720-94-5|4,4,4-Trifluoro-1-(p-tolyl)butane-1,3-dione| Ambeed

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Quality Control of [ 720-94-5 ] Purity: 97% SDS Specification

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Product Details of [ 720-94-5 ]

CAS No. :	720-94-5
Formula :	C₁₁H₉F₃O₂
M.W :	230.18
SMILES Code :	CC1=CC=C(C=C1)C(=O)CC(=O)C(F)(F)F
MDL No. :	MFCD00517909
InChI Key :	WRZMHTIRFOFFPY-UHFFFAOYSA-N
Pubchem ID :	550193

Safety of [ 720-94-5 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 720-94-5 ] Show Less

Physicochemical Properties

Num. heavy atoms	16
Num. arom. heavy atoms	6
Fraction Csp3	0.27
Num. rotatable bonds	4
Num. H-bond acceptors	5.0
Num. H-bond donors	0.0
Molar Refractivity	51.61
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	34.14 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.56
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	2.94
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	3.96
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	2.1
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	3.48
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.81

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.13
Solubility	0.17 mg/ml ; 0.000736 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-3.32
Solubility	0.11 mg/ml ; 0.00048 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-3.98
Solubility	0.0241 mg/ml ; 0.000105 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	Yes
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-5.62 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	0.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	1.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	1.43

Application In Synthesis of [ 720-94-5 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 720-94-5 ]

[ 720-94-5 ] Synthesis Path-Downstream 1~35

1
[ 720-94-5 ]
(Z)-3-Chloro-4,4,4-trifluoro-1-p-tolyl-but-2-en-1-one [ No CAS ]
(E)-4-Chloro-1,1,1-trifluoro-4-p-tolyl-but-3-en-2-one [ No CAS ]
(Z)-4-Chloro-1,1,1-trifluoro-4-p-tolyl-but-3-en-2-one [ No CAS ]

References: [1]Bulletin of the Academy of Sciences of the USSR Division of Chemical Science,1986,vol. 35,p. 1937 - 1940.
Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya,1986,p. 2125 - 2127.

2
[ 720-94-5 ]
[ 17852-52-7 ]
[ 169590-42-5 ]

Yield	Reaction Conditions	Operation in experiment
99%	at 90℃;	General procedure: 4,4,4-Trifluoro-l-(4-methyl-phenyl)-butane-l,3-dione 5 stock solution (7 mL) and (4-Sulfamoylphenyl)hydrazine hydrochloride 6 stock solution (7 mL) were each pumped at a flow rate of 0.125 mL.min 1 into the 2 mL glass mixing chip at room temperature and through the 14 mL PTFE coil heated to 90C. The output of the reactor was collected until no further product was eluted and the solvent removed in vacuo. The solid obtained was suspended in ethyl acetate (30 mL) followed by vacuum filtration. The filtrate was concentrated to obtain a pale yellow solid (0.393 g, 1.0 mmol, 99%). Rf= 0.33 (20% methanol/dichloromethane).
90%	In ethanol;Reflux;	C01 (23.55 g, 102.3 mmol) was refluxed with 4-sulphonamidophenyl hydrazine HCl (23.95 g, 127.9 mmol) in 700 mL ethanol overnight. The reaction was evaporated, dissolved in 700 mL ethyl acetate, washed with water and brine, dried over magnesium sulfate and evaporated to -100 mL ethyl acetate. The product was crystalized by the addition of ~ 400 mL isooctane. After 15 minutes, the white crystalline solid was broken up, washed with isooctane and dried under vacuum (35.15 g, 90% yield). 1H NMR (400 MHz, CDC13) delta 7.94-7.91 (m, 2H), 7.51-7.49 (m, 2H), 7.21-7.20 (m, 2H), 7.15-7.13 (m, 2H), 6.77 (s, 1H), 2.41 (s, 3H). LC tr=4.27 minutes (C-18 column, 5 to 95% acetonitrile/water over 6 minutes at 1.7 mL/min with detection 254 nm, at 23 C). ES(neg)MS m/z 380 (M-H calcd for C17H14F3N302S requires 380).
80%	In ethanol; for 20h;Reflux;	A suspension of 2.21 g (9.61 mmol) 3 and 2.36 g (10.57 mmol) 4-hydrazinylbenzensulfonamidehydrochloride, 5, in 25 mL abs. EtOHwas refluxed for 20 h. The resulting solution was concentrated in vaccum. Theresidue was dissolved in 50 mL ethyl acetate, washed with water (2 x 50 mL) andbrine (50 mL). The organic phase was dried over Na2SO4, filtrated andconcentrated in vacuum. The crude product was purified by column chromatographyeluting with n-hexane and ethyl acetate (2:1) to afford 2.91 g (80%) Celecoxib. Modified ADDIN EN.CITEPenning1997111117ThomasD. PenningJohn J.TalleyStephen R.BertenshawJeffery S.CarterPaul W. CollinsStephenDocterMatthew J.GranetoLen F.LeeJames W.MalechaJulie M.MiyashiroRoland S.RogersD. J.RogierStella S. YuGaryD. AndersonEarl G.BurtonJ. NitaCogburnSusan A.GregoryCarol M.KoboldtWilliam E.PerkinsKarenSeibertAmy W. VeenhuizenYanY. ZhangPeter C.IsaksonSynthesisand Biological Evaluation of the 1,5-Diarylpyrazole Class of Cyclooxygenase-2Inhibitors: Identification of4-[5-(4-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide(SC-58635, Celecoxib)J. Med.Chem.J.Med.Chem.1347-13654091997[2] 1H-NMR(250 MHz, CDCl3): delta = 7.89 (d, 2H, J = 8.9 Hz, 2H,6H-Ph),7.46 (d, 2H, J = 8.9 Hz, 3H,5H-Ph), 7.14 (pq, 4H, J1 = 8.0 Hz, J2 = 8.3 Hz, Tolyl), 6.74 (s,1H, Pyr), 5.03 (s, 2H, SO2-NH2),2.37 (s, 3H, -CH3). Mp = 159.6 C, m/z = 382.2 [M+H]+

46%	In ethanol; for 24h;Heating / reflux;	To the dione from Step 1 (4. 14 g, 18. 0 mmol) in 75 mL absolute ethanol, 4.26 g (19.0 mmol) 4-sulphonamidophenylhydrazine hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid, having a melting point (mp) of 157 -159 C ; and a calculated composition of C17 H14 N3 2 SF3 ; C, 53.54 ; H, 3.70 ; N, 11.02. The composition that was found by analysis was: C, 53.17 ; H, 3.81 ; N, 10.90.
46%	In ethanol; for 24h;Heating / reflux;	To the dione from Step 1 (4. 14 g, 18.0 mmol) in 75 mL absolute ethanol, 4.26 g (19.0 mmol) 4-sulphonamidophenylhydrazine hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature PC26183 46 and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3. 11 g (8. 2 mmol, 46%) of the product as a pale yellow solid, having a melting point (mp) of 157-159C ; and a calculated composition of C17 H14 N3 02 SF3 ; C, 53.54 ; H, 3. 70 ; N, 11.02. The composition that was found by analysis was: C, 53.17 ; H, 3.81 ; N, 10.90.
46%	In ethanol; for 24h;Heating / reflux;	Step 2: Preparation of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide. To the dione from Step 1 (4.14 g, 18.0 mmol) in 75 mL absolute ethanol, 4.26 g (19.0 mmol) 4-sulphonamidophenylhydrazine hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid, having a melting point (mp) of 157-159 C.; and a calculated composition of C17H14N3O2SF3; C, 53.54; H, 3.70; N, 11.02. The composition that was found by analysis was: C, 53.17;H, 3.81; N, 10.90.
46%	In ethanol; for 24h;Heating / reflux;	Step 2: Preparation of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide. To the dione from Step 1 (4.14 g, 18.0 mmol) in 75 mL absolute ethanol, 4.26 g (19.0 mmol) 4-sulphonamido-phenylhydrazine hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid, having a melting point (mp) of 157-159 C.; and a calculated composition of C17H14N3O2SF3; C, 53.54; H, 3.70; N, 11.02. The composition that was found by analysis was: C, 53.17; H, 3.81; N, 10.90.
46%	In ethanol; for 24h;Heating / reflux;	To the dione from Step 1 (4.14 g, 18.0 mmol) in 75 mL absolute ethanol, 4.26 g (19.0 mmol) 4-sulphonamidophenylhydrazine hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid, having a melting point (mp) of 157-159C ; and a calculated composition of C17 H14 N3 02 SF3 ; C, 53.54 ; H, 3.70 ; N, 11.02. The composition that was found by analysis was: C, 53.17 ; H, 3.81 ; N, 10.90.
46%	In ethanol; for 24h;Heating / reflux;	Step 2: Preparation of 4- [5- (4-methylphenyl)-3- (trifluoromethyl)-1 H-pyrazol-1-yl] benzenesulfonamide. [000203] To the dione from Step 1 (4.14 g, 18.0 MMOL) in 75 mL absolute ethanol, 4.26 g (19.0 MMOL) 4-SULPHONAMIDOPHENYLHYDRAZINE hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was RECRYSTALLIZED from methylene chloride/hexane to give 3.11 g (8. 2 MMOL, 46%) of the product as a pale yellow solid, having a melting point (mp) of 157-159C
46%	In ethanol; for 24h;Heating / reflux;	To the dione from Step 1 (4.14 g, 18.0 MMOL) in 75 mL absolute ethanol, 4.26 g (19.0 MMOL) 4-sulphonamidophenylhydrazine hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene CHLORIDE/HEXANE to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid, having a melting point (mp) of 157-159C ; and a calculated composition of C17 H14 N3 02 SF3 ; C, 53.54 ; H, 3.70 ; N, 11.02. The composition that was found by analysis was: C, 53.17 ; H, 3.81 ; N, 10.90.
46%	In ethanol; for 24h;Heating / reflux;	To the dione from Step 1 (4.14 g, 18.0 MMOL) in 75 mL absolute ethanol, 4.26 g (19.0 MMOL) 4-SULPHONAMIDOPHENYLHYDRAZINE hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was RECRYSTALLIZED from methylene chloride/hexane to give 3.11 g (8.2 MMOL, 46%) of the product as a pale yellow solid, having a melting point (mp) of 157-159C ; and a calculated composition of C17 HR4 N3 02 SF3 ; C, 53. 54 ; H, 3.70 ; N, 11.02. The composition that was found by analysis was: C, 53.17 ; H, 3.81 ; N, 10.90.
46%	In ethanol; for 24h;Heating / reflux;	To the digne from Step 1 (4.14 g, 18.0 mmol) in 75 mL absolute ethanol, 4.26 g (19.0 mmol) 4-sulphonamidophenylhydrazine hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid, having a melting point (mp) of 157-159C ; and a calculated composition of C17 H14 N3 2 SF3 ; C, 53.54 ; H, 3.70 ; N, 11.02. The composition that was found by analysis was: C, 53.17 ; H, 3.81 ; N, 10.90.
		To a 100 mL Morton flask was charged [1G 4-SAPH-HCI] and 20 mL THF. To this slurry, under nitrogen at room temperature, was added 4.5 mL [NAOH] [(1 M] in [H20)] to pH 11.2. The solution turned homogeneous. After 30 minutes the pH of the solution was adjusted to 0.9 with [TRIFLUOROACETIC] acid. At room temperature, 105 mg diketone, in 10 mL THF, was added. Aliquots were taken periodically as the reaction proceeded and analyzed by HPLC on a 4.6 mm, 5 micron Supelco [SUPELCOSILE] LC-DP column. HPLC analysis in all of the following examples was done by the same method. Results are given in table 1 a below.
		A 50 mL [3-NECK] Morton flask was fitted with a thermometer, a reflux condenser and a nitrogen inlet. To this reactor was charged 25 mL isopropanol and [1G] (4.5 [MMOL)] [4-SAPH-HCI,] followed by the addition of 0.5 g triethylamine (4.4 [MMOL)] to free base the 4-SAPH. The reaction mixture was allowed to stir for 15 minutes at room temperature. To the resultant slurry was added 0.87g (9.2 [MMOL)] chloroacetic acid. The mixture was allowed to stir at room temperature for 15 minutes. After this time period, [1 G] (4.3 [MMOL)] diketone was added and the reaction mixture was heated to 60 [C] and held at this temperature for 2.5 hr. An aliquot was taken and analyzed via HPLC. The reaction was repeated with each of the following acids: acetic, [DICHLOROACETIC,] trichoroacetic, and [TRIFLUOROACETIC.] Comparative results are given in table 2 below.
		A 50 mL [3-NECK] Morton flask was fitted with a thermometer, a reflux condenser and a nitrogen inlet. To this reactor was charged 25 mL isopropanol and [1G] (4.5 [MMOL)] [4-SAPH-HCI,] followed by the addition of 0.5 g triethylamine (4.4 [MMOL)] to free base the 4-SAPH. The reaction mixture was allowed to stir for 15 minutes at room temperature. To the resultant slurry was added 0.87g (9.2 [MMOL)] chloroacetic acid. The mixture was allowed to stir at room temperature for 15 minutes. After this time period, [1 G] (4.3 [MMOL)] diketone was added and the reaction mixture was heated to 60 [C] and held at this temperature for 2.5 hr. An aliquot was taken and analyzed via HPLC. The reaction was repeated with each of the following acids: acetic, [DICHLOROACETIC,] trichoroacetic, and [TRIFLUOROACETIC.] Comparative results are given in table 2 below.
		A 50 mL [3-NECK] Morton flask was fitted with a thermometer, a reflux condenser and a nitrogen inlet. To this reactor was charged 25 mL isopropanol and [1G] (4.5 [MMOL)] [4-SAPH-HCI,] followed by the addition of 0.5 g triethylamine (4.4 [MMOL)] to free base the 4-SAPH. The reaction mixture was allowed to stir for 15 minutes at room temperature. To the resultant slurry was added 0.87g (9.2 [MMOL)] chloroacetic acid. The mixture was allowed to stir at room temperature for 15 minutes. After this time period, [1 G] (4.3 [MMOL)] diketone was added and the reaction mixture was heated to 60 [C] and held at this temperature for 2.5 hr. An aliquot was taken and analyzed via HPLC. The reaction was repeated with each of the following acids: acetic, [DICHLOROACETIC,] trichoroacetic, and [TRIFLUOROACETIC.] Comparative results are given in table 2 below.
		A 50 mL [3-NECK] Morton flask was fitted with a thermometer, a reflux condenser and a nitrogen inlet. To this reactor was charged 25 mL isopropanol and [1G] (4.5 [MMOL)] [4-SAPH-HCI,] followed by the addition of 0.5 g triethylamine (4.4 [MMOL)] to free base the 4-SAPH. The reaction mixture was allowed to stir for 15 minutes at room temperature. To the resultant slurry was added 0.87g (9.2 [MMOL)] chloroacetic acid. The mixture was allowed to stir at room temperature for 15 minutes. After this time period, [1 G] (4.3 [MMOL)] diketone was added and the reaction mixture was heated to 60 [C] and held at this temperature for 2.5 hr. An aliquot was taken and analyzed via HPLC. The reaction was repeated with each of the following acids: acetic, [DICHLOROACETIC,] trichoroacetic, and [TRIFLUOROACETIC.] Comparative results are given in table 2 below.
		A 50 mL [3-NECK] Morton flask was fitted with a thermometer, a reflux condenser and a nitrogen inlet. To this reactor was charged 25 mL isopropanol and [1G] (4.5 [MMOL)] [4-SAPH-HCI,] followed by the addition of 0.5 g triethylamine (4.4 [MMOL)] to free base the 4-SAPH. The reaction mixture was allowed to stir for 15 minutes at room temperature. To the resultant slurry was added 0.87g (9.2 [MMOL)] chloroacetic acid. The mixture was allowed to stir at room temperature for 15 minutes. After this time period, [1 G] (4.3 [MMOL)] diketone was added and the reaction mixture was heated to 60 [C] and held at this temperature for 2.5 hr. An aliquot was taken and analyzed via HPLC. The reaction was repeated with each of the following acids: acetic, [DICHLOROACETIC,] trichoroacetic, and [TRIFLUOROACETIC.] Comparative results are given in table 2 below.
		A 100 mL 3-neck Morton flask was fitted with a reflux condenser, a nitrogen inlet, a thermometer and a glass stopper. This setup was purged with nitrogen for 15 min after which time 1 g (4.47 [MMOL)] [4-SAPH-HCI] and 25 mL anhydrous methyl alcohol was charged to the flask. To the slurry was added 0.5 g (4.95 [MMOL)] triethylamine at room temperature. After 15 minutes, 1 g (8.77 [MMOL)] [TRIFLUOROACETIC] acid was added at room temperature. After 15 minutes at room temperature, the reaction mixture was heated to 55 [C,] 1 g solid diketone (4.3 [MMOL)] was added all at once followed by 5 mL methyl alcohol to wash the addition funnel. Aliquots from the reaction mixture were taken and analyzed by HPLC. Results in mole% by-product formed based on celecoxib at reaction completion are show in table 3 below. The reaction was repeated for the following solvents: Ethyl alcohol, n- Propyl alcohol, i-Propyl alcohol, Trifluoroethanol, and t-Butyl alcohol.
		To a 100 mL Morton flask was charged 1.03g 4-SAPH and 20 mL THF. To this slurry, under nitrogen at room temperature, was added 1g NaOMe (25 wt% in [MEOH)] to pH 10.4. The solution turned homogeneous. After 30 minutes the pH of the solution was adjusted to 1.1 with [TRIFLUOROACETIC] acid. At room temperature, 104 mg diketone, in 10 mL THF, was added. Aliquots were taken periodically as the reaction proceeded and analyzed by HPLC. Results are given in table [1B] below.
	In ethanol; for 20h;Inert atmosphere; Reflux;	General procedure: 4-Hydrazinylbenzenesulfonamide hydrochloride (3?HCl) (982 mg, 4.4 mmol) was added to the stirred solution of diketone 2 (4.0 mmol) in EtOH (60 mL). If free base 3 was used to replace 3?HCl, additional HCl (3 N, 2.0 mL) is needed. The mixture was heated to reflux for 20 h. Then the reaction mixture was concentrated in vacuo. The residue was added EtOAc, washed with water, dried, filtered, and concentrated. The crude product was purified by column chromatography on silica gel (12% MeOH/CH2Cl2) to give a white solid 4 in 85 +/- 5% (n = 3) yield, Rf = 0.78-0.82 (10% MeOH/CH2Cl2).
24.06g	With trifluoroacetic acid; In water; isopropyl alcohol; at 55 - 65℃; for 1h;	Take another 500 mL three-necked glass vial, add 50 mL of isopropanol, to a solution of hydrazinobenzenesulfonamide hydrochloride (17.4 g, 0.078, 1101) and trifluoroacetic acid (0.428, 0.0037111001), and the temperature was raised to 55 (after adding reaction solution 3, reaction 111, adding50mL water, the temperature rose to 65 C full solution, cooling 10 C per hour, down to 15 C, pumping, 45 C under reduced pressure drying to get celecoxib eight crystal 24.068, the yield of 85% Ie ^: detection purity of 99.7%.
	In ethanol; for 24h;Heating / reflux;	To the dione from Step 1 (4.14 g, 18.0 mmol) in 75 mL absolute ethanol, 4.26 g (19.0 mmol) 4-sulphonamidophenylhydrazine hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid, having a melting point of 157-159C ; and a calculated composition of C17Hl4N302SF3 ; C, 53.54 ; H, 3.70 ; N, 11.02. The composition that was found by analysis was: C, 53.17 ; H, 3. 81 ; N, 10.90.
	In ethanol; for 24h;Heating / reflux;	To the dione from Step 1 (4.14 g, 18.0 mmol) in 75 mL absolute ethanol, 4.26 g (19.0 mmol) 4-sulphonamidophenylhydrazine hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid, having a melting point of 157-159C ; and a calculated composition of C17Hl4N302SF3 ; C, 53.54 ; H, 3.70 ; N, 11.02. The composition that was found by analysis was: C, 53.17 ; H, 3. 81 ; N, 10.90.

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3
[ 383-63-1 ]
[ 122-00-9 ]
[ 720-94-5 ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium; In ethanol; at 20℃; for 3.2h;	A solution of sodium (0.12 g, 5.2 mmol, 1.4 eq.) was dissolved in absolute ethanol (3.9 mL) followed by the dropwise addition of ethyl trifluoroacetate (4, 0.5 m L, 4.1 mmol, 1.1 eq.). Thereafter 4'-methylacetophenone (3, 0.50 ml, 3.8 mmol, 1.0 eq) in absolute ethanol (1.4 ml) was added dropwise over 15 minutes. The reaction mixture was stirred at room temperature for 3 hours. The mixture was concentrated in vacuo and the solid obtained suspended in hexane (15 ml) with vigorous stirring followed by vacuum filtration and washing with hexane (2 x 2 ml) to obtain a cream-coloured solid (0.86 g, 3.7mmol, 100%). /?/ = 0.23 (25 % EtOAc/hexane). 1H NMR (400 MHz c/e-DMSO) 7.69 (d, 2H, J 7.69, Ar-H); 7.19 (d, 2H, J 7.18, Ar-H); 5.92 (s, 1H, COCH2CO); 2.31 (s, 3H, CH3). 13C N MR (100 MHz d6-DMSO) 185.62, 169.27, 168.99, 168.71, 168.44, 139.89, 138.96, 128.70, 126.66, 123.78?, 120.88?, 117.98?, 115.07?, 86.84, 20.91. 19F NMR (377 MHz, c/6-DMSO) -74.42. *?Signals exhibit splitting due to coupling with fluorine.
99.08%	With potassium carbonate; In isopropyl alcohol; acetonitrile; at 40℃; for 24h;	To a 500 mL one-necked flask was added 200 mL of acetonitrile-isopropanol (1: 1), 200 mmol (26.8 mL) of p-methylacetophenone (I), 600 mmol (72 mL) of ethyl trifluoroacetate (II), 360 mmol Diameter of 600nm potassium carbonate, 40 C reaction 24h Filtration recovery of potassium carbonate and potassium bicarbonate, high temperature treatment can be reused. Mother liquor distillation, recovery of solvent and unreacted raw materials for the next reaction. Add equal volume of water to the distillation residue, adjust the pH to 6 with 10% hydrochloric acid, extract with ethyl acetate 4 times, 70mL each time, combine the organic phase, concentrate and freeze to obtain the pale yellow solid product (III) 45.6 G, the yield was 99.08%.
99.8%	With tert-butyl methyl ether; sodium ethanolate; In ethanol; at 25℃; for 24h;Inert atmosphere;	Under nitrogen protection, Separately add methyl tert-butyl ether (3.0 L) and 20 wt% sodium ethoxide in ethanol solution (3.55 kg, 10.43 mol), replacing nitrogen 3 times. Control temperature does not exceed 25±5C, mechanical stirring, Ethyl trifluoroacetate (3) was added in batches (1.27kg, 8.94mol) and p-methylacetophenone (4) (1.0 kg, 7.45 mol). Under nitrogen protection, The control reaction temperature is 25±5C, mechanical stirring for 24h. TLC detected that the disappearance of the raw materials was completed (developer: petroleum ether/ethyl acetate, volume ratio 1/1). Stop the reaction, the reaction solution was added 5wt% hydrochloric acid solution (6.5L) to adjust the pH of 7.0 ~ 8.0, let stand for 15min, Separate the layers and collect the organic phase. The aqueous phase was extracted with ethyl acetate (2.0 L); the organic phases were combined and purified water (8 L) and saturated water were added in order. Wash with brine (5.0 L), dry the organic phase over anhydrous sodium sulfate (1.0 kg), suction filter, and rinse the filter cake with a small amount of ethyl acetate. Concentrate to dryness under reduced pressure at 45 C to give compound 1 as a red-brown oil. Yield 99.8%, HPLC purity 98.4%

94%	With sodium methylate; In methanol; for 24h;Heating / reflux;	Following the disclosure provided in U. S. Patent No. 5,760, 068, 4'-Methylacetophenone (5.26 g, 39.2mmol) was dissolved in 25 mL of methanol under argon and 12 mL (52.5mmol) sodium methoxide in methanol (25%) was added. The mixture was stirred for 5 minutes and 5.5 mL (46.2mmol) ethyl trifluoroacetate was added. After refluxing for 24 hours, the mixture was cooled to room temperature and concentrated. 100 mL 10% HCI was added and the mixture extracted with 4 x 75 mL ethyl acetate. The extracts were dried overMgS04, filtered and concentrated to afford 8.47 g (94%) of a brown oil which was carried on without further purification.
94%		Following the disclosure provided in U. S. Patent No. 5,760, 068,4'- Methylacetophenone (5. 26 g, 39.2 mmol) was dissolved in 25 mL of methanol under argon and 12 mL (52.5 mmol) sodium methoxide in methanol (25%) was added. The mixture was stirred for 5 minutes and 5. 5 mL (46.2 mmbl) ethyl trifluoroacetate was added. After refluxing for 24 hours, the mixture was cooled to room temperature and concentrated. 100 mL 10% HCI was added and the mixture extracted with 4 x 75 mL ethyl acetate. The extracts were dried over MgS04, filtered and concentrated to afford 8.47 g (94%) of a brown oil which was carried on without further purification.
94%		Step 1: Preparation of 1-(4-methylphenyl)-4,4,4-trifluorobutane-1,3-dione. Following the disclosure provided in U.S. Pat. No. 5,760,068, 4'-Methylacetophenone (5.26 g, 39.2 mmol) was dissolved in 25 mL of methanol under argon and 12 mL (52.5 mmol) sodium methoxide in methanol (25%) was added. The mixture was stirred for 5 minutes and 5.5 mL (46.2 mmol) ethyl trifluoroacetate was added. After refluxing for 24 hours, the mixture was cooled to room temperature and concentrated. 100 mL 10% HCl was added and the mixture extracted with 4*75 mL ethyl acetate. The extracts were dried over MgSO4, filtered and concentrated to afford 8.47 g (94%) of a brown oil which was carried on without further purification.
94%		Step 1: Preparation of 1-(4-methylphenyl)-4,4,4-trifluorobutane-1,3-dione. Following the disclosure provided in U.S. Pat. No. 5,760,068, 4'-methylacetophenone (5.26 g, 39.2 mmol) was dissolved in 25 mL of methanol under argon and 12 mL (52.5 mmol) sodium methoxide in methanol (25%) was added. The mixture was stirred for 5 minutes and 5.5 mL (46.2 mmol) ethyl trifluoroacetate was added. After refluxing for 24 hours, the mixture was cooled to room temperature and concentrated. 100 mL 10% HCl was added and the mixture extracted with 4*75 mL ethyl acetate. The extracts were dried over MgSO4, filtered and concentrated to afford 8.47 g (94%) of a brown oil which was carried on without further purification.
94%		Following the disclosure provided in U. S. Patent No. 5,760, 068, 4'-Methylacetophenone (5.26 g, 39.2 mmol) was dissolved in 25 mL of methanol under argon and 12 mL (52.5 mmol) sodium methoxide in methanol (25%) was added. The mixture was stirred for 5 minutes and 5.5 mL (46.2 mmol) ethyl trifluoroacetate was added. After refluxing for 24 hours, the mixture was cooled to room temperature and concentrated. 100 mL 10% HCI was added and the mixture extracted with 4 x 75 mL ethyl acetate. The extracts were dried over MgS04, filtered and concentrated to afford 8.47 g (94%) of a brown oil which was carried on without further purification.
94%		Step 1: Preparation of 1- (4-METHYLPHENYL)-4, 4,4- trifluorobutane-1, 3-dione. [000201] Following the disclosure provided in U. S. Patent No. 5,760, 068, 4'-Methylacetophenone (5.26 g, 39.2 MMOL) was dissolved in 25 mL of methanol under argon and 12 mL (52.5 MMOL) sodium methoxide in methanol (25%) was added. The mixture was stirred for 5 minutes and 5.5 mL (46.2 MMOL) ETHYL TRIFLUOROACETATE was added. After refluxing for 24 hours, the mixture was cooled to room temperature and concentrated. 100 mL 10% HCI was added and the mixture extracted with 4 x 75 mL ethyl acetate. The extracts were dried over MGS04, filtered and concentrated to afford 8.47 g (94%) of a brown oil which was carried on without further purification.
94%		Following the disclosure provided in U. S. Patent No. 5,760, 068, 4'-Methylacetophenone (5.26 g, 39.2 MMOL) was dissolved in 25 mL of methanol under argon and 12 mL (52.5 MMOL) sodium methoxide in methanol (25%) was added. The mixture was stirred for 5 minutes and 5.5 mL (46.2 mmol) ethyl trifluoroacetate was added. After refluxing for 24 hours, the mixture was cooled to room temperature and concentrated. 100 mL 10% HCI was added and the mixture extracted with 4 x 75 mL ethyl acetate. The extracts were dried over MGS04, FILTERED and concentrated to afford 8.47 g (94%) of a brown oil which was carried on without further purification.
94%		Following the disclosure provided in U. S. Patent No. 5,760, 068, 4'-Methylacetophenone (5.26 g, 39.2 mmol) was dissolved in 25 mL of methanol under argon and 12 mL (52.5 mmol) sodium methoxide in methanol (25%) was added. The mixture was stirred for 5 minutes and 5.5 mL (46.2 mmol) ethyl trifluoroacetate was added. After refluxing for 24 hours, the mixture was cooled to room temperature and concentrated. 100 mL 10% HCI was added and the mixture extracted with 4 x 75 mL ethyl acetate. The extracts were dried over MgS04, filtered and concentrated to afford 8.47 g (94%) of a brown oil which was carried on without further purification.
94%		4'-methylacetophenone (5.26 g, 39.2 mmol) was dissolved in 25 mL of methanol under argon and 12 mL (52.5 mmol) sodium methoxide in methanol (25%) was added. The mixture was stirred for 5 minutes and 5.5 mL (46.2 mmol) ethyl trifluoroacetate was added. After refluxing for 24 hours, the mixture was cooled to room temperature and concentrated. 100 mL 10% HCl was added and the mixture extracted with 4 x 75 mL ethyl acetate. The extracts were dried over MgS04, filtered and concentrated to afford 8.47 g (94%) of a brown oil which was carried on without further purification.
94%		4'-methylacetophenone (5.26 g, 39.2 mmol) was dissolved in 25 mL of methanol under argon and 12 mL (52.5 mmol) sodium methoxide in methanol (25%) was added. The mixture was stirred for 5 minutes and 5.5 mL (46.2 mmol) ethyl trifluoroacetate was added. After refluxing for 24 hours, the mixture was cooled to room temperature and concentrated. 100 mL 10% HCl was added and the mixture extracted with 4 x 75 mL ethyl acetate. The extracts were dried over MgS04, filtered and concentrated to afford 8.47 g (94%) of a brown oil which was carried on without further purification.
94.8%	With sodium methylate; In toluene; at 20 - 30℃; for 5h;	In a 1000 ml reaction flask, add 500.0 g of toluene and 187.9 g (1.40 mol)P-methylacetophenone, 94.1 g of sodium methoxide (1.68 mol), slowly dropwise add 238.8 g of ethyl trifluoroacetate (1.54 mol), and keep it at 20-30 C. After the dropwise addition, continue to react for 5 hours. A good 5N hydrochloric acid solution is used to adjust the pH to 2, and then washed twice with 500 g of purified water; the washed organic phase is slowly cooled to -10 C to -5 C, crystallized for 2 hours, and filtered and dried to obtain 305.5 g of light yellow. Solid, molar yield 94.8%, purity 99.8%.
89%		(1) To a 100 mL round bottom flask was added 14.9 mmol of 4-methylacetophenone (Compound 3b)Dry THF 30 mL,Cooling to -5 ~ 0 ,NaH 0.715 g (29.8 mmol) was added portionwise under nitrogen,Stir at this temperature for 30 min,Was added 3.175 g (22.4 mmol) of ethyl trifluoroacetate,The reaction was stirred at room temperature for 6 h,The solvent was distilled off under reduced pressure, diluted with ice water,The pH of the solution was adjusted to 6 with 1 mol / L HCl,The organic layer was washed with 5 mL of water and dried over anhydrous magnesium sulfate. The solvent was dried and the concentrated product was dried. The organic layer was washed with 5 mL of water,To give compound 4b (4,4,4-trifluoro-1- (4-methylphenyl) -1,3-butanedione) in 89% yield;
87%		25% sodium methoxide in methanol (51.3 ml, 223.5 mmol) and ethyl trifluoroacetate (24.4 ml, 204.9 mmol) were dissolved in 110 mL methyl tert-butyl ether under N2, at room temperature. 4'-methyl acetophenone (25.0 ml, 186.3 mmol) was added and stirred at room temperature overnight. The reaction was washed with 3M HC1 and dried over magnesium sulfate. The solution was then evaporated and the resulting oil dried under vacuum overnight. The resulting light orange crystalline solid was washed with cold isooctane and dried under vacuum to yield an off white crystalline solid (37.3 g, 87% yield). LC tr=3.49 minutes (C- 18 column, 5 to 95% acetonitrile/water over 6 minutes at 1.7 mL/min with detection 254 nm, at 23 C).
87.3%		Will p-methyl acetophenone (0.67g, 5mmol)Soluble in 20mL dry THF,NaH (0.24 g, 10 mmol) was added at 0C.Stir for 10 min.Adding ethyl trifluoroacetate under N2 protection(0.9 mL, 7.5 mmol) into the reaction solution,The drop was transferred to room temperature and the reaction was continued for 12 h.After the reaction was completed, it was quenched with saturated aqueous sodium bicarbonate (50 mL).And extracted with ethyl acetate (50 mL x 3).Combine the organic phase,Dry, concentrate.The crude product was purified by column chromatography to give 1 g of a yellow solid.Yield 87.3%.
86%	With sodium; In methanol; for 24h;Reflux;	Add 4.5 g of metallic sodium to 70 ml of anhydrous methanol.After the reaction is completed, it is cooled to room temperature.Slowly add p-methylacetophenone 13.5g (100mmol)And ethyl trifluoroacetate 17g (120mmol), after the addition is completed,The mixture was heated to reflux for 24 hours and concentrated to a yellow viscous liquid.Add 2mol/L hydrochloric acid to adjust the pH to 2~3, extract with ethyl acetate.Drying with magnesium sulfate,The solvent was evaporated to give a yellow oil, 1-p-tolyl-4,4,4-trifluorobutane-1,3dione, 20 g, yield 86%.
85%		Intermediate 10: 4,4,4-trifluoro-1-(p-tolyl)butane-1,3-dione To a solution of MeONa prepared from sodium (1.919 g, 83.0 mmol) and methanol (60 mL) was added ethyl 2,2,2-trifluoroacetate (ALDRICH, 8.19 ml_, 54.8 mmol) and the reaction was stirred at rt 30 min. Then 1-(p-tolyl)ethanone (ALDRICH, 6.97 mL, 52.2 mmol) was added, the reaction mixture was heated at 60C overnight. The reaction was checked by LCMS and the end of the reaction was observed. The reaction mixture was concentrated under vacuum and partitioned between sodium carbonate (10%) 25 mL and DCM (25 mL), the organic layer was separated, dried over Na2S04, filtered and concentrated under vacuum to afford a brown solid (10.2 g, 44.3 mmol, 85%). 1H NMR (400 MHz, CDCI3) delta ppm: 7.85 (d, 2H), 7.30 (d, 2H), 6.56 (s, 1 H), 2.45 (s, 3H).
85%		To a solution of MeONa prepared from sodium (1.919 g, 83.0 mmol) and methanol (60 mL) was added ethyl 2,2,2-trifluoroacetate (ALDRICH, 8.19 mL, 54.8 mmol) and the reaction was stirred at rt 30 min. Then 1-(p-tolyl)ethanone (ALDRICH, 6.97 mL, 52.2 mmol) was added, the reaction mixture was heated at 60 C. overnight. The reaction was checked by LCMS and the end of the reaction was observed. The reaction mixture was concentrated under vacuum and partitioned between sodium carbonate (10%) 25 mL and DCM (25 mL), the organic layer was separated, dried over Na2SO4, filtered and concentrated under vacuum to afford a brown solid (10.2 g, 44.3 mmol, 85%). 1H NMR (400 MHz, CDCl3) delta ppm: 7.85 (d, 2H), 7.30 (d, 2H), 6.56 (s, 1H), 2.45 (s, 3H).
8.47 g (94%)	With hydrogenchloride; In methanol;	Step 1: Preparation of 1-(4-methylphenyl)-4,4,4-trifluorobutane-1,3-dione. Following the disclosure provided in U.S. Pat. No. 5,760,068, 4'-Methylacetophenone (5.26 g, 39.2 mmol) was dissolved in 25 mL of methanol under argon and 12 mL (52.5 mmol) sodium methoxide in methanol (25%) was added. The mixture was.stirred for 5 minutes and 5.5 mL (46.2 mmol) ethyl trifluoroacetate was added. After refluxing for 24 hours, the mixture was cooled to room temperature and concentrated. 100 mL 10% HCl was added and the mixture extracted with 4*75 mL ethyl acetate. The extracts were dried over MgSO4, filtered and concentrated to afford 8.47 g (94%) of a brown oil which was carried on without further purification.
8.47 g (94%)	With hydrogenchloride; In methanol;	Step 1: Preparation of 1-(4-methylphenyl)-4,4,4-trifluorobutane-1,3-dione. Following the disclosure provided in U.S. Pat. No. 5,760,068, 4'-Methylacetophenone (5.26 g, 39.2 mmol) was dissolved in 25 mL of methanol under argon and 12 mL (52.5 mmol) sodium methoxide in methanol (25%) was added. The mixture was stirred for 5 minutes and 5.5 mL (46.2 mmol) ethyl trifluoroacetate was added. After refluxing for 24 hours, the mixture was cooled to room temperature and concentrated. 100 mL 10% HCl was added and the mixture extracted with 4*75 mL ethyl acetate. The extracts were dried over MgSO4, filtered and concentrated to afford 8.47 g (94%) of a brown oil which was carried on without further purification.
8.47 g (94%)	With hydrogenchloride; In methanol;	Step 1 Preparation of 1-(4-methylphenyl)-4,4,4-trifluorobutane-1,3-dione Following the disclosure provided in U.S. Pat. No. 5,760,068, 4'-Methylacetophenone (5.26 g, 39.2 mmol) was dissolved in 25 mL of methanol under argon and 12 mL (52.5 mmol) sodium methoxide in methanol (25%) was added. The mixture was stirred for 5 minutes and 5.5 mL (46.2 mmol) ethyl trifluoroacetate was added. After refluxing for 24 hours, the mixture was cooled to room temperature and concentrated. 100 mL 10% HCl was added and the mixture extracted with 4*75 mL ethyl acetate. The extracts were dried over MgSO4, filtered and concentrated to afford 8.47 g (94%) of a brown oil which was carried on without further purification.
	With hydrogenchloride; sodium methylate; In methanol;	Step a 1-(4-methylphenyl)-4,4,4-trifluorobutane-1,3-dione 4'-Methylacetophenone was dissolved in methanol (25 ml) under nitrogen atmosphere. To the stirred solution was added 25% sodium methoxide in methanol (12 ml). The reaction mixture was stirred for 5 minutes and ethyltrifluoroacetate (5.5 ml) was added. After refluxing under nitrogen atmosphere for 24 hours the mixture was cooled to room temperature and concentrated. 10% hydrochloric acid (100 ml) was added. The mixture was extracted with ethyl acetate (4*75 ml). The combined organic layer was dried over MgSO4, filtered and concentrated. The product was obtained as an oily residue.
8.47 g (94%)	With hydrogenchloride; In methanol;	Step 1 Preparation of 1-(4-methylphenyl)-4,4,4-trifluorobutane-1,3-dione 4'-Methylacetophenone (5.26 g, 39.2 mmol) was dissolved in 25 mL of methanol under argon and 12 mL (52.5 mmol) sodium methoxide in methanol (25%) was added. The mixture was stirred for 5 minutes and 5.5 mL (46.2 mmol) ethyl trifluoroacetate was added. After refluxing for 24 hours, the mixture was cooled to room temperature and concentrated. 100 mL 10% HCl was added and the mixture extracted with 4*75 mL ethyl acetate. The extracts were dried over MgSO4, filtered and concentrated to afford 8.47 g (94%) of a brown oil which was carried on without further purification.
8.47 g (94%)	With hydrogenchloride; In methanol;	Step 1: Preparation of 1-(4-methylphenyl)-4,4,4-trifluorobutane-1,3-dione 4'-Methylacetophenone (5.26 g, 39.2 mmol) was dissolved in 25 mL of methanol under argon and 12 mL (52.5 mmol) sodium methoxide in methanol (25%) was added. The mixture was stirred for 5 minutes and 5.5 mL (46.2 mmol) ethyl trifluoroacetate was added. After refluxing for 24 hours, the mixture was cooled to room temperature and concentrated. 100 mL 10% HCl was added and the mixture extracted with 4*75 mL ethyl acetate. The extracts were dried over MgSO4, filtered and concentrated to afford 8.47 g (94%) of a brown oil which was carried on without further purification.
8.47 g (94%)	With hydrogenchloride; In methanol;	Step 1: Preparation of 1-(4-methylphenyl)-4,4,4-trifluorobutane-1,3-dione. Following the disclosure provided in U.S. Pat. No. 5,760,068, 4'-Methylacetophenone (5.26 g, 39.2 mmol) was dissolved in 25 mL of methanol under argon and 12 mL (52.5 mmol) sodium methoxide in methanol (25%) was added. The mixture was stirred for 5 minutes and 5.5 mL (46.2 mmol) ethyl trifluoroacetate was added. After refluxing for 24 hours, the mixture was cooled to room temperature and concentrated. 100 mL 10% HCl was added and the mixture extracted with 4*75 mL ethyl acetate. The extracts were dried over MgSO4, filtered and concentrated to afford 8.47 g (94%) of a brown oil which was carried on without further purification.
	With sodium methylate; In methanol; toluene; at 25 - 60℃;	Stage-1:Preparation of l-(4-methylphenyl)-4,4,4-trifluorobutane-l,3-dione (IV)4-Methylacetophenone (50 g, 0.373 mol) was dissolved in toluene (250 ml) and 30% methanolic sodium methoxide solution (80.6 g, 0.447 mol), followed by 1- ethyltrifluoro acetate (63.58 g, 0.447 mol) were added at 25-3O0C. Temperature of the reaction mass was raised to 55-600C and stirred ~ 4 hr to complete the reaction. The reaction mass was cooled to 20-250C and washed with 10% aqueous hydrochloric acid (200 ml). The layers were separated and concentrated the organic layer at 50-550C under reduced pressure to produce 80 g of l-(4-methylphenyl)-4,4,4-trifluoiObutane- 1,3-dione (IV) as an oily mass.
		General procedure: Substituted acetophenone 1 (149 mmol) was dissolved in dry THF (300 mL) under nitrogen atmosphere and NaH (7.15 g, 298 mmol) was added in portions maintaining the temperature between -5 and 0 C. After stirring at this temperature for 30 min, ethyl trifluoroacetate (31.75 g, 224 mmol) was added and the reaction mixture was allowed to stir at room temperature for 6 h. The reaction mixture was evaporated, added with ice-water, acidified with HCl (1 N) to pH 6, and extracted with EtOAc (3 × 100 mL). The combined organic layer was washed with water (50 mL), dried over MgSO4, and concentrated. The solid residue was washed with hexane and dried under high vacuum to provide a solid mass, which was re-dissolved in CH2Cl2, and dried under high vacuum to give a white solid diketone 2 in 92 +/- 2% (n = 3) yield, Rf = 0.22-0.25 (25% EtOAc/Hexanes).
		General procedure: Step a. To a suspension of ethyl trifluoroacetate (850 mg, 6 mmol, 1.2 equiv) and NaH (150 mg, 6.25 mmol, 1.25 equiv) in anhydrous THF, individual ketone substrates (5 mmol, 1 equiv) in anhydrous THF were slowly added at 25 C. The resulting mixture was stirred for 5 h, concentrated, diluted with ethyl acetate, washed, in tandem, with water, 1 N HCl and brine. The organic phase was dried over sodium sulfate, filtered and concentrated. The residue was purified by flash column chromatography (EtOAc-hexane, 1:4) to afford pure 1,3-diketone in fair to good yields.
	With sodium methylate; In methanol; for 2h;Reflux;	General procedure: Referring to Scheme 1, to the appropriate acetophenone derivative (0.05 mol) and ethyltrifluoroacetate (0.075 mol) in methanol (20 mL), sodium methoxide solution (0.1 mol of Na + 15 mL ofCH3OH) was added dropwise at room temperature, and the mixture was refluxed for 2 h. After themethanol was evaporated under vacuum, the residue was dissolved in ethyl acetate (50 mL), washedwith 5% HCl (25 mL) and water (25 mL), and dried over sodium sulfate. After the solvent wasevaporated under vacuum, the corresponding compound II was obtained.
63.5 g	With sodium; In ethanol; toluene; at 100℃; for 4h;	Sodium metal (6.9g, 0.3mol) and toluene (150 mL) made of an off-white suspension, was added absolute ethanol (20 mL), at 65 C for 1 hour, cooled to room temperature. Added p-methylacetophenone (40.2g, 0.3mmol) and ethyl trifluoroacetate (60mL, 0.6mmol), was slowly warmed to 100 C for 4 hours. Toluene was evaporated, and the residue was added to a mixture of ice and glacial acetic acid (containing 33% glacial acetic acid), and extracted four times with ethyl acetate. The combined extracts were washed with water, dried over anhydrous sodium sulfate, the solvent was evaporated to obtain a brown solid 63.5g.
	With sodium methylate; In methanol; isopropyl alcohol; at 50℃; for 4h;	In a 250 mL three-necked glass flask, p-methylacetophenone (10 g, 0.075 mol) and ethyl trifluoroacetate(13.7 g, 0.096 mol), 18.2 g of sodium methoxide in methanol (25% concentration) and 20 mL of isopropanol were added and the temperature was raised to 50 C, after holding for 4 h, the temporary solution for the reaction a.
		A solution of 27 p-methylacetophenone (0.67g, 5mmol) in dry 28 THF (20mL) was added dropwise to 29 NaH (0.24g, 10mmol) in dry THF (50mL) under nitrogen atomosphere and the mixture was stirred for 1h at 0C. Then a solution of 30 ethyl trifluoroacetate (0.9mL, 7.5mmol) in dry THF (10mL) was added dropwise. The mixture was warmed to room temperature for 12h. The reaction was quenched with saturation NaHCO3 and extracted with ethyl acetate (50mL×3). The combined organic extracts were washed with brine (50mL), dried with Na2SO4 and evaporated. Finally, the resulting residue was purified by column chromatography on silica gel as indicated to give 6a as canary yellow solid. (0015) To a solution of 6a (0.46g, 2mmol) in 31 ethyl alcohol (50mL) was added 32 4-hydrazinyl-N-hydroxybenzamide hydrochloride (0.53g, 2.6mmol). Then the temperature was raised to 70C for 5h. The mixture solution was concentrated to dryness, added 33 water (50mL) and extracted with ethyl acetate (30mL×3). The combined organic extracts were washed with brine (30mL), dried with Na2SO4 and concentrated. Finally, the resulting residue was purified by column chromatography on silica gel as indicated to give 7 as white solid. (0016) To a solution of 7 (0.36g, 1mmol) in 34 methyl alcohol (30mL) were added 1M aqueous solution of 35 NaOH (3mL) and 36 NH2OH (50wt% in water, 3mL) dropwise successively at 0C. The reaction was warmed to room temperature for 3h. The mixture solution was concentrated to dryness, and the obtained solid was dissolved in water. The pH was adjusted to 7 with 1M aqueous solution of 37 HCl. The resulting precipitate was filtered to give 38 8 as white solid. Yield: 63.2%. Mp: 104.5-105.9C. ESI-MS: m/z, 360.3 [M-H]-. 1H NMR (600MHz, DMSO-d6) delta: 11.33 (s, 1H), 9.13 (s, 1H), 7.80 (d, J=8.6 Hz, 2H), 7.42 (d, J=8.6 Hz, 2H), 7.21-7.18 (m, 4H), 7.17 (s, 1H), 2.30 (s, 3H). 13C NMR (151MHz, DMSO) delta: 145.19, 140.87, 139.03, 132.90, 129.56, 129.43, 128.77, 128.00, 126.86, 125.60, 125.54, 105.91, 20.86. HRMS (ESI+) m/z calcd for C18H14F3N3O2 [M-H]- 360.1038, found: 360.1047.
		Following the disclosure provided in U. S. Patent No. 5,760, 068, 4'-Methylacetophenone (5.26 g, 39.2 MMOL) was dissolved in 25 mL of methanol under argon and 12 mL (52.5 MMOL) sodium methoxide in methanol (25%) was added. The mixture was stirred for 5 minutes and 5.5 mL (46.2 MMOL) ethyl TRIFLUOROACETATE was added. After refluxing for 24 hours, the mixture was cooled to room temperature and concentrated. 100 mL 10% HCI was added and the mixture extracted with 4 x 75 mL ethyl acetate. The extracts were dried over MGS04, filtered and concentrated to afford 8.47 g (94%) of a brown oil which was carried on without further purification.

References: [1]Patent: WO2019/64139,2019,A1 .Location in patent: Page/Page column 12-16.
[2]Patent: CN103951549,2016,B .Location in patent: Paragraph 0008; 0027-0028.
[3]Patent: CN107759519,2018,A .Location in patent: Paragraph 0033-0035.
[4]Journal of Medicinal Chemistry,2007,vol. 50,p. 4444 - 4452.
[5]Journal of Medicinal Chemistry,1997,vol. 40,p. 1347 - 1365.
[6]Patent: WO2005/49014,2005,A1 .Location in patent: Page/Page column 137.
[7]Patent: WO2005/39565,2005,A1 .Location in patent: Page/Page column 45.
[8]Patent: US2005/14729,2005,A1 .Location in patent: Page 64.
[9]Patent: US2005/187172,2005,A1 .Location in patent: Page/Page column 62.
[10]Patent: WO2005/84654,2005,A2 .Location in patent: Page/Page column 183-184.
[11]Patent: WO2005/20895,2005,A2 .Location in patent: Page/Page column 90-91.
[12]Patent: WO2005/21004,2005,A1 .Location in patent: Page/Page column 57.
[13]Patent: WO2005/41864,2005,A2 .Location in patent: Page/Page column 143.
[14]Patent: WO2005/41879,2005,A2 .Location in patent: Page/Page column 164.
[15]Patent: WO2005/44194,2005,A2 .Location in patent: Page/Page column 161-162.
[16]Patent: CN110407683,2019,A .Location in patent: Paragraph 0019-0025.
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[18]Patent: CN104974135,2017,B .Location in patent: Paragraph 0112.
[19]ACS Medicinal Chemistry Letters,2013,vol. 4,p. 451 - 455.
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4
[ 1118-61-2 ]
[ 720-94-5 ]
3-cyano-2-methyl-6-(4-methylphenyl)-4-trifluoromethylpyridine [ No CAS ]

References: [1]Synthesis,1997,p. 1321 - 1324.

5
[ 720-94-5 ]
[ 626-34-6 ]
2-Methyl-6-p-tolyl-4-trifluoromethyl-nicotinic acid ethyl ester [ No CAS ]

References: [1]Synthesis,1997,p. 1321 - 1324.

6
[ 720-94-5 ]
[ 307531-57-3 ]

References: [1]Synthesis,2005,p. 2871 - 2874.
[2]Russian Journal of Organic Chemistry,2000,vol. 36,p. 486 - 488.

7
[ 720-94-5 ]
[ 107-91-5 ]
[ 147381-60-0 ]

References: [1]Russian Chemical Bulletin,2001,vol. 50,p. 669 - 672.
[2]Chemistry of Heterocyclic Compounds,2001,vol. 37,p. 872 - 875.

8
[ 720-94-5 ]
[ 100-16-3 ]
[ 365530-10-5 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In ethanol;Reflux;	General procedure: Step b. A mixture of the 1,3-diketone from step a (3 mmol, 1 equiv), individual hydrazaine substrates (3.75 mmol, 1.25 equiv), and concentrated HCl (0.4 mL, 1.5 equiv) in ethyl alcohol was refluxed until the reaction completed (monitored with TLC; EtOAc-hexane, 3:7). The resulting mixture was concentrated, diluted with ethyl acetate, and washed with water and brine. The organic phase was dried over sodium sulfate, filtered and concentrated. The residue was purified by flash column chromatography (EtOAc-hexane, 3:7) to yield pure pyrazole ring derivatives.

References: [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 3039 - 3042.
[2]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 4653 - 4660.

9
[ 720-94-5 ]
[ 100-16-3 ]
[ 365530-09-2 ]

References: [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 3039 - 3042.

10
[ 720-94-5 ]
[ 100-63-0 ]
[ 515845-18-8 ]

References: [1]Journal of Fluorine Chemistry,2002,vol. 118,p. 135 - 147.

11
[ 720-94-5 ]
(1,1-dioxo-2,3-dihydro-1H-1λ⁶-benzo[b]thiophen-5-yl)-hydrazine; hydrochloride [ No CAS ]
1-(1,1-dioxo-2,3-dihydro-1H-1λ⁶-benzo[b]thiophen-5-yl)-5-p-tolyl-3-trifluoromethyl-1H-pyrazole [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 499 - 504.

12
[ 720-94-5 ]
4-hydrazino-2-hydroxymethyl-1-benzenesulfonamide hydrochloride [ No CAS ]
[ 678987-46-7 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 499 - 504.

13
[ 720-94-5 ]
N-(5-hydrazino-2-sulfamoyl-benzyl)-acetamide; hydrochloride [ No CAS ]
N-[2-sulfamoyl-5-(5-p-tolyl-3-trifluoromethyl-pyrazol-1-yl)-benzyl]-acetamide [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 499 - 504.

14
[ 720-94-5 ]
[ 59-88-1 ]
[ 515845-18-8 ]

References: [1]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 5273 - 5280.

15
[ 720-94-5 ]
[ 2863-98-1 ]
4-[5-(4-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	In ethanol; for 7h;Reflux;	General procedure: To a warm ethanolic solution (10mL) of 4-hydrazinylbenzonitrile hydrochloride 4 (350mg, 2.0mmol) was added appropriate trifluoromethyl-beta-diketone 5a?5i (2.0mmol) while stirring and the contents were refluxed for 7h. The progress of the reaction was monitored by TLC. When the reaction was completed, excess solvent was evaporated to reduce the volume to one half whereupon reaction mixture was allowed to cool to 20?25°C and the solid thus obtained was filtered to obtain 2a?2i (85?93percent).

References: [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 4581 - 4590.
[2]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 4483 - 4487.

16
[ 945224-59-9 ]
[ 720-94-5 ]
C₂₆H₁₄F₆N₄ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 3445 - 3453.

17
[ 945224-60-2 ]
[ 720-94-5 ]
C₂₆H₁₄F₆N₄ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 3445 - 3453.

18
[ 720-94-5 ]
[ 57412-05-2 ]
C₁₉H₁₅F₃N₂O₂ [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 4444 - 4452.

19
[ 720-94-5 ]
[ 24589-77-3 ]
4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzoic acid [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 4444 - 4452.

20
[ 64-17-5 ]
[ 720-94-5 ]
[ 24589-77-3 ]
C₂₀H₁₇F₃N₂O₂ [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 4444 - 4452.

21
[ 720-94-5 ]
[ 637-60-5 ]
1,5-di-p-tolyl-3-(trifluoromethyl)-1H-pyrazole [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 4444 - 4452.

22
[ 720-94-5 ]
[ 58626-97-4 ]
[ 616209-43-9 ]

References: [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 4444 - 4452.

23
[ 720-94-5 ]
[ 613-94-5 ]
1-benzoyl-3-(4-methylphenyl)-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-ol [ No CAS ]
1-benzoyl-5-(4-methylphenyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-ol [ No CAS ]

References: [1]Russian Journal of General Chemistry,2007,vol. 77,p. 1732 - 1741.

24
[ 720-94-5 ]
[ 613-94-5 ]
1-benzoyl-5-(4-methylphenyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-ol [ No CAS ]

References: [1]Russian Journal of General Chemistry,2007,vol. 77,p. 1732 - 1741.

25
[ 720-94-5 ]
[ 675605-72-8 ]

References: [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 4444 - 4452.

26
[ 720-94-5 ]
[ 190711-47-8 ]

References: [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 4444 - 4452.

27
[ 720-94-5 ]
4-(4-methylphenyl)-1-[4-(5-tetrazolyl)phenyl]-3-(trifluoromethyl)-1H-pyrazole [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 4483 - 4487.

28
[ 720-94-5 ]
[ 872186-82-8 ]

References: [1]Synthesis,2005,p. 2871 - 2874.

29
[ 720-94-5 ]
3-[5-(4-methylphenyl)-3-trifluoromethylpyrazol-1-yl]benzenesulfonyl chloride [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 5273 - 5280.

30
[ 720-94-5 ]
3-(5-p-tolyl-3-trifluoromethyl-pyrazol-1-yl)-benzenesulfonyl azide [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 5273 - 5280.

31
[ 720-94-5 ]
5-sulfamoyl-2-(5-p-tolyl-3-trifluoromethyl-pyrazol-1-yl)-benzenesulfonyl chloride [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 5273 - 5280.

32
[ 720-94-5 ]
5-sulfamoyl-2-(5-p-tolyl-3-trifluoromethyl-pyrazol-1-yl)-benzenesulfonyl azide [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 5273 - 5280.

33
[ 720-94-5 ]
propionic acid 2-sulfamoyl-5-(5-p-tolyl-3-trifluoromethyl-pyrazol-1-yl)-benzyl ester [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 499 - 504.

34
[ 720-94-5 ]
[ 417701-81-6 ]

References: [1]Chemistry of Heterocyclic Compounds,2001,vol. 37,p. 872 - 875.

35
[ 720-94-5 ]
5-p-tolyl-7-trifluoromethyl-2,3-dihydro-imidazo[1,2-a]pyridine-8-carbonitrile [ No CAS ]

References: [1]Chemistry of Heterocyclic Compounds,2001,vol. 37,p. 872 - 875.

Historical Records

Technical Information

• Alkyl Halide Occurrence • Baeyer-Villiger Oxidation • Barbier Coupling Reaction • Baylis-Hillman Reaction • Bucherer-Bergs Reaction • Clemmensen Reduction • Corey-Bakshi-Shibata (CBS) Reduction • Corey-Chaykovsky Reaction • Fischer Indole Synthesis • Grignard Reaction • Henry Nitroaldol Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • Lawesson's Reagent • Leuckart-Wallach Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Peterson Olefination • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Amines • Prins Reaction • Reactions of Aldehydes and Ketones • Reactions of Amines • Reformatsky Reaction • Robinson Annulation • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Specialized Acylation Reagents-Ketenes • Stobbe Condensation • Tebbe Olefination • Ugi Reaction • Wittig Reaction • Wolff-Kishner Reduction

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
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Prevention
Code	Phrase
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Response
Code	Phrase
P301	IF SWALLOWED:
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P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
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P337	If eye irritation persists:
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P342	If experiencing respiratory symptoms:
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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.
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P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
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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.
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P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
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P337 + P313	IF eye irritation persists: Get medical advice/attention.
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Storage
Code	Phrase
P401
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P402 + P404	Store in a dry place. Store in a closed container.
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P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

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CAS No.: 720-94-5

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CAS No.: 720-94-5

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