2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

Query Query H N

1. Query

Results

Date

80 reactions in Reaxys

2018-08-20 21h:53m:40s (UTC)

O

O

O

Search as: Product, As drawn, No mixtures ) AND (IDE.RN='118-48-9') AND (IDE.INCHI='TXJUTRJFNRYTHH-UHFFFAOYSA-N') NOT (RX.RXRN=136786))

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

H N

O

NH O O

O

O

Rx-ID: 548025 View in Reaxys 1/80 Yield 100 %

Conditions & References in acetonitrile, Time= 24h, T= 20 °C , Inert atmosphere, Photolysis Al-Jalal, Nader; Al-Awadi, Nouria A.; Ibrahim, Maher R.; Elnagdi, Mohamed H.; Arkivoc; vol. 2011; nb. 10; (2011); p.

288 - 297 View in Reaxys

88 %

With diphenyl diselenide, dihydrogen peroxide in N,N-dimethyl-formamide, acetonitrile, Time= 8h, T= 25 °C , Schlenk technique, Green chemistry, Baeyer-Villiger Ketone Oxidation, Solvent, Temperature, Reagent/catalyst, Time Yu, Lei; Ye, Jianqing; Zhang, Xu; Ding, Yuanhua; Xu, Qing; Catalysis Science and Technology; vol. 5; nb. 10; (2015); p.

4830 - 4838 View in Reaxys

79 %

With sulfuric acid, dihydrogen peroxide in water, acetic acid, Time= 2h, T= 60 - 70 °C Reissenweber, Gernot; Mangold, Dietrich; Angewandte Chemie; vol. 92; nb. 3; (1980); p. 196 - 197 View in Reaxys

78 %

With Oxone in water, acetonitrile, T= 20 °C , regioselective reaction Nelson, Amber C.; Kalinowski, Emily S.; Czerniecki, Nikolas J.; Jacobson, Taylor L.; Grundt, Peter; Organic and Biomolecular Chemistry; vol. 11; nb. 43; (2013); p. 7455 - 7457 View in Reaxys With chromium(VI) oxide, acetic acid, T= 60 °C Kolbe; Journal fuer Praktische Chemie (Leipzig); vol. <2> 30; (1884); p. 85,469 View in Reaxys With ozone, ethyl acetate van Alphen; Recueil des Travaux Chimiques des Pays-Bas; vol. 57; (1938); p. 915,919 View in Reaxys 2 : EXAMPLE 2 EXAMPLE 2 14.7 parts of isatin are suspended in 80 parts of formic acid.

20 parts of 30 percent strength hydrogen peroxide solution are added dropwise, with slight cooling.

The mixture is then stirred for 60 minutes at 25° C., after which it is worked up in a conventional manner. 13.2 parts of isatoic anhydride are obtained; melting point 252°-253° C., with decomposition.

With dihydrogen peroxide in formic acid Patent; BASF Aktiengesellschaft; US4316020; (1982); (A) English View in Reaxys With sulfuric acid, dihydrogen peroxide, acetic acid, Time= 4h, T= 60 - 70 °C Yang, Shuangshuang; Li, Xishuai; Hu, Fangfang; Li, Yinlong; Yang, Yunyun; Yan, Junkai; Kuang, Chunxiang; Yang, Qing; Journal of Medicinal Chemistry; vol. 56; nb. 21; (2013); p. 8321 - 8331 View in Reaxys 1 :In a round bottom flask was added 1.47 g of isatin (10 mmol),0. 16 g diphenyl diselenide (0. 5 mmol).With stirring,The temperature of the mixing system was maintained at 25 ° C,And 25 ml of a DMF-acetonitrile mixed solution (DMF volume content: 10percent) in which 20 mmol of 30percent hydrogen peroxide was dissolved was slowly added dropwise.The mixture was stirred at a system temperature of 25 ° CShould be 24 hours.After completion of the reaction, 30 ml of a 5percent aqueous solution of ferrous chloride was added, and the mixture was extracted with ethyl acetate (50 ml, 3 times)The organic layer was dried over

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

anhydrous sodium sulfate and the solvent was evaporated. The residue was purified by column chromatography to give 1.39 g of isatoic anhydride (yield 85percent).

With diphenyl diselenide, dihydrogen peroxide in N,N-dimethyl-formamide, acetonitrile, Time= 24h, T= 25 °C , Solvent, Reagent/catalyst Patent; Yangzhou University; Zhang, Xu; Li, Hongyan; Yu, Lei; Ye, Jianqing; Zhang, Ming; Xu, Qing; (7 pag.); CN103848794; (2016); (B) Chinese View in Reaxys With tert.-butylhydroperoxide, caesium carbonate in dimethyl sulfoxide, T= 100 °C Jiang, Shi-Fen; Xu, Cheng; Zhou, Zhi-Wen; Zhang, Qin; Wen, Xiao-Hui; Jia, Feng-Cheng; Wu, An-Xin; Organic Letters; vol. 20; nb. 14; (2018); p. 4231 - 4234 View in Reaxys

O

Cl

O

O

Cl O Cl

H N

H 2N

Cl

Cl O

O

Cl HO

O

Rx-ID: 8762054 View in Reaxys 2/80 Yield 100 %

Conditions & References 1H-Benzo[d][1,3]oxazine-2,4-dion, (19).

Synthesis according to Darras,et al.4 2-Aminobenzoic acid (1.00 g, 7.29 mmol, 1.0 eq) was dissolved in dry THF (15 mL) before triphosgene (0.74 g, 2.48 mmol, 0.3 eq) was added. The mixture was heated over night at 45 °C. The solvent was removed and an off-white solid was obtained in quantitative yield. Analytical Data for C8H5NO3 (163.13 g/mol): Rf =0.47 (SiO2, petroleum ether/ethyl acetate 1:1, 2 drops triethylamine). Mp=176.6 – 179.2 °C. 1H-NMR (400 MHz, DMSO-d6, 300 K): δ= 11.76 (s, 1H, NH), 7.96 (d,J= 7.8 Hz, 1H, Ar-H), 7.83–7.73 (m, 1H, Ar-H), 7.29 (t,J= 7.6 Hz, 1H, Ar-H), 7.20 (d,J=8.2Hz, 1H, Ar-H) ppm.

Spectral data is in accordance with the literature.4 in tetrahydrofuran, Time= 12h, T= 45 °C Wehle, Sarah; Espargaró, Alba; Sabaté, Raimon; Decker, Michael; Tetrahedron; vol. 72; nb. 20; (2016); p. 2535 - 2543 View in Reaxys

95 %

in tetrahydrofuran, Time= 4h, Reflux Dong, Guoqiang; Wang, Shengzheng; Miao, Zhenyuan; Yao, Jianzhong; Zhang, Yongqiang; Guo, Zizhao; Zhang, Wannian; Sheng, Chunquan; Journal of Medicinal Chemistry; vol. 55; nb. 17; (2012); p. 7593 - 7613 View in Reaxys

95 %

1 :A mixture of anthranilic acid (822 mg, 6.0 mmol, 1.0 eq) and triphosgene (605 mg, 2.04 mmol, 0.34 eq) in dry tetrahydrofuran (30 mL) was stirred for 4 h at 40-50 °C under an argon atmosphere. The mixture was concentrated in vacuo and the resulting solid was filtered and washed with hexane. No further purification was needed to afford the desired product (2δ-benzo[d][1,3]oxazine-2,4(1H)-dione, 930 mg, 95percent) as a dark green solid: NMR (DMSO-d6, 500 MHz) δ 11.71 (s, 1H), 7.89 (d, J = 7.5 Hz, 1H), 7.72 (t, J = 7.5 Hz, 1H), 7.23 (t, J= 7.5 Hz, 1H), 7.13 (d, J = 8.0 Hz, 1H) ppm; 13C NMR (DMSO-d6, 125 MHz) δ 160.4, 147.6, 141.9, 137.4, 129.4, 124.0, 115.8, 110.8 ppm. These data are in agreement with those previously reported. in tetrahydrofuran, Time= 4h, T= 40 - 50 °C , Inert atmosphere Patent; THE REGENTS OF THE UNIVERSITY OF CALIFORNIA; UNITED STATES GOVERNMENT, REPRESENTED BY THE DEPARTMENT OF VETERANS AFFAIRS; GERA, Joseph, F.; LICHTENSTEIN, Alan; JUNG, Michael, E.; LEE, Jihye; HOLMES, Brent; BENAVIDES-SERRATO, Angelica; (94 pag.); WO2017/192665; (2017); (A1) English View in Reaxys

94.4 %

in pyridine, dichloromethane, acetonitrile, Time= 2h, T= 50 - 55 °C Huang, Junmin; Chen, Hui; Chen, Ruyu; Heteroatom Chemistry; vol. 13; nb. 1; (2002); p. 63 - 71 View in Reaxys

94.4 %

With pyridine in dichloromethane, acetonitrile, Time= 2h, T= 50 - 55 °C

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

Huang, Jun-Min; Chen, Hui; Chen, Ru-Yu; Synthetic Communications; vol. 32; nb. 14; (2002); p. 2215 - 2225 View in Reaxys 90 %

With triethylamine, T= 20 °C , Inert atmosphere Bose, D. Subhas; Chary, M. Venu; Synthesis; nb. 4; (2010); p. 643 - 650; Art.No: Z20909SS View in Reaxys

89 %

in tetrahydrofuran, T= 0 - 20 °C Kalusa, Andrew; Chessum, Nicola; Jones, Keith; Tetrahedron Letters; vol. 49; nb. 41; (2008); p. 5840 - 5842 View in Reaxys

86 %

1.1 : 1) The Preparation of Benzoxazine Ketone To a solution of anthranilic acid 13.70 g (0.1 mol) in150 mL tetrahydroffiran was added 19.80 g (0.067 mol) solid phosgene in batches at room temperature for 1.5 hours. Then the reaction mixture was continued stirring at room temperature for another 2-3 hours and monitored by TLC. After the reaction was over, the mixture was concentrated under reduced pressure, the residual was poured into 80 ml water and stirred until excessive phosgene was completely decomposed, the solid was then filtered, washed with 50 ml of water and 50 ml ofpetroleum ether successively, dried to give 14.00 g benzoxazine ketone as white solid with yield of 86.0percent, m.p.239-240° C. With phosgene in tetrahydrofuran, T= 20 °C Patent; SHENYANG RESEARCH INSTITUTE OF CHEMICAL INDUSTRY CO., LTD.; SINOCHEM CORPORATION; Liu, Changling; Wang, Lizeng; Li, Zhinian; Sun, Xufeng; Lan, Jie; Ren, Lanhui; Wu, Qiang; Chi, Huiwei; US2013/225585; (2013); (A1) English View in Reaxys

86 %

1.1 : 1) The preparation of benzoxazine ketone To a solution of anthranilic acid 13.70g (0.1mol) in 150 mL tetrahydrofuran was added 19.80 g (0.067 mol) solid phosgene in batches at room temperature for 1.5 hours. Then the reaction mixture was continued stirring at room temperature for another 2-3 hours and monitored by TLC. After the reaction was over, the mixture was concentrated under reduced pressure, the residual was poured into 80ml water and stirred until excessive phosgene was completely decomposed, the solid was then filtered, washed with 50ml of water and 50ml of petroleum ether successively, dried to give 14.00g benzoxazine ketone as white solid with yield of 86.0percent, m.p. 239-240°C. in tetrahydrofuran, T= 20 °C Patent; Sinochem Corporation; Shenyang Research Institute of Chemical Industry Co., Ltd.; REN, Lanhui; LIU, Changling; WANG, Lizeng; LI, Zhinian; SUN, Xufeng; LAN, Jie; WU, Qiang; CHI, Huiwei; EP2636669; (2013); (A1) English View in Reaxys

82 %

in tetrahydrofuran, Time= 3h, T= 40 - 50 °C Darras, Fouad H.; Kling, Beata; Heilmann, Jörg; Decker, Michael; ACS Medicinal Chemistry Letters; vol. 3; nb. 11; (2012); p. 914 - 919 View in Reaxys

70-98%

1 : General Procedure to Prepare Isatoic Anhydrides Example 1 General Procedure to Prepare Isatoic Anhydrides An ice-cold solution of triphosgene (3.0 g, 10 mmol, 0.4 eq) in 10 mL of anhydrous THF was added to a mixture or solution of anthranilic acid (or 2-amino-benzoic acid) (25 mmol) in 15 mL of dry THF with slow cooling.

The mixture was then stirred or shaken for 24-48 h at room temperature and cooled in a refrigerator (0° C. to -10° C.) for 12-24 h.

The resulting solid was collected by filtration and washed with cold methyl t-butyl ether (MTBE) and dried to give the isatoic anhydride in 70-98percent yield.

About 30 isatoic anhydrides were prepared in this manner. in tetrahydrofuran Patent; Sepracor Inc.; US6184377; (2001); (B2) English View in Reaxys

70-98%

6 : General Procedure for the Preparation of Isatoic Anhydride

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

General Procedure for the Preparation of Isatoic Anhydride An ice-cold solution of triphosgene (3.0 g, 10 mmol, 0.4 eq) in 10 mL of anhydrous THF was added to a mixture or solution of anthranilic acid (or 2-amino-benzoic acid) (25 mmol) in 15 mL of dry THF and cooled slowly.

The mixture as then stirred or shaken for 24-48 h at room temperature nd cooled in a refrigerator (0° C. to -10° C.) for 12-24 h.

The resulting solid was collected by filtration and washed with cold methyl t-butyl ether (MTBE) and dried to give the isatoic anhydride in 70-98percent yield.

About 30 isatoic anhydrides were prepared in this manner. in tetrahydrofuran Patent; Sepracor Inc.; US6274383; (2001); (B1) English View in Reaxys 50 %

With pyridine in dichloromethane, acetonitrile, Time= 2h, T= 50 - 55 °C Zheng, Chunling; Yuan, Ailin; Zhang, Zhengyu; Shen, Hong; Bai, Shuyuan; Wang, Haibo; Journal of Fluorescence; vol.

23; nb. 4; (2013); p. 785 - 791 View in Reaxys Huang, Junmin; Chen, Ruyu; Heteroatom Chemistry; vol. 12; nb. 2; (2001); p. 97 - 101 View in Reaxys Huang, Junmin; Chen, Hui; Chen, Ruyu; Journal of Chemical Crystallography; vol. 31; nb. 9-10; (2001); p. 445 - 452 View in Reaxys in 1,4-dioxane, Time= 3h, T= 0 °C Tomassoli, Isabelle; Ismaili, Lhassane; Pudlo, Marc; De Los Rios, Cristobal; Soriano, Elena; Colmena, Ines; Gandia, Luis; Rivas, Luis; Samadi, Abdelouahid; Marco-Contelles, Jose; Refouvelet, Bernard; European Journal of Medicinal Chemistry; vol. 46; nb. 1; (2011); p. 1 - 10 View in Reaxys in tetrahydrofuran, dichloromethane, T= 20 °C Grue-Sorensen, Gunnar; Liang, Xifu; Mansson, Kristoffer; Vedso, Per; Dahl Sorensen, Morten; Soor, Anke; Stahlhut, Martin; Bertelsen, Malene; Engell, Karen Margrethe; Hoegberg, Thomas; Bioorganic and Medicinal Chemistry Letters; vol. 24; nb. 1; (2014); p. 54 - 60 View in Reaxys 1. General procedure for preparation of isotaic anhydrides To the solution of appropriate 2-aminobenzoic acid in dried THF or 1,4- dioxane was added triphosgene (0.35 eq). The mixture was stirred under reflux for 4-8 hrs. Then the solvent was removed in vacuo to give the isotaic anhydride as a solid in theoretical yield. 1H NMR indicated the product was of sufficient purity and was used in the next step without further purification. , Reflux, Inert atmosphere Huang, Guozheng; Roos, Dominika; Stadtmüller, Patricia; Decker, Michael; Tetrahedron Letters; vol. 55; nb. 26; (2014); p.

3607 - 3609 View in Reaxys in tetrahydrofuran, Time= 4h, T= 0 - 20 °C , Inert atmosphere Jamali, Haya; Khan, Hasan A.; Stringer, Joseph R.; Chowdhury, Somenath; Ellman, Jonathan A.; Journal of the American Chemical Society; vol. 137; nb. 10; (2015); p. 3616 - 3621 View in Reaxys in tetrahydrofuran, Time= 19h, T= -10 - 20 °C Wang, Gaolei; Chen, Xiulei; Deng, Yayun; Li, Zhong; Xu, Xiaoyong; Journal of Agricultural and Food Chemistry; vol. 63; nb. 31; (2015); p. 6883 - 6889 View in Reaxys in tetrahydrofuran, T= 25 °C Kong, Xiang-Fei; Zhan, Feng; He, Guo-Xue; Pan, Cheng-Xue; Gu, Chen-Xi; Lu, Ke; Mo, Dong-Liang; Su, Gui-Fa; Journal of Organic Chemistry; vol. 83; nb. 4; (2018); p. 2006 - 2017 View in Reaxys

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

H N

O

H 2N O

O

C

O

O

I O

Rx-ID: 46789069 View in Reaxys 3/80 Yield

Conditions & References With tetrakis(triphenylphosphine) palladium(0), cesium acetate in tetrahydrofuran, Time= 16h, T= 60 °C

90 %

Zhang, Wen-Zhen; Zhang, Ning; Sun, Yu-Qian; Ding, Yu-Wei; Lu, Xiao-Bing; ACS Catalysis; vol. 7; nb. 12; (2017); p.

8072 - 8076 View in Reaxys

O

Cl

O

H 2N

Cl O Cl

H N

H 2N

Cl

Cl O

O

Cl O

O

Rx-ID: 44522560 View in Reaxys 4/80 Yield

Conditions & References Synthesis of the N-substituted 2-aminobenzamide 1b-m To a solution of 2-amino-5-methylbenzamide (1.5 g,10 mmol) in THF (20 mL) was added triphosgene (0.99 g, 3.3 mmol) portionwise about 20 min. The mixture was cooled to rt when the reaction was completed. Through filtration, the crude isatoic anhydride was got. A stirred solution of isatoic anhydride was suspending in THF which was heated to 60°C, then the solution of amine was added dropwise. Progress of the reaction was monitored using TLC. After completion of the reaction, the resulting solution was cooled to room temperature and the solvent was removed under high vacuum to give the crude product. Then recrystallization from Et2O afforded the pure product. 2-Amino-N-methylbenzamide (1b). Orange solid; mp: 79-80°C; Rf 0.22 (40percent ethyl acetate in petroleum ether); 1H NMR (600 MHz, CDCl3) d (ppm): 2.96 (d, 3H, J4.8 Hz), 5.50 (brs, 2H),6.10 (brs, 1H), 6.63 (t, 1H, J7.5 Hz), 6.67 (d, 1H, J8.2 Hz), 7.19 (t, 1H,J7.7 Hz), 7.29 (d,1H, J7.8 Hz); 13C NMR (150 MHz, CDCl3) d (ppm):26.5, 116.3, 116.6, 117.2, 127.3, 132.1, 148.5, 170.1; mass spectrum(ESI): m/e (percent relative intensity) 173.4 (100) (M +Na). in tetrahydrofuran, Time= 0.333333h Wang, Zhen-Zhen; Tang, Yu; Tetrahedron; vol. 72; nb. 10; (2016); p. 1330 - 1336 View in Reaxys Rx-ID: 41424226 View in Reaxys 5/80

Yield

Conditions & References With oxygen in dimethyl sulfoxide, UV-irradiation Witkos̈, Katarzyna; Lech, Katarzyna; Jarosz, MacIej; Journal of Mass Spectrometry; vol. 50; nb. 11; (2015); p. 1245 - 1251 View in Reaxys Rx-ID: 41424227 View in Reaxys 6/80

Yield

Conditions & References With oxygen in methanol, UV-irradiation Witkos̈, Katarzyna; Lech, Katarzyna; Jarosz, MacIej; Journal of Mass Spectrometry; vol. 50; nb. 11; (2015); p. 1245 - 1251 View in Reaxys Rx-ID: 41424228 View in Reaxys 7/80

Yield

Conditions & References With oxygen in dimethyl sulfoxide, UV-irradiation Witkos̈, Katarzyna; Lech, Katarzyna; Jarosz, MacIej; Journal of Mass Spectrometry; vol. 50; nb. 11; (2015); p. 1245 - 1251 View in Reaxys

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

O N O

N

N

H N

O

OH

O

O

O

Rx-ID: 43281548 View in Reaxys 8/80 Yield

Conditions & References

99 %

EX-17 :General procedure: First of all, water of 0.5mL (In the case of Ex. No. 1) oran organic solvent ( In the case of Ex. Nos. 2 to 17) was charged into thereaction vessel, and orthoazide benzoate used in the reaction (81.6mg :0.0005mol), Orthoazide benzoic acid withan equivalent amount (0.0005mol) triphenylphosphine (131.2mg: 0.0005mol) and1.5 times equivalent amount(0.00075mol) CTMABr of orthoazide benzoic acid wereadded to this solvent and the mixture wasstirred for 5 minutes at 20 .Thereafter, water or pH7.6 potassium dihydrogen phosphate (KH2P04)/ sodium hydroxide (NaOH) buffer solution 4.5mL was added and the reactionsystem was made as an aqueous solvent, and reaction vessel was degassed, and after the reaction vessel was made as a carbondioxide atmosphere using a balloon inflated with carbon dioxide, it was allowed to react with stirring under the conditions of 20, 18 hours.

With cetyltrimethylammonim bromide, triphenylphosphine in acetonitrile, Time= 24h, T= 60 °C , p= 760.051Torr , Solvent, Temperature Patent; THE UNIVERSITY OF TOKYO; NIPPON STEEL & SUMITOMO METAL CORPORATION; KOBAYASHI, SHU; YOO, WOO-JIN; IMAIZUMI, TAKAKI; DONOMAE, HITOSHI; YAMANE, NORIYUKI; (15 pag.); JP2015/172008; (2015); (A) Japanese View in Reaxys H N

O

Cl

O

Cl

Cl Cl O

O

O

Cl

Cl O

Rx-ID: 37895076 View in Reaxys 9/80 Yield

Conditions & References Procedure B: Quinazolinedione Formation (Triphosgene) Procedure B: Quinazolinedione Formation (Triphosgene) A suspension of the amide (1 mmol) in dioxane (5 ml) is treated with triphosgene (0.5M in dioxane; 0.6 mmol).

The reaction is stirred at 70° C. for 1.5 h.

The reaction mixture is cooled to rt and treated with sat. aq. NaHCO3 (2 ml) and further stirred at rt for 30 min.

The resulting crystals are filtered and washed with water.

The solid is collected, stirred in MeOH/ether and filtered. in 1,4-dioxane Patent; ACTELION PHARMACEUTICALS LTD.; Hubschwerlen, Christian; Rueedi, Georg; Surivet, Jean-Philippe; Zumbrunn Acklin, Cornelia; US2014/171425; (2014); (A1) English View in Reaxys

H 2N

H N

O

O C

O

O HO

O

Rx-ID: 37961639 View in Reaxys 10/80 Yield 99 %

Conditions & References With oxygen, copper diacetate, palladium diacetate, potassium iodide in acetonitrile, Time= 4h, T= 60 °C , p= 760.051Torr , Catalytic behavior, Reagent/catalyst Gao, Sha; Chen, Ming; Zhao, Mi-Na; Du, Wei; Ren, Zhi-Hui; Wang, Yao-Yu; Guan, Zheng-Hui; Journal of Organic Chemistry; vol. 79; nb. 9; (2014); p. 4196 - 4200 View in Reaxys

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

H N

O

H 2N C

O

O

I O

Rx-ID: 37961646 View in Reaxys 11/80 Yield

Conditions & References

68 %

With potassium phosphate, oxygen, palladium diacetate, potassium iodide, calcium chloride, copper dichloride, Trimethylacetic acid in acetonitrile, Time= 24h, T= 100 °C , p= 2280.15Torr , Catalytic behavior, Reagent/catalyst, Solvent Gao, Sha; Chen, Ming; Zhao, Mi-Na; Du, Wei; Ren, Zhi-Hui; Wang, Yao-Yu; Guan, Zheng-Hui; Journal of Organic Chemistry; vol. 79; nb. 9; (2014); p. 4196 - 4200 View in Reaxys

O

H N

NH

O

O O

N NH 2

O O

NH O

O

Rx-ID: 39064752 View in Reaxys 12/80 Yield

Conditions & References With urea hydrogen peroxide adduct in toluene, Time= 1h, T= 75 °C Abe, Takumi; Itoh, Tomoki; Choshi, Tominari; Hibino, Satoshi; Ishikura, Minoru; Tetrahedron Letters; vol. 55; nb. 38; (2014); p. 5268 - 5270 View in Reaxys H N

N N

O

O

HN O

Rx-ID: 36043987 View in Reaxys 13/80 Yield 78 %

Conditions & References With Oxone in nitromethane, T= 100 °C Lian, Xiao-Li; Lei, Hao; Quan, Xue-Jing; Ren, Zhi-Hui; Wang, Yao-Yu; Guan, Zheng-Hui; Chemical Communications; vol. 49; nb. 74; (2013); p. 8196 - 8198 View in Reaxys

OH

H N

O

O

O O N

O O

Rx-ID: 36066005 View in Reaxys 14/80 Yield

Conditions & References Reaction Steps: 2 1.1: hydrazine hydrate; sodium hydroxide; 5% Pd/C / water / 6 h / 50 - 60 °C 1.2: pH 3 - 4 2.1: pyridine / acetonitrile; dichloromethane / 2 h / 50 - 55 °C With pyridine, 5% Pd/C, hydrazine hydrate, sodium hydroxide in dichloromethane, water, acetonitrile

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

Zheng, Chunling; Yuan, Ailin; Zhang, Zhengyu; Shen, Hong; Bai, Shuyuan; Wang, Haibo; Journal of Fluorescence; vol.

23; nb. 4; (2013); p. 785 - 791 View in Reaxys

H N

O

N

S

S

NH 2

N

O

HN

S OH

O NH

Cl

O

O

HN Cl

O

O

O

O

O

S O

O

Rx-ID: 36433034 View in Reaxys 15/80 Yield 46 %, 76 %

Conditions & References Stage 1: With water, sodium hydroxide, Time= 30h, T= 20 °C Stage 2: With hydrogenchloride, water, pH= 6 Brzozowski, Zdzislaw; Slawinski, Jaroslaw; Journal of Heterocyclic Chemistry; vol. 50; nb. 5; (2013); p. 1099 - 1107 View in Reaxys H N

O

NH

O

O

Rx-ID: 36549808 View in Reaxys 16/80 Yield 83 %

Conditions & References With Oxone in water, N,N-dimethyl-formamide, Time= 16h, T= 20 °C , Solvent Nelson, Amber C.; Kalinowski, Emily S.; Czerniecki, Nikolas J.; Jacobson, Taylor L.; Grundt, Peter; Organic and Biomolecular Chemistry; vol. 11; nb. 43; (2013); p. 7455 - 7457 View in Reaxys H N

NH

O

O

O

O

Rx-ID: 36549817 View in Reaxys 17/80 Yield 85 %

Conditions & References With Oxone in water, N,N-dimethyl-formamide, T= 20 °C Nelson, Amber C.; Kalinowski, Emily S.; Czerniecki, Nikolas J.; Jacobson, Taylor L.; Grundt, Peter; Organic and Biomolecular Chemistry; vol. 11; nb. 43; (2013); p. 7455 - 7457 View in Reaxys O

H N

O

NH

O HN O

O

Rx-ID: 36549820 View in Reaxys 18/80 Yield 76 %

Conditions & References With Oxone in water, acetonitrile, Time= 1h, T= 60 °C

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

Nelson, Amber C.; Kalinowski, Emily S.; Czerniecki, Nikolas J.; Jacobson, Taylor L.; Grundt, Peter; Organic and Biomolecular Chemistry; vol. 11; nb. 43; (2013); p. 7455 - 7457 View in Reaxys O O

H N

NH

O

HN

HN

O

N

N

O O

O

O

Rx-ID: 36721967 View in Reaxys 19/80 Yield

Conditions & References

42 %, 6 %, 12 %

With Oxone in water, acetonitrile, Time= 16h, T= 20 °C Nelson, Amber C.; Kalinowski, Emily S.; Jacobson, Taylor L.; Grundt, Peter; Tetrahedron Letters; vol. 54; nb. 50; (2013); p. 6804 - 6806 View in Reaxys H N

H 2N

O

O

O

Rx-ID: 36935660 View in Reaxys 20/80 Yield

Conditions & References Reaction Steps: 3 1: hydroxylamine hydrochloride; hydrogenchloride; sodium sulfate / water / 100 °C 2: sulfuric acid / 1 h / 65 °C 3: sulfuric acid; acetic acid; dihydrogen peroxide / 4 h / 60 - 70 °C With hydrogenchloride, sulfuric acid, hydroxylamine hydrochloride, dihydrogen peroxide, acetic acid, sodium sulfate in water Yang, Shuangshuang; Li, Xishuai; Hu, Fangfang; Li, Yinlong; Yang, Yunyun; Yan, Junkai; Kuang, Chunxiang; Yang, Qing; Journal of Medicinal Chemistry; vol. 56; nb. 21; (2013); p. 8321 - 8331 View in Reaxys

H N

HO

H N

O

N

O O

O

Rx-ID: 36935709 View in Reaxys 21/80 Yield

Conditions & References Reaction Steps: 2 1: sulfuric acid / 1 h / 65 °C 2: sulfuric acid; acetic acid; dihydrogen peroxide / 4 h / 60 - 70 °C With sulfuric acid, dihydrogen peroxide, acetic acid Yang, Shuangshuang; Li, Xishuai; Hu, Fangfang; Li, Yinlong; Yang, Yunyun; Yan, Junkai; Kuang, Chunxiang; Yang, Qing; Journal of Medicinal Chemistry; vol. 56; nb. 21; (2013); p. 8321 - 8331 View in Reaxys

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

H N

O

HO

O

O

N H O

O

OH

Rx-ID: 33978972 View in Reaxys 22/80 Yield

Conditions & References 2 :Commercially available isatoic acid (manufactured by BASF AG, HPLC purity: 97.5percent, Na content: 2000 ppm) was dissolved in dimethyl formamide (DMF) at 60° C. in a 500 ml four-necked flask equipped with a thermometer, a stirrer, a reflux condenser, a dropping funnel, a nitrogen gas introduction unit and a gas lead-out unit connected to a hydrogen halide removing device to be recrystallized. The resulting mixture was left to be cooled, and the crystal was filtered and dried to obtain purified isatoic anhydride.Thereafter, 25 g of the purified and dried isatoic anhydride was dissolved in 250 g of dry pyridine at a temperature of about 60° C. 15.8 g of terephthaloyl dichloride manufactured by E.I. du Pont de Nemours and Company was gradually added to the isatoic anhydride mixture under agitation while it was slightly cooled to maintain the temperature of the solution.

The precipitate was filtered, cleaned and dried to obtain 43.86 g of slightly yellowish crystalline 2,2'-phenylenebis(3,1-benzoxazin-4-one) (comparative product 2).The obtained comparative product 2 had an HPLC purity of 96.7percent, a content of the compound of the formula (7) of 0.26 wt percent, a maximum peak in the measurement of light reflectance at 450 nm, a maximum light reflectance of 91percent, a metal sodium content of 13 ppm and a YI value of -5.8. Its yield was 85.0percent. in N,N-dimethyl-formamide, T= 60 °C Patent; Ibusuki, Shun; Koga, Takashi; Miyake, Akira; Hayashi, Masayuki; Yoshida, Masaya; US2012/252941; (2012); (A1) English View in Reaxys 2 :Commercially available isatoic acid (manufactured by BASF AG, HPLC purity: 97.5 percent, Na content: 2000 ppm) was dissolved in dimethyl formamide (DMF) at 60°C in a 500 ml four-necked flask equipped with a thermometer, a stirrer, a reflux condenser, a dropping funnel, a nitrogen gas introduction unit and a gas lead-out unit connected to a hydrogen halide removing device to be recrystallized. The resulting mixture was left to be cooled, and the crystal was filtered and dried to obtain purified isatoic anhydride. Thereafter, 25 g of the purified and dried isatoic anhydride was dissolved in 250 g of dry pyridine at a temperature of about 60°C. 15.8 g of terephthaloyl dichloride manufactured by E.I. du Pont de Nemours and Company was gradually added to the isatoic anhydride mixture under agitation while it was slightly cooled to maintain the temperature of the solution.

The precipitate was filtered, cleaned and dried to obtain 43.86 g of slightly yellowish crystalline 2,2-phenylenebis(3,1-benzoxazin-4-one) (comparative product 2). The obtained comparative product 2 had an HPLC purity of 96.7 percent, a content of the compound of the formula (7) of 0.26 wtpercent, a maximum peak in the measurement of light reflectance at 450 nm, a maximum light reflectance of 91 percent, a metal sodium content of 13 ppm and a YI value of -5.8. Its yield was 85.0 percent. in N,N-dimethyl-formamide, Inert atmosphere Patent; Teijin Chemicals, Ltd.; EP2505585; (2012); (A1) English View in Reaxys

H 2N

Cl

O

H N

O

O

O

O HO

O

Rx-ID: 552610 View in Reaxys 23/80 Yield 78 %

Conditions & References With triethylamine, Time= 22.17h, T= 20 - 100 °C , Inert atmosphere Bose, D. Subhas; Chary, M. Venu; Synthesis; nb. 4; (2010); p. 643 - 650; Art.No: Z20909SS View in Reaxys Erdmann; Chemische Berichte; vol. 32; (1899); p. 2164; Chem. Zentralbl.; vol. 71; nb. II; (1900); p. 506 View in Reaxys Niementowski; Rozanski; Chemische Berichte; vol. 22; (1889); p. 1673,1674 View in Reaxys Niementowski; Rozanski; Chemische Berichte; vol. 22; (1889); p. 1673,1674

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

View in Reaxys H N

Br O

O

O –C

O

N+

O

Rx-ID: 28660365 View in Reaxys 24/80 Yield

Conditions & References

61 %

Stage 1: With n-butyllithium in tetrahydrofuran, hexane, Time= 0.333333h, T= -78 °C , Inert atmosphere Stage 2: in tetrahydrofuran, hexane, Time= 1h, T= -78 °C , Further stages Lygin, Alexander V.; De Meijere, Armin; Journal of Organic Chemistry; vol. 74; nb. 12; (2009); p. 4554 - 4559 View in Reaxys O

O

H N

N N

O

O

NH

O

O

O

Rx-ID: 28577741 View in Reaxys 25/80 Yield

Conditions & References Time= 0.0833333h, T= 80 - 100 °C , Neat (no solvent) Klenov; Churakov; Anikin; Strelenko; Fedyanin; Lyssenko; Tartakovsky; Russian Chemical Bulletin; vol. 57; nb. 3; (2008); p. 638 - 643 View in Reaxys H N

H 2N

O O

Cl

O

Cl O

Cl

O

Cl

HO

O

Rx-ID: 2732847 View in Reaxys 26/80 Yield 63 %

Conditions & References 2 :1H-Benzo[d][1,3]oxazine-2,4-dione (Intermediate compound): A solution of 2-amino benzoic acid (10 g, 72.92 mmol) and pyridine 23.6 mmol, 292 mmol) in a mixture of CH2CI2 (100 ml_) and CH3CN (100 ml_) under N2 atmosphere was carefully added a solution of diphosgene (4.4 ml_, 36.5 mmol) in CH2CI2 (25 ml_). The reaction mixture was then heated to 500C over night after which it was cooled and poured into ethyl acetate and a half saturated aqueous NaCI solution. The organic phase was dried using MgSO4, filtered and evaporated to dryness. The crude product was trituated in diethyl ether to give 7.5 g (63percent) of the title compound.

With pyridine in dichloromethane, acetonitrile, T= 50 °C Patent; NEUROSEARCH A/S; WO2007/57447; (2007); (A1) English View in Reaxys With N,N-dimethyl-aniline Tsubota, Motohiro; Hamashima, Motome; Heterocycles; vol. 21; nb. 2; (1984); p. 706 View in Reaxys

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

H N

H 2N

Cl

Cl

O

O

O

O HO

O

Rx-ID: 623242 View in Reaxys 27/80 Yield

Conditions & References With hydrogenchloride Wagner; Fegley; Organic Syntheses; vol. 27; (1947); p. 45 View in Reaxys Patent; I. G. Farbenind.; DE500916; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 17; p. 500 View in Reaxys Clark; Wagner; Journal of Organic Chemistry; vol. 9; (1944); p. 55,61, 63 View in Reaxys (i) ClSiMe3, Et3N, CH2Cl2, (ii) /BRN= 1098367/, benzene, Multistep reaction Kricheldorf,H.R.; Chemische Berichte; vol. 103; (1970); p. 3353 - 3355 View in Reaxys in hydrogenchloride, Time= 1.5h Baronnet; Callendret; Blanchard; et al.; European Journal of Medicinal Chemistry; vol. 18; nb. 3; (1983); p. 241 - 247 View in Reaxys in 1,4-dioxane, Time= 1h, T= 20 °C Joensson, Stig; Andersson, Gunnar; Fex, Tomas; Fristedt, Tomas; Hedlund, Gunnar; Jansson, Karl; Abramo, Lisbeth; Fritzson, Ingela; Pekarski, Olga; Runstroem, Anna; Sandin, Helena; Thuvesson, Ingela; Bjoerk, Anders; Journal of Medicinal Chemistry; vol. 47; nb. 8; (2004); p. 2075 - 2088 View in Reaxys I H N

O C

O

O

H N

H N

O

O

O

O

N

O

O

O

Rx-ID: 9775548 View in Reaxys 28/80 Yield 47 %, 18 %

Conditions & References With pyridine, palladium diacetate, tetrabutyl-ammonium chloride in N,N-dimethyl-formamide, Time= 24h, T= 100 °C , p= 760Torr Kadnikov, Dmitry V.; Larock, Richard C.; Journal of Organic Chemistry; vol. 69; nb. 20; (2004); p. 6772 - 6780 View in Reaxys

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

H N

O

H 2N

PS-Wang resin-cyanoacetate

O

I O

Rx-ID: 13251503 View in Reaxys 29/80 Yield

Conditions & References Reaction Steps: 2 1: 95 percent / K2CO3 / acetone / 3 h / 20 °C 2: pyridine; n-Bu4NCl; Pd(OAc)2 / dimethylformamide / 24 h / 100 °C / 760 Torr With pyridine, palladium diacetate, tetrabutyl-ammonium chloride, potassium carbonate in N,N-dimethyl-formamide, acetone Kadnikov, Dmitry V.; Larock, Richard C.; Journal of Organic Chemistry; vol. 69; nb. 20; (2004); p. 6772 - 6780 View in Reaxys

O

Cl

O

Cl

Cl

O

Cl O

O

Cl

O

Cl

HO H 2N H N

O

1,2-dihydro-5,7-dimethoxy-3,1-benzoxazine-2,4-dione (4,6dimethoxyisatoic anhydride)

O

O

Rx-ID: 23920370 View in Reaxys 30/80 Yield 79.2 g (92%)

Conditions & References 5 : 1,2-dihydro-5,7-dimethoxy-3,1-benzoxazine-2,4-dione (4,6-dimethoxyisatoic anhydride) EXAMPLE 5 1,2-dihydro-5,7-dimethoxy-3,1-benzoxazine-2,4-dione (4,6-dimethoxyisatoic anhydride) To a cooled (0° C.) brown solution of 4,6-dimethoxy anthranilic acid (76.0 g, 0.385 mol), prepared as in Example 2, in tetrahydrofuran (1.3 L) was added triphosgene (40.0 g, 0.135 mol) in portions over a 20 min period.

After 30 min, the reaction was warmed to room temperature and stirred for an additional 1.5 h.

The reaction mixture was poured into an Erlenmeyer flask containing water and cooled to 0° C. with an ice bath.

Additional water was added to facilitate the stirring of the thick solid formed.

After stirring for 30 min, the reaction mixture was filtered to give a beige solid.

The solid was washed with water, air-dried, and then dried under high vacuum to give 79.2 g (92percent) of the isatoic anhydride.

C10H9NO5=223.18 g/mol; HPLC purity=>96percent; ESI-LC/MS (M-H)-=221.9.: MP:287-293° C. decomposes; 1H NMR (400 MHz, DMSO-d ): δ11.51 (bs, 1H), 6.36 (d, J=1.76 Hz, 1H), 6.20 (d, J=1.76 Hz, 1H), 3.86 (s, 3H), 3.85 (s, 3H).

6 in tetrahydrofuran, water Patent; Gungor, Timur; Corte, James R.; US2003/220227; (2003); (A1) English View in Reaxys H N

H 2N

O

Cl

O

Cl O

O I

Cl

O

Cl

OH

O

Rx-ID: 23991312 View in Reaxys 31/80 Yield

Conditions & References 40.1 : Step 1 Step 1

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

Methyl 2-amino-5-iodobenzoate To a solution of 2-amino-5-iodobenzoic acid (10 g, 38 mmol) in dry dioxane (280 ml) was added dropwise with stirring trichloromethylchloroformate (4.6 ml, 38 mmol).

The vessel was allowed to stir for 1 hour at ambient temperature after which the solvent was removed at 50° C. by rotary evaporation.

The residue was suspended in water (100 ml) and filtered and dried in a vacuum desiccator overnight to give the crude isatoic anhydride (13 g) IR; C=O stretch; 1795, cm-1 and NH stretch; 3184-3088 cm-1. in 1,4-dioxane, water Patent; Gustavsson, Anna-Lena; Jendeberg, Lena; Roussel, Patrick; Slater, Martin; Thor, Markus; US2003/73862; (2003); (A1) English View in Reaxys H N

O

O

O

Rx-ID: 5436518 View in Reaxys 32/80 Yield

Conditions & References Barišić; Batistić; Physica Scripta; vol. 1989; nb. T27; (1989); p. 78 - 81 View in Reaxys Iwakura,Y. et al.; Journal of Organic Chemistry; vol. 31; (1966); p. 142 - 146 View in Reaxys Kurita,K. et al.; Journal of Organic Chemistry; vol. 41; (1976); p. 2070 - 2071 View in Reaxys Patent; Sherwin-Williams; US3947416; (1976); ; vol. 85; nb. 33073 View in Reaxys Beckwith; Hickman; Journal of the Chemical Society [Section] C: Organic; (1968); p. 2756 View in Reaxys Patent; The Sherwin-Williams Comp.; US3828038; (1974); ; vol. 81; nb. 136171 View in Reaxys Geckeler; Metz; Archiv der Pharmazie (Weinheim, Germany); vol. 312; nb. 10; (1979); p. 842,844 View in Reaxys Tohyama et al.; Bulletin of the Chemical Society of Japan; vol. 43; (1970); p. 1246 View in Reaxys Patent; Sherwin-Williams; US3947442; (1976); ; vol. 85; nb. 5683 View in Reaxys Patent; Sherwin-Williams Comp.; US3887550; (1975); ; vol. 83; nb. 147504 View in Reaxys Patent; The Sherwin-Williams Co.; CH558352; (1974); DE2152722; ; vol. 79; nb. 32065 View in Reaxys Patent; BASF AG; CH592073; (1977); DE2258150; ; vol. 81; nb. 105532 View in Reaxys Patent; Beckwith. Athelstan L. J. (Australien); DE1926475; (1970); ; vol. 74; nb. 76430 View in Reaxys Dora-Horvath; Clauder; Acta Chimica Academiae Scientiarum Hungaricae; vol. 84; (1975); p. 93,95 View in Reaxys Kappe; Ziegler; Monatshefte fuer Chemie; vol. 95; (1964); p. 415,419 View in Reaxys Goldhamer et al.; Tetrahedron Letters; (1968); p. 4077 View in Reaxys Kozyukov et al.; J. Gen. Chem. USSR (Engl. Transl.); vol. 49; (1979); p. 784,679,680,681 View in Reaxys Piskov et al.; Pharmaceutical Chemistry Journal; vol. 7; nb. 6; (1973); p. 340,342,343; Khimiko-Farmatsevticheskii Zhurnal; vol. 7; nb. 6; (1973); p. 8 View in Reaxys 2 : 1.2Dihydro-4-hydroxy-5-chloro-1-methyl-2-oxo-quinoline-3-carboxylic acid ethyl ester EXAMPLE 2

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

1.2Dihydro-4-hydroxy-5-chloro-1-methyl-2-oxo-quinoline-3-carboxylic acid ethyl ester Phosgene (51 g, 0.52 mol) dissolved in 150 ml of dioxane was added in portions to a mechanically stirred slurry of 2-amino-6chloro-benzoic acid (30 g, 0.175 mol) and sodium bicarbonate (44 g, 0.52 mol) in 300 ml of dioxane.

Violent reaction with gas evolution occurred and the reaction mixture was cooled to keep the temperature below 50° C. Then stirring was continued at 50° C. for 1 hour.

The reaction mixture was cooled to 15° C., the resulting precipitate was collected, washed with water and dried to give the isatoic anhydride.

Patent; Active Biotech AB; US6133285; (2000); (A) English View in Reaxys 1.a : E. a.

Formylaminomethyl-carboxamide oxime.

0.55 mmol of freshly liberated hydroxylamine dissolved in 370 ml methanol was added to 53.6 g (0.638 mmol) N-formylaminoacetonitrile.

An ice bath was used to keep the temperature below 20° C. during addition.

The solution was allowed to stand at room temperature overnight, whereafter it was evaporated to give the title compound as pale crystals. Decomp. 104°-110° C. Patent; A/S Ferrosan; US4771051; (1988); (A) English View in Reaxys 1 : A Isatoic anhydride 7.5 g of 2-amino benzoic acid hydrochloride was mixed with i0 ml of diphosgene and the mixture was stirred in 150 ml of dioxane for 40 minutes at reflux.

EXAMPLE 1 A Isatoic anhydride 7.5 g of 2-amino benzoic acid hydrochloride was mixed with i0 ml of diphosgene and the mixture was stirred in 150 ml of dioxane for 40 minutes at reflux.

The resulting mixture was cooled and filtered. Yield: 5.7 g of title compound.

Patent; A/S Ferrosan; US4873244; (1989); (A) English View in Reaxys 25.7 parts (99.5% by weight)

1.b : EXAMPLE 1 b. a solution at 25°C of 480 parts by volume of water and 78 parts by volume of hypochlorite solution (containing 13.2 parts of sodium hypohalite) is added at 25°C to a solution of 62 parts by volume of the solution from Example 1(a), 60 parts by volume of water and 0.2 part of sulfamide.

After 12 seconds at 33°C 15 parts by volume of 25percent by weight aqueous sulfuric acid is added and the mixture is stirred for another 5 minutes.

The mixture is then suction filtered and the filtered material is washed and dried in vacuo at 60°C. The yield is 25.7 parts (99.5percent by weight) of isatoic anhydride having the decomposition point 235°C, corresponding to 91.4percent of theory.

Patent; BASF Aktiengesellschaft; US3984406; (1976); (A) English View in Reaxys

26.1 parts (99.7% by weight)

2 : EXAMPLE 2 EXAMPLE 2 A solution at 25°C of 480 parts by volume of water and 78 parts by volume hypochlorite solution (with a content of 13.2 parts of sodium hypohalite) is added to a mixture of 62 parts by volume of the solution from Example 1(a), 60 parts by volume of water and 1 part of sodium iodide at 25°C. Fifteen seconds later at 33°C 15 parts by volume of 25percent by weight aqueous sulfuric acid is added and the whole is stirred for 5 minutes.

The mixture is then suction filtered and the filter cake is washed and dried.

The yield is 26.1 parts (99.7percent by weight) of isatoic anhydride of the decomposition point 235°C, corresponding to 93percent of theory.

Patent; BASF Aktiengesellschaft; US3984406; (1976); (A) English View in Reaxys 52 : (2-Carbamoyl-4,5-dimethylphenyl)oxamic acid ethyl ester. 100 EXAMPLE 52 (2-Carbamoyl-4,5-dimethylphenyl)oxamic acid ethyl ester. 100

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

Liquid phosgene (55 g.) is added to a stirred solution of 30.1 g. (0.182 mole) of 4,5-dimethylanthranilic acid in 800 ml. of dioxane.

The temperature is raised to 40°-45° C. and held for 2 hours, and then sitrred overnight at room temperature.

The mixture is filtered and the cake washed with diethyl ether, giving 33 g. of the isatoic anhydride: m.p. > 300° C. Patent; American Home Products Corporation; US4069343; (1978); (A) English View in Reaxys Cl

Cl

Cl

H N

O

O

O

O

HO

O

H 2N

Rx-ID: 24351649 View in Reaxys 33/80 Yield

Conditions & References 5 : 1,2-Dihydro-4-hydroxy-5-chloro-1-methyl-2-oxo-quinoline-3-carboxylic acid ethyl ester EXAMPLE 5 1,2-Dihydro-4-hydroxy-5-chloro-1-methyl-2-oxo-quinoline-3-carboxylic acid ethyl ester Phosgene (51 g, 0.52 mol) dissolved in dioxane (150 ml) was added in portions to a mechanically stirred slurry of sodium bicarbonate (44 g, 0.52 mol) and 2-amino-6chloro-benzoic acid (30 g, 0.175 mol) in dioxane (300 ml).

Violent reaction with gas evolution occurred and the reaction mixture was cooled to keep the temperature below 50° C. After 30 minutes the reaction mixture was kept at 50° C. for 1 hour.

After cooling to 15° C. the resulting precipitate was collected, stirred with 50 ml of glacial acetic acid in 500 ml of water, collected again and dried to give the isatoic anhydride (30.3 g, 0.15 mol). in 1,4-dioxane, water, sodium hydrogencarbonate, acetic acid Patent; Active Biotech AB; US6077851; (2000); (A) English View in Reaxys

H N

Cl

O

Cl

O

O

N H

O O

OH

O

Rx-ID: 24427403 View in Reaxys 34/80 Yield

Conditions & References 1 : 1,2-Dihydro-4-hydroxy-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxylic acid ethyl ester The 6-methoxy-N-methyl-anthranilic acid (32 g, 0.18 mol), and sodium bicarbonate (38 g. 0.45 mol) were suspended in 500 ml of 1,4-dioxane.

Phosgene (25 ml. 0.45 mol) was slowly added under cooling in an ice bath.

The mixture was warmed at 40° C. for 1 hour, cooled to 15° C., and then 150 ml of water was added.

The isatoic anhydride formed was collected by filtration.

With sodium hydrogencarbonate in 1,4-dioxane, water Patent; Active Biotech AB; US6133285; (2000); (A) English View in Reaxys

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

OH

H N

O

O

HN O

N

O

O

O

Rx-ID: 5199479 View in Reaxys 35/80 Yield

Conditions & References

68 %

With hydrogenchloride, Time= 0.0333333h, Heating, Cyclization Guetschow, Michael; Journal of Organic Chemistry; vol. 64; nb. 14; (1999); p. 5109 - 5115 View in Reaxys

H N

O

N

O

O

N H O

O

OH

Rx-ID: 5200892 View in Reaxys 36/80 Yield

Conditions & References With hydrogenchloride, Time= 0.166667h, Heating, Cyclization Guetschow, Michael; Journal of Organic Chemistry; vol. 64; nb. 14; (1999); p. 5109 - 5115 View in Reaxys OH

H N

O

HN

O

O

N

O

O

Rx-ID: 5228153 View in Reaxys 37/80 Yield

Conditions & References With hydrogenchloride, Time= 0.0333333h, Heating, Cyclization Guetschow, Michael; Journal of Organic Chemistry; vol. 64; nb. 14; (1999); p. 5109 - 5115 View in Reaxys

H N N

O

N

Fmoc amino acid derivatized Wang-resin

O O

O O

Rx-ID: 16254085 View in Reaxys 38/80 Yield

Conditions & References Reaction Steps: 3 1: 85 percent / acetone / 72 h / 20 °C 2: 63 percent / aq. HCl / 336 h / 5 °C 3: aq. HCl / 0.17 h / Heating With hydrogenchloride in acetone, 1: Ring cleavage / 2: Elimination / 3: Cyclization

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

Guetschow, Michael; Journal of Organic Chemistry; vol. 64; nb. 14; (1999); p. 5109 - 5115 View in Reaxys

O H N

O

O

Fmoc amino acid derivatized Wang-resin

O

HN O

N

O

O

Rx-ID: 16254468 View in Reaxys 39/80 Yield

Conditions & References Reaction Steps: 4 1: conc. H2SO4 / 3 h / 20 °C 2: 84 percent / acetone / 24 h / 20 °C 3: 91 percent / aq. HCl / 336 h / 5 °C 4: 68 percent / aq. HCl / 0.03 h / Heating With hydrogenchloride, sulfuric acid in acetone, 1: Cyclization / 2: Ring cleavage / 3: Elimination / 4: Cyclization Guetschow, Michael; Journal of Organic Chemistry; vol. 64; nb. 14; (1999); p. 5109 - 5115 View in Reaxys O

O S N

H N

O

O

O

Fmoc amino acid derivatized Wang-resin

O

O

O

Rx-ID: 16260431 View in Reaxys 40/80 Yield

Conditions & References Reaction Steps: 3 1: 70 percent / toluene / 7 h / 20 °C 2: aq. HCl / 336 h / 5 °C 3: aq. HCl / 0.03 h / Heating With hydrogenchloride in toluene, 1: Ring cleavage / 2: Elimination / 3: Cyclization Guetschow, Michael; Journal of Organic Chemistry; vol. 64; nb. 14; (1999); p. 5109 - 5115 View in Reaxys

O N

O H N

O

HN O

Fmoc amino acid derivatized Wang-resin

O O

N

O

Rx-ID: 16275404 View in Reaxys 41/80 Yield

Conditions & References Reaction Steps: 2 1: 91 percent / aq. HCl / 336 h / 5 °C

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

2: 68 percent / aq. HCl / 0.03 h / Heating With hydrogenchloride, 1: Elimination / 2: Cyclization Guetschow, Michael; Journal of Organic Chemistry; vol. 64; nb. 14; (1999); p. 5109 - 5115 View in Reaxys

O

N

H N N H

O

O O

Fmoc amino acid derivatized Wang-resin

N

O

Rx-ID: 16285790 View in Reaxys 42/80 Yield

Conditions & References Reaction Steps: 4 1: conc. H2SO4 / 3 h / 80 °C 2: 85 percent / acetone / 72 h / 20 °C 3: 63 percent / aq. HCl / 336 h / 5 °C 4: aq. HCl / 0.17 h / Heating With hydrogenchloride, sulfuric acid in acetone, 1: Cyclization / 2: Ring cleavage / 3: Elimination / 4: Cyclization Guetschow, Michael; Journal of Organic Chemistry; vol. 64; nb. 14; (1999); p. 5109 - 5115 View in Reaxys Reaction Steps: 2 1: aq. HCl / 336 h / 5 °C 2: aq. HCl / 0.17 h / Heating With hydrogenchloride, 1: Elimination / 2: Cyclization Guetschow, Michael; Journal of Organic Chemistry; vol. 64; nb. 14; (1999); p. 5109 - 5115 View in Reaxys

N

O H N

O

HN

O

O

Fmoc amino acid derivatized Wang-resin

O

N

O

Rx-ID: 16287366 View in Reaxys 43/80 Yield

Conditions & References Reaction Steps: 2 1: 63 percent / aq. HCl / 336 h / 5 °C 2: aq. HCl / 0.17 h / Heating With hydrogenchloride, 1: Elimination / 2: Cyclization Guetschow, Michael; Journal of Organic Chemistry; vol. 64; nb. 14; (1999); p. 5109 - 5115 View in Reaxys

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

N

O

H N

O

HN

Fmoc amino acid derivatized Wang-resin

O O

O N

Rx-ID: 16288017 View in Reaxys 44/80 Yield

Conditions & References Reaction Steps: 2 1: aq. HCl / 336 h / 5 °C 2: aq. HCl / 0.03 h / Heating With hydrogenchloride, 1: Elimination / 2: Cyclization Guetschow, Michael; Journal of Organic Chemistry; vol. 64; nb. 14; (1999); p. 5109 - 5115 View in Reaxys

H N

O N

O

N

Fmoc amino acid derivatized Wang-resin

O O

O O

Rx-ID: 16298610 View in Reaxys 45/80 Yield

Conditions & References Reaction Steps: 3 1: 84 percent / acetone / 24 h / 20 °C 2: 91 percent / aq. HCl / 336 h / 5 °C 3: 68 percent / aq. HCl / 0.03 h / Heating With hydrogenchloride in acetone, 1: Ring cleavage / 2: Elimination / 3: Cyclization Guetschow, Michael; Journal of Organic Chemistry; vol. 64; nb. 14; (1999); p. 5109 - 5115 View in Reaxys

H N

O

O N

O

O O

OH

O

Rx-ID: 24460265 View in Reaxys 46/80 Yield

Conditions & References 33 : preparation of 1-Hexyl-3-Formyl-4-Methoxy-2(1H)-Quinolinone (Formula 1.26) EXAMPLE 33 preparation of 1-Hexyl-3-Formyl-4-Methoxy-2(1H)-Quinolinone (Formula 1.26) Following steps (2-3) in Preparation A, and using hexyl bromide and isatoic anhydride, 1-hexyl-3-ethoxycarbonyl-4-hydroxy-2(1H)-quinolinone was obtained.

Patent; Schering Corporation; US5412104; (1995); (A) English

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

View in Reaxys

H 2N

O

H N

O NH

O

O N

N

Rx-ID: 25002835 View in Reaxys 47/80 Yield

Conditions & References 7 : 2-Amino-N-[3-(1H-imidazol-1-yl)-2-methylpropyl]-5-methylbenzamide EXAMPLE 7 2-Amino-N-[3-(1H-imidazol-1-yl)-2-methylpropyl]-5-methylbenzamide A mixture of 8.85 g of 5-methylisatoic anhydride, 6.7 ml of 3-(1H-imidazol-1-yl)-2-methylpropanamine and 40 ml of dimethyl sulfoxide was stirred for 20 hours at room temperature and then treated with 100 ml of water, 25 ml of 1N sodium hydroxide and 300 ml of methylene chloride.

The layers were separated and the organic layer was washed with water, dried over magnesium sulfate and concentrated.

The viscous residue was triturated with ether and the desired product precipitated as a hemi-hydrate, mp 120°-122° C. Following the procedure of this example and using the appropriate isatoic anhydride, the products of Examples 8 and 9 were obtained as set forth in Table IV below.

Patent; American Cyanamid Company; US4710502; (1987); (A) English View in Reaxys 114 : 2-Amino-N-[3-(1H-imidazol-1-yl)-2-methylpropyl]-5-methylbenzamide Example 114 2-Amino-N-[3-(1H-imidazol-1-yl)-2-methylpropyl]-5-methylbenzamide A mixture of 8.85g of 5-methylisatoic anhydride, 6.7ml of 3-(1 H -imidazol-1-yl)-2-methylpropanamine and 40ml of dimethyl sulfoxide was stirred for 20 hours at room temperature and then treated with 100ml of water, 25ml of 1N sodium hydroxide and 300ml of methylene chloride.

The layers were separated and the organic layer was washed with water, dried over magnesium sulfate and concentrated.

The viscous residue was triturated with ether and the desired product precipitated as a hemi-hydrate, mp 120-122°C. Following the procedure of this example and using the appropriate isatoic anhydride, the products of Examples 115 and 116 were obtained as set forth in Table XVI below.

Patent; AMERICAN CYANAMID COMPANY; EP293500; (1988); (A1) English View in Reaxys H N

H -imidazole-1-propanamine

O

O

O N O

O

NH 2 H N

N

O

O

N H O

N

O

N O

O

Rx-ID: 25456157 View in Reaxys 48/80 Yield

Conditions & References 6 : 2-Amino-N-[3-(1H-imidazol-1-yl)propyl]-5-nitrobenzamide Example 6

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

2-Amino-N-[3-(1H-imidazol-1-yl)propyl]-5-nitrobenzamide A mixture of 8.32 g of 5-nitro isatoic anhydride, 5.0 g of 1 H -imidazole-1-propanamine and 80 ml of ethanol was stirred at room temperature for 20 hours and concentrated.

The residue was washed onto a filter with ethanol and washed with ether.

Recrystallization from ethanol resulted in the pure product, mp 168-170°C. Following the procedure of this example and using the appropriate isatoic anhydride and amine, the products of Examples 7-8 were obtained as set forth in Table IV below. in ethanol Patent; AMERICAN CYANAMID COMPANY; EP293500; (1988); (A1) English View in Reaxys

O O

O

O

Cl

NH 2

HN

H N

O

O

N

N O

O

O

Cl

Cl

Rx-ID: 2756729 View in Reaxys 49/80 Yield

Conditions & References With aluminium trichloride, 1) ethylene chloride, 1 h 2) ethylene chloride, 3 h, Yield given. Multistep reaction. Yields of byproduct given Acharya, Baman P.; Rao, Y. Ramachandra; Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry; vol. 26; nb. 1-12; (1987); p. 1133 - 1139 View in Reaxys O

O

Cl

N

H 2N

H N

H N

O

O O

N

HN

O

HN O

HN

O O

Rx-ID: 3372103 View in Reaxys 50/80 Yield

Conditions & References With aluminium trichloride, 1) ethylene chloride, 1 h 2) ethylene chloride, 3 h, Yield given. Multistep reaction. Yields of byproduct given Acharya, Baman P.; Rao, Y. Ramachandra; Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry; vol. 26; nb. 1-12; (1987); p. 1133 - 1139 View in Reaxys With aluminium trichloride, multistep reaction; reaction with other nucleophiles (MeOH, other amines), Mechanism

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

Acharya, Baman P.; Rao, Y. Ramachandra; Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry; vol. 26; nb. 1-12; (1987); p. 1133 - 1139 View in Reaxys O

O

Cl

O

N

NH 2

O

O

O H N

H N

O

O O

O

HN

HN

O O O

Rx-ID: 3843445 View in Reaxys 51/80 Yield

Conditions & References With aluminium trichloride, 1) ethylene chloride, 1 h 2) ethylene chloride, 3 h, Yield given. Multistep reaction. Yields of byproduct given Acharya, Baman P.; Rao, Y. Ramachandra; Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry; vol. 26; nb. 1-12; (1987); p. 1133 - 1139 View in Reaxys H N

aminoiminoisoindolenine

O

O

O

Rx-ID: 24982242 View in Reaxys 52/80 Yield

Conditions & References 1.a : EXAMPLE 1 (a) 5.5 g of hydrazine hydrate are added, at 110° C., to 50 g of the reaction product of aminoimino-isoindolenine with isatoic anhydride, in a mixture of 500 ml of nitrobenzene and 20 ml of glacial acetic acid.

Stirring is continued for 5 hours at 110° C. and for 3 hours at 150° C., the product is filtered off under suction from the hot mixture, and 26 g of a yellow pigment of the formula STR14 are obtained.

Melting point: 360° C. Mass spectrum m/e (relative intensity): 492 M+ (100percent), 404 (54), 435 (15), 219 (30), 204 (50), 90 (60), 76 (45).

Patent; Bayer Aktiengesellschaft; US4666526; (1987); (A) English View in Reaxys

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

H 2N

O

H N

H N

O N

O

O

O

O

N H O

N

N

N

NH 2

O

O

N O

N

O

Rx-ID: 25038565 View in Reaxys 53/80 Yield

Conditions & References 6 : 2-Amino-N-[3-(1H-imidazol-1-yl)propyl]-5-nitrobenzamide EXAMPLE 6 2-Amino-N-[3-(1H-imidazol-1-yl)propyl]-5-nitrobenzamide A mixture of 8.32 g of 5-nitro isatoic anhydride, 5.0 g of 1H-imidazole-1-propanamine and 80 ml of ethanol was stirred at room temperature for 20 hours and concentrated.

The residue was washed onto a filter with ethanol and washed with ether.

Recrystallization from ethanol resulted in the pure product, mp 168°-170° C. Following the procedure of this example and using the appropriate isatoic anhydride and amine, the products of Examples 7-8 were obtained as set forth in Table IV below. in ethanol Patent; American Cyanamid Company; US4684654; (1987); (A) English View in Reaxys H N

H 2N

O O Cl

Cl

O

Cl

H

O

Cl

O

Cl

HO

O

Rx-ID: 25048838 View in Reaxys 54/80 Yield

Conditions & References I.A : Isatoic anhydride A. Isatoic anhydride 7.5 g of 2-aminobenzoic acid hydrochloride was mixed with 10 ml of diphosgene and the mixture was stirred in 150 ml dioxanefor 40 minutes at reflux.

The resulting mixture was cooled and filtered.

Yield: 5.7 g of title compound.

Patent; A/S Ferrosan; US4670433; (1987); (A) English View in Reaxys

H N

N

O

N Cl

H

O

O O

O

Rx-ID: 3060974 View in Reaxys 55/80 Yield

Conditions & References With hydrogenchloride Bitter, I.; Szoecs, L.; Toeke, L.; Acta Chimica Academiae Scientiarum Hungaricae; vol. 107; (1981); p. 57 - 66 View in Reaxys

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

H N

H 2N

O

O O

O O

Rx-ID: 20939041 View in Reaxys 56/80 Yield

Conditions & References Reaction Steps: 2 1: 81 percent / CH2Cl2 / 40 °C 2: aq. HCl With hydrogenchloride in dichloromethane Bitter, I.; Szoecs, L.; Toeke, L.; Acta Chimica Academiae Scientiarum Hungaricae; vol. 107; (1981); p. 57 - 66 View in Reaxys

O

O

Cl

O H N

N

Br

OH

Mg

O

O

H N

O

N

N H O

O

O O

O

Rx-ID: 2105038 View in Reaxys 57/80 Yield

Conditions & References

6 %, 5 %, 10 %, 70 %

in diethyl ether, Time= 3h, T= 25 - 30 °C Misra, B. K.; Rao, Y. R.; Mahapatra, S. N.; Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry; vol. 19; nb. 10; (1980); p. 908 - 911 View in Reaxys

6 %, 5 %, 10 %, 70 %

in diethyl ether, Time= 3h, T= 25 - 30 °C , other 2-Isocyanatobenzoyl chloride Misra, B. K.; Rao, Y. R.; Mahapatra, S. N.; Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry; vol. 19; nb. 10; (1980); p. 908 - 911 View in Reaxys O

OH

H N

O

H N

HO N

O O

O

Rx-ID: 1137328 View in Reaxys 58/80 Yield

Conditions & References With pyridine, benzenesulfonyl chloride, Time= 0.333333h, Heating Crabtree,E.V. et al.; Journal of Organic Chemistry; vol. 43; (1978); p. 268 - 272 View in Reaxys

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

O H N

O

H 2N O

O O

OH

Rx-ID: 25273516 View in Reaxys 59/80 Yield

Conditions & References I : Preparation of Isatoic Anhydride EXAMPLE I Preparation of Isatoic Anhydride A 250 ml. flask was charged with 2.0 g. phthalamic acid* suspended in 100 ml. dry benzene, and heated to boiling.

A 5.4 g. portion of lead tetra-acetate was added to the boiling suspension, and the reaction mixture was heated under reflux, with stirring, for 48 hours.

The reaction mixture was then cooled and solids were separated therefrom by filtration.

The residue was washed 2 times with water; isatoic anhydride was recrystallized from dioxane, and dried in vacuo for 2 hours.

The final yield of isatoic anhydride amounted to 0.87 g. tan solids, melting point 243°, and represented 44 percent of theory based on the phthalamic acid.

The structure was confirmed by infrared spectroscopy. * E. Chapman and H. Stephen, J. Chem. Soc., 1925, 127, 1791 With lead(IV) acetate in benzene Patent; The Sherwin-Williams Company; US3947416; (1976); (A) English View in Reaxys II : Preparation of Isatoic Anhydride EXAMPLE II Preparation of Isatoic Anhydride A 100 ml. flask was charged with 2.0 g. phthalamic acid suspended in 20 ml. dimethylformamide at room temperature.

A 5.4 g. portion of lead tetra-acetate was added to the suspension, and the reaction mixture was held at room temperature for 40 minutes.

The reaction mixture was poured into 30 ml. water.

Isatoic anhydride was filtered from the water, recrystallized from dioxane, and dried in vacuo for 2 hours.

The final yield of isatoic anhydride amounted to 1.07 g. tan solids, melting point 243°, and represented 54 percent of theory based on the phthalamic acid.

With lead(IV) acetate in N-methyl-acetamide Patent; The Sherwin-Williams Company; US3947416; (1976); (A) English View in Reaxys O

O

O

H N

O

N

O

O

Rx-ID: 946045 View in Reaxys 60/80 Yield

Conditions & References With COCl2 Peet,N.P.; Sunder,S.; Journal of Organic Chemistry; vol. 39; (1974); p. 1931 - 1935 View in Reaxys

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

Cl

H N O

HN

O

O

O O

O

Rx-ID: 1133931 View in Reaxys 61/80 Yield

Conditions & References Time= 2h, T= 100 °C Peet,N.P.; Sunder,S.; Journal of Organic Chemistry; vol. 39; (1974); p. 1931 - 1935 View in Reaxys H N

H 2N

Cl

O

Cl O O

O O O

Rx-ID: 1324267 View in Reaxys 62/80 Yield

Conditions & References in ethyl acetate Peet,N.P.; Sunder,S.; Journal of Organic Chemistry; vol. 39; (1974); p. 1931 - 1935 View in Reaxys

H N

Si N

O

O O O O

O

Rx-ID: 941807 View in Reaxys 63/80 Yield

Conditions & References in ethanol Washburne,S.S. et al.; Journal of Organic Chemistry; vol. 37; (1972); p. 1738 - 1742 View in Reaxys O

H N

O

activated aluminium

O

O

O

O

Rx-ID: 22510432 View in Reaxys 64/80 Yield

Conditions & References Reaction Steps: 2 1: benzene / Heating 2: aq. ethanol in ethanol, benzene Washburne,S.S. et al.; Journal of Organic Chemistry; vol. 37; (1972); p. 1738 - 1742 View in Reaxys

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

O

OH

H N

O

H N

O

O

O O

Rx-ID: 396874 View in Reaxys 65/80 Yield

Conditions & References With phosphorus tribromide Ben-Ishai; Katchalski; Journal of the American Chemical Society; vol. 74; (1952); p. 3688 View in Reaxys O

OH

H N

O

H N

O

O O

O

Rx-ID: 801644 View in Reaxys 66/80 Yield

Conditions & References With phosphorus tribromide Ben-Ishai; Katchalski; Journal of the American Chemical Society; vol. 74; (1952); p. 3688 View in Reaxys H N

sodium-compound of/the/ N-benzoyloxy-phthalamic acid

O

O

O

Rx-ID: 5436522 View in Reaxys 67/80 Yield

Conditions & References With toluene Hurd et al.; Journal of Organic Chemistry; vol. 17; (1952); p. 865,871 View in Reaxys O

H N

O

O

O

O

O

Rx-ID: 87260 View in Reaxys 68/80 Yield

Conditions & References With sodium azide, sulfuric acid Caronna; Gazzetta Chimica Italiana; vol. 71; (1941); p. 189,192 View in Reaxys O OH

O HO

S OO

sodium azide

O

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

H N

O

H 2N O

NH O

O

NH

HO

O

Rx-ID: 5673682 View in Reaxys 69/80 Yield

Conditions & References Caronna; Gazzetta Chimica Italiana; vol. 71; (1941); p. 189,192 View in Reaxys O

H N

O

NH

O HN

O

O

Rx-ID: 820467 View in Reaxys 70/80 Yield

Conditions & References With ozone, ethyl acetate van Alphen; Recueil des Travaux Chimiques des Pays-Bas; vol. 57; (1938); p. 915,919 View in Reaxys N

H N

N

O

OH

N

O

O

O

O

Rx-ID: 137486 View in Reaxys 71/80 Yield

Conditions & References Karrer; Diechmann; Haebler; Helvetica Chimica Acta; vol. 7; (1924); p. 1036 View in Reaxys H N

O

cyanoformyl-anthranil

O

O

Rx-ID: 5436521 View in Reaxys 72/80 Yield

Conditions & References With ethanol Karrer; Diechmann; Haebler; Helvetica Chimica Acta; vol. 7; (1924); p. 1036 View in Reaxys H N N

Cl

O

O

O

O

O O

Rx-ID: 338716 View in Reaxys 73/80 Yield

Conditions & References T= 140 °C , im Rohr Friedlaender; Schreiber; Chemische Berichte; vol. 28; (1895); p. 1385 View in Reaxys

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

Heller; Chemische Berichte; vol. 49; (1916); p. 547 View in Reaxys Bamberger; Chemische Berichte; vol. 36; (1903); p. 819; Chemische Berichte; vol. 42; (1909); p. 1664 View in Reaxys Friedlaender; Wleuegel; Chemische Berichte; vol. 16; (1883); p. 2229 View in Reaxys v. Meyer; Bellmann; Journal fuer Praktische Chemie (Leipzig); vol. <2> 33; (1886); p. 19 View in Reaxys v. Meyer; Journal fuer Praktische Chemie (Leipzig); vol. <2> 30; (1884); p. 486 View in Reaxys Schmidt,G.; Journal fuer Praktische Chemie (Leipzig); vol. <2> 36; (1887); p. 374 View in Reaxys Erdmann; Chemische Berichte; vol. 32; (1899); p. 2164; Chem. Zentralbl.; vol. 71; nb. II; (1900); p. 506 View in Reaxys Niementowski; Rozanski; Chemische Berichte; vol. 22; (1889); p. 1673,1674 View in Reaxys T= 120 - 140 °C Friedlaender; Wleuegel; Chemische Berichte; vol. 16; (1883); p. 2229 View in Reaxys O

NH

alkaline solution

sodium hypochlorite

O

O

H N

OH

O H N

O NH 2

O

O

Rx-ID: 5493328 View in Reaxys 74/80 Yield

Conditions & References Patent; Hoechster Farbw.; DE127138; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 6; p. 156 View in Reaxys Mohr; Journal fuer Praktische Chemie (Leipzig); vol. <2>79; (1909); p. 281; Journal fuer Praktische Chemie (Leipzig); vol. <2>80; (1909); p. 1,14,18,22 View in Reaxys Meyer; Chemische Berichte; vol. 39; (1906); p. 1451 View in Reaxys Mohr; Koehler; Chemische Berichte; vol. 39; (1906); p. 1057 View in Reaxys O

H N

NH

O

O

O

sodium salt of/the/ anthranoyl-anthranilic acid

O

Rx-ID: 5745308 View in Reaxys 75/80 Yield

Conditions & References With sodium hydroxide, sodium hypochlorite, water Mohr; Journal fuer Praktische Chemie (Leipzig); vol. <2> 80; (1909); p. 10,14, 18, 24 View in Reaxys Patent; Hoechster Farbw.; DE127138; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 6; p. 156 View in Reaxys

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

O O

OH

H N

O

H N

Cl

O

O O

O

Rx-ID: 692922 View in Reaxys 76/80 Yield

Conditions & References Patent; Bayer and Co.; DE112976; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 6; p. 154 View in Reaxys Bredt; Hof; Chemische Berichte; vol. 33; (1900); p. 23 View in Reaxys Bredt; Hof; Chemische Berichte; vol. 33; (1900); p. 23 View in Reaxys

H N

O

O NH

O

O

O

O O

Rx-ID: 22226786 View in Reaxys 77/80 Yield

Conditions & References Reaction Steps: 2 1: sodium ethylate; absolute alcohol With ethanol, sodium ethanolate Bredt; Hof; Chemische Berichte; vol. 33; (1900); p. 23 View in Reaxys H N

Cl

O

Cl

anthranilate sodium

O

O O

Rx-ID: 5436519 View in Reaxys 78/80 Yield

Conditions & References With water Patent; Erdmann; DE110577; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 5; p. 148 View in Reaxys Erdmann; Chemische Berichte; vol. 32; (1899); p. 2164; Chem. Zentralbl.; vol. 71; nb. II; (1900); p. 506 View in Reaxys H N

NH

O

O

OH

O

chromium trioxide

O

O

O

Rx-ID: 5436520 View in Reaxys 79/80 Yield

Conditions & References Erdmann; Chemische Berichte; vol. 32; (1899); p. 2164; Chem. Zentralbl.; vol. 71; nb. II; (1900); p. 506 View in Reaxys Kolbe; Journal fuer Praktische Chemie (Leipzig); vol. <2>30; nb. 85; (1884); p. 469 View in Reaxys

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2H-3,1-Benzoxazine-2,4(1H)-dione (Isatoic anhydride) [C8H5NO3]

O

Cl

O

OH

H N

O

H N

O

O

O O

O

Rx-ID: 552906 View in Reaxys 80/80 Yield

Conditions & References Niementowski; Rozanski; Chemische Berichte; vol. 22; (1889); p. 1673,1674 View in Reaxys Niementowski; Rozanski; Chemische Berichte; vol. 22; (1889); p. 1673,1674 View in Reaxys

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