UA24545U - A method for obtaining substituted 3,4-dihydroisocumarines - Google Patents

Abstract

A method for obtaining substituted 3,4-dihydroisocumarines comprises dinitration of derivatives of anthranilic acid and subsequent interaction of obtained arendiazonium salts with unsaturated compounds in the presence of catalysts of CuCl2. Esters of antthranilic acids dinitrate sodium with nitrate in aqueous HBr, obtained bromides of 2-alkoxycarbonyldiazonium are entered into reaction with unsaturated compounds in the aqueous-acetone medium. And as catalyst CuBr and substituted 3,4-dihydroisocumarines are used.

Description

Description of the invention

A useful model concerns organic chemistry, namely useful organic compounds, such as substituted 2 3,4-dihydroisocoumarins, which can be used as reagents for organic and combinatorial synthesis of biologically active compounds.

Z,4-dihydrocoumarins are an important class of natural compounds |NIiYi K.A. Maishigayu ossigtipud ivososhtagipv

Peogespg. Spent Maishtsgwi. -1986. -MoI.49. -R.1-78). They show a wide spectrum of biological action (No! K.A.

Myshgainyu ossitipud isososstagipe //Rogespg. Spent MaiyShgei. -1986. -MoI.49. -R.1-78; Vatu K.O. Ivosoitagipv 70 Oemeiortepi vzipse 1950 //Spet. Kew. -1964. -MoI.64, Mo3 -P.229-260), in particular diuretic and antihypertensive

INashiyap MU.)., Madeivop 34). AtipoaiiKuiizospgotapv apa isososstagipv //Angl. patent cl. C2C (C0707/40

Ab1K27/00) Mo1674337; quote according to RZ Chem 1975, 210136P Nashinap MU.)., Madeizop .). Tepiagu atypoeipuiizospgotapz apa isosotstagipv // Latent USA cl. 260-343.2K (C07a7/24) Mo3880885; quote according to RZh Chem 1976, 70164P), tranquilizing (|Nashiyap MU.)., Madeivop 39.0 3-(4-Naiorpepu!1)-3-(2-rugiau!)-3,4-dinudgoiisosoitagipe //Patent 72 USA cl. 260-295.E (C07071/34) Mo3824244; quote according to RZh Chem 1975, 40103P), antimicrobial and antiviral |NIIII K.A.

Myshgainyu ossigtipud isosotstagipe //Rogespg. Set. Mayitsgei. -1986. -MoI.49. -R.1-78; Apiovs: R.)., Meivop O.V.

Tpe vigisiige apa spetivigu oi asiiporoYiypy /). At. Spent wasps -1970. -MoI.92, Mo16. -P.4933-49421 activity.

In this connection, dihydroisocoumarins of natural origin and methods of their synthesis are intensively studied

Ivomiseii R. Zapentsi A., Vegpipi K., Iiraineiiyi R. Ohiipsiopa|iigaiop oi asimayeid te(Nuiieepez Bu dite(puIdiohigape: ap easu sopmegviop oi isospgotape ipio isosostagipe //Teigapedgop - 1997. -Mo1Ї.53, Mo28. -R. 9755-9760; Vomisei R., Irannei R., Stevsepli V. Zapetsii A. Vetpipi K. Ohidayop (oi

Z-aguivospgotape Bu aitei (puidohigape. Ap easu goshe (o zirziyshey Z-aguizosotstagipz) //Teigapedgop -1999, -MoI.55. -R.14719-14728; Movzpikaja M, Zpitada N, Madi M, Mygakati M, Zpitoda N. Yuemeiortepi oi Bioasiime

Tipsyopz ip Nudgapdeae Optsisiv Roiisht. E. Zupipezez oi (pypregdipoiv A apa E apa Neig 3'-deohu-deghimaimev ivipu hediozresiis Iasiopigayop oiviShrepe sagrohuiiis asii. Zigysiyhev apa ippyryogu asimyu op Piziatipe stv) heiIease oi pudgatasgorpuioiv A apa V. /Spet. React. howl -1996. - Mine!.44, Mo10. - R. 1890-1898).

There is a known method of obtaining derivatives of 3,4-dihydroisocoumarin from derivatives of homophthalic acid, its anhydrides and esters (EI-Kauwez M.K., A.NA.A. ).

Rgakk Speth. -1975 -Va. 317, Mob. -5.1040-1048; EI-Kauwez M.K., Ai A.N.A. Te 5iorre Sopdepzayop m/p o

Oitesu! NothorpNaiaye. |. /). Selfless. Set. -1976. - MoY.13, Mo1. -R.83-88). Due to the active methylene group, homophthalic acid derivatives at the first stage condense with carbonyl compounds in the presence of strong bases (sodium hydride, potassium tert-butylate). In the second stage, the obtained condensation products o are cyclized under the action of sodium acetate in acetic acid or mineral acid to derivatives "f

Z,4-dihydroisocoumarin according to the scheme: o c t

R p NI She I Re.

S and yours sho t ch drink sorghum and the same. eat -at

I" V

B is alkyl, aryl, aralkyl, hetaryl, cycle; VZ-N, SNU

The disadvantage of the method is the difficulty of obtaining the starting reagents (derivatives of homophthalic acid), its two-stage nature, and the low yield of final products compared to commercially available starting compounds.

A known method of obtaining 3,4-dihydroisocoumarin derivatives by palladium-catalytic reactions

ChK" of ortho-halogenobenzoic acids with functionalized olefins or alkynes, one- or two-stage synthesis of sl (Agosk K.S., Yuoiu M.), Nap H. Zupipeviv oi ivosoutagipev apa A-rugopez mia raiYIIIadiit-sagaiuledy appshayop oi ipiegpa! aiKupev //). Ogd. Spent -1999. -MoI.64, Mo24. - R. 8770-8779; Iagosk K.S., Nagtizop | MU. Megsigu ip

ChK» 50 ogdapis sPpetivigh. 26. Bupipeviz oi Pefegosusiev mia ipigatoIesciag voYmotegsigayop oi agu! aseiuiepev //). Mr. At. Spent Boss. -1984. -MoI.106, Mo15. - R. 4218-4227; Mao T., Yagosk K.S. Bupipevov oi isosostagipz apa

A-rugopez mia eiesigorpiiis susiigaiop //). Oh Spent -2003. -MoI.68, Mo15. -P.5936-5942), 3-substituted isocoumarins are obtained by this method, for example:

SOT | РИ(РРЕ),, BM, 7пСИ, оо |- сой с I сн Б В о з

Ka) in sh-- Fa na in 6o V ol pot vn e

K-nNa), AK, Ag

The disadvantage of this method is the use of expensive catalysts, organic ligands for Ra-catalysis (triphenylphosphine, etc.). In addition, by this method, isocoumarin derivatives are synthesized, from which the corresponding 65 C,4-dihydroisocoumarins can be obtained by an additional reduction procedure.

The method of obtaining C3-cyano-3,4-dahydroisocoumarin is closest to the proposed one - a prototype

IMaiipomuzKi 5. O rem/pusp heaxiaspy 2mid2Kom dutsagomzhusi 2e 2mid2Kati piepazusoputi. | /Kosgpiki Spet. -1952. - Vol. 26, Mo1. -5.85-97), which consists in the fact that, first, anthranilic acid is diazotized and the resulting 2-carboxybenzenediazonium chloride is introduced into a reaction with acrylonitrile in the presence of a SIS catalyst! in

Water-acetone environment. The resulting 2-(2-chloro-2-cyanoethyl)benzoic acid is then heated with sodium in benzene, resulting in cyclization. C-cyano-3,4-dihydroisocoumarin is obtained with a yield of 12905, counting on anthranilic acid.

The disadvantage of the method is the two-step process, a small yield of the target product, the use of sodium metal, which requires additional drying operations and safety measures, variable limitation of the substituent in the 7/0 position of 3,4-dihydroisocoumarin.

The basis of a useful model is the task of improving the method of obtaining substitutes

C,4-dihydroisocoumarins by using the interaction of diazotized esters of anthranilic acid with unsaturated compounds, which will simplify the process and increase the yield of the target product.

The task is achieved by the fact that in the method of obtaining substituted 3,4-dihydroisocoumarins, which /5 includes diazotization of anthranilic acid derivatives and further interaction of the obtained arenediazonium salts with unsaturated compounds in the presence of a SiSi catalyst, anthranilic acid esters are diazotized with sodium nitrite in aqueous NHg, obtained 2-Alkoxycarbonylbenzenediazonium bromides are introduced into a reaction with unsaturated compounds in an aqueous-acetone environment, and SiHg is used as a catalyst, as a result of which substituted 3,4-dihydroisocoumarins of the general formula are obtained: cho a de K"-H, 5-СНа, 6-СООСН» , 7-СНа, 7-СИ, 7-Вг;

В?-СООСН», СОСН», СеНв, 4-СНаСеНа, 4-СНЗОССН», 4-СИСНА

To obtain substituted 3,4-dihydroisocoumarins, the authors used the reaction of 2-alkoxycarbonyldiazoniums from bromides obtained by diazotization of anthranilic acid esters with unsaturated compounds in an aqueous-acetone medium in the presence of a catalyst - SiVg at room temperature.

The method of obtaining substituted 3,4-dihydroisocoumarins can be illustrated by the following example: from the "o" of the current Ua, he took the "de K"-H, 5-СНа, 6-СООСН», 7-СНа, 7-СИ, 7-Вг;

В?-SOOSN», SOSN», SeNv, 4-SNaSeNa, 4-SNZOSsN», 4-SISSNA yu

Example. Mix 60.4g (52ml) of methyl ester of anthranilic acid, 1b0ml of water and 1b00ml of hydrogen bromide "H acid (4090)" and gradually drip a solution of ZZg Mamo" into 150ml of water at a temperature of -5-02С. The diazo solution prepared according to this procedure is added dropwise to a mixture of 400 ml of acetone, 36 b.2 ml of methyl acrylate and 7 g of SiHg within 0.5-1.00 hours at a temperature of 15-30. After adding all the diazo solution, the mixture is stirred for another 1-2 hours until the end of nitrogen release. Add 0.000 ml of water to the reaction mixture. If the reaction product precipitates, it is filtered off, and if not, the organic layer is separated, dried, the solvent is removed and distilled under vacuum. The interpretation of the substituents B" and BK? and examples of compounds obtained by this method and their yields after recrystallization are given in Table 1. Their structure is confirmed by NMR "H spectroscopy data recorded "" on VgyKeg OKX 500 (500 MHz) and Megsig devices 400 (400 MHz) in DMSO (Table 2). 65 65 65 Compound number Chemical shifts in 1H NMR spectra , 5, m.ch7

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M. p

Mass spectra of some synthesized compounds were obtained on a Rippidap MAT IMKO5-50 chromato-mass spectrometer at 70 eV 1: 206 (M, 5), 147 (100), 119 (93.5), 91 (61); 2: 190 (IM'"), 10), 156 (100), 128 (24), 91 (25), 50 (31); 10: 220 (M, 9.7), 175 (12.1), 162 (11.4), 161 (100), 133 (62.1), 105 (30.4), 77 (16.3), 51 (5.4); 12: 284 (M, 11.7) , « 239 (10.0), 227 (100), 225 (88.6), 197 (50.05), 171 (23.2), 169 (33.2), 118 (13.9), 89 (49.0), 75 (6.0), 63 (22.3), 50 (6.9), 44 (9.4). and using commercially available raw materials, which favorably distinguishes it from known methods, which is" confirms the expected technical result.

Claims (1)

7 Formula of the invention t The method of obtaining substituted 3,4-dihydroisocoumarins, which includes diazotization of anthranilic 1 acid derivatives and subsequent interaction of the obtained arenediazonium salts with unsaturated compounds in the presence of a 50 SiCSi catalyst, which is characterized by the fact that anthranilic acid esters diazotize sodium nitrite in aqueous HBg, the resulting 2-alkoxycarbonylbenzenediazonium bromides are reacted with unsaturated sp compounds in a water-acetone medium, and SiHg is used as a catalyst, and substituted 3,4-dihydroisocoumarins of the general formula are obtained: 2 , св В! . t s a de K"-H, 5-СНа, 6-СООСН», 7-СНа, 7-С1, 7-Вг; because Б?-СООСН», СОСН», SeNv, 4-СНаСеНа, 4-СНАЗОСс Na , 4-SISeNuU. Official bulletin "Industrial Property". Book 1 "Inventions, useful models, topographies of integrated microcircuits", 2007, M 10, 10.07.2007. State Department of Intellectual Property of the Ministry of Education and Science of Ukraine. b5