50-43-1|2,4,6-Trichlorobenzoic acid| Ambeed

CAS No. :	50-43-1
Formula :	C₇H₃Cl₃O₂
M.W :	225.46
SMILES Code :	O=C(O)C1=C(Cl)C=C(Cl)C=C1Cl
MDL No. :	MFCD00060699
InChI Key :	RAFFVQBMVYYTQS-UHFFFAOYSA-N
Pubchem ID :	5764

Safety of [ 50-43-1 ]

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

Computational Chemistry of [ 50-43-1 ] Show Less

Physicochemical Properties

Num. heavy atoms	12
Num. arom. heavy atoms	6
Fraction Csp3	0.0
Num. rotatable bonds	1
Num. H-bond acceptors	2.0
Num. H-bond donors	1.0
Molar Refractivity	48.43
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	37.3 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.62
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	2.86
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	3.35
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.	3.36
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	3.16
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.87

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.34
Solubility	0.102 mg/ml ; 0.000453 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.	-3.3
Solubility	0.112 mg/ml ; 0.000499 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	-3.63
Solubility	0.0532 mg/ml ; 0.000236 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	No
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.	-5.64 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.	0.56

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	0.0 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)	1.28

Application In Synthesis of [ 50-43-1 ]

* 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 [ 50-43-1 ]

[ 50-43-1 ] Synthesis Path-Downstream 1~54

1
[ 50-43-1 ]
[ 4136-95-2 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride;Reflux;	A solution of <strong>[50-43-1]2,4,6-trichlorobenzoic acid</strong> (337 mg, 1.5 mmol) in SOCl2 (10 ml) was heated at reflux overnight and then cooled to room temperature. The reaction was concentrated under reduced pressure and to afford the desired acid chloride intermediate in quantitative yield. This material was used in the following step without purification
	With thionyl chloride; at 70℃; for 2h;	Step 1 )A solution of commercially available compound 1 (448 mg, 2 mmol) in SOC (5 mL) was stirred at 70 C for 2 h, followed by concentration under reduced pressure to afford compound 2 as the crude product.

References: [1]Journal of the American Chemical Society,1932,vol. 54,p. 4380,4382.
[2]Journal of the Chemical Society,1894,vol. 65,p. 1030.
[3]Bulletin of the Chemical Society of Japan,1979,vol. 52,p. 1989 - 1993.
[4]Bioorganic and Medicinal Chemistry Letters,2002,vol. 12,p. 171 - 175.
[5]Patent: US2010/317643,2010,A1 .Location in patent: Page/Page column 100.
[6]Patent: WO2013/72300,2013,A1 .Location in patent: Page/Page column 123.
[7]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 5513 - 5521.

2
[ 50-43-1 ]
[ 71372-03-7 ]

Yield	Reaction Conditions	Operation in experiment
	With nitric acid; In sulfuric acid;	PREPARATION 1 Concentrated sulfuric acid (2.8 ml) was added dropwise to 70% nitric acid (4.0 ml) in an ice-water bath. This mixture was added to a solution of <strong>[50-43-1]2,4,6-trichlorobenzoic acid</strong> (5.13 g) in concentrated sulfuric acid (23 ml) dropwise for 20 minutes in an ice-water bath. The mixture was stirred for 16 hours at ambient temperature and poured into ice-water (300 ml) slowly. This mixture was stirred for 1 hour at ambient temperature. The precipitate was collected by vacuum filtration and washed with water to give 2,4,6-trichloro-3-nitrobenzoic acid (5.26 g) as colorless fine crystals. mp: 162-164 C. NMR (CDCl3, delta): 5.72 (1H, br s), 7.60 (1H, s)

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1902,vol. 21,p. 384.
[2]Journal of Medicinal Chemistry,1998,vol. 41,p. 564 - 578.
[3]Patent: US5574042,1996,A .

3
[ 6575-05-9 ]
[ 50-43-1 ]

References: [1]Chemische Berichte,1894,vol. 27,p. 3151.
[2]Journal of the American Chemical Society,1932,vol. 54,p. 4380,4382.

4
[ 23749-65-7 ]
[ 50-43-1 ]

References: [1]Journal of the Chemical Society,1902,vol. 81,p. 1335.
Journal of the Chemical Society,1906,vol. 89,p. 1454.

5
[ 186581-53-3 ]
[ 50-43-1 ]
[ 86569-78-0 ]

References: [1]Journal of Organic Chemistry,1991,vol. 56,p. 103 - 110.

6
[ 108-70-3 ]
[ 124-38-9 ]
[ 50-43-1 ]

References: [1]Journal of Medicinal Chemistry,1991,vol. 34,p. 2843 - 2852.
[2]Liebigs Annalen der Chemie,1983,vol. No. 6,p. 939 - 949.

7
[ 50-43-1 ]
[ 23400-04-6 ]

References: [1]Journal of Organic Chemistry,1991,vol. 56,p. 103 - 110.

8
[ 14379-95-4 ]
[ 50-43-1 ]

References: [1]Journal of Organic Chemistry,1991,vol. 56,p. 103 - 110.

9
[ 24473-01-6 ]
[ 50-43-1 ]

References: [1]Bulletin de la Societe Chimique de France,1969,p. 3111 - 3115.

10
[ 30361-33-2 ]
[ 50-43-1 ]
C₁₇H₁₇Cl₃O₃ [ No CAS ]

References: [1]Tetrahedron,1995,vol. 51,p. 7347 - 7360.

11
[ 50-43-1 ]
(2S,3R)-2-(1-Carboxy-propyl)-3-hydroxy-pyrrolidine-1-carboxylic acid ethyl ester [ No CAS ]
(2S,3R)-3-Hydroxy-2-[1-(2,4,6-trichloro-benzoyloxycarbonyl)-propyl]-pyrrolidine-1-carboxylic acid ethyl ester [ No CAS ]

References: [1]Synlett,1998,p. 1378 - 1380.

12
[ 50-43-1 ]
(2R,3R)-2-(Carboxy-methylsulfanyl-methyl)-3-hydroxy-pyrrolidine-1-carboxylic acid ethyl ester [ No CAS ]
(2R,3R)-3-Hydroxy-2-[1-methylsulfanyl-2-oxo-2-(2,4,6-trichloro-benzoyloxy)-ethyl]-pyrrolidine-1-carboxylic acid ethyl ester [ No CAS ]

References: [1]Synlett,1998,p. 1378 - 1380.

13
[ 50-43-1 ]
(2S,3R)-2-(1-Carboxy-but-3-ynyl)-3-hydroxy-pyrrolidine-1-carboxylic acid ethyl ester [ No CAS ]
(2S,3R)-3-Hydroxy-2-[1-(2,4,6-trichloro-benzoyloxycarbonyl)-but-3-ynyl]-pyrrolidine-1-carboxylic acid ethyl ester [ No CAS ]

References: [1]Synlett,1998,p. 1378 - 1380.

14
[ 50-43-1 ]
(2S,3R)-2-(1-Carboxy-2-cyano-ethyl)-3-hydroxy-pyrrolidine-1-carboxylic acid ethyl ester [ No CAS ]
(2S,3R)-2-[2-Cyano-1-(2,4,6-trichloro-benzoyloxycarbonyl)-ethyl]-3-hydroxy-pyrrolidine-1-carboxylic acid ethyl ester [ No CAS ]

References: [1]Synlett,1998,p. 1378 - 1380.

15
[ 50-43-1 ]
(2R,3S)-2-(1-Carboxy-cyclopent-3-enyl)-3-hydroxy-pyrrolidine-1-carboxylic acid benzyl ester [ No CAS ]
(2R,3S)-3-Hydroxy-2-[1-(2,4,6-trichloro-benzoyloxycarbonyl)-cyclopent-3-enyl]-pyrrolidine-1-carboxylic acid benzyl ester [ No CAS ]

References: [1]Synlett,1998,p. 1378 - 1380.

16
[ 50-43-1 ]
(2S,3R)-2-(1-Carboxy-but-3-enyl)-3-hydroxy-pyrrolidine-1-carboxylic acid benzyl ester [ No CAS ]
(2S,3R)-3-Hydroxy-2-[1-(2,4,6-trichloro-benzoyloxycarbonyl)-but-3-enyl]-pyrrolidine-1-carboxylic acid benzyl ester [ No CAS ]

References: [1]Synlett,1998,p. 1378 - 1380.

Yield	Reaction Conditions	Operation in experiment
		Oakwood Products, Inc., 1741 Old Dunbar Road, West Columbia, S.C. 29172, USA. TCI America, 9211 N. Harborgate Street, Portland, Oreg. 97203, USA ... 2,3,4,5-tetrafluoro-6-chlorobenzoic acid; 3,4,5,6-tetrafluoro-2-hydroxy-benzoic acid; 2,3,5,6-tetrafluoro-4-methylbenzoic acid; 2,3,5,6-tetramethylbenzoic acid; 2,4,6-trichlorobenzoic acid; 2,3,4-trifluorobenzoic acid; 2,4,5-trifluorobenzoic acid; 2,4,6-trifluoro-3,5-dimethylbenzoic acid; ...

18
2.2.2-trichloro-1-<2.4.6-trichloro-phenyl>-ethanone-(1) [ No CAS ]
[ 50-43-1 ]

References: [1]Journal of the American Chemical Society,1937,vol. 59,p. 1508.

19
[ 50-43-1 ]
[ 7697-37-2 ]
[ 71372-03-7 ]

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1902,vol. 21,p. 384.

20
[ 7647-01-0 ]
[ 6575-05-9 ]
[ 50-43-1 ]

References: [1]Chemische Berichte,1894,vol. 27,p. 3132.

21
[ 23749-65-7 ]
[ 7697-37-2 ]
[ 50-43-1 ]

References: [1]Journal of the Chemical Society,1902,vol. 81,p. 1335.
Journal of the Chemical Society,1906,vol. 89,p. 1454.

22
[ 7664-93-9 ]
[ 23400-04-6 ]
sodium nitrite [ No CAS ]
[ 50-43-1 ]

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1902,vol. 21,p. 384.

23
[ 854651-12-0 ]
concentrated aq. NaOH solution [ No CAS ]
[ 50-43-1 ]

References: [1]Journal of the American Chemical Society,1932,vol. 54,p. 4380,4382.

24
[ 6324-50-1 ]
[ 124-38-9 ]
[ 50-43-1 ]
2,4,6-trichloro-3-iodobenzoic acid [ No CAS ]

References: [1]European Journal of Organic Chemistry,2001,p. 2771 - 2777.

25
[ 4136-95-2 ]
[ 50-43-1 ]

References: [1]Organic Letters,2006,vol. 8,p. 47 - 50.
[2]Journal of Chemical Research,2011,vol. 35,p. 647 - 653,7.

26
[ 50-43-1 ]
6-[1-(2,4,6-trichloro-benzoyloxy)-ethyl]-phenazine-1-carboxylic acid [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2002,vol. 12,p. 171 - 175.

27
[ 108-70-3 ]
[ 50-43-1 ]

References: [1]European Journal of Organic Chemistry,2001,p. 2771 - 2777.
[2]Journal of Organic Chemistry,1991,vol. 56,p. 103 - 110.

28
[ 50-43-1 ]
[ 160647-00-7 ]