ｎ −（３
’、４’−ジメトキシシンナモイル）−アントラニル酸
製造上の原料としても有用である。DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention relates to a method for producing a quinazolinone compound. The quinazolinone compound produced by the present invention has excellent antibacterial activity and is an extremely useful compound as an antibacterial agent. In addition, N-(3) is a therapeutic agent for diseases caused by allergies.
It is also useful as a raw material for producing ',4'-dimethoxycinnamoyl)-anthranilic acid.
（従来の技術）
２−（β−アリールエチニル）−５−−ｒリールキナゾ
リノン化合物の製造方法は、すでに数件の文献に記載が
ある。例えば１次のとおりである。(Prior Art) Methods for producing 2-(β-arylethynyl)-5-r arylquinazolinone compounds have already been described in several documents. For example, the first order is as follows.
１）ジャーナル・オブ・ケミストリー・Ｕ、Ａ、Ｒ。1) Journal of Chemistry U, A, R.
（Ｊ、Ｃｈｅｎ、Ｕ、Ａ、Ｒ，）、１２．５７（１９６
７）に記載されている方法は、次式（ＩＶ）
で示されるスチリルベンゾオキサシンと了り−ルアミン
を直接反応させることから成る。(J, Chen, U, A, R,), 12.57 (196
The method described in 7) consists of directly reacting a styrylbenzoxacin of the following formula (IV) with an amine.
２）エジプシャン・ジャーナル・オプ・ケミストリー（
Ｅ ｇｙｐｔ、 Ｊ、 Ｃｈｅｍ、）、１９ 、 （２
０）、３４１（１９７６）に記載されている方法は、３
−アリール−２−メチルキナゾリノンと了り−ルアルデ
ヒドとを、ナトリウムエトキシドの存在下。2) Egyptian Journal Op Chemistry (
E gypt, J, Chem,), 19, (2
0), 341 (1976).
-Aryl-2-methylquinazolinone and Raldehyde in the presence of sodium ethoxide.
ドライエタノール中で２４時間反応させることからなる
。It consists of a 24 hour reaction in dry ethanol.
３）また、パルマジエ（Ｐ ａｒｍａＺｌｅ ） ＃
” ＃ Ｈ＃１１．７５３（１？７９）に記載されてい
る方法は、３−アリール−２−メチルキナゾリノンとア
リールアルデヒドとを加熱による脱水縮合させることか
らなる。3) Also, ParmaZle #
The method described in #H#11.753 (1?79) consists of dehydration condensation of 3-aryl-2-methylquinazolinone and aryl aldehyde by heating.
（発明が解決しようとする問題点）
しかし、１）の方法においては、２位のβ−丁り一ルエ
テニル基の立体障害のために、アリールアミンの求核攻
撃が妨げられ、収率が低く、また、長時間の反応が必要
となる。２）の方法では１強塩基であるナトリウムエト
キシドを用いる反応であるため、３−アリール−２−メ
チルキナゾリノンの自己縮合がおこり、副生物の生成が
認められる。(Problems to be Solved by the Invention) However, in method 1), the nucleophilic attack of the arylamine is hindered due to the steric hindrance of the β-di-ethenyl group at the 2-position, resulting in a low yield. , and also require a long reaction time. In method 2), since the reaction uses sodium ethoxide, which is one strong base, self-condensation of 3-aryl-2-methylquinazolinone occurs, and by-products are produced.
さらに、３）の方法においては、熱のみによる脱水縮合
である次め１反応時間が長く、また、高温による熱分解
が生じ、副生物の生成が認められる。Furthermore, in method 3), the second reaction time, which is dehydration condensation using only heat, is long, and thermal decomposition occurs due to high temperatures, resulting in the formation of by-products.
本発明は、上述の諸問題を解決し、工業的かつ経済的な
３−アリール−２（５’、４’−ジメトキシスチリル）
キナゾリノンの製造法を提供するものである。The present invention solves the above-mentioned problems and provides industrial and economical 3-aryl-2(5',4'-dimethoxystyryl).
A method for producing quinazolinone is provided.
（問題点を解決するための手段および作用）上記の問題
点を解決するため、鋭意検討した結果、一般弐〇）
（式中、Ｘはハロゲンまたは低級アルコキシ基を表わし
、ｎは０〜３の整数を表わす。）で示される２−メチル
−３−７リールー（３Ｈ）−キナゾリノンと、次式（ｎ
）
で示される４−ジメトキシベンズアルデヒドとを。(Means and effects for solving the problems) In order to solve the above problems, as a result of intensive studies, we found that the general 2-methyl-3-7lyru(3H)-quinazolinone represented by the formula (representing an integer) and the following formula (n
) with 4-dimethoxybenzaldehyde.
酸性触媒の存在下脱水縮合することＫよシ、一般式（Ｉ
ＩＩ）
（式中、Ｘはハロゲンまたは低級アルコキシ基を表わし
、ｎは０へ３の整数を表わす。）で示される２ −（５
’、４’−ジメトキシスチリル）−３−丁リールキナゾ
リノンを製造することに成功した。By dehydration condensation in the presence of an acidic catalyst, the general formula (I
II) 2-(5
',4'-dimethoxystyryl)-3-diarylquinazolinone was successfully produced.
式中、Ｘはハロゲンまたは低級アルコキシ基を表わし、
ｎは０から３までの整数を表わし、ハロゲンとしては１
例えば、塩素、臭素等であり、アルコキシ基としては１
例えば、メトキシ基、エトキシ基等である。In the formula, X represents a halogen or a lower alkoxy group,
n represents an integer from 0 to 3, and halogen is 1
For example, chlorine, bromine, etc., and the alkoxy group is 1
For example, methoxy group, ethoxy group, etc.
以下に１本発明の実施方法をさらに詳しく説明する。Below, a method for carrying out the present invention will be explained in more detail.
本発明の出発物質である一般式（Ｉ）の２−メチル−３
−７リールー（３Ｈ）−キナゾリノンは１次式（Ｖ）
で示される無水イサト酸を当量の７リールアミンと、加
熱下に縮合し、一般式（ＶＩ）
（式中、Ｘはハロゲンま九は低級アルコキシ基。2-methyl-3 of general formula (I) which is the starting material of the present invention
-7-lyru(3H)-quinazolinone is produced by condensing isatoic anhydride represented by the primary formula (V) with an equivalent amount of 7-lyl amine under heating to produce the general formula (VI) (wherein, X is a halogen and Lower alkoxy group.
ｎは０〜３の整数を表わす。）で示されるアントラニル
アニリド誘導体を得た後、これを無水酢酸によジアセチ
ル化し、次いで、加熱下に脱水することにより、あるい
は次式（■）
で示されるアントラニルを加熱下にアリールアミンと脱
水縮合することによシ製造できる。n represents an integer from 0 to 3. ) After obtaining an anthranilide derivative represented by the formula (■), this is diacetylated with acetic anhydride and then dehydrated under heating, or anthranyl represented by the following formula (■) is dehydrated and condensed with an arylamine under heating. It can be manufactured by doing this.
本発明に用いることができる酸性触媒としては。Examples of acidic catalysts that can be used in the present invention are:
例えば、硫酸や塩酸のような鉱酸、無水リン酸やピロリ
ン酸のようなリン酸類１％にパラトルエンスルホン酸や
メタンスルホン酸のようなスルホン酸化合物を用いるこ
とが望ましい。この際用いられる酸性触媒の当量は、一
般式α）に対して０．０１Ｓ１倍当量、特に望ましくは
０．０１〜０．２倍当量である。次に１本反応に用いら
れる溶媒としては。For example, it is desirable to use a sulfonic acid compound such as para-toluenesulfonic acid or methanesulfonic acid in 1% of a mineral acid such as sulfuric acid or hydrochloric acid, or a phosphoric acid such as phosphoric anhydride or pyrophosphoric acid. The equivalent of the acidic catalyst used at this time is 0.01 S1 equivalent, particularly preferably 0.01 to 0.2 times equivalent, relative to the general formula α). Next, as a solvent used in one reaction.
例えハ、ベンゼン、トルエン、キシレン、クメンなどの
芳香族系溶媒あるいはＴＨ’Ｐ、１．４−ジオキサン、
ダイグライムなどのエーテル系溶媒またはＤＭＦ、ＤＭ
ＳＯなどを挙げることができる。For example, aromatic solvents such as benzene, toluene, xylene, cumene, TH'P, 1,4-dioxane,
Ether solvents such as diglyme or DMF, DM
Examples include SO.
特に好ましくは、本反広中、脱離した水と共沸混合物を
生じ、共沸留去後、水と分離が可能な溶媒を用いること
が望ましい。Particularly preferably, it is desirable to use a solvent that forms an azeotrope with the desorbed water during the process and can be separated from the water after azeotropic distillation.
本発明の脱水縮合反応は、一般式（Ｉ）の３−了り−ル
ー２−メチルーキナゾリノンと式（ＩＩ）の３，４−ジ
メトキシベンズアルデヒドを溶媒中、酸性触媒の存在下
、５０Ｃから水と溶媒の共沸温度まで、望ましくは共沸
温度で、１〜１０時間望ましくは１へ５時間、水を共沸
留去することによって行なわれる。In the dehydration condensation reaction of the present invention, 3-dimethyl-2-methyl-quinazolinone of general formula (I) and 3,4-dimethoxybenzaldehyde of formula (II) are mixed in a solvent in the presence of an acidic catalyst, and the solvent, preferably at the azeotropic temperature, for 1 to 10 hours, preferably 1 to 5 hours, by azeotropically distilling off the water.
（発明の効果）
本発明の２− （３’、４’−ジメトキシスチリル）−
３−アリールキナゾリノン化合物の製造方法は。(Effect of the invention) 2-(3',4'-dimethoxystyryl)- of the present invention
What is the method for producing a 3-arylquinazolinone compound?
副反応を抑制し、高収率、短時間で２− （３’、４’
−ジメトキシスチリル）−３−アリールキナゾリノンを
提供するものである。また、本発明で得られる２ −（
３’、４’−ジメトキシスチリル）−３−アリールキナ
ゾリノン化合物は、アレルギーに起因する疾患の治療剤
Ｎ −（３’、４’−ジメトキシシンナモイル）アント
ラニル酸輿造上の原料として有用である。By suppressing side reactions, 2-(3',4'
-dimethoxystyryl)-3-arylquinazolinone. Furthermore, 2-(
The 3',4'-dimethoxystyryl)-3-arylquinazolinone compound is useful as a raw material for the preparation of N-(3',4'-dimethoxycinnamoyl)anthranilic acid, a therapeutic agent for diseases caused by allergies.
（実施例）
実施例１
２−メチル−３−フェニル−（３Ｈ）−キナゾリノン２
．３７ ｆ （１０ｍｍｏｔ）、 ３ｅ４−ジメトキシ
ベンズアルデヒド１．６６９ （１０ｍｍｏｔ）および
パラトルエンスルホン酸−一水和物０，１９ ｔ （１
ｍｍｏｔ）をキシレン５−に加え、キシレンと共沸留去
することにより、２時間脱水縮合反応を行なった。反応
液からキシレンを減圧留去しｆＩ−後、エタノールから
再結し、 ２− （５’、４’−ジメトキシスチリル
）−５−フェニルキナゾリノンｓ、ｙ ２ ｆ （９ｙ
％ ）を得た。(Example) Example 1 2-Methyl-3-phenyl-(3H)-quinazolinone 2
．． 37 f (10 mmot), 3e4-dimethoxybenzaldehyde 1.669 (10 mmot) and para-toluenesulfonic acid monohydrate 0,19 t (1
mmot) was added to xylene 5-, and azeotropically distilled off with xylene, a dehydration condensation reaction was carried out for 2 hours. After xylene was distilled off under reduced pressure from the reaction solution and reconsolidated from ethanol, 2-(5',4'-dimethoxystyryl)-5-phenylquinazolinone s, y 2 f (9y
%) was obtained.
ｍｐ １６７−１６８Ｃ ｌ６７−１６８ＣＮ ）’δ ３．７４（３Ｈ，ｓ）。mp 167-168C l67-168CN)'δ 3.74 (3H, s).
３．８１（３Ｈ，Ｓ）。3.81 (3H, S).
６．１−８．５（１４Ｈ、ｍ ）
ＩＲ（ＫＢｒ）：１６７００Ｂ−Ｉ Ｊ／Ｃ０１２６
０（ＩＩ″″１ シＣ−０−Ｃ元素分析値 ｃｔａＨ
ｔ。Ｎ！０゜
計算値 Ｃ： ７４．９ ＋３チ
Ｈ： ５．２４チ
Ｎ： ７．２９係
実測値 Ｃ： ７４．７２チ
Ｈ： ５．０９ｅｌＪ
Ｎニア、１を係
実施例２
２−メチル−３−７二二、ルー（３Ｈ）−キナシリノア
２．３７９（１０ｒｒｌｒｒＩＯＬ）と３，４−ジメト
キシベンズアルデヒド１．６６ ？ （１０ｍｍｏｌ
）およびメタンスルホン酸ｏ、ｚ Ｏ？（ｔｍｍｏｔ）
をキシレン５−に加え、キシレンと共沸留去することに
よシ、２時間脱水縮合反応を行なった。反応液からキシ
レンを減圧留去した後、エタノールから再結し、２−（
３’、４’−ジメトキシスチリル）−３−フェニルキナ
ゾリノン３．６５ ？ （９５％）ｌＩた。6.1-8.5 (14H, m) IR (KBr): 16700B-I J/C0126
0(II″″1 C-0-C elemental analysis value ctaH
t. N! 0° Calculated value C: 74.9 +3H: 5.24H N: 7.29 Actual value C: 74.72H: 5.09elJ Nia, 1 Example 2 2-methyl-3 -722, Rou(3H)-quinacylinoa 2.379 (10rrlrrIOL) and 3,4-dimethoxybenzaldehyde 1.66? (10 mmol
) and methanesulfonic acid o,z O? (tmmot)
was added to xylene 5- and azeotropically distilled off with xylene to carry out a dehydration condensation reaction for 2 hours. After removing xylene from the reaction solution under reduced pressure, it was reconsolidated from ethanol to obtain 2-(
3',4'-dimethoxystyryl)-3-phenylquinazolinone 3.65 ? (95%) II.
実施例３
２−メチル−３−（ｐ−クロロフェニル）−（３Ｈ）−
キナゾリンｙ ２．７ ｔ ？ （１０ｍｍｏｔ）。Example 3 2-methyl-3-(p-chlorophenyl)-(3H)-
Quinazoline y 2.7t? (10 mmot).
５．４−ジメトキシベンズアルデヒド１．６６ ｆ（１
０ｍｍｏｔ） オよヒバラドルエンスルホン酸・−水和
物０．１９？（ｔｍｍｏｔ）をキシレン５−に加え、キ
シレンと共沸留去することにより、２時間脱水網合反応
を行なった。反応液からキシレンを減圧留去した後、イ
ソプロパツールから再結し、２− （３’、４’−ジメ
トキシスチリル）−３−（ｐ−クロロフェニル）キナゾ
リノン５，７７１Ｆ（９（］１）を得た。5.4-dimethoxybenzaldehyde 1.66 f(1
0mmot) Oyohibaradruenesulfonic acid-hydrate 0.19? (tmmot) was added to xylene 5- and azeotropically distilled off with xylene to perform a dehydration network reaction for 2 hours. After removing xylene from the reaction solution under reduced pressure, it was reconsolidated from isopropanol to obtain 2-(3',4'-dimethoxystyryl)-3-(p-chlorophenyl)quinazolinone 5,771F (9(]1). Obtained.
ｍｐ ２０Ｇ−２０１Ｃ’
ＮＭＲ（ＣＤＣ１，）： δ ５．６９（３Ｒ，ｓ
）。mp 20G-201C' NMR (CDC1,): δ 5.69 (3R, s
).
５．７３（ＡＨ，Ｓ）。5.73 (AH, S).
６．０ − ８．２ （１３Ｈ、ｍ ） ＩＲ（ＫＢｒ）： １６８！１ｉＱｓ４ ｙｃ。6.0 - 8.2 (13H, m) IR (KBr): 168!1iQs4 yc.
１２７Ｑ（ｌｘ’ ｙＣ−０−Ｃ元素分析値 Ｃ
！ａＨｔ＊Ｎ＊Ｏｓ ＣＩ。127Q(lx' yC-0-C elemental analysis value C
! aHt*N*Os CI.
計算値 Ｃ：６８．８２係
Ｈ：４，５７ チ
Ｎ：６．６９１４
Ｃ１： ８．４６ 係
実測値 Ｃ：６８．５３％
Ｈ：４．２９ ％
Ｎ：６．４５ チ
、 Ｃ２： ８．７５ ％
実施例４
２−１ ｆ ルー ５− （ｐ−メトキシフェニル）−
（３Ｈ）−キナゾリノン２．６６ ｔ （１０ｍｍｏｔ
）。Calculated value C: 68.82 Coefficient H: 4,57 Chi N: 6.6914 C1: 8.46 Coefficient actual value C: 68.53% H: 4.29% N: 6.45 Chi, C2: 8. 75% Example 4 2-1 f Roux 5- (p-methoxyphenyl)-
(3H)-quinazolinone 2.66 t (10 mmot
).
５．４−ジメトキシベンズアルデヒド１．６６９（１０
ｍｍｏｔ）およびメタンスルホン酸０，１ ｒＪ ｆ（
ｔｍｍｏｔ）ヲキシレン５−に加え、キシレンと共沸留
去することにより、２時間脱水網合反応を行なった。反
応液からキシレンを減圧留去した後。5.4-dimethoxybenzaldehyde 1.669 (10
mmot) and methanesulfonic acid 0,1 rJ f(
tmmot) In addition to xylene 5-, a dehydration network reaction was carried out for 2 hours by azeotropic distillation with xylene. After xylene was distilled off from the reaction solution under reduced pressure.
インプａ ハノールから再結し、２− （３’、４’−
ジメトキシスチリル）−３−（ｐ−メトキシフェニル）
キナゾリノン５．８５ ？ （９Ｓチ）を得た。Imp a recombines from Hanol, 2- (3', 4'-
dimethoxystyryl)-3-(p-methoxyphenyl)
Quinazolinone 5.85? (9S Chi) was obtained.
ｍｐ １９３ｌ９３−１ ９４ＣＮ ＣＤＣ１，）：δ ３．６７（３Ｈ，Ｓ）。mp 193l93-1 94CN CDC1,): δ 3.67 (3H, S).
３．７０（３Ｈ，Ｓ）。3.70 (3H, S).
ｓ、ａ３（３ｎ、ｓ）。s, a3 (3n, s).
６．０−８，２ （ｔｓｍ、ｍ） ＩＲ（ＫＢｒ）：１４７０ｍ−” ｙｃ。6.0-8,2 (tsm, m) IR (KBr): 1470m-”yc.
１２５５傷−重 シＣ−０Ｃ−
０−Ｃ１ｚ６ｓ ｙＣ−０−Ｃ
元素分析値 Ｃ□Ｎ□Ｎ、０゜
計算値 Ｃ： ７２．４５チ
Ｉ（： ５．５５％
Ｎ：６．７６％
実測値 Ｃニア２．２？チ
Ｈ： ５．１９ 係
Ｎ： ６．７０ 係
試験例
実施例１．３および４で得られた化合物について抗菌活
性試験を行なった。抗菌試験は、動物用抗生物質製剤検
定基準（昭和４８年６月）に準じて実施した。カップは
外径が９１ｍのものを使用し、抗菌力の強さは、阻止内
の直径（ｔｓｍ ）を表わした。1255 Damage - Severe C-0C- 0-C1z6s yC-0-C Elemental analysis value C□N□N, 0° Calculated value C: 72.45 Chi (: 5.55% N: 6.76% Actual measurement Value C Near 2.2?C H: 5.19 N: 6.70 Test Example An antibacterial activity test was conducted on the compounds obtained in Examples 1.3 and 4. The antibacterial test was conducted using animal antibiotics. Testing was carried out in accordance with the Preparation Certification Standards (June 1970). A cup with an outer diameter of 91 m was used, and the strength of antibacterial activity was expressed as the diameter within the inhibition (tsm).
試験結果を表１に示す。The test results are shown in Table 1.
参考例
本発明の化合物からＮ−（３′、４′−ジメトキシシン
ナモイル）−アントラニル酸を合成する一例禽以下に示
す。Reference Example An example of the synthesis of N-(3',4'-dimethoxycinnamoyl)-anthranilic acid from the compound of the present invention is shown below.
２−（５’、４’−ジメトキシスチリル）−３−フェニ
ルキナゾリノン２．２２ ｆ （５，８ｍｍｏｔ）のイ
ンプロパノール１８ｄ溶液に水酸化ナトリウム２．８
ｑ ｆ （７２，１ｍｍｏｔ）の水溶液６ｄを加え、４
時間還流攪拌した。４０〜ｓａＣに冷却後、濃塩酸１０
−を徐々に滴下し、１０分間攪拌した。A solution of 2.22 f (5,8 mmot) of 2-(5',4'-dimethoxystyryl)-3-phenylquinazolinone in 18 d of inpropanol and 2.8 d of sodium hydroxide
Add 6d of an aqueous solution of q f (72,1 mmot),
Stir at reflux for an hour. After cooling to 40~saC, concentrated hydrochloric acid 10
- was gradually added dropwise and stirred for 10 minutes.
反応終了後、水を加え析出した結晶をｐ別乾燥した。さ
らに、この結晶をクロロホルムから再結することにより
、Ｎ −（Ｓ’、４’−ジメトキシシンナモイル）−ア
ントラニル酸１．４２９ （収率７５チ）を得た。After the reaction was completed, water was added and the precipitated crystals were dried separately. Furthermore, by recrystallizing this crystal from chloroform, 1.429% of N-(S',4'-dimethoxycinnamoyl)-anthranilic acid (yield: 75%) was obtained.
ｍｐ ２０９−２１００
Ｎ Ｍ Ｒ（ＣＤＣｔｊ ）：δ ３，８７（３Ｈ，ｓ
）。mp 209-2100 NMR (CDCtj): δ 3,87 (3H, s
).
ｓ、９ｚ（ｓＨ，ｓ）。s,9z(sH,s).
６、Ｑ −９，０
（１５Ｈ，ｍ）
ＩＲ（ＫＢｒ）：２９ｏＯａｓ−’（ν ｃＯＯＲ）１
６７００１−”（ν Ｃ０）
１２５５ｃＩｓ−’（ｙＣ−０−Ｃ）
元素分析値 ＣＩＩＨ１？ＮＯ！
計算値Ｃ： ６６．０５チ
Ｈ： ５．２４％
Ｎ： ４．２８チ
実測値Ｃ： ６６．２１チ
Ｈ： ５．１７係
Ｎ： ４．２５４6, Q -9,0 (15H, m) IR (KBr): 29oOas-' (ν cOOR)1
67001-" (ν C0) 1255cIs-' (yC-0-C) Elemental analysis value CIIH1?NO! Calculated value C: 66.05 cm H: 5.24% N: 4.28 cm Actual value C: 66. 21st H: 5.17th N: 4.254
Claims (2)
、ｎは０〜３の整数を表わす。） で示される２−メチル−３−アリール（３Ｈ）−キナゾ
リノンと、次式（II） ▲数式、化学式、表等があります▼（II） で示される３，４−ジメトキシベンズアルデヒドとを、
酸性触媒の存在下脱水縮合することを特徴とする一般式
（III） ▲数式、化学式、表等があります▼（III） （式中、Ｘはハロゲンまたは低級アルコキシ基を表わし
、ｎは０〜３の整数を表わす。） で示される３−アリール−２（３′，４′−ジメトキシ
スチリル）−キナゾリノン化合物の製造方法。(1) General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, X represents a halogen or lower alkoxy group, and n represents an integer from 0 to 3.) 2 -Methyl-3-aryl(3H)-quinazolinone and 3,4-dimethoxybenzaldehyde represented by the following formula (II) ▲Mathematical formula, chemical formula, table, etc.▼(II)
General formula (III) characterized by dehydration condensation in the presence of an acidic catalyst ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ (III) (In the formula, X represents a halogen or lower alkoxy group, and n is 0 to 3 ) A method for producing a 3-aryl-2(3',4'-dimethoxystyryl)-quinazolinone compound.
ホン酸である特許請求の範囲第１項記載の製造方法。(2) The manufacturing method according to claim 1, wherein the acidic catalyst is p-toluenesulfonic acid or methanesulfonic acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62266490A JPH01110676A (en) | 1987-10-23 | 1987-10-23 | Production of quinazolinone compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62266490A JPH01110676A (en) | 1987-10-23 | 1987-10-23 | Production of quinazolinone compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01110676A true JPH01110676A (en) | 1989-04-27 |
| JPH0584313B2 JPH0584313B2 (en) | 1993-12-01 |
Family
ID=17431652
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62266490A Granted JPH01110676A (en) | 1987-10-23 | 1987-10-23 | Production of quinazolinone compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH01110676A (en) |
-
1987
- 1987-10-23 JP JP62266490A patent/JPH01110676A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0584313B2 (en) | 1993-12-01 |
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