Name: 2170-03-8|3-Methylenedihydrofuran-2,5-dione|99%
Brand: Ambeed
SKU: A209795
Price: 11.0 USD
Availability: InStock
Rating: 93 (29 reviews)

1
[ 97-65-4 ]
[ 2170-03-8 ]

Yield	Reaction Conditions	Operation in experiment
100%	With trimethylsilylethoxyacetylene In dichloromethane at 40℃; for 5h;
92%	With acetic anhydride at 80℃; for 4h;
92%	With hydrogenchloride; acetic anhydride at 40℃; for 1h;

92%	With niobium(V) oxide hydrate In 1,3,5-trimethyl-benzene at 200℃; for 36h; Inert atmosphere; Molecular sieve;
83%	With magnesium chloride In tetrahydrofuran at 40℃; for 2.5h;
75%	With acetyl chloride for 2.5h; Heating;
64%	With thionyl chloride at 76℃; for 6h;	As the starting reagent for the synthesis, itaconic anhydride was used, which was preparedas follows: 10.0 g of itaconic acid (Aldrich, 99%) and 50 ml of thionylchloride were placed in a 100-ml round-bottom flask. A reflux condenserwith a calcium chloride tube was attached to the flask, and the contents ofthe flask was stirred on boiling (76 °C) for 6 h. The homogeneous reaction mixture was cooled and added to a tenfold amount of carbon tetrachloride.The crystals formed were washed with CCl4 (3×50 ml) and dried on a glassfilter and then in vacuo. Yield, 5.51 g (64%).
	With acetic anhydride at 80℃;
	With acetyl chloride
	With phosphorus pentaoxide; toluene
	With thionyl chloride
	With trimethylsilylethoxyacetylene In dichloromethane for 5h; Heating; Yield given;
	With acetyl chloride In toluene Heating;
	With methanesulfonic acid In propylene glycol dimethyl ether dimer at 150℃; Inert atmosphere;	1 Methane sulfonic acid (0.135 milliliter (ml_), 2.1 micromole (umol)) was added via micropipette to dipropylene glycol dimethyl ether (DPGDME) (40.00 grams (g), 247 millimole (mmol)), and the resulting solution was stirred. Itaconic acid (20 g, 151 mmol) was added and the reaction heated to 150°C under 250 mmHg vacuum. A Dean Stark trap and condenser allowed for water removal (2.7g, 151 mmol). NMR testing indicated substantially complete conversion of the itaconic acid. Upon completion, the DPGDME solvent was removed in vacuo resulting in the product, itaconic anhydride.
63 %Chromat.	With uranium hexafluoride In 1,1,2-Trichloro-1,2,2-trifluoroethane at 20℃; for 17h; Inert atmosphere;

Reference： [1]Kita, Yasuyuki; Akai, Shuji; Ajimura, Naomi; Yoshigi, Mayumi; Tsugoshi, Teruhisa; et al. [Journal of Organic Chemistry, 1986, vol. 51, # 22, p. 4150 - 4158]
[2]Kuchar, Miroslav; Poppova, Marie; Zunova, Hana; Knezova, Eva; Vosatka, Vaclav; Prihoda, Marek [Collection of Czechoslovak Chemical Communications, 1994, vol. 59, # 12, p. 2705 - 2713]
[3]Filimoshkin; Kosolapova; Petrenko; Aksenov; Poleshchuk [Russian Journal of Organic Chemistry, 2004, vol. 40, # 4, p. 462 - 466]
[4]Rashed, Md. N.; Siddiki; Ali, Md. A.; Moromi, Sondomoyee K.; Touchy, Abeda S.; Kon, Kenichi; Toyao, Takashi; Shimizu, Ken-Ichi [Green Chemistry, 2017, vol. 19, # 14, p. 3238 - 3242]
[5]Barner-Kowollik, Christopher; Bui, Aaron H.; Raston, Colin L.; Truong, Vinh X.; Tuten, Bryan T.; Wiedbrauk, Sandra [Chemical Communications, 2021, vol. 57, # 67, p. 8328 - 8331]
[6]Martinez-Garcia, Ariel; Martinez, Ricardo [Synthetic Communications, 2008, vol. 38, # 12, p. 1917 - 1925]
[7]Shlyakhtin, Andrei V.; Lemenovskii, Dmitrii A.; Nifant'Ev, Ilya E. [Mendeleev Communications, 2013, vol. 23, # 5, p. 277 - 278]
[8]Fittig; Bock [Justus Liebigs Annalen der Chemie, 1904, vol. 331, p. 174]
[9]Abati; Vergari [Gazzetta Chimica Italiana, 1909, vol. 39 II, p. 153] Anschuetz; Petri [Chemische Berichte, 1880, vol. 13, p. 1540]
[10]Bakunin [Gazzetta Chimica Italiana, 1900, vol. 30 II, p. 348][Gazzetta Chimica Italiana, 1901, vol. 31 II, p. 83]
[11]Meyer,H. [Monatshefte fur Chemie, 1901, vol. 22, p. 418][Monatshefte fuer Chemie, 1906, vol. 27, p. 43]
[12]Kita, Y.; Akai, S.; Yoshigi, M.; Nakajima, Y.; Yasuda, H.; Tamura, Y. [Tetrahedron Letters, 1984, vol. 25, # 52, p. 6027 - 6030]
[13]Galanti, Michele C.; Galanti, Anthony V. [Journal of Organic Chemistry, 1982, vol. 47, # 8, p. 1572 - 1574]
[14]Current Patent Assignee: STEPAN CO - WO2011/109047, 2011, A2 Location in patent: Page/Page column 32
[15]Roy, Olivier; Marquet, Bernard; Alric, Jean-Paul; Jourdan, Alex; Morel, Bertrand; Langlois, Bernard R.; Billard, Thierry [Journal of Fluorine Chemistry, 2014, vol. 167, p. 74 - 78]

2
[ 2170-03-8 ]
[ 104-94-9 ]
[ 73926-98-4 ]

Yield	Reaction Conditions	Operation in experiment
54%	Stage #1: itaconic acid anhydride; 4-methoxy-aniline In diethyl ether; dichloromethane for 5h; Inert atmosphere; Stage #2: With sodium acetate; acetic anhydride at 100℃; for 0.5h; Inert atmosphere;	General Procedure for the synthesis of N-arylitaconimides 1a-d. General procedure: A solution of 5.6 g (5 mmol) of itaconic anhydride and 5 mmol of corresponding aniline in a mixture of dichloromethane (80 ml) and diethylether (150 ml) was stirred during 5 hours. The precipitate was filtered off and dried. Then acetic anhydride (40 ml) and sodium acetate (2.5 g) was added and the mixture was heated at 100 °C during 30 min. Reaction mixture was poured into cold water and the precipitate was filtered off and recrystallized from a mixture of benzene-ethanol.
	at 130℃;
	With acetic acid In diethyl ether Reflux;	2.1.1. General Procedures for the Synthesis of the Studied Compounds General procedure: The compounds were obtained by the action of the respective anhydrides with appropriate amines in ether, or directly refluxed with acetic acid as previously described[1,15]. The product was mostly filtered, but in the absence of precipitate, it was extracted with chloroform. The combined organic layers were dried with Na2SO4, filtered and evaporated.The final product was purified by recrystallization with the suitable solvent, or by through column chromatography over silica gel using the chloroform: methanol gradient eluent, giving yields of 20 to 55%.

Reference： [1]Teterina, Polina S.; Efremova, Mariia M.; Sirotkina, Ekaterina V.; Novikov, Alexander S.; Khoroshilova, Olesya V.; Molchanov, Alexander P. [Tetrahedron Letters, 2019, vol. 60, # 39]
[2]Piutti [Gazzetta Chimica Italiana, 1906, vol. 36, p. II 365][Gazzetta Chimica Italiana, 1910, vol. 40 I, p. 542] Piutti [Chemische Berichte, 1906, vol. 39, p. 2771][Gazzetta Chimica Italiana, 1906, vol. 36 II, p. 370]
[3]Stiz, Dorimar; Corrêa, Rogério; D'Auria, Felicia D.; Simonetti, Giovanna; Cechinel-Filho, Valdir [Medicinal Chemistry, 2016, vol. 12, # 7, p. 647 - 654]

3
[ 2170-03-8 ]
[ 100-61-8 ]
[ 408308-26-9 ]

Yield	Reaction Conditions	Operation in experiment
92.5%	In toluene at 70 - 75℃; for 1.25h;	1 Example 1Preparation of 2-Methylene-succinic acid 4-methylanilide (Compound ofFormula a)ltaconic W-MethylanilineAn hd rideReagents ProcedureTo a stirred suspension of ltaconic Anhydride (500 g, 4.46 mol) in Toluene (1500 mL) at 70 0C was added over 1 hr λ/-Methylaniline (503 mL, 4.64 mol) such that the internal temperature did not exceed 75 0C. The mixture was then heated to 80 0C and stirred a further 15 mins before being allowed to cool. Having cooled to 40 0C, the mixture was poured into Hexane (585 mL) and cooled, with stirring, to 0 0C for 30 mins. The resulting white solid was collected by filtration and dried over night in a vacuum oven to afford the title compound 903 g (92.5 % yield).
46%	In chloroform at 0 - 20℃; for 2h;
	With toluene

In toluene at 70 - 80℃; for 1.5h;

Biobased Amides 1a-j; General Procedure. Step 1. General procedure: A solution of N-alkylaniline (5 mmol) in toluene (2 mL) was added to a stirred suspension of itaconic anhydride (0.68 g, 6 mmol) in toluene (5 mL) via a syringe pump at 70 °C (this addition was performed over 1 h). Then, the reaction mixture was stirred for 30 min at 80 °C. The solvent was removed under reduced pressure to yield the crude product, 4-(alkyl(aryl)amino)-2-methylene-4-oxobutanoic acid, which was used in the next step without further purification.

Reference： [1]Current Patent Assignee: THE MCCLAY FOUNDATION - WO2008/35086, 2008, A2 Location in patent: Page/Page column 36-37; 28
[2]Dong, Kaiwu; Ji, Xiaolei; Ren, Xinyi; Shen, Chaoren; Tang, Lin; Tian, Xinxin; Wang, Zhen [Angewandte Chemie - International Edition, 2021, vol. 60, # 32, p. 17693 - 17700][Angew. Chem., 2021, vol. 133, # 32, p. 17834 - 17841]
[3]Baker et al. [Journal of Organic Chemistry, 1952, vol. 17, p. 149,153]
[4]Hornink, Milene Macedo; Lopes, Alice Uva; Andrade, Leandro Helgueira [Synthesis, 2021, vol. 53, # 2, p. 296 - 308]

4
[ 2170-03-8 ]
[ 105-13-5 ]
[ 60427-77-2 ]

Yield	Reaction Conditions	Operation in experiment
100%	In hexane; toluene at 60℃; for 36h; Inert atmosphere;
90%	at 55 - 60℃; for 40h;	1A A mixture of itaconic anhydride (19 g, 0.169 mole) and p-methoxybenzyl alcohol (50 mL) was stirred in a 250 mL round-bottomed flask at 55-60 °C for 40 h. After cooling to room temperature, the reaction mixture was diluted with 150 mL of diethyl ether and the solution was poured into saturated aqueous sodium bicarbonate (200 mL). The layers were separated and the aqueous layer was acidified to pH 3 with conc. HC1. The precipitate formed was collected by filtration and dried in vacuuo. Recrystallization from ethyl acetate-hexane furnished 38 g of the desired ester as a white crystalline solid (90%); Mp 87.5 °C (lit 86.8-87.2 °C, Carson, et al., 1976); IR (film) 3000-3400, 2935, 1720, 1681, 1634, 1612, 1515 cm-1; 1H NMR δ (CDCl3) 3.3 (s, 2H), 3.7 (s, 3H), 5.0 (s, 2H), 5.7 (d, 1H, J = 0.8 Hzz), 6.43 (s, 1H), 6.80 (d, 2H, J = 8.8 Hz), 7.24 (d, 2H, J = 8.4 Hz).
88%	In hexane; toluene at 60℃; for 36h;

Reference： [1]Cheng, Xiamin; Li, Lin; Uttamchandani, Mahesh; Yao, Shao Q. [Organic Letters, 2014, vol. 16, # 5, p. 1414 - 1417]
[2]Current Patent Assignee: FAS SECURED CREDITORS HOLDCO - EP869784, 2005, B1 Location in patent: Page/Page column 10
[3]Biel, Markus; Kretsovali, Androniki; Karatzali, Efthymia; Papamatheakis, Joseph; Giannis, Athanassios [Angewandte Chemie - International Edition, 2004, vol. 43, # 30, p. 3974 - 3976]
[4]Carlson,R.M.; Oyler,A.R. [Journal of Organic Chemistry, 1976, vol. 41, # 26, p. 4065 - 4069]

5
[ 2170-03-8 ]
[ 71-43-2 ]
[ 15732-75-9 ]

Yield	Reaction Conditions	Operation in experiment
85%	With aluminum (III) chloride In dichloromethane at 20℃; for 2h; Inert atmosphere; Schlenk technique;
74%	With aluminium trichloride at 100℃; for 4h;
56%	With aluminium trichloride at 35 - 40℃; for 3h;

50.1%	With aluminium trichloride In 1,2-dichloro-ethane
49%	Stage #1: itaconic acid anhydride; benzene With aluminum (III) chloride In 1,2-dichloro-ethane at 20 - 27℃; for 4.5h; Stage #2: With hydrogenchloride In water; 1,2-dichloro-ethane	5.A To a stirred slurry of benzene (4.50 mL, 50.3 mmol) and itaconic anhydride (5.64 g, 50.3 mmol) in 1,2-dichloroethane at room temperature under argon, was added aluminum chloride (13.42 g, 100.7 mmol) in portions over 30 min A dark green solution formed as the temperature rose to 27° C. before subsiding. After 4 h, the now brown solution was poured rapidly into a stirred mixture of ice (200 g) and concentrated hydrochloric acid (15 mL). The resulting beige solids were filtered and air-dried to give the title compound (4.69 gm, 49%). MS [M+H]+: found 191.
18%	Stage #1: itaconic acid anhydride With aluminum (III) chloride In dichloromethane at 0℃; for 0.5h; Inert atmosphere; Stage #2: benzene In dichloromethane at 0 - 20℃; for 3.5h; Inert atmosphere;
	With aluminium trichloride
	With aluminum (III) chloride In dichloromethane at 20℃; for 2h;

Reference： [1]Chen, Caiyou; Zhang, Zhefan; Jin, Shicheng; Fan, Xiangru; Geng, Mingyu; Zhou, Yan; Wen, Songwei; Wang, Xinrui; Chung, Lung Wa; Dong, Xiu-Qin; Zhang, Xumu [Angewandte Chemie - International Edition, 2017, vol. 56, # 24, p. 6808 - 6812][Angew. Chem., 2017, vol. 129, p. 6912 - 6916,5]
[2]Siddiqui, Anees A.; Wani, Sachin M. [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2004, vol. 43, # 7, p. 1574 - 1579]
[3]Cousse; Mouzin; Rieu; et al. [European Journal of Medicinal Chemistry, 1987, vol. 22, # 1, p. 45 - 57]
[4]Kameo; Ogawa; Takeshita; Nakaike; Tomisawa; Sota [Chemical and Pharmaceutical Bulletin, 1988, vol. 36, # 6, p. 2050 - 2060]
[5]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - US2006/155126, 2006, A1 Location in patent: Page/Page column 13
[6]Poklukar, Gašper; Stephan, Michel; Mohar, Barbara [Advanced Synthesis and Catalysis, 2018, vol. 360, # 13, p. 2566 - 2570]
[7]El-Ghandour,N. et al. [Bulletin de la Societe Chimique de France, 1972, p. 2817 - 2829]
[8]Dong, Kaiwu; Ji, Xiaolei; Ren, Xinyi; Shen, Chaoren; Tang, Lin; Tian, Xinxin; Wang, Zhen [Angewandte Chemie - International Edition, 2021, vol. 60, # 32, p. 17693 - 17700][Angew. Chem., 2021, vol. 133, # 32, p. 17834 - 17841]

6
[ 67-56-1 ]
[ 707-37-9 ]
[ 2170-03-8 ]
[ 141102-68-3 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1992,vol. 65,p. 846 - 852

7
[ 101-84-8 ]
[ 2170-03-8 ]
[ 58182-60-8 ]

Yield	Reaction Conditions	Operation in experiment
85%	With aluminum (III) chloride In dichloromethane at 20℃; for 2h;
65%	With aluminium trichloride In dichloromethane at 35 - 40℃; for 3h;
61%	With aluminium trichloride In nitrobenzene at 20℃; for 6h;

48.5%	With aluminium trichloride In dichloromethane for 4h; Ambient temperature;
48.5%	With aluminium trichloride In 1,2-dichloro-ethane
	With aluminium trichloride In 1,2-dichloro-ethane

Reference： [1]Dong, Kaiwu; Ji, Xiaolei; Ren, Xinyi; Shen, Chaoren; Tang, Lin; Tian, Xinxin; Wang, Zhen [Angewandte Chemie - International Edition, 2021, vol. 60, # 32, p. 17693 - 17700][Angew. Chem., 2021, vol. 133, # 32, p. 17834 - 17841]
[2]Cousse; Mouzin; Rieu; et al. [European Journal of Medicinal Chemistry, 1987, vol. 22, # 1, p. 45 - 57]
[3]Siddiqui, Anees A.; Wani, Sachin M. [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2004, vol. 43, # 7, p. 1574 - 1579]
[4]Tomisawa; Kameo; Matsunaga; Saito; Hosoda; Asami; Sota [Chemical and Pharmaceutical Bulletin, 1986, vol. 34, # 2, p. 701 - 712]
[5]Kameo; Ogawa; Takeshita; Nakaike; Tomisawa; Sota [Chemical and Pharmaceutical Bulletin, 1988, vol. 36, # 6, p. 2050 - 2060]
[6]Tumey, L. Nathan; Huck, Bayard; Gleason, Elizabeth; Wang, Jianmin; Silver, Daniel; Brunden, Kurt; Boozer, Sherry; Rundlett, Stephen; Sherf, Bruce; Murphy, Steven; Bailey, Andrew; Dent, Tom; Leventhal, Christina; Harrington, John; Bennani, Youssef L. [Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 19, p. 4915 - 4918]

8
[ 91-20-3 ]
[ 2170-03-8 ]
[ 60186-01-8 ]

Yield	Reaction Conditions	Operation in experiment
86%	With aluminium trichloride In dichloromethane at 35 - 40℃; for 3h;
52%	With aluminium trichloride In nitrobenzene at 20℃;
38%	With aluminum (III) chloride In dichloromethane at 20℃; for 2h; Inert atmosphere; Schlenk technique;

Reference： [1]Cousse; Mouzin; Rieu; et al. [European Journal of Medicinal Chemistry, 1987, vol. 22, # 1, p. 45 - 57]
[2]Siddiqui, Anees A.; Wani, Sachin M. [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2004, vol. 43, # 7, p. 1574 - 1579]
[3]Chen, Caiyou; Zhang, Zhefan; Jin, Shicheng; Fan, Xiangru; Geng, Mingyu; Zhou, Yan; Wen, Songwei; Wang, Xinrui; Chung, Lung Wa; Dong, Xiu-Qin; Zhang, Xumu [Angewandte Chemie - International Edition, 2017, vol. 56, # 24, p. 6808 - 6812][Angew. Chem., 2017, vol. 129, p. 6912 - 6916,5]

9
[ 112-53-8 ]
[ 2170-03-8 ]
[ 23405-96-1 ]

Yield	Reaction Conditions	Operation in experiment
	1) 110 deg C, 20 min, 2) 130, 30 min;
	at 110℃; for 2h; Inert atmosphere;	1 Itaconic anhydride (17.27 g, 151 mmol) and primary fatty alcohol ( ao C1214N, 29.50g , 151 mmol) were combined and heated to 110°C for 120 min. resulting in the product, ?-Mono.laurylitaconate. NMR testing indicated substantially complete conversion of the itaconic anhydride.
	at 110 - 120℃; for 0.833333h;

	at 116℃; for 1h;
	In toluene at 80℃; for 4h;
	In n-heptane at 110℃; for 4h;	Synthesis General procedure: A typical synthesis example is given herewith for dodecylmaleate. 1-dodecanol (38.16 g, 0.20 mole) was introduced in a one-neck flask and heated at 110C. After melting the alcohol, maleicanhydride (20.08 g, 0.20 mole) was added. The reaction mixturetemperature was maintained at 110C and the medium was stirredfor 90 min. The reaction product was poured in heptane (100 mL)under magnetic stirring and left at room temperature for 4 h. Theformed precipitate was collected by filtration. White crystals ofdodecyl 1a)1H NMR (300 MHz, CDCl3, 20C) (ppm): 0.89 (3H, t, CH3),1.28 (10H, m, CH2), 1.72 (2H, q, CH2), 4.28 (2H, t, CH2), 6.38 (1H, d,CH), 6.48 (1H, d, CH).
	In chloroform Reflux;	1 Step 1 - Synthesis of monolauryl itaconate Itaconate anhydride (1 Og, 76.9 mmol) and lauryl alcohol (17.1 g, 92.3 mmol) were dissolved in 100 ml of dry chloroform and refluxed overnight (16h). The reaction mixture was concentrated with minimum amount of chloroform followed by addition of hexane afforded white precipitate which was filtered. The white precipitate was collected and dried in vacuum.

Reference： [1]Naitoh, Kouichi; Ishii, Yasuo; Tsujii, Kaoru [Journal of Physical Chemistry, 1991, vol. 95, # 20, p. 7915 - 7918]
[2]Current Patent Assignee: STEPAN CO - WO2011/109047, 2011, A2 Location in patent: Page/Page column 32
[3]Qin, Hai Li; Wang, Dong; Huang, Zeng Li; Wu, Dong Min; Zeng, Zhi Cong; Ren, Bin; Xu, Ke; Jin, Jian [Journal of the American Chemical Society, 2013, vol. 135, # 34, p. 12544 - 12547]
[4]Wang, Dong; Niu, Jian; Wang, Zhenggong; Jin, Jian [Langmuir, 2015, vol. 31, # 5, p. 1670 - 1674]
[5]Dakin, Jackson M.; Shanmugam, Karthik Vikram Siva; Twigg, Christopher; Whitney, Ralph A.; Parent, J. Scott [Journal of Polymer Science, Part A: Polymer Chemistry, 2015, vol. 53, # 1, p. 123 - 132]
[6]Richard, Jean-Victor; Delaite, Christelle; Riess, Gérard; Schuller, Anne-Sophie [Thermochimica Acta, 2016, vol. 623, p. 136 - 143]
[7]Current Patent Assignee: UNILEVER (PLC & NV) - WO2020/144144, 2020, A1 Location in patent: Page/Page column 13

10
[ 707-37-9 ]
[ 2170-03-8 ]
[ 141102-66-1 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1992,vol. 65,p. 846 - 852

11
[ 827-52-1 ]
[ 2170-03-8 ]
[ 80832-49-1 ]

Reference： [1]European Journal of Medicinal Chemistry,1987,vol. 22,p. 45 - 57

12
[ 321-60-8 ]
[ 2170-03-8 ]
[ 111259-26-8 ]

Yield	Reaction Conditions	Operation in experiment
60%	With aluminium trichloride In dichloromethane at 35 - 40℃; for 3h;

Reference： [1]Cousse; Mouzin; Rieu; et al. [European Journal of Medicinal Chemistry, 1987, vol. 22, # 1, p. 45 - 57]

13
[ 2170-03-8 ]
[ 100-66-3 ]
[ 101973-94-8 ]

Yield	Reaction Conditions	Operation in experiment
89%	With aluminum (III) chloride In dichloromethane at 20℃; for 2h; Inert atmosphere; Schlenk technique;
88%	With aluminium trichloride In dichloromethane; nitrobenzene for 1h;
76%	With aluminium trichloride at 35 - 40℃; for 3h;

76%	With aluminium trichloride In nitrobenzene at 70℃; for 4h;
44%	With aluminium trichloride In 1,2-dichloro-ethane
	With aluminum (III) chloride In dichloromethane at 20℃; for 2h;

Reference： [1]Chen, Caiyou; Zhang, Zhefan; Jin, Shicheng; Fan, Xiangru; Geng, Mingyu; Zhou, Yan; Wen, Songwei; Wang, Xinrui; Chung, Lung Wa; Dong, Xiu-Qin; Zhang, Xumu [Angewandte Chemie - International Edition, 2017, vol. 56, # 24, p. 6808 - 6812][Angew. Chem., 2017, vol. 129, p. 6912 - 6916,5]
[2]Zhang, Jun; Cerny, Matt A.; Lawson, Matt; Mosadeghi, Ruzbeh; Cashman, John R. [Journal of Biochemical and Molecular Toxicology, 2007, vol. 21, # 4, p. 206 - 215]
[3]Cousse; Mouzin; Rieu; et al. [European Journal of Medicinal Chemistry, 1987, vol. 22, # 1, p. 45 - 57]
[4]Siddiqui, Anees A.; Wani, Sachin M. [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2004, vol. 43, # 7, p. 1574 - 1579]
[5]Kameo; Ogawa; Takeshita; Nakaike; Tomisawa; Sota [Chemical and Pharmaceutical Bulletin, 1988, vol. 36, # 6, p. 2050 - 2060]
[6]Dong, Kaiwu; Ji, Xiaolei; Ren, Xinyi; Shen, Chaoren; Tang, Lin; Tian, Xinxin; Wang, Zhen [Angewandte Chemie - International Edition, 2021, vol. 60, # 32, p. 17693 - 17700][Angew. Chem., 2021, vol. 133, # 32, p. 17834 - 17841]

14
[ 2170-03-8 ]
[ 108-90-7 ]
[ 58182-59-5 ]

Yield	Reaction Conditions	Operation in experiment
79%	With aluminium trichloride at 35 - 40℃; for 3h;
66%	With aluminium trichloride at 120℃; for 6h;
48%	With aluminum (III) chloride In dichloromethane at 20℃; for 2h; Inert atmosphere; Schlenk technique;

38.3%	With aluminium trichloride In 1,2-dichloro-ethane
	With aluminum (III) chloride In dichloromethane at 20℃; for 2h;

Reference： [1]Cousse; Mouzin; Rieu; et al. [European Journal of Medicinal Chemistry, 1987, vol. 22, # 1, p. 45 - 57]
[2]Siddiqui, Anees A.; Wani, Sachin M. [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2004, vol. 43, # 7, p. 1574 - 1579]
[3]Chen, Caiyou; Zhang, Zhefan; Jin, Shicheng; Fan, Xiangru; Geng, Mingyu; Zhou, Yan; Wen, Songwei; Wang, Xinrui; Chung, Lung Wa; Dong, Xiu-Qin; Zhang, Xumu [Angewandte Chemie - International Edition, 2017, vol. 56, # 24, p. 6808 - 6812][Angew. Chem., 2017, vol. 129, p. 6912 - 6916,5]
[4]Kameo; Ogawa; Takeshita; Nakaike; Tomisawa; Sota [Chemical and Pharmaceutical Bulletin, 1988, vol. 36, # 6, p. 2050 - 2060]
[5]Dong, Kaiwu; Ji, Xiaolei; Ren, Xinyi; Shen, Chaoren; Tang, Lin; Tian, Xinxin; Wang, Zhen [Angewandte Chemie - International Edition, 2021, vol. 60, # 32, p. 17693 - 17700][Angew. Chem., 2021, vol. 133, # 32, p. 17834 - 17841]

15
[ 707-37-9 ]
[ 2170-03-8 ]
[ 67-63-0 ]
[ 141102-70-7 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1992,vol. 65,p. 846 - 852

16
[ 2170-03-8 ]
[ 108-88-3 ]
[ 19340-33-1 ]

Yield	Reaction Conditions	Operation in experiment
91%	With aluminum (III) chloride In dichloromethane at 20℃; for 2h; Inert atmosphere; Schlenk technique;
72%	With aluminium trichloride at 100℃; for 4h;
68.4%	With aluminium trichloride In nitrobenzene at 50℃; for 2h;

52.4%	With aluminium trichloride In 1,2-dichloro-ethane
	In various solvent(s) at 20℃; for 0.5h;
	With aluminum (III) chloride In dichloromethane at 20℃; for 2h;

Reference： [1]Chen, Caiyou; Zhang, Zhefan; Jin, Shicheng; Fan, Xiangru; Geng, Mingyu; Zhou, Yan; Wen, Songwei; Wang, Xinrui; Chung, Lung Wa; Dong, Xiu-Qin; Zhang, Xumu [Angewandte Chemie - International Edition, 2017, vol. 56, # 24, p. 6808 - 6812][Angew. Chem., 2017, vol. 129, p. 6912 - 6916,5]
[2]Siddiqui, Anees A.; Wani, Sachin M. [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2004, vol. 43, # 7, p. 1574 - 1579]
[3]Noguchi, Toshiya; Onodera, Akira; Ito, Masato; Yoshida, Mamoru; Yokomori, Sadakazu [Synthetic Communications, 2003, vol. 33, # 15, p. 2657 - 2670]
[4]Kameo; Ogawa; Takeshita; Nakaike; Tomisawa; Sota [Chemical and Pharmaceutical Bulletin, 1988, vol. 36, # 6, p. 2050 - 2060]
[5]Yoshida, Hideo; Kohno, Yoshiro; Endo, Hiromi; Yamaguchi, Jun-Ichi; Fukushima, Kiyomi; Suwa, Toshio; Hayashi, Masahiro [Biochemical Pharmacology, 1997, vol. 53, # 2, p. 179 - 187]
[6]Dong, Kaiwu; Ji, Xiaolei; Ren, Xinyi; Shen, Chaoren; Tang, Lin; Tian, Xinxin; Wang, Zhen [Angewandte Chemie - International Edition, 2021, vol. 60, # 32, p. 17693 - 17700][Angew. Chem., 2021, vol. 133, # 32, p. 17834 - 17841]

17
[ 37847-52-2 ]
[ 2170-03-8 ]
[ 161692-81-5 ]

Reference： [1]Collection of Czechoslovak Chemical Communications,1994,vol. 59,p. 2705 - 2713

18
[ 123-01-3 ]
[ 2170-03-8 ]
4-(4-Dodecyl-phenyl)-2-methylene-4-oxo-butyric acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
20%	With aluminium trichloride In carbon disulfide at 50℃; for 2h;

Reference： [1]Nuhn, Peter; Radman; Hermann; Marx [Pharmazie, 1998, vol. 53, # 12, p. 825 - 829]

19
[ 2170-03-8 ]
[ 5981-09-9 ]
3-(4-{bis-[4-(2-carboxymethyl-acryloylamino)-phenyl]-amino}-phenylcarbamoyl)-but-3-enoic acid [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2004,vol. 126,p. 12200 - 12201

20
[ 2170-03-8 ]
[ 62-53-3 ]
[ 34105-39-0 ]

Yield	Reaction Conditions	Operation in experiment
63%	Stage #1: itaconic acid anhydride; aniline In diethyl ether; dichloromethane for 5h; Inert atmosphere; Stage #2: With sodium acetate; acetic anhydride at 100℃; for 0.5h; Inert atmosphere;	General Procedure for the synthesis of N-arylitaconimides 1a-d. General procedure: A solution of 5.6 g (5 mmol) of itaconic anhydride and 5 mmol of corresponding aniline in a mixture of dichloromethane (80 ml) and diethylether (150 ml) was stirred during 5 hours. The precipitate was filtered off and dried. Then acetic anhydride (40 ml) and sodium acetate (2.5 g) was added and the mixture was heated at 100 °C during 30 min. Reaction mixture was poured into cold water and the precipitate was filtered off and recrystallized from a mixture of benzene-ethanol.
	at 120℃;
	With acetic acid In diethyl ether Reflux;	2.1.1. General Procedures for the Synthesis of the Studied Compounds General procedure: The compounds were obtained by the action of the respective anhydrides with appropriate amines in ether, or directly refluxed with acetic acid as previously described[1,15]. The product was mostly filtered, but in the absence of precipitate, it was extracted with chloroform. The combined organic layers were dried with Na2SO4, filtered and evaporated.The final product was purified by recrystallization with the suitable solvent, or by through column chromatography over silica gel using the chloroform: methanol gradient eluent, giving yields of 20 to 55%.

Stage #1: itaconic acid anhydride; aniline In diethyl ether at 0 - 5℃; for 3h; Stage #2: With sodium acetate; acetic anhydride for 0.5h;

2.2. Synthesis of Itaconimide Derivatives. All N-(substitutedphenyl)itaconimide derivatives (N-(RPh)IM) were prepared by two steps described by Adam [6]. In the 2rst step, 1 mol of itaconic anhydride was dissolved in dry diethyl ether and then,1 mol of the primary amine dissolved in the same solvent was slowly added to the itaconic anhydride at 0-5°C for 3 hours. The resulted acid N-(substituted phenyl)itaconic acid was filtered,washed, and dried. The following step was cyclization which occurred by adding acetic acid anhydride and fused sodium acetate in a steam bath for 30 minutes. The resulted monomer was crystallized from aqueous ethanol. Table 1 shows the melting points of prepared itaconimide derivatives

Reference： [1]Teterina, Polina S.; Efremova, Mariia M.; Sirotkina, Ekaterina V.; Novikov, Alexander S.; Khoroshilova, Olesya V.; Molchanov, Alexander P. [Tetrahedron Letters, 2019, vol. 60, # 39]
[2]Hegazy, Mohamed-Elamir F.; Shishido, Kozo; Hirata, Toshifumi [Tetrahedron Asymmetry, 2006, vol. 17, # 12, p. 1859 - 1862]
[3]Stiz, Dorimar; Corrêa, Rogério; D'Auria, Felicia D.; Simonetti, Giovanna; Cechinel-Filho, Valdir [Medicinal Chemistry, 2016, vol. 12, # 7, p. 647 - 654]
[4]Elsharif, Asma M.; Al-Ghamdi, Azza A.; Abdel-Naby, Abir S. [Journal of Chemistry, 2019, vol. 2019]

21
[ 2170-03-8 ]
[ 654-70-6 ]
[ 1003838-30-9 ]

Yield	Reaction Conditions	Operation in experiment
		<strong>[654-70-6]4-cyano-3-trifluoromethyl-aniline</strong> is reacted with itaconic anhydride (66) to yield intermediate 67. Further epoxidation and opening of the epoxide ring with p-CN-phenol 50 yields compound XLVI as presented in Figure IG.

Reference： [1]Patent: WO2008/11072,2008,A2 .Location in patent: Page/Page column 139; Sheet 3

22
[ 33228-45-4 ]
[ 2170-03-8 ]
C₁₇H₂₃NO₃ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 5269 - 5280

23
[ 2170-03-8 ]
[ 101973-77-7 ]

Reference： [1]Synthetic Communications,2003,vol. 33,p. 2657 - 2670
[2]Chemical and pharmaceutical bulletin,2002,vol. 50,p. 1407 - 1412
[3]Chemical and Pharmaceutical Bulletin,1988,vol. 36,p. 2050 - 2060

24
[ 2170-03-8 ]
[ 64-04-0 ]
[ 206864-94-0 ]

Yield	Reaction Conditions	Operation in experiment
64%	In chloroform at 0 - 20℃; for 2h;
50%	In acetonitrile at 20℃; for 72h;	1.A Step A Step A A solution of itaconic anhydride (5.00 g, 44.6 mmol) and phenethylamine (5.95 g, 49.1 mmol) in 100 mL of acetonitrile is stirred at room temperature under nitrogen for 72 hours. The mixture (solid forms) is concentrated, then partitioned between EtOAc and 1N HCl. The organic extract is washed with brine, dried (MgSO4), concentrated, and the residue crystallized from diethyl ether to give 5.24 g (50%) of 2-(phenethylcarbamoyl-methyl)-acrylic acid as a white solid: mp 133-140°C. MS (APCI) m/z 234.2 (M+1, 67.4%) and 216.2 (M-17, 100%).

Reference： [1]Dong, Kaiwu; Ji, Xiaolei; Ren, Xinyi; Shen, Chaoren; Tang, Lin; Tian, Xinxin; Wang, Zhen [Angewandte Chemie - International Edition, 2021, vol. 60, # 32, p. 17693 - 17700][Angew. Chem., 2021, vol. 133, # 32, p. 17834 - 17841]
[2]Current Patent Assignee: PFIZER INC - EP1082127, 2005, B1 Location in patent: Page/Page column 24

25
[ 1295-35-8 ]
[ 2170-03-8 ]
(N(CH₃)2C₂H₄N(CH₃)2)(NiOCOC(CH₂)CH₂) [ No CAS ]
[ 153095-61-5 ]

Reference： [1]Zeitschrift fur Anorganische und Allgemeine Chemie,
Zeitschrift fuer Anorganische und Allgemeine Chemie,1993,vol. 619,p. 1512 - 1518

26
[ 2170-03-8 ]
[ 214484-11-4 ]
4-[[4-[(3-Bromophenyl)amino]-3-cyano-6-quinolinyl]-amino]-2-methylene-4-oxo-butanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	In ethyl acetate at 20℃;	186 Itaconic anhydride (0.14g, 1.25mmol) was added portionwise to a solution of 0.1 g (0.30mmol) of 6-amino-4-[(3-bromophenyl)amino]-3-quinolinecarbonitrile in 2mL of ethyl acetate under N2. After stirring at room temperature overnight, the reaction solution was added into ice water and hexane. The product was collected, washed with water, ether and hexane, and dried in vacuo to give 0.09g (68%) of yellowish brown solid; ESMS m/z 451.2 (M+H+).

Reference： [1]Current Patent Assignee: PFIZER INC - EP973746, 2003, B1 Location in patent: Page/Page column 69

27
[ 2170-03-8 ]
[ 148043-73-6 ]
[ 1096155-06-4 ]

Yield	Reaction Conditions	Operation in experiment
	sulfuric acid; In dichloromethane; acetonitrile; at 60℃;Heating / reflux;	In an oven-dried 250ml round bottom flask was added, under the flushing of dry nitrogen; Itaconic anhydride, 12.236g (109.16 mmol), methylene chloride 60 ml, acetonitrile 120 ml, <strong>[148043-73-6]4,4,5,5,5-pentafluoropentanol</strong> 19.653g (1 10.35 mmol), concentrated sulfuric acid 30 drops. The reaction mixture was refluxed at 600C overnight. After silica gel column purification <strong>[148043-73-6]4,4,5,5,5-pentafluoropentanol</strong> itaconic acid was obtained. The proposed structure was confirmed by NMR and GC MS etc. NMR and MS <n="19"/>NMR: 1H: 1.858 ppm, quintuplet; 1.938 ppm, multiplet; 2,084 ppm, multiplet; 3.344 ppm, singlet; 3.769, multiplet; 4.176 ppm, triplet; 5.831 ppm, singlet; 6.461 ppm, singlet; 11.650 ppm, broad:13C: 20.246 ppm, singlet; 25.768 ppm, singlet; 27.696 ppm, triplet; 37.483 ppm, singlet; 63.606 ppm, singlet; 68.096 ppm, singlet; 115.681 ppm, singlet; 1 16.049 ppm, singlet; 131.136 ppm, singlet; 133.359 ppm, singlet; 170.621 ppm, singlet; 171.642 ppm, singlet.GC MS: predominant peak at 6.3 minute, M+=290, fragments confirm the structure, 161, 130, 1 13, 85; 47ESI MS: MTNa+ = 313.01
	sulfuric acid; In dichloromethane; acetonitrile; for 96h;Heating / reflux;	To a thoroughly dried 250-mL, 3-neck round bottom flask equipped with nitrogen inlet tube and drying tube was charged 6.555 g (55.557 mmol) itaconic anhydride, 40ml anhydrous acetonitrile, 15ml anhydrous methylene chloride and 9.860 g (54.810 mmol) 4,4,5,5.5-pentafluoro-l- pentanol through syringes. Then 10 drops of concentrated sulfuric acid was added. The contents were refluxed and stirred. Samples were taken out periodically for GC analyses. After 4 days, the solvent was stripped to give 13.308 g while solid. After column chromatography, 6.70 grams of purified product was recovered.NMR: 1H0: 1.858 ppm, quintuplet; 1.938 ppm, multiplet; 2.084 ppm, multiplet; 3.344 ppm, singlet; 3.769, multiplet 4.176 ppm, triplet; 5.831 ppm, singlet; 6.461 ppm, singlet; 11.650 ppm, broad.13C0: 20.246 ppm, singlet; 25.768 ppm, singlet; 27.696 ppm, triplet; 37.483 ppm, singlet; 63,606 ppm, singlet; 68.096 ppm, singlet; 115.681 ppm, singlet; 116.049 ppm, singlet; 131.136 ppm, singlet; 133.359 ppm, singlet; 170.621 ppm, singlet; 171.642 ppm, singlet.GC MS: predominant peak at 6.3 minute, M+=290, fragments confirm the structure, 161, 130, 113, 85, 47ESI MS: M/Na+ =313.01

Reference： [1]Patent: WO2009/45886,2009,A1 .Location in patent: Page/Page column title page; 16-17; 1/1
[2]Patent: WO2009/5954,2009,A2 .Location in patent: Page/Page column 16

28
[ 56281-06-2 ]
[ 2170-03-8 ]
[ 1203508-57-9 ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid In toluene at 113℃; for 19h;	8 Itaconic anhydride (0.75 g, 6.7 mmol), C4F9CH2CF2CH2CH2OH (4.37 g, 13 mmol, prepared as descibed above), /?-toluenesulfonic acid monohydrate (0.13 g, 0.67 mmol) and toluene (50 mL) were refluxed for a period of 19 h at a temperature of 113°C. The resulting pale yellow liquid (4.53 g, 90.6% yield, 72% purity) was analyzed by ^H NMR and LC/MS to confirm the structure asC4F9CH2CF2CH2CH2OC(O)CH2C(=CH2)C(O)OCH2CH2CF2CH2C4F9.
	With toluene-4-sulfonic acid In toluene at 113℃; for 19h;	8 Itaconic anhydride (0.75 g, 6.7 mmol), C4F9CH2CF2CH2CH2OH (4.37 g, 13 mmol, prepared as described above), p-toluenesulfonic acid monohydrate (0.13 g, 0.67 mmol) and toluene (50 mL) were refluxed for a period of 19 h at a temperature of 113° C. The resulting pale yellow liquid (4.53 g, 90.6% yield, 72% purity) was analyzed by 1H NMR and LC/MS to confirm the structure as C4F9CH2CF2CH2CH2OC(O)CH2C(CH2)C(O)OCH2CH2CF2CH2C4F9.

Reference： [1]Current Patent Assignee: The Chemours Company - WO2010/2623, 2010, A2 Location in patent: Page/Page column 26
[2]Current Patent Assignee: DUPONT DE NEMOURS INC - US2010/4478, 2010, A1 Location in patent: Page/Page column 10 Current Patent Assignee: DUPONT DE NEMOURS INC - US2010/4482, 2010, A1 Location in patent: Page/Page column 10

29
[ 904055-94-3 ]
[ 2170-03-8 ]
[ 1203508-56-8 ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid In toluene at 111℃; for 25h;	7 Itaconic anhydride (0.67 g, 6.0 mmol), C3F7OCF(CF3)CONHCH2CH2- OH (4.44 g, 12 mmol, prepared as described above), /?-toluenesulfonic acid monohydrate (0.1 Ig, 0.60 mmol), and toluene (5OmL) were stirred continuously and heated to reflux at 111°C for a period of 25 h. The toluene was decanted off to leave a yellow, viscous solid. The product was firstly air-dried and then placed in a vacuum oven for 2 h. The product (3.62g, 72.4%, 65% purity) was analyzed by IfI NMR and LC/MS to confirm complete conversion and the structure as C3F7OCF(CF3)C(O)NHCH2CH2OC(O)CH2C(=CH2)C(O)OCH2CH2- NHC(O)CF(CF3)OC3F7.
	With toluene-4-sulfonic acid In toluene at 111℃; for 25h;	7 Itaconic anhydride (0.67 g, 6.0 mmol), C3F7OCF(CF3)CONHCH2CH2OH (4.44 g, 12 mmol, prepared as described above), p-toluenesulfonic acid monohydrate (0.1 μg, 0.60 mmol), and toluene (50 mL) were stirred continuously and heated to reflux at 111° C. for a period of 25 h. The toluene was decanted off to leave a yellow, viscous solid. The product was firstly air-dried and then placed in a vacuum oven for 2 h. The product (3.62 g, 72.4%, 65% purity) was analyzed by 1H NMR and LC/MS to confirm complete conversion and the structure as C3F7OCF(CF3)C(O)NHCH2CH2OC(O)CH2C(CH2)C(O)OCH2CH2-NHC(O)CF(CF3)OC3F7.

Reference： [1]Current Patent Assignee: The Chemours Company - WO2010/2623, 2010, A2 Location in patent: Page/Page column 26
[2]Current Patent Assignee: DUPONT DE NEMOURS INC - US2010/4478, 2010, A1 Location in patent: Page/Page column 10 Current Patent Assignee: DUPONT DE NEMOURS INC - US2010/4482, 2010, A1 Location in patent: Page/Page column 10

30
[ 2170-03-8 ]
[ 68000-92-0 ]
[ 1227280-13-8 ]

Yield	Reaction Conditions	Operation in experiment
82%	Stage #1: itaconic acid anhydride; trans,trans-farnesyl-L-cysteine With potassium carbonate In tetrahydrofuran at 5 - 20℃; Stage #2: With hydrogenchloride In tetrahydrofuran	3 S-trans, trans- Farnesyl-L-cysteine (500 mg, 1.54 mmol) was dissolved in mixture of THF and a first portion of K2CO3 (3 mmol) and the resulting solution was cooled to 5 C with vigorous stirring. To this stirred solution was added 3-methylenedihydro-2,5-furandione (302 mg, 3.07 mmol) portionwise while maintaining the pH at 9.0-10.0 with another portion Of K2CO3 (3 mmol). The mixture was stirred at room temperature for 3 h. HPLC analysis showed completion of the reaction. The pH of the reaction mixture then adjusted to 2.0 by the addition of 2 N HCl solution. The acidic solution was extracted three times with 15 mL of ethyl acetate. The combined organic extract was washed with water, brine and dried over Na2SO4, the solvent was removed under reduced pressure to afford crude Compound F, which was further purified by preparative HPLC (552 mg, 82%) to yield Compound F. 1H-NMR (500 MHz, CDCl3): δ 1.59 (s,6H), 1.67 (s, 3H), 1.68 (s, 3H), 2.05 (m, 8H), 2.88 (dd, J = 6.5, 14.0, IH), 2.95 (dd, J = 6.5, 14.0, IH), 3.17-3.15 (m, 2H), 3.36 (d, J = 14 Hz, IH), 4.77(dd, J = 6, 12.5 Hz, IH), 5.09 (bt, 2H), 5.22 (t, J = 7.5 Hz, IH), 5.93(s, IH), 6.46 (s, IH). 13C-NMR (125 MHz, CDCl3): δ 16.0, 16.2, 17.7, 25.7, 26.7, 29.9, 32.8, 39.6, 39.7, 40.2, 52.0, 119.4, 123.7, 131.3, 132.0, 135.4, 140.3, 170.3, 171.5, 176.0; ES-MS: mass calcd for Chemical Formula: C23H35NO5S 437.6. Found (M+Na) m/z 446.

Reference： [1]Current Patent Assignee: SIGNUM BIOSCIENCES, INC. - WO2010/56778, 2010, A1 Location in patent: Page/Page column 139

31
[ 2170-03-8 ]
[ 42918-08-1 ]
[ 1393447-77-2 ]

Yield	Reaction Conditions	Operation in experiment
56%	In diethyl ether at 20℃; for 168h;	2-((4-(phenyl-5-(pyridin-2-yl)-4H-1,2,4-triazol-3-yl)methyl)acrylicacid (12) General procedure: Amidrazones 1-7 [1] and itaconic anhydride weredissolved in anhydrous diethyl ether prior to mixing them together at molarratio of 1:1 and left in ambient temperature for 7 days. Obtained precipitatewas collected by filtration and washed with anhydrous ether. Compounds 8-14 were purified by crystallizationfrom water.
15%	In diethyl ether at 20℃; for 168h;	2.2. Synthesis of 2-((4-phenyl-5-(pyridin-2-yl)-4H-1,2,4-triazol-3-yl)methyl)acrylic acid (3) The carbohydrazonamide 1 (2.12 g, 10 mmol) and itaconic anhydride 2 (1.12 g, 10 mmol) were dissolved in anhydrous diethyl ether (50 mL) and the reaction mixture was left at room temperature for 7 days. The solid product that precipitated was collected by filtration and washed with diethyl ether. Then, the solid was dissolved in chloroform (30 mL), heated at reflux for 5 min. and filtered. The filtrate was evaporated to dryness and the solid residue was washed with anhydrous diethyl ether, dried and purified by crystallization from water to give 0.46 g (1.5 mmol, 15%) of 3. M.p. 164-166 °C. 1H NMR (300 MHz, DMSO-d6): δ = 3.56 (s, 2 H, CH2), 5.58 (s, 1 H, CH), 6.13 (s, 1 H, CH), 7.30-7.37 (m, 3 H, CH), 7.45-7.48 (m, 3 H, CH), 7.89 (t, J = 6,0 Hz, 1 H, CH), 7.96 (d, J = 6.0 Hz, 1H, CH), 8.29 (d, J = 6.0 Hz, 1 H, CH), 12.59 (bs, 1 H, COOH) ppm. 13C NMR (100 MHz, DMSO-d6): δ = 29.3, 125.5, 126.0, 128.7, 129.2, 130.9, 131.0, 136.9, 137.9, 139.0, 148.5, 150.7, 154.3, 155.8, 168.9. FT-IR (KBr, cm-1): 3426m, 3078m, 1711s, 1635m, 1591m, 1500s, 1457s, 1417m, 1218m, 1164m, 1008m, 954w, 792m, 781m, 700m. ESI-MS m/z (%): 306 (57%), 261 (100%), 130 (28%), 78 (41%), 77 (50%). Anal. Calc. for C17H14N4O2: C, 66.66; H, 4.61; N, 18.29%; found: C, 66.46; H, 4.62; N, 18.07%.

Reference： [1]Paprocka, Renata; Wiese, Malgorzata; Eljaszewicz, Andrzej; Helmin-Basa, Anna; Gzella, Andrzej; Modzelewska-Banachiewicz, Bozena; Michalkiewicz, Jacek [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 13, p. 2664 - 2667]
[2]Location in patent: experimental part Modzelewska-Banachiewicz, Bozena; Paprocka, Renata; Mazur, Liliana; Saczewski, Jarosław; Kutkowska, Jolanta; Stepień, Dorota K.; Cyrański, Michał [Journal of Molecular Structure, 2012, vol. 1022, p. 211 - 219]

32
[ 75-91-2 ]
[ 2170-03-8 ]
[ 100-52-7 ]
[ 1415690-20-8 ]

Yield	Reaction Conditions	Operation in experiment
53%	With iron(II) chloride In decane; acetonitrile at 85℃; for 3h; Inert atmosphere;	General procedure for the products 4 General procedure: To a mixture of alkene 1 (0.5 mmol), aldehyde 2 (2.5 mmol), and FeCl2 (1.6 mg, 0.0125 mmol), acetonitrile (3.0 mL) was added under nitrogen at room temperature. Then tert-butyl hydroperoxide 3 (TBHP, 2.0 mmol, 5-6 M in decane) was dropped into the mixture under nitrogen at room temperature. The resulting mixture was stirred under 85 oC for 1 h. The temperature of reaction was cooled to room temperature. The resulting reaction solution was directly filtered through a pad of silica by ethyl acetate. The solvent was evaporated in vacuo to give the crude products. NMR yields are determined by 1H NMR using dibromomethane as an internal standard. Solvent was evaporated and the residue was purified by flash column chromatography on silica gel with ethyl acetate/petroleum ether as eluent to afford the pure product 4.

Reference： [1]Liu, Kaisheng; Li, Yuanming; Zheng, Xiaojian; Liu, Weiping; Li, Zhiping [Tetrahedron, 2012, vol. 68, # 50, p. 10333 - 10337]

33
[ 2170-03-8 ]
[ 10191-41-0 ]
DL-α-tocopheryl monoitaconate [ No CAS ]

Reference： [1]Carbohydrate Polymers,2013,vol. 92,p. 856 - 864

34
[ 2170-03-8 ]
[ 6149-33-3 ]
C₁₇H₁₂N₂O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72.8%	Stage #1: itaconic acid anhydride; 4-(4-nitrophenoxy)aniline In acetone for 6h; Inert atmosphere; Reflux; Stage #2: With sodium acetate; acetic anhydride In acetone for 12h; Reflux;	1 Synthesis of imide-functionalized amine 2.2.1 4-Nitrophenoxy itaconimide (NPI) In a 250 mL two-necked round-bottomed flask equipped with a nitrogen inlet and a reflux condenser, NPA (25 g, 0.109 mol) was dissolved in 100 mL of dry acetone. Itaconic anhydride (12.21 g, 0.109 mol) was slowly added to the flask, and the contents were refluxed for 6 h. Then, sodium acetate (3 g) and acetic anhydride (22.25 g, 0.218 mol) were added to the flask, and the solution was refluxed for 12 h. The contents were then cooled and precipitated into ice water. The pale yellow precipitate was washed with a 0.5 N sodium bicarbonate solution, neutralized and finally washed with distilled water, dried and recrystallized from chloroform. Yield: 72.8%; 1H NMR (300 MHz, CDCl3-d6, δ): 8.24-8.22 (d, 2H, Ar-NO2), 6.98-7.44 (d, 6H, ArH), 6.51 and 5.79 (s, 2H, C=CH2), 3.55 (s, 2H, CH2).

Reference： [1]Nalakathu Kolanadiyil, Sini; Bijwe, Jayashree; Varma, Indra K. [Reactive and functional polymers, 2013, vol. 73, # 11, p. 1544 - 1552]

35
[ 2170-03-8 ]
[ 139031-06-4 ]
[ 1591652-64-0 ]

Yield	Reaction Conditions	Operation in experiment
96%	With triethylamine In 1,2-dimethoxyethane; toluene at 20℃; for 12h; Schlenk technique; Inert atmosphere;	II.4a General method for the preparation of acylphosphanes starting from phosphines and phosphides General procedure: A solution of the phosphane or phosphide and optionally triethylamine in either dimethoxyethane (dme) or tetrahydrofurane (thf) was prepared in a 50 mL Schlenk flask under an inert atmosphere of argon (first solution). Subsequently, a solution of a compound selected from those of formulae (IVa) to (IVe) in dme or thf or the neat compound (hereinafter collectively referred to as second solution) was slowly added. After stirring for twelve hours at room temperature, a 2M solution of hydrochloric acid in diethylether was added in an equimolar amount to neutralize the triethylamine. The reaction mixture was stirred for another hour at room temperature, before the solvent was removed under reduced pressure. The solid residue was dissolved in toluene and the insoluble precipitate of triethylamine hydrochloride was separated by filtration. The solution volume was reduced in vacuo to half of its volume and layered with half of the remaining volume of hexane. The obtained crystalline solid was collected and dried under high vacuum for twelve hours. First solution: HP(COMes)2 (3 g, 9.19 mmol) and triethylamine (0.92 mmol) in dme (20 mL) Second solution: itaconic anhydride (1.03 g, 9.19 mmol) in dme (10 mL) Amount of toluene: 40 mL Yield: 3.87 g, 96 % th. 31P{1H} NMR (121.5 MHz, C6D6, 298 K): δ = 48.7 ppm.

Reference： [1]Current Patent Assignee: EIDGENÖSSISCHE TECHNISCHE HOCHSCHULE ZÜRICH - WO2014/53455, 2014, A1 Location in patent: Page/Page column 33; 34

36
[ 2170-03-8 ]
[ 99-03-6 ]
[ 1623012-35-0 ]

Yield	Reaction Conditions	Operation in experiment
85%	In acetone at 20℃; for 2h;	2.2 Synthesis of 4-[(3-Acetylphenyl)amino]-2-methylidene-4-oxobutanoic acid (1) ITA (0.112 g, 1 mmol) dissolved in a 30 mL acetone and it was stirred at ambient temperature and 3-aminoacetophenone (0.135 g, 1 mmol) was added portion wise over 30 mins.The mixture turned into pale yellow slurry. After stirring 1.5 hr, the slurry was filtered.The solid was washed with acetone and dried to give title compound 1. Single crystals weregrown from methanol by the slow evaporation method. Yield: Light orange powder (85%),mp 180-182 °C.
80%	In acetone at 20℃; for 2h;	4-[(3-Acetylphenyl)amino]-2-methylidene-4-oxobutanoic acid(3b) ITA (2) (0.112 g, 1 mmol) was dissolved in acetone(30 mL), and 3-amino acetophenone (0.135 g, 1 mmol)was added in small portions under stirring at room temperatureover time span of 30 min. The mixture becameyellow slurry. Stirring was continued for 1.5 h, after whichthe solution was filtered. The obtained solid was washedwith acetone and dried. The crude product was furtherpurified by recrystallization method, and single crystalswere grown from methanol by the slow evaporationmethod. The product was obtained as a light yellow solidwith 80 % yield. m.p. 180-182 °C; IR (KBr): νmax (cm-1),3282 (OH), 3055 (NH), 2900 (Ar-H), 2634 (aliphatic C-H)1685 (amide C=O), 1591 (C=C). 1H-NMR (400 MHz,DMSO-d6): δ ppm, 2.55 (3H, s, -CH3), 3.35(2H, s, O=CCH2),5.75 (1H, d, JAB = 1.6 Hz, HA), 6.18 (1H, d,JAB = 1.6 Hz, HB), 7.43-8.17 (4H, m, Ar-H), 10.23 (1H,s, NH), 12.55 (1H, s, OH). LCMS (m/z): 248 (M? ? 1).Calcd. for C13H13NO4: C, 63.15; H, 5.30; N, 5.67; Found:C, 63.13; H, 5.32; N, 5.65 %. XRD data: triclinic, P-1,a = 4.9485 (3) A ° , b = 5.3614 (6) A ° , c = 22.457 (2) A ° ,V = 592.77(9) A ° 3, Z = 2.
	In acetone at 20℃; for 2h;	Experimental Itaconic anhydride (0.112 g, 1 mmol) dissolved in a 30 mL acetoneand it was stirred at ambient temperature and 3-aminoacetophenone (0.135 g, 1 mmol) was added portion wise over 30 min.The mixture turned into pale yellow slurry. After stirring 1.5 h, the slurry was filtered. The solid was washed with acetone and dried to give the title compound. Single crystals were grown from methanol by the slow evaporation method. XRD analysis was done using a Bruker SMART APEXII equipped with an X’ calibur CCD area detector diffractometer. The structure was solved by direct method using the program SHELX97 [18] and were refined by least squares technique. The ORTEP diagram and crystal packing are shown in Figs. S1 and S2 (Supporting materials). In the crystal, moleculesare held together by strong N-H-O and O-H-O intermolecular interactions. The crystal data and parameters for structure refinement of the title compound and given in Table S1 (Supporting material). FT-IR spectrum (Fig. 1) was recorded on Shimadzu-FTIR infrared spectrometer and 1H NMR (400 MHz) spectrum was recorded on a Varian 400 spectrometer.1H NMR spectrum wasrecorded on a Varian 400 spectrometer.

Reference： [1]Nayak, Prakash S.; Narayana, Badiadka; Anthal, Sumati; Gupta, Vivek K.; Kant, Rajni; Yathirajan [Molecular Crystals and Liquid Crystals, 2014, vol. 592, # 1, p. 249 - 258]
[2]Nayak, Prakash S.; Narayana; Sarojini; Fernades, Jennifer; Bharath; Madhu [Medicinal Chemistry Research, 2015, vol. 24, # 12, p. 4191 - 4206]
[3]Raju, Rahul; Panicker, C. Yohannan; Nayak, Prakash S.; Narayana; Sarojini; Van Alsenoy; Al-Saadi, Abdulaziz A. [Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2015, vol. 134, p. 63 - 72]

37
[ 2170-03-8 ]
[ 2038-98-4 ]
2-((2,4-diphenyl-4H-1,2,4-triazol-3-yl)methyl)acrylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	In diethyl ether at 20℃; for 168h;	2-((2,4-diphenyl-4H-1,2,4-triazol-3-yl)methyl)acrylic acid (8) General procedure: Amidrazones 1-7 [1] and itaconic anhydride weredissolved in anhydrous diethyl ether prior to mixing them together at molarratio of 1:1 and left in ambient temperature for 7 days. Obtained precipitatewas collected by filtration and washed with anhydrous ether. Compounds 8-14 were purified by crystallizationfrom water.

Reference： [1]Paprocka, Renata; Wiese, Malgorzata; Eljaszewicz, Andrzej; Helmin-Basa, Anna; Gzella, Andrzej; Modzelewska-Banachiewicz, Bozena; Michalkiewicz, Jacek [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 13, p. 2664 - 2667]

38
[ 2170-03-8 ]
[ 14331-68-1 ]
2-((4-(4-nitrophenyl)-5-phenyl-4H-1,2,4-triazol-3-yl)methyl)acrylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	In diethyl ether at 20℃; for 168h;	2-((4-(4-nitrophenyl)-5-phenyl-4H-1,2,4-triazol-3-yl)methyl)acrylic acid (9) General procedure: Amidrazones 1-7 [1] and itaconic anhydride weredissolved in anhydrous diethyl ether prior to mixing them together at molarratio of 1:1 and left in ambient temperature for 7 days. Obtained precipitatewas collected by filtration and washed with anhydrous ether. Compounds 8-14 were purified by crystallizationfrom water.

Reference： [1]Paprocka, Renata; Wiese, Malgorzata; Eljaszewicz, Andrzej; Helmin-Basa, Anna; Gzella, Andrzej; Modzelewska-Banachiewicz, Bozena; Michalkiewicz, Jacek [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 13, p. 2664 - 2667]

39
[ 2170-03-8 ]
C₁₃H₁₄N₄ [ No CAS ]
2-((5-(pyridin-4-yl)-4-p-tolyl-4H-1,2,4-triazol-3-yl)methyl)acrylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	In diethyl ether at 20℃; for 168h;	2-((5-(pyridin-4-yl)-4-p-tolyl-4H-1,2,4-triazol-3-yl)methyl)acrylicacid (10) General procedure: Amidrazones 1-7 [1] and itaconic anhydride weredissolved in anhydrous diethyl ether prior to mixing them together at molarratio of 1:1 and left in ambient temperature for 7 days. Obtained precipitatewas collected by filtration and washed with anhydrous ether. Compounds 8-14 were purified by crystallizationfrom water.

Reference： [1]Paprocka, Renata; Wiese, Malgorzata; Eljaszewicz, Andrzej; Helmin-Basa, Anna; Gzella, Andrzej; Modzelewska-Banachiewicz, Bozena; Michalkiewicz, Jacek [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 13, p. 2664 - 2667]

40
[ 2170-03-8 ]
N₃-4-nitrophenyl-2-picolinamidrazone [ No CAS ]
2-methylidene-4-[2-[[(4-nitrophenyl)amino](pyridin-2-yl)methylidene]hydrazinyl]-4-oxobutanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	In diethyl ether at 20℃; for 2h;	General method for the preparationof compounds 5-8 General procedure: In each case, a mixture of amidrazone 1-4 (1 mmol) [20]and itaconic anhydride (1 mmol) was dissolved in 30 cm3anhydrous diethyl ether and stirred for 2 h at ambienttemperature. The obtained precipitates of 5-8 were collectedby filtration and washed with anhydrous diethylether. Compounds 5 and 6 were additionally purified bycrystallization from ethanol and ethanol-water mixture(1:1), respectively.
	In diethyl ether at 20℃; for 168h;	2-((4-(4-nitrophenyl)-5-(pyridin-2-yl)-4H-1,2,4-triazol-3-yl)methyl)acrylic acid(14) General procedure: Amidrazones 1-7 [1] and itaconic anhydride weredissolved in anhydrous diethyl ether prior to mixing them together at molarratio of 1:1 and left in ambient temperature for 7 days. Obtained precipitatewas collected by filtration and washed with anhydrous ether. Compounds 8-14 were purified by crystallizationfrom water.

Reference： [1]Paprocka, Renata; Wiese-Szadkowska, Małgorzata; Helmin-Basa, Anna; Mazur, Liliana; Kutkowska, Jolanta; Michałkiewicz, Jacek; Modzelewska-Banachiewicz, Bożena; Pazderski, Leszek [Monatshefte fur Chemie, 2018, vol. 149, # 8, p. 1493 - 1500]
[2]Paprocka, Renata; Wiese, Malgorzata; Eljaszewicz, Andrzej; Helmin-Basa, Anna; Gzella, Andrzej; Modzelewska-Banachiewicz, Bozena; Michalkiewicz, Jacek [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 13, p. 2664 - 2667]

41
[ 2170-03-8 ]
[ 479-27-6 ]
2-((1H-perimidin-2- yl)methyl)acrylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	In chloroform at 25℃; for 2h;	1 5.2. Synthesis of 2-substituted H-peremidines Itaconic anhydride (1 g, 0.004 mol) was added to a solution of NDA (0.6328 g, 0.004 mol) in 50 mL of chloroform, THF or ethyl acetate and the reaction mixture was stirred for 2 h. A pale yellow powder precipitated from the reaction mixture was filtered off, than washed with ethanol (200 ml) at continuous stirring for another 1 h in order to remove the unreacted residues, then filtered off again and dried in vacuum to a constant weight. The yields were 98% in CHCl3 and 89% in THF, and EtAc at room temperature. Slightly lower yield of 92% in CHCl3 was obtained at -78 °C; mp=215 °C; IR (ATR): 2100-3100 (hydrogen bonds), 1657 (C=O), 1548 (C-N) cm-1; 1H NMR (400 MHz, DMSO, δ, ppm): 3.24 (s, 2H)(1'), 5.76 (d, J=1.4 Hz, 1H)(2a'), 6.16 (d, J=1.4 Hz, 1H)(2a'), 6.37 (dd, J=7.4, 0.9 Hz, 2H)(4 and 9), 6.97 (dd, J=8.4, 0.9 Hz, 2H)(6 and 7), 7.08 (dd, J=8.3, 7.4 Hz, 2H)(5 and 8); 13C NMR (101 MHz, DMSO, δ, ppm): 167.5 (quart)(3'), 155.3 (quart)(2), 141.6 (3a and 9a)(quart), 136.3 (quart), 135.1 (quart)(6a), 128.2 (tert)(5 and 8), 126.9 (sec)(2a'), 121.4 (quart)(9b), 118.1 (tert)(6 and 7), 107.3 (tert)(4 and 9), 37.1 (sec)(1'); HRMS (DART+) calcd for [C15H13N2O2] 253.0977 found 253.09762.
	In chloroform at 20℃;

Reference： [1]Fernández-Gijón, César Augusto; Del Río-Portilla, Federico; Ríos-Jara, David; Fomine, Sergei; Santana, Guillermo; Alexandrova, Larissa [Tetrahedron, 2015, vol. 71, # 38, p. 7063 - 7069]
[2]Alexandrova, Larissa; Barba-Behrens, Noráh; Fernández-Gijón, César Augusto; Lagadec, Ronan Le; Olvera-Mancilla, Jessica; Rico-Bautista, Hugo; Toscano, Rubén A. [Journal of Molecular Structure, 2022, vol. 1252]

42
[ 2170-03-8 ]
[ 99-92-3 ]
4-[(4-acetylphenyl)amino]-2-methylidene-4-oxobutanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	at 20℃;
84%	In acetone at 20℃; for 2h;	4-[(4-Acetylphenyl)amino]-2-methylidene-4-oxobutanoicacid (3a) ITA (2) (0.112 g, 1 mmol) was dissolved inacetone (30 mL), and 4-amino acetophenone (0.135 g, 1 mmol) was added in small portions under stirring at roomtemperature over time span of 30 min. The mixture becameyellow slurry. Stirring was continued for 1.5 h, after whichthe solution was filtered. The solid obtained was washedwith acetone and dried. The crude product was furtherpurified by recrystallization method, and single crystalswere grown from methanol by the slow evaporation. Theproduct was obtained as a light yellow solid with a yield of84 %, m.p. 188-190 °C; IR (KBr): νmax (cm-1), 3282(OH), 3055 (NH), 2900 (Ar-H), 2634 (aliphatic C-H) 1685(amide C=O), 1650 (acid C=O), 1591 (C=C). 1H-NMR(400 MHz, DMSO-d6): δ ppm, 2.53 (3H, s, CH3), 3.35(2H, s, O=C-CH2), 5.75 (1H, d, JAB = 1.6 Hz, HA), 6.18(1H, d, JAB = 1.6 Hz, HB), 7.69-7.93 (4H, m, Ar-H),10.37 (1H, s, NH), 12.57 (1H, s, OH). LCMS (m/z): 248(M? ? 1). Calcd. for C13H13NO4: C, 63.15; H, 5.30; N,5.67; Found: C, 63.13; H, 5.32; N, 5.65 %. XRD data:triclinic, P 1; a = 5.0164(5) A ° , b = 5.2908(4) A ° ,c = 21.8464(18) A ° , V = 575.67(8) A ° 3, Z = 2.
	In acetone for 2h;	3-Methylidenedihydrofuran-2,5-dione (0.112g, 1mmol) and 30ml acetone were mixed together and stirred at ambient temperature. To this mixture, 4-aminoacetophenone (0.135g, 1mmol) in 20mL acetone was added over 30min. After stirring for 1.5h the slurry was filtered, washed with acetone and dried to give the title compound. The FT-IR (Fig.S1-supporting material) and FT-Raman spectra (Fig.S2-supporting material) were obtained on a DR/Jasco FT-IR spectrometer and on a Bruker RFS 100/s, Germany.

In chloroform at 20℃; for 2h;

Reference： [1]Mary, Sheena Y.; Al-Abdullah, Ebtehal S.; Aljohar, Haya I.; Narayana, Badiadka; Nayak, Prakash S.; Sarojini, Baladka K.; Armaković, Stevan; Armaković, Sanja J.; Alsenoy, Christian Van; El-Emam, Ali A. [Journal of the Serbian Chemical Society, 2018, vol. 83, # 1, p. 1 - 18]
[2]Nayak, Prakash S.; Narayana; Sarojini; Fernades, Jennifer; Bharath; Madhu [Medicinal Chemistry Research, 2015, vol. 24, # 12, p. 4191 - 4206]
[3]Mary, Y. Sheena; Mary, Y. Shyma; Panicker, C. Yohannan; Armaković, Stevan; Armaković, Sanja J.; Narayana; Sarojini; Van Alsenoy [Journal of Molecular Structure, 2017, vol. 1148, p. 266 - 275]
[4]Konstantinović, Jelena; Yahiaoui, Samir; Alhayek, Alaa; Haupenthal, Jörg; Schönauer, Esther; Andreas, Anastasia; Kany, Andreas M.; Müller, Rolf; Koehnke, Jesko; Berger, Fabian K.; Bischoff, Markus; Hartmann, Rolf W.; Brandstetter, Hans; Hirsch, Anna K. H. [Journal of Medicinal Chemistry, 2020, vol. 63, # 15, p. 8359 - 8368]

43
[ 623-17-6 ]
[ 2170-03-8 ]
C₁₂H₁₂O₆ [ No CAS ]
C₁₂H₁₂O₆ [ No CAS ]
C₁₂H₁₂O₆ [ No CAS ]
C₁₂H₁₂O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	at 20℃;	An excess amount of the furan (ca. 20 equiv) was added to a capped flask containing 1 (1 equiv) to form a slurry. The mixture was allowed to stir at room temperature. Aliquots of the mixture were periodically removed in order to monitor the progress of the DA reaction by 1H NMR analysis, that was carried out immediately after each NMR sample was prepared. To obtain useful signal to noise levels of the 1H NMR resonances for the minor amounts of product often being observed, relatively concentrated solutions of CDCl3 NMR samples were used. The percent conversion to DA adducts was recorded as the equilibrium conversion in Table 10. When the relative amounts of observed species remained constant in two consecutive aliquots, it was deemed that equilibrium had been reached. The reaction time required to reach half of the equilibrium conversion is provided as t1/2 in Table 10. FIGS. 4-7 display the final equilibrium 1H NMR spectrum for each of the reactions shown in entries 1-4 of Table 10. 2-Acetoxymethylfuran (10) was another diene substrate that was studied (Table 10, entry 4). At equilibrium, the IA DA adducts 11 were formed, again to an extent intermediate between that of 4 vs. 7. This was observed to be the slowest of all reactions we studied, consistent with the acetoxymethyl substituent having weakly electron withdrawing character. As was the case for 9, at equilibrium the distal isomers predominated. The assignments of structure to the distal vs. proximal substitution patterns among the isomers of 9 and 11 were based on the difference in coupling patterns of the resonances for the bridgehead protons (at C4) in each (see SI). HMQC and HMBC NMR analyses also were consistent with these assignments.

Reference： [1]Organic Letters,2016,vol. 18,p. 2584 - 2587
[2]Patent: US2017/291906,2017,A1 .Location in patent: Paragraph 0335; 0343; 0346

44
[ 98-00-0 ]
[ 2170-03-8 ]
(±)-2-((3aR,6R,7aR)-1-oxo-6,7-dihydro-3H-3a,6-epoxyisobenzofuran-7a(1H)-yl)acetic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	at 23℃;
70%	at 23℃; for 48h;	1.B.B Preparation of (+-)-2-((3aR,6R,7aR)-1-oxo-6,7-dihydro-3H-3a,6-epoxyisobenzofuran-7a(1H)-yl) acetic acid (14) Preparation of (+-)-2-((3aR,6R,7aR)-1-oxo-6,7-dihydro-3H-3a,6-epoxyisobenzofuran-7a(1H)-yl) acetic acid (14) Method A: Itaconic anhydride (1, 3.0 g, 26.7 mmol) was suspended in furfuryl alcohol (2, 2.3 mL, 2.6 g, 26.7 mmol) and this slurry was allowed to stir (magnetically) at ambient temperature. After approximately five hours, the suspension had thickened to a paste and could no longer be stirred. After approximately 12 hours, this mixture had turned to a solid light brown mass. The lactone 14 could be stored indefinitely as a tan crystalline solid. Method B: Itaconic anhydride (1, 1.5 g, 13.3 mmol) was added to furfuryl alcohol (2, 2.3 mL, 2.6 g, 26.7 mmol). This slurry was allowed to stir (magnetically) at ambient temperature and it turned into a clear solution in 30 minutes. After five hours, lactone acid 14 began to precipitate from this solution. After 48 hours the slurry was filtered and the solid was washed with 5 mL of dichloromethane to give 14 as a white solid (1.97 g, 70%). 1H NMR (500 MHz, CDCl3, sparingly soluble) δ 6.59 (dd, J=5.8, 1.7 Hz, 1H, H15), 6.49 (d, J=5.8 Hz, 1H, H4), 5.06 (dd, J=4.7, 1.6 Hz, 1H, H6), 4.83 (d, J=10.8 Hz, 1H, C3HaHb), 4.64 (d, J=10.8 Hz, 1H, C3HaHb), 2.58 (dd, J=12.3, 4.7 Hz, 1H, C7HendoHexo), 2.54 (d, J=15.1 Hz, 1H, C8HaHb), 2.40 (d, J=15.1 Hz, 1H, C8HaHb), and 1.52 (d, J=12.3 Hz, 1H, C7HendoHexo). 1H NMR (500 MHz, acetone-d6) δ 6.62 (dd, J=5.8, 1.5 Hz, 1H, H5), 6.59 (d, J=5.8 Hz, 1H, H4), 5.03 (dd, J=4.7, 1.3 Hz, 1H, H6), 4.94 (d, J=10.8 Hz, 1H, C3HaHb), 4.51 (d, J=10.8 Hz, 1H, C3HaHb), 2.44 (d, J=15.0 Hz, 1H, C8HaHb), 2.39 (d, J=15.0 Hz, 1H, C8HaHb), 2.35 (dd, J=12.2, 4.8 Hz, 1H, C7HexoHendo), and 1.58 (d, J=12.2 Hz, 1H, C7HexoHendo). 13C NMR (125 MHz, acetone-d6) δ 177.8, 171.2, 139.0, 131.5, 95.1, 79.6, 69.1, 52.6, 40.2, and 37.4. IR (neat): 3300-2500 (br), 2994, 1705, 1397, 1324, 1154, 974, 709, and 646 cm-1. HRMS (ESI-TOF): Calcd for C10H9O5 [M-1-] requires 209.0455; found 209.0453. mp: 137-139° C.
68%	In neat (no solvent) at 25℃; for 24h;

68%

In neat (no solvent) at 20℃; for 24h;

4.2.1. 2-[(1S*,5S*,7S*)-4-oxo-3,10-dioxatricyclo[5.2.1.0^1,5]dec-8-en-5-yl]acetic acid (12) Acid 12 was prepared from itaconic anhydride and furfuryl alcohol using either of the procedures described below. Solvent free: Itaconic anhydride (3.0 g, 27 mmol, 1.0 eq.) was suspended in furfuryl alcohol (2.3 mL, 27 mmol, 1.0 eq.), the slurry obtained was allowed to stir at ambient temperature. After circa 5 h, the suspension had thickened to a paste which could no longer be stirred. The reaction mixture was left for a further 19 h until a tan solid had formed. The crude material was then purified by recrystallization from acetone to give the target acid 12 as an off-white crystalline solid (3.8 g, 68%). Reaction solvent: Itaconic anhydride (25.0 g, 223 mmol, 1.0 eq.) and furfuryl alcohol (19.4 mL, 223 mmol, 1.0 eq.) were suspended in acetonitrile (12 mL) and the slurry allowed to stir at ambient temperature, after 24 h a white suspension had formed. The solid was removed by filtration and the filtrate was concentrated in vacuo. The concentrated filtrate was suspended in EtOAc (100 mL) and filtered. The obtained solids were combined and recrystallized from acetone, to give the target acid 12 as an off-white crystalline solid (20.0 g, 43%). m.p. 130.9-131.5 C°; IR (Neat) νmax 3100 (m), 1776 (s) and 1733 (s) cm-1; 1H NMR (400 MHz, CD3OD): δ 6.59 (dd, J = 5.9, 1.7 Hz, 1H, 1-H), 6.55 (d, J = 5.9 Hz, 1H, 2-H), 5.02 (dd, J = 4.7, 1.6 Hz, 1H, 6-H), 4.92 (d, J = 10.8 Hz, 1H, 7-H), 4.54 (d, J = 10.8 Hz, 1H, 7-H), 2.44-2.35 (m, 3H, 5/9-H), 1.55 (d, J = 12.3 Hz, 1H, 5-H); 13C NMR (100 MHz, CD3OD): δ 180.0 (8), 173.0 (10), 139.3 (1), 131.5 (2), 95.6 (3), 80.1 (6), 70.0 (7), 53.3 (4), 40.7 (9), 37.7 (5); HRMS (ESI) m/z calculated for C10H10NaO5 233.0420 (M+Na)+, found 233.0417, 1.2 ppm error. Data is consistent with previously reported characterization data [36].

Reference： [1]Pehere, Ashok D.; Xu, Shu; Thompson, Severin K.; Hillmyer, Marc A.; Hoye, Thomas R. [Organic Letters, 2016, vol. 18, # 11, p. 2584 - 2587]
[2]Current Patent Assignee: UNIVERSITY OF MINNESOTA SYSTEM - US2017/291906, 2017, A1 Location in patent: Paragraph 0238-0247
[3]Bai, Yinjuan; De Bruyn, Mario; Clark, James H.; Dodson, Jennifer R.; Farmer, Thomas J.; Honoré, Mathilde; Ingram, Ian D. V.; Naguib, Mohamed; Whitwood, Adrian C.; North, Michael [Green Chemistry, 2016, vol. 18, # 14, p. 3945 - 3948]
[4]Lawrenson, Stefan B.; Pearce, Amanda K.; Hart, Sam; Whitwood, Adrian C.; O'Reilly, Rachel K.; North, Michael [Tetrahedron, 2021, vol. 77]

45
[ 2170-03-8 ]
[ 50446-17-8 ]
3'-benzoyl-2'-phenyl-2',3'-dihydrospiroisoxazolino[5':3]succinic anhydride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	Stage #1: itaconic acid anhydride; C-benzoyl-N-phenylnitrone With hydroquinone In ethyl acetate at 20℃; for 24h; Inert atmosphere; Schlenk technique; Stage #2: In diethyl ether Inert atmosphere; Schlenk technique; Sonication; stereospecific reaction;	cycloadditions of 3-methylenedihydro-(3H)-furan-2-one (1) and itaconic anhydride (2) with C-aroyl-N-phenylnitrones (7a-d) General procedure: In a Schlenk tube were added 5 mmol of methylene-lactone (1-2), 5 mmol of C-aroyl-N-phenylnitrones (7a-d), 0.05 g (0.45 mmol) of hydroquinone and 20 mL of EtOAc. The mixture was stirred at room temperature for 24 h under nitrogen atmosphere and the solvent removed under reduced pressure leading to a crude oil. For spiroheterocyles (19), EtOH (20 mL) was added to the crude oil and the mixture subjected to ultrasonication. The resulting solids were recrystallised from EtOH. For spiroheterocycles (20), Et20 (20 mL) was added to the crude oil and the mixture was subjected to ultrasonication. The resulting solids were recrystallised from a mixture of CH2Cl2-Et20 (1:1).

Reference： [1]Roussel, Christophe; Ciamala, Kabula; Vebrel, Joël; Riche, Claude [Heterocycles, 2009, vol. 78, # 8, p. 1977 - 1991]

46
[ 2170-03-8 ]
C₁₅H₁₃NO₂ [ No CAS ]
3'-(4-methylbenzoyl)-2'-phenyl-2',3'-dihydrospiroisoxazoino[5':3]succinic anhydride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	Stage #1: itaconic acid anhydride; C₁₅H₁₃NO₂ With hydroquinone In ethyl acetate at 20℃; for 24h; Inert atmosphere; Schlenk technique; Stage #2: In diethyl ether Inert atmosphere; Schlenk technique; Sonication; stereospecific reaction;	cycloadditions of 3-methylenedihydro-(3H)-furan-2-one (1) and itaconic anhydride (2) with C-aroyl-N-phenylnitrones (7a-d) General procedure: In a Schlenk tube were added 5 mmol of methylene-lactone (1-2), 5 mmol of C-aroyl-N-phenylnitrones (7a-d), 0.05 g (0.45 mmol) of hydroquinone and 20 mL of EtOAc. The mixture was stirred at room temperature for 24 h under nitrogen atmosphere and the solvent removed under reduced pressure leading to a crude oil. For spiroheterocyles (19), EtOH (20 mL) was added to the crude oil and the mixture subjected to ultrasonication. The resulting solids were recrystallised from EtOH. For spiroheterocycles (20), Et20 (20 mL) was added to the crude oil and the mixture was subjected to ultrasonication. The resulting solids were recrystallised from a mixture of CH2Cl2-Et20 (1:1).

Reference： [1]Roussel, Christophe; Ciamala, Kabula; Vebrel, Joël; Riche, Claude [Heterocycles, 2009, vol. 78, # 8, p. 1977 - 1991]

47
[ 2170-03-8 ]
[ 99391-08-9 ]
3'-(4-methoxybenzoyl)-2'-phenyl-2',3'-dihydrospiroisoxazolino[5':3]succinic anhydride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	Stage #1: itaconic acid anhydride; N-phenyl-C-(4-methoxybenzoyl)nitrone With hydroquinone In ethyl acetate at 20℃; for 24h; Inert atmosphere; Schlenk technique; Stage #2: In diethyl ether Inert atmosphere; Schlenk technique; Sonication; stereospecific reaction;	cycloadditions of 3-methylenedihydro-(3H)-furan-2-one (1) and itaconic anhydride (2) with C-aroyl-N-phenylnitrones (7a-d) General procedure: In a Schlenk tube were added 5 mmol of methylene-lactone (1-2), 5 mmol of C-aroyl-N-phenylnitrones (7a-d), 0.05 g (0.45 mmol) of hydroquinone and 20 mL of EtOAc. The mixture was stirred at room temperature for 24 h under nitrogen atmosphere and the solvent removed under reduced pressure leading to a crude oil. For spiroheterocyles (19), EtOH (20 mL) was added to the crude oil and the mixture subjected to ultrasonication. The resulting solids were recrystallised from EtOH. For spiroheterocycles (20), Et20 (20 mL) was added to the crude oil and the mixture was subjected to ultrasonication. The resulting solids were recrystallised from a mixture of CH2Cl2-Et20 (1:1).

Reference： [1]Roussel, Christophe; Ciamala, Kabula; Vebrel, Joël; Riche, Claude [Heterocycles, 2009, vol. 78, # 8, p. 1977 - 1991]

48
[ 2170-03-8 ]
[ 22269-68-7 ]
3'-(4-nitrobenzoyl)-2'-phenyl-2',3'-dihydrospiroisoxazolino[5':3]succinic anhydride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	Stage #1: itaconic acid anhydride; N-phenyl-C-(4-nitrobenzoyl)nitrone With hydroquinone In ethyl acetate at 20℃; for 24h; Inert atmosphere; Schlenk technique; Stage #2: In diethyl ether Inert atmosphere; Schlenk technique; Sonication; stereospecific reaction;	cycloadditions of 3-methylenedihydro-(3H)-furan-2-one (1) and itaconic anhydride (2) with C-aroyl-N-phenylnitrones (7a-d) General procedure: In a Schlenk tube were added 5 mmol of methylene-lactone (1-2), 5 mmol of C-aroyl-N-phenylnitrones (7a-d), 0.05 g (0.45 mmol) of hydroquinone and 20 mL of EtOAc. The mixture was stirred at room temperature for 24 h under nitrogen atmosphere and the solvent removed under reduced pressure leading to a crude oil. For spiroheterocyles (19), EtOH (20 mL) was added to the crude oil and the mixture subjected to ultrasonication. The resulting solids were recrystallised from EtOH. For spiroheterocycles (20), Et20 (20 mL) was added to the crude oil and the mixture was subjected to ultrasonication. The resulting solids were recrystallised from a mixture of CH2Cl2-Et20 (1:1).

Reference： [1]Roussel, Christophe; Ciamala, Kabula; Vebrel, Joël; Riche, Claude [Heterocycles, 2009, vol. 78, # 8, p. 1977 - 1991]

49
[ 2170-03-8 ]
[ 54468-53-0 ]
[ 54468-52-9 ]

Yield	Reaction Conditions	Operation in experiment
80%	With ammonium hydroxide In water at 3 - 10℃;	In an exemplary embodiment, ammonium hydroxide (28%, 157 mL, 2.3 moles) can be placed in a 1 Liter-3-neck Morton flask. The flask can be placed in an ice bath to cool the solution to 3° C. Once cooled, dihydro-3-methylene-2,5-furandione (102 g, 0.9099 moles) can be added in 5 gram portions as a solid in order to maintain the reaction temperature at or below 10° C. After the reaction is complete, the solution can be evaporated to near dryness and then additional water (50 mL) can be added and the solution can be evaporated again. This can be repeated until the pH of the aqueous solution tests to pH 4.5. At this point, ethanol (100 mL) can be added and the mixture can be evaporated to dry the product by azeotropic distillation. The resulting solid (117 grams, 99% yield) can be stirred in ethanol to separate the minor 4-amino-3-methylene-4-oxo-butanoic acid product, which is soluble in ethanol. The target 4-amino-2-methylene-4-oxo-butanoic acid solid product can be filtered and dried in a vacuum oven to yield 93 grams (80% yield) of a colorless solid. It should be understood that the amounts, sizes, and temperatures provided in this example are only intended to be illustrative and are not intended to limit the scope of the possible embodiments. Other amounts, sizes, and temperatures may be used in other embodiments.

Reference： [1]Current Patent Assignee: MILLENNIUM ENTPR; MILLENNIUM ENTERPRISES - US2017/197908, 2017, A1 Location in patent: Paragraph 0035

50
[ 107-10-8 ]
[ 2170-03-8 ]
itaconic acid 4-propylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	With sulfuric acid In dichloromethane at 20℃; Cooling with ice;	2 Synthesis of itaconic acid 4-propyl-amide. Itaconic anhydride (5.0 g, 44.6 mmol) was dissolved in dichloromethane (DCM) (20 mL) and H2SO4 (conc., 0.1 mL) was added. The solution was ice cooled for 15 min. Then the n-propylamine (4.0 mL, 2.9 g, 49.1 mmol, 1.1 eq) in DCM (10 mL) was added dropwise over 30 min. After another 10 min the ice bath was removed and the solution was stirred overnight at room temperature. Subsequently the precipitate (pure product) was removed by filtration and dried at dynamic vacuum overnight. The product was obtained as colorless solid. The structure of the obtained monomer and the proton numbering for 1H-NMR assignment are shown below. (0184) (0185) Yield: 3.9 g; 22.8 mmol; 50% (0186) MS (ESI, 4-5 kV): m/z = [M+Na] = 194.08 (0187) 1H NMR (250 MHz, Acetone-d6): δ = 11.46 (br. s, OH), 7.24 (br. s., NH), 6.22 (s, 1-H), 5.73 (s, 1’-H), 3.24 (s, 3-CH2), 3.17 (td, J=6.50 Hz, 5-CH2), 1.51 (tq, J=7.30 Hz, 6-CH2), 0.90 (t, J=7.42 Hz, 7-CH3). (0188) 13C NMR (63 MHz, Acetone-d6): ? = 170.22 (s, 4-CO), 167.57 (s, 2’-CO), 136.42 (s, 2-C), 127.38 (s, 1-C), 41.18 (s, 5-C), 39.40 (s, 3-C), 22.92 (s, 6-C), 11.13 (s, 7-C).

Reference： [1]Current Patent Assignee: ALBERT-LUDWIGS-UNIVERSITÄT FREIBURG - WO2018/91467, 2018, A2 Location in patent: Page/Page column 50

51
[ 2170-03-8 ]
N₃-(2-pyridyl)-2-picolinamidrazone [ No CAS ]
2-methylidene-4-oxo-4-[2-[pyridin-2-yl(pyridin-2-ylamino)methylidene]hydrazinyl]butanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	In diethyl ether at 20℃; for 2h;	General method for the preparationof compounds 5-8 General procedure: In each case, a mixture of amidrazone 1-4 (1 mmol) [20]and itaconic anhydride (1 mmol) was dissolved in 30 cm3anhydrous diethyl ether and stirred for 2 h at ambienttemperature. The obtained precipitates of 5-8 were collectedby filtration and washed with anhydrous diethylether. Compounds 5 and 6 were additionally purified bycrystallization from ethanol and ethanol-water mixture(1:1), respectively.

Reference： [1]Paprocka, Renata; Wiese-Szadkowska, Małgorzata; Helmin-Basa, Anna; Mazur, Liliana; Kutkowska, Jolanta; Michałkiewicz, Jacek; Modzelewska-Banachiewicz, Bożena; Pazderski, Leszek [Monatshefte fur Chemie, 2018, vol. 149, # 8, p. 1493 - 1500]

52
[ 76686-90-3 ]
[ 2170-03-8 ]
2-methylidene-4-[2-[[(4-methylphenyl)amino](pyridin-2-yl)methylidene]hydrazinyl]-4-oxobutanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	In diethyl ether at 20℃; for 2h;	General method for the preparationof compounds 5-8 General procedure: In each case, a mixture of amidrazone 1-4 (1 mmol) [20]and itaconic anhydride (1 mmol) was dissolved in 30 cm3anhydrous diethyl ether and stirred for 2 h at ambienttemperature. The obtained precipitates of 5-8 were collectedby filtration and washed with anhydrous diethylether. Compounds 5 and 6 were additionally purified bycrystallization from ethanol and ethanol-water mixture(1:1), respectively.

Reference： [1]Paprocka, Renata; Wiese-Szadkowska, Małgorzata; Helmin-Basa, Anna; Mazur, Liliana; Kutkowska, Jolanta; Michałkiewicz, Jacek; Modzelewska-Banachiewicz, Bożena; Pazderski, Leszek [Monatshefte fur Chemie, 2018, vol. 149, # 8, p. 1493 - 1500]

53
[ 2170-03-8 ]
[ 14331-68-1 ]
2-methylidene-4-[2-[[(4-nitrophenyl)amino](phenyl)methylidene]hydrazinyl]-4-oxobutanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	In diethyl ether at 20℃; for 2h;	General method for the preparationof compounds 5-8 General procedure: In each case, a mixture of amidrazone 1-4 (1 mmol) [20]and itaconic anhydride (1 mmol) was dissolved in 30 cm3anhydrous diethyl ether and stirred for 2 h at ambienttemperature. The obtained precipitates of 5-8 were collectedby filtration and washed with anhydrous diethylether. Compounds 5 and 6 were additionally purified bycrystallization from ethanol and ethanol-water mixture(1:1), respectively.

Reference： [1]Paprocka, Renata; Wiese-Szadkowska, Małgorzata; Helmin-Basa, Anna; Mazur, Liliana; Kutkowska, Jolanta; Michałkiewicz, Jacek; Modzelewska-Banachiewicz, Bożena; Pazderski, Leszek [Monatshefte fur Chemie, 2018, vol. 149, # 8, p. 1493 - 1500]

54
[ 61-54-1 ]
[ 2044-64-6 ]
[ 2170-03-8 ]
C₂₁H₂₅N₃O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	Stage #1: tryptamine; N,N-Dimethylacetoacetamid In chloroform at 50℃; for 24h; Molecular sieve; Stage #2: itaconic acid anhydride In 1,4-dioxane at 40℃; for 7h; Stage #3: With hydrogenchloride In 1,4-dioxane at 40℃; for 3h;	1.1 (1) 2 -((1S,3R,12bS)-1-(dimethylaminomethyl)-12bmethyl-4-oxo-1,2,3,4,6,7,12,12b-Arhydroindole [2,3-a]quinolizin-3-yl)acetic acid (preparation of intermediate 1) Dissolve 160 mg of tryptamine in 5 mL of chloroform and add 129 mg of N,N-dimethylacetoacetamide and 500 mg of 4 Å molecular sieve.The reaction system was heated at 50 ° C for 24 hours, and the temperature of the reaction system was lowered to room temperature.The molecular sieve is removed by filtration, and the filtrate is concentrated in vacuo to obtain a crude product;To the crude product were added 112 mg of itaconic anhydride and 3 mL of 1,4-dioxane. The reaction mixture was heated at 40 ° C for 7 hours.Then 0.39 mL of a 4 M hydrochloric acid / 1,4-dioxane solution was added dropwise.The reaction was continued at the same temperature for 3 hours.The reaction mixture was then diluted with 20 mL of ethyl acetate and extracted twice with distilled water.The organic phase was combined, washed twice with brine brine, dried over anhydrous sodium sulfateThe crude product was purified by silica gel chromatography.The product was obtained in 280 mg.The eluent is CH2Cl2/MeOH = 20:1 (volume ratio);The reaction yield was 73%;The product is a white solid at room temperature.Melting point 115.3-115.6 ° C.

Reference： [1]Current Patent Assignee: FUZHOU UNIVERSITY - CN107629052, 2018, A Location in patent: Paragraph 0013

55
[ 2170-03-8 ]
[ 106797-53-9 ]
[ 121-44-8 ]
C₁₇H₂₀O₇*C₆H₁₅N [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		The structural formula of compound 3 is:2-hydroxy-1-(4-(2-hydroxyethoxy)phenyl)-2-methylacetone (Darocur 2959)(33.69g, 0.15mol),Itaconic anhydride (11.22g, 0.1mol),The catalyst anhydrous AlCl3 (10.67, 0.08 mol) and 800 ml of toluene solution were placed in a 250 ml three-necked flask equipped with a mechanical stirring and constant pressure dropping funnel, and stirred at 90 C for 60 min.After the reaction is completed, the solid impurities are removed by filtration, washed with water, separated by liquid three times to remove the aqueous phase, and the toluene is removed by rotary evaporation, and finally the solvent and water are removed by vacuum drying to obtain an intermediate product A;Intermediate III and triethylamine (10.22 g, 0.1 mol) dissolved in 60 ml of carbon tetrachlorideAdd to a 250 ml three-necked flask equipped with a mechanical stirrer and a constant pressure dropping funnel.Stir at room temperature for 16 h.After completion of the reaction, the mixture was washed three times with hydrochloric acid or ethyl acetate, and the solvent was evaporated to dryness, and further purified by gel column separation to obtain the pure product 3, and the structure was identified by nuclear magnetic resonance spectroscopy.

Reference： [1]Patent: CN109384670,2019,A .Location in patent: Paragraph 0027-0031

56
[ 2170-03-8 ]
[ 106-40-1 ]
1-(4-bromophenyl)-3-methylenepyrrolidine-2,5-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	Stage #1: itaconic acid anhydride; 4-bromo-aniline In diethyl ether; dichloromethane for 5h; Inert atmosphere; Stage #2: With sodium acetate; acetic anhydride at 100℃; for 0.5h; Inert atmosphere;	General Procedure for the synthesis of N-arylitaconimides 1a-d. General procedure: A solution of 5.6 g (5 mmol) of itaconic anhydride and 5 mmol of corresponding aniline in a mixture of dichloromethane (80 ml) and diethylether (150 ml) was stirred during 5 hours. The precipitate was filtered off and dried. Then acetic anhydride (40 ml) and sodium acetate (2.5 g) was added and the mixture was heated at 100 °C during 30 min. Reaction mixture was poured into cold water and the precipitate was filtered off and recrystallized from a mixture of benzene-ethanol.
	Stage #1: itaconic acid anhydride; 4-bromo-aniline In diethyl ether at 0 - 5℃; for 3h; Stage #2: With sodium acetate; acetic anhydride for 0.5h;	2.2. Synthesis of Itaconimide Derivatives. All N-(substitutedphenyl)itaconimide derivatives (N-(RPh)IM) were prepared by two steps described by Adam [6]. In the 2rst step, 1 mol of itaconic anhydride was dissolved in dry diethyl ether and then,1 mol of the primary amine dissolved in the same solvent was slowly added to the itaconic anhydride at 0-5°C for 3 hours. The resulted acid N-(substituted phenyl)itaconic acid was filtered,washed, and dried. The following step was cyclization which occurred by adding acetic acid anhydride and fused sodium acetate in a steam bath for 30 minutes. The resulted monomer was crystallized from aqueous ethanol. Table 1 shows the melting points of prepared itaconimide derivatives

Reference： [1]Teterina, Polina S.; Efremova, Mariia M.; Sirotkina, Ekaterina V.; Novikov, Alexander S.; Khoroshilova, Olesya V.; Molchanov, Alexander P. [Tetrahedron Letters, 2019, vol. 60, # 39]
[2]Elsharif, Asma M.; Al-Ghamdi, Azza A.; Abdel-Naby, Abir S. [Journal of Chemistry, 2019, vol. 2019]

57
[ 2170-03-8 ]
[ 626-43-7 ]
[ 26958-82-7 ]

Yield	Reaction Conditions	Operation in experiment
60%	Stage #1: itaconic acid anhydride; 3,5-Dichloroaniline In diethyl ether; dichloromethane for 5h; Inert atmosphere; Stage #2: With sodium acetate; acetic anhydride at 100℃; for 0.5h; Inert atmosphere;	General Procedure for the synthesis of N-arylitaconimides 1a-d. General procedure: A solution of 5.6 g (5 mmol) of itaconic anhydride and 5 mmol of corresponding aniline in a mixture of dichloromethane (80 ml) and diethylether (150 ml) was stirred during 5 hours. The precipitate was filtered off and dried. Then acetic anhydride (40 ml) and sodium acetate (2.5 g) was added and the mixture was heated at 100 °C during 30 min. Reaction mixture was poured into cold water and the precipitate was filtered off and recrystallized from a mixture of benzene-ethanol.

Reference： [1]Teterina, Polina S.; Efremova, Mariia M.; Sirotkina, Ekaterina V.; Novikov, Alexander S.; Khoroshilova, Olesya V.; Molchanov, Alexander P. [Tetrahedron Letters, 2019, vol. 60, # 39]

58
[ 2350-01-8 ]
[ 2170-03-8 ]
[ 784169-58-0 ]

Yield	Reaction Conditions	Operation in experiment
38%	Stage #1: 4-aminotriphenylamine; itaconic acid anhydride In ethyl acetate at 50℃; for 2h; Stage #2: With sodium acetate; acetic anhydride at 80℃; for 13h;	1-(4-(diphenylamino)phenyl)-itaconimide (Dye 2) Itaconic anhydride(0.56 g, 5 mmol) and acetone (10 mL) were added to a 100 mLflask, and the solution was heated to 50 °C. An acetone solution (8 mL)of 4-aminotriphenylamine (0.98 g, 3.5 mmol) was added dropwise to thereaction flask, and the mixture was reacted at 50 °C for 2 h. The reactionmixture was filtered to give yellow precipitate. After drying undervacuum, the yellow precipitate was added to a 100 mL flask. Sodiumacetate (0.42 g) and acetic anhydride (4.4 mL) were also added, thereaction mixture was heated to 80 °C for 13 h. After cooling to roomtemperature, the red solution was poured to deionized water (300 mL).The product was extracted by dichloromethane for three times and driedby anhydrous magnesium sulfate. The dichloromethane solution wasconcentrated under reduced pressure. The crude product was purified bysilica gel column chromatography with dichloromethane/n-hexane (4/3, v/v) as eluent to give yellow solid (0.47 g) with a yield of 38%. 2 wasrecrystallized three times from hexane/dichloromethane (4/1, v/v) toyield yellow crystals. Mp: 159-160 °C. 1H NMR (400 MHz, CDCl3, ppm): δ = 3.51 (t, J = 2.1, 2.4Hz, 2H, -COCH2-), 5.74 (t, J = 1.5, 2.1Hz, 1H,=CHH), 6.48 (t, J = 2.4, 2.1Hz, 1H, =CHH), 7.07 (t, J = 7.53Hz, 2H,ArH), 7.11-7.31 (m, 12H, ArH). 13C NMR (DMSO-d6, ppm): δ = 33.82,119.8, 122.3, 123.6, 124.2, 124.5, 128.0, 129.7, 134.4, 146.9, 168.7,147.1, 173.4. IR (KBr pellet, cm -1): 516, 615, 694, 756, 831, 888, 951,1145, 1275, 1322, 1384, 1500, 1588, 1658, 1714, 2925. HRMS (APCI,Fig. S8): m/z calcd for C23H18N2O2[M+H]+: 355.1441; Found:355.1444.

Reference： [1]Gong, Junbo; Wang, Ying; Zhang, Qi; Zhang, Xin [Dyes and Pigments, 2021, vol. 184]

59
[ 2170-03-8 ]
[ 3182-93-2 ]
(S)-4-((1-ethoxy-1-oxo-3-phenylpropan-2-yl)amino)-2-methylene-4-oxobutanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With potassium carbonate In tetrahydrofuran at 0℃; for 16h;	5 (S)-4-((1-Ethoxy-1-oxo-3-phenylpropan-2-yl)amino)-2-methylene-4-oxobutanoic acid (IS-100-127) Itaconic anhydride (50 mg, 0.45 mmol) was dissolved in anhydrous THF (5 mL) and solid potassium carbonate (0.19 g, 1.34 mmol) followed by L-phenylalanine ethyl ester hydrochloride (0.1 g, 0.45 mmol) were added. Reaction mixture was stirred at room temperature for 16 hours. Volatiles were then evaporated, residue was redissolved in DCM (30 mL) and extracted with 1M aqueous HC1 (10 mL) and brine (10 mL). The organic phase was dried over Na2SO4, volatiles were evaporated and the residue was subjected to final purification on a reverse phase HPLCto afford 100 mg (73 %) of the desired compound as a colorless semi-solid.NMR (401 MHz, DMSO-d6):δH1.25 (t, J = 7.1 Hz, 3H), 3.13 (dd, J = 13.9, 5.9 Hz, 2H), 3.28 (s, 2H), 4.18 (q, J = 7.2 Hz, 2H), 4.86 (dt, J = 7.8, 6.0 Hz, 1H), 5.90 (s, 1H),6.46 (s, 1H), 6.65 (d, J = 8.0 Hz, 1H), 7.06 - 7.38 (m, 5H), 9.98 (s, 1H). ESI MS: 304.1 ([M - H]+).HRMS (ESI): Calcd. for C16810O5N 304.11905. Found: 304.11910.

Reference： [1]Current Patent Assignee: CZECH ACADEMY OF SCIENCES; THE JOHNS HOPKINS UNIVERSITY - WO2021/87082, 2021, A1 Location in patent: Page/Page column 47-48

60
[ 621-23-8 ]
[ 2170-03-8 ]
3-(2,4,6-trimethoxybenzyl)dihydrofuran-2,5-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With trifluorormethanesulfonic acid In toluene at 30℃; for 24h;	Catalyst screening General procedure: Prior to the screening, CF3SO3H toluene solution was prepared from CF3SO3H (106 mL, 1.2 mmol) and toluene (10 mL) in a 20 mL vial (SV-20, 27 mm x 55 mm; Nichiden Rika-Glass Co., Kobe, Japan). Entry 17: To a 12 mL vial (S-5, 19 mm x 70 mm; Nichiden Rika-Glass Co.) containing a solution of 1,3,5-trimethoxybenzene (1a) (101 mg, 0.60 mmol) and N-methylmaleimide (2a) (66.7 mg, 0.60 mmol) in dry toluene (1.9 mL) was added CF3SO3H toluene solution (0.50 mL, 0.06 mmol) prepared as above. A cap was attached and closed, and the whole mixture was stirred at 100 °C for 5 h. After the mixture was cooled by an ice-bath, an aliquot (0.24 mL) was taken from the mixture, diluted with EtOAc (2 mL), and neutralized with saturated aq. NaHCO3 (2 mL). Conversion was calculated by comparison of the 1H NMR (CDCl3) signal ratios at 4.45 (dd, J = 9.6 and 5.3 Hz, C(3)H of 3a) and 6.70 (s, C(3)H of 2a) to be 94%. The remaining mixture was treated with EtOAc (5 mL) and saturated aq. NaHCO3 (5 mL). The organic phase was separated and the aqueous phase was back-extracted with EtOAc (5 mL X 2). The combined organic phase was dried over Na2SO4, evaporated, and dried under reduced pressure to give a crude product, which was purified together with the NMR sample by the normal-phase MPLC (SI-25, size 20, hexane:EtOAc = 69:31 → 48:52) to afford N-methyl-3-(2,4,6-trimethoxyphenyl)succinimide (3a) (141 mg, 84%)

Reference： [1]Hor, Seanghai; Koga, Nobuaki; Oyama, Kin-ichi; Tsukamoto, Masaki [Tetrahedron Letters, 2021, vol. 74]

61
[ 2170-03-8 ]
[ 83247-83-0 ]

Yield	Reaction Conditions	Operation in experiment
96.9%	With [ruthenium(II)(η⁶-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]₂; hydrogen; 1,2-bis((2S,5S)-2,5-dimethylphospholano)benzene In ethyl acetate at 35℃; for 24h; Inert atmosphere;	1 1. Preparation of R-methyl succinic anhydride (1) Add itaconic anhydride (50g, 446.4mmol) to a 500ml hydrogenation kettle And ethyl acetate (250ml), bubbling with argon for 10min, Add (S,S)-Me-Duphos (136.6mg, 0.45mmol) And p-cymene ruthenium dichloride (275.6mg, 0.45mmol), pressurized hydrogen to 5MPa, React at 35°C for 24h, TLC detects the reaction to complete, concentrate to 100ml, A white solid precipitated out, and it was filtered off with suction to obtain a white solid 1 (49.3 g%, yield 96.9%).

Reference： [1]Current Patent Assignee: ZHEJIANG MEDICINE CO., LTD. - CN113121342, 2021, A Location in patent: Paragraph 0041-0044

62
[ 488-23-3 ]
[ 2170-03-8 ]
2-methylene-4-oxo-4-(2,3,4,5-tetramethylphenyl)butanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
33%	With aluminum (III) chloride In dichloromethane at 20℃; for 2h;

Reference： [1]Dong, Kaiwu; Ji, Xiaolei; Ren, Xinyi; Shen, Chaoren; Tang, Lin; Tian, Xinxin; Wang, Zhen [Angewandte Chemie - International Edition, 2021, vol. 60, # 32, p. 17693 - 17700][Angew. Chem., 2021, vol. 133, # 32, p. 17834 - 17841]

63
[ 488-23-3 ]
[ 2170-03-8 ]
dimethyl 2-(2-oxo-2-(2,3,4,5-tetramethylphenyl)ethyl)succinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: aluminum (III) chloride / dichloromethane / 2 h / 20 °C 2: palladium diacetate; 5,5’-bis(diphenylphosphino)-2,2,2’,2’-tetrafluoro-4,4’-bi-1,3-benzodioxole; toluene-4-sulfonic acid / toluene / 24 h / 40 °C / 22502.3 Torr / Autoclave

Reference： [1]Dong, Kaiwu; Ji, Xiaolei; Ren, Xinyi; Shen, Chaoren; Tang, Lin; Tian, Xinxin; Wang, Zhen [Angewandte Chemie - International Edition, 2021, vol. 60, # 32, p. 17693 - 17700][Angew. Chem., 2021, vol. 133, # 32, p. 17834 - 17841]

64
[ 1701-57-1 ]
[ 2170-03-8 ]
2-methylene-4-oxo-4-(2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)butanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	In chloroform at 0 - 20℃; for 2h;

Reference： [1]Dong, Kaiwu; Ji, Xiaolei; Ren, Xinyi; Shen, Chaoren; Tang, Lin; Tian, Xinxin; Wang, Zhen [Angewandte Chemie - International Edition, 2021, vol. 60, # 32, p. 17693 - 17700][Angew. Chem., 2021, vol. 133, # 32, p. 17834 - 17841]

65
[ 2170-03-8 ]
[ 106-91-2 ]
[ 839-90-7 ]
[ 35948-25-5 ]
C₇₈H₇₈N₃O₃₀P₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: itaconic acid anhydride; 1,3,5-tris(2-hydroxyethyl)-S-triazine-2,4,6-trione In 1,4-dioxane; phenol at 95℃; for 4h; Stage #2: 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide In 1,4-dioxane; phenol at 95℃; for 8.5h; Stage #3: 2,3-Epoxypropyl methacrylate In 1,4-dioxane; phenol at 115℃;	1; 4; 5; 6; 7 26.1 g (0.1 mol) tris(2-hydroxyethyl)cyanuric acid, 33.7 g (0.3 mol) itaconic anhydride, 0.1 wt %Hydroxybenzene plus phenol and 40mL 1,4-dioxane were added to the flask at one time, and reacted at 95°C for 4h; then 64.8g(0.3mol) 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide and 32mL 1,4-dioxane solution were added dropwise within 0.5hAdd in the reactor, continue to react at 95°C for 8h; then add 42.3g (0.3mol) glycidyl methacrylate and 262mL1,4-Dioxane was added to the flask, and reacted at 115°C until the acid value of the system remained unchanged. After the reaction was completed, the reaction solution was subjected to rotary evaporation.After concentrating and vacuum drying, transparent phosphor-nitrogen light-curing flame-retardant acrylic resin is obtained.

Reference： [1]Current Patent Assignee: TAIZHOU ZHENGDA CHEMICAL; JIANGNAN UNIVERSITY - CN113880882, 2022, A Location in patent: Paragraph 0033-0040; 0051-0070

66
[ 2170-03-8 ]
[ 106-91-2 ]
[ 868-85-9 ]
[ 839-90-7 ]
C₄₈H₇₂N₃O₃₃P₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: itaconic acid anhydride; 1,3,5-tris(2-hydroxyethyl)-S-triazine-2,4,6-trione In toluene; phenol at 110℃; for 3h; Stage #2: Dimethyl phosphite In toluene; phenol at 100℃; for 6.5h; Stage #3: 2,3-Epoxypropyl methacrylate In toluene; phenol at 115℃;	2 26.1g (0.1mol) tris(2-hydroxyethyl)cyanuric acid, 31.5g (0.28mol) itaconic anhydride, 0.05wt%P-Hydroxybenzene plus phenol and 60mL of toluene were added to the flask at one time, and reacted at 110°C for 3h;Then 30,8 g (0.28 mol) of dimethyl phosphonate and 32mL of toluene solution were added dropwise to the reactor within 0.5h, and the reaction was continued at 100°C for 6h; then 45.1g of(0.32mol) glycidyl methacrylate and 43mL toluene were added to the flask,Reaction at 115°C until the acid value of the system is notAfter the reaction is completed, the reaction solution is concentrated by rotary evaporation, and after vacuum drying, a transparent phosphor-nitrogen light-curing flame retardant acrylic acid is obtained.acrylic resin.

Reference： [1]Current Patent Assignee: TAIZHOU ZHENGDA CHEMICAL; JIANGNAN UNIVERSITY - CN113880882, 2022, A Location in patent: Paragraph 0041-0045

67
[ 4712-55-4 ]
[ 2170-03-8 ]
[ 106-91-2 ]
[ 839-90-7 ]
C₇₈H₈₄N₃O₃₃P₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: itaconic acid anhydride; 1,3,5-tris(2-hydroxyethyl)-S-triazine-2,4,6-trione With hydroquinone In N,N-dimethyl-formamide at 110℃; for 5h; Stage #2: diphenyl hydrogen phosphite In N,N-dimethyl-formamide at 110℃; for 10.5h; Stage #3: 2,3-Epoxypropyl methacrylate In N,N-dimethyl-formamide at 115℃;	3 26.1g (0.1mol) tris(2-hydroxyethyl)cyanuric acid , 35,9g (0.32mol) itaconic anhydride, 0.2wt%Hydroquinone and 30mL N,N-dimethylformamide were added to the flask at one time, and reacted at 110°C for 5h; then 65.6g(0.28mol) diphenyl phosphonate and 35mL N,N-dimethylformamide solution were added dropwise to the reactor within 0.5h, and continued in110C reaction for 10h; then add 39,5g (0.28mol) glycidyl methacrylate and 150mL N,N-dimethylformamide.In the flask, react at 115°C until the acid value of the system does not change, after the reaction is completed, the reaction solution is concentrated by rotary evaporation, and the vacuumAfter drying, a transparent phosphor-nitrogen light-curing flame-retardant acrylic resin is obtained.

Reference： [1]Current Patent Assignee: TAIZHOU ZHENGDA CHEMICAL; JIANGNAN UNIVERSITY - CN113880882, 2022, A Location in patent: Paragraph 0046-0050

68
[ 6351-10-6 ]
[ 2170-03-8 ]
[ 697-64-3 ]
[ 25501-32-0 ]
(R)-4-((2,3-dihydro-1H-inden-1-yl)oxy)-2-methylene-4-oxobutanoic acid [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2022,vol. 20,p. 2693 - 2703

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	2170-03-8	MDL No. :	MFCD00005530
Formula :	C₅H₄O₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	OFNISBHGPNMTMS-UHFFFAOYSA-N
M.W :	112.08	Pubchem ID :	75110
Synonyms :

Num. heavy atoms :	8
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.2
Num. rotatable bonds :	0
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	25.05
TPSA :	43.37 Å²

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.86 cm/s

Log Po/w (iLOGP) :	0.86
Log Po/w (XLOGP3) :	0.17
Log Po/w (WLOGP) :	0.02
Log Po/w (MLOGP) :	0.23
Log Po/w (SILICOS-IT) :	1.26
Consensus Log Po/w :	0.51

[ CAS No. 2170-03-8 ]

Quality Control of [ 2170-03-8 ]

Related Doc. of [ 2170-03-8 ]

Product Details of [ 2170-03-8 ]

Calculated chemistry of [ 2170-03-8 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 2170-03-8 ]

Application In Synthesis of [ 2170-03-8 ]

[ 2170-03-8 ] Synthesis Path-Upstream 1~2

[ 2170-03-8 ] Synthesis Path-Downstream 1~68

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Log S (ESOL) :	-0.64
Solubility :	25.6 mg/ml ; 0.228 mol/l
Class :	Very soluble
Log S (Ali) :	-0.64
Solubility :	25.8 mg/ml ; 0.23 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.83
Solubility :	16.5 mg/ml ; 0.147 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	3.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.83

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling