320-72-9|3,5-Dichloro-2-hydroxybenzoic acid| Ambeed

CAS No. :	320-72-9
Formula :	C₇H₄Cl₂O₃
M.W :	207.01
SMILES Code :	OC(=O)C1=CC(Cl)=CC(Cl)=C1O
MDL No. :	MFCD00002442
InChI Key :	CNJGWCQEGROXEE-UHFFFAOYSA-N
Pubchem ID :	9445

Safety of [ 320-72-9 ]

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

Computational Chemistry of [ 320-72-9 ] 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	3.0
Num. H-bond donors	2.0
Molar Refractivity	45.44
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	57.53 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.6
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	3.31
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.4
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.	2.17
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	2.04
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.1

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.51
Solubility	0.0636 mg/ml ; 0.000307 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.	-4.19
Solubility	0.0132 mg/ml ; 0.000064 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately 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	-2.43
Solubility	0.762 mg/ml ; 0.00368 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.	-5.21 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)	1.37

Application In Synthesis of [ 320-72-9 ]

* 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 [ 320-72-9 ]

[ 320-72-9 ] Synthesis Path-Downstream 1~54

1
[ 20300-61-2 ]
[ 320-72-9 ]

References: [1]Journal of the Chemical Society,1924,vol. 125,p. 561.

2
[ 13334-73-1 ]
[ 320-72-9 ]

References: [1]Gazzetta Chimica Italiana,1899,vol. 29 II,p. 60.

3
[ 84473-96-1 ]
[ 320-72-9 ]

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1954,vol. 73,p. 1022,1026.

4
[ 320-72-9 ]
[ 2040-83-7 ]

References: [1]Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences,1928,vol. 186,p. 1555.

5
[ 320-72-9 ]
[ 609-89-2 ]

References: [1]American Chemical Journal,1886,vol. 8,p. 98.
Jahresbericht ueber die Fortschritte der Chemie und Verwandter Theile Anderer Wissenschaften,1886,p. 1441.

6
[ 320-72-9 ]
[ 6641-02-7 ]

References: [1]Chemische Berichte,1906,vol. 39,p. 2938.
[2]Organic Letters,2019,vol. 21,p. 7258 - 7261.

7
[ 320-72-9 ]
[ 40932-60-3 ]

References: [1]Tetrahedron Letters,2019,vol. 60,p. 1032 - 1036.
[2]Australian Journal of Chemistry,1984,vol. 37,p. 73 - 86.
[3]Journal of the American Chemical Society,1940,vol. 62,p. 1237,1240.

8
[ 320-72-9 ]
[ 39614-80-7 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; In N,N-dimethyl-formamide; toluene;	Step 1 Production of 3,5-dichloro-2-hydroxybenzoyl chloride 3,5-Dichloro-2-hydroxybenzoic acid (600 mg) was suspended in toluene (6 mL), and thionyl chloride (0.275 mL) and N,N-dimethylformamide (1 drop) were added. After stirring with heating at 70 C. for 2 hrs, and the mixture was concentrated and azeotroped with toluene to give the title compound as a pale-yellow solid.
	With thionyl chloride;N,N-dimethyl-formamide; In dichloromethane;Heating / reflux;	25 g of <strong>[320-72-9]3,5-dichlorosalicylic acid</strong> were suspended in 150 ml dichloromethane and 30 ml of thionyl chloride and 0.5 ml of DMF were added. The mixture was refluxed until a clear solution was obtained and the solvent evaporated, the temperature being maintained below 40 C., to yield a product used as such in Preparation 2. 1H NMR (DMSO-d6): 9.92 (1H,s), 7.98 (1H, d, J=2 Hz), 7.68 (1H, d, J=2 Hz)
	With thionyl chloride; In dichloromethane; N,N-dimethyl-formamide; at 40℃;Heating / reflux;	Preparation 1 3,5-Dichloro-2-hydroxy-benzoyl chloride 25 g of <strong>[320-72-9]3,5-dichlorosalicylic acid</strong> were suspended in 150 ml dichloromethane and 30 ml of thionyl chloride and 0.5 ml of DMF were added. The mixture was refluxed until a clear solution was obtained and the solvent evaporated, the temperature being maintained below 40 C., to yield a product used as such in Preparation 2. 1H NMR (DMSO-d6): 9.92 (1H,s), 7.98 (1H, d, J=2 Hz), 7.68 (1H, d, J=2 Hz)

	With thionyl chloride; In N,N-dimethyl-formamide; toluene; at 70℃; for 2h;	Step 1 Production of 3,5-dichloro-2-hydroxybenzoyl chloride 3,5-Dichloro-2-hydroxybenzoic acid (600 mg) was suspended in toluene (6 mL), and thionyl chloride (0.275 mL) and N,N-dimethylformamide (1 drop) were added. After stirring with heating at 70 C. for 2 hrs, and the mixture was concentrated and azeotroped with toluene to give the title compound as a pale-yellow solid.
	With thionyl chloride;N,N-dimethyl-formamide; In toluene; at 0 - 70℃; for 2h;	Step 1 Production of 3,5-dichloro-2-hydroxybenzoyl chloride 3,5-Dichloro-2-hydroxybenzoic acid (600 mg) was suspended in toluene (6 mL), and thionyl chloride (0.275 mL) and N,N-dimethylformamide (1 drop) were added. After stirring with heating at 70 C. for 2 hrs, and the mixture was concentrated and azeotroped with toluene to give the title compound as a pale-yellow solid.

References: [1]Justus Liebigs Annalen der Chemie,1906,vol. 346,p. 301.
[2]Arzneimittel-Forschung/Drug Research,1993,vol. 43,p. 689 - 694.
[3]Journal of Medicinal Chemistry,1998,vol. 41,p. 2939 - 2945.
[4]Russian Journal of General Chemistry,2004,vol. 74,p. 738 - 743.
[5]Synthetic Communications,2005,vol. 35,p. 55 - 66.
[6]Patent: US2008/305169,2008,A1 .
[7]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 3173 - 3177.
[8]Patent: US2005/124664,2005,A1 .Location in patent: Page/Page column 14.
[9]Patent: US2005/143384,2005,A1 .Location in patent: Page/Page column 14; 15.
[10]Patent: US2007/10670,2007,A1 .Location in patent: Page/Page column 93.
[11]Journal of Medicinal Chemistry,2011,vol. 54,p. 5403 - 5413.
[12]Journal of Medicinal Chemistry,2015,vol. 58,p. 6678 - 6696.
[13]Patent: US2008/64871,2008,A1 .Location in patent: Page/Page column 56.
[14]Patent: DE89596, .
Fortschr. Teerfarbenfabr. Verw. Industriezweige,vol. 4,p. 156.
[15]Angewandte Chemie - International Edition,2019,vol. 58,p. 12476 - 12480.
Angew. Chem.,2019,vol. 131,p. 12606 - 12610,5.

9
[ 320-72-9 ]
[ 68276-69-7 ]

References: [1]Gazzetta Chimica Italiana,1899,vol. 29 II,p. 60.

10
[ 320-72-9 ]
3,5-dichloro-2-tetrachlorophosphoranyloxy-benzoyl chloride [ No CAS ]

References: [1]Justus Liebigs Annalen der Chemie,1927,vol. 454,p. 107.

11
[ 320-72-9 ]
[ 120-83-2 ]

References: [1]Justus Liebigs Annalen der Chemie,1891,vol. 261,p. 254.

12
[ 1820-99-1 ]
[ 320-72-9 ]

References: [1]Journal of the Indian Chemical Society,1948,vol. 25,p. 43,44.

13
3.5-dichloro-2-(buten-(2<i>t</i>)-yloxy)-benzoic acid [ No CAS ]
[ 320-72-9 ]
[ 861009-44-1 ]

References: [1]Journal of the American Chemical Society,1942,vol. 64,p. 607,611.
[2]Journal of the American Chemical Society,1942,vol. 64,p. 607,611.

14
[ 908104-88-1 ]
[ 320-72-9 ]

References: [1]Chemische Berichte,1904,vol. 37,p. 4027.

15
[ 518978-12-6 ]
[ 320-72-9 ]
3,5-dichloro-2-hydroxy-benzoic acid benzyl ester [ No CAS ]

References: [1]Journal of the American Chemical Society,1943,vol. 65,p. 2149,2151.
[2]Journal of the American Chemical Society,1943,vol. 65,p. 2149,2151.
[3]Journal of the American Chemical Society,1943,vol. 65,p. 2149,2151.

16
[ 855471-02-2 ]
[ 320-72-9 ]
3,5-dichloro-2-hydroxy-benzoic acid-[2]naphthylmethyl ester [ No CAS ]

References: [1]Journal of the American Chemical Society,1943,vol. 65,p. 2149,2151.

17
3,5-dichloro-2-hydroxy-benzoic acid-(1-chloro-[2]naphthyl ester) [ No CAS ]
[ 633-99-8 ]
[ 320-72-9 ]

References: [1]Gazzetta Chimica Italiana,1898,vol. 28 I,p. 154,155.

18
[ 855471-00-0 ]
[ 320-72-9 ]
[ 855156-69-3 ]

References: [1]Journal of the American Chemical Society,1943,vol. 65,p. 2149,2151.

19
[ 855471-00-0 ]
[ 320-72-9 ]
[ 855156-69-3 ]
[ 15719-64-9 ]

References: [1]Journal of the American Chemical Society,1943,vol. 65,p. 2149,2151.

20
[ 320-72-9 ]
[ 141-43-5 ]
[ 410527-03-6 ]

References: [1]Patent: US2714082,1953, .

21
[ 500310-54-3 ]
[ 121-69-7 ]
[ 7606-87-3 ]
[ 320-72-9 ]

References: [1]Journal of the American Chemical Society,1942,vol. 64,p. 607,611.

22
[ 518978-12-6 ]
[ 121-69-7 ]
[ 320-72-9 ]
3,5-dichloro-2-hydroxy-benzoic acid benzyl ester [ No CAS ]

References: [1]Journal of the American Chemical Society,1943,vol. 65,p. 2149,2151.

23
[ 69-72-7 ]
[ 321-14-2 ]
[ 320-72-9 ]

References: [1]American Chemical Journal,1879,vol. 1,p. 176.
Chemische Berichte,1880,vol. 13,p. 34.
[2]Journal of Physical Chemistry,1980,vol. 84,p. 629 - 631.
[3]American Chemical Journal,1890,vol. 12,p. 505.
[4]Journal fur praktische Chemie (Leipzig 1954),1876,vol. <2> 13,p. 427.

24
[ 69-72-7 ]
[ 320-72-9 ]

References: [1]Russian Journal of General Chemistry,2004,vol. 74,p. 738 - 743.
[2]Synthetic Communications,2012,vol. 42,p. 3655 - 3663,9.
[3]Tetrahedron,1996,vol. 52,p. 8863 - 8866.
[4]American Chemical Journal,1890,vol. 12,p. 505.
[5]Chemische Berichte,1878,vol. 11,p. 1225.
[6]Gazzetta Chimica Italiana,1900,vol. 30 II,p. 491.
[7]Proceedings - Indian Academy of Sciences, Section A,1938,vol. <A> 8,p. 208,212, 213.
[8],1939,vol. 66,p. 191.
Chemisches Zentralblatt,1939,vol. 110,p. 961.
[9]Bulletin de la Societe Chimique de France,1927,vol. <4> 41,p. 1363.
[10]Journal of the American Chemical Society,1919,vol. 41,p. 2037.

25
[ 111-87-5 ]
[ 320-72-9 ]
[ 71527-64-5 ]

References: [1]Australian Journal of Chemistry,1984,vol. 37,p. 73 - 86.

26
[ 123-51-3 ]
[ 320-72-9 ]
[ 71527-63-4 ]

References: [1]Australian Journal of Chemistry,1984,vol. 37,p. 73 - 86.

27
[ 71-41-0 ]
[ 320-72-9 ]
[ 71527-62-3 ]

References: [1]Australian Journal of Chemistry,1984,vol. 37,p. 73 - 86.

28
[ 321-14-2 ]
[ 320-72-9 ]

References: [1]Australian Journal of Chemistry,1984,vol. 37,p. 73 - 86.

29
[ 320-72-9 ]
[ 13194-68-8 ]
[ 90425-98-2 ]

References: [1]Chemical and Pharmaceutical Bulletin,1984,vol. 32,p. 305 - 312.

30
[ 320-72-9 ]
[ 367-25-9 ]
[ 80033-99-4 ]

References: [1]Chemical and Pharmaceutical Bulletin,1984,vol. 32,p. 305 - 312.

31
[ 320-72-9 ]
[ 20244-55-7 ]

References: [1]Australian Journal of Chemistry,1984,vol. 37,p. 73 - 86.

32
[ 320-72-9 ]
[ 87-87-6 ]
[ 40932-60-3 ]
[ 118-75-2 ]
tri(3,5,6-trichlorosalicylide) [ No CAS ]

References: [1]Australian Journal of Chemistry,1984,vol. 37,p. 73 - 86.
[2]Australian Journal of Chemistry,1984,vol. 37,p. 73 - 86.

33
[ 54223-75-5 ]
[ 320-72-9 ]
[ 64-19-7 ]

References: [1]Chemical and Pharmaceutical Bulletin,1984,vol. 32,p. 3715 - 3719.

34
[ 320-72-9 ]
[ 108-24-7 ]
[ 54223-75-5 ]

References: [1]Journal of Medicinal Chemistry,1985,vol. 28,p. 328 - 332.
[2]Chemical and Pharmaceutical Bulletin,1984,vol. 32,p. 3715 - 3719.
[3]Australian Journal of Chemistry,1984,vol. 37,p. 73 - 86.

35
[ 320-72-9 ]
[ 554-00-7 ]
[ 4214-45-3 ]

References: [1]Chemical and Pharmaceutical Bulletin,1984,vol. 32,p. 305 - 312.

36
[ 320-72-9 ]
[ 89-63-4 ]
[ 90426-05-4 ]

References: [1]Chemical and Pharmaceutical Bulletin,1984,vol. 32,p. 305 - 312.

37
[ 320-72-9 ]
[ 137-07-5 ]
[ 30616-42-3 ]

References: [1]Journal of the Chemical Society. Perkin transactions II,1984,p. 2111 - 2118.

38
[ 320-72-9 ]
[ 77-78-1 ]
[ 64122-23-2 ]

References: [1]Liebigs Annalen der Chemie,1989,p. 863 - 882.

39
[ 320-72-9 ]
[ 583-75-5 ]
[ 79402-03-2 ]

References: [1]Chemical and Pharmaceutical Bulletin,1984,vol. 32,p. 305 - 312.

40
[ 97-05-2 ]
[ 320-72-9 ]

References: [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1984,vol. 23,p. 575 - 576.

41
[ 320-72-9 ]
[ 99-52-5 ]
[ 90426-03-2 ]

References: [1]Chemical and Pharmaceutical Bulletin,1984,vol. 32,p. 305 - 312.

42
[ 320-72-9 ]
[ 95-69-2 ]
[ 79402-01-0 ]

References: [1]Chemical and Pharmaceutical Bulletin,1984,vol. 32,p. 305 - 312.

43
[ 320-72-9 ]
[ 71-36-3 ]
[ 71527-61-2 ]

References: [1]Australian Journal of Chemistry,1984,vol. 37,p. 73 - 86.

44
[ 67-56-1 ]
[ 320-72-9 ]
[ 7606-87-3 ]

Yield	Reaction Conditions	Operation in experiment
80%	With sulfuric acid; for 10h;Reflux;	Compound (I'-54): A mixture of 1.5 g (7.25 mmole) of 3,5-dichloro salicylic acid, 0.71 g of concentrated sulfuric acid and methanol was heated to reflux with stirring for 10 hours. The reaction solution was concentrated under reduced pressure, and was alkalified with saturated NaHCO3. The precipitated crystal was filtered to give 1.0 g (80%) of a title compound as a colorless crystal. 1H-NMR(CDCl3): delta(ppm) 3.96 (3H, s), 7.73 (1H, d, J=2.5Hz), 7.89 (1H, dd, J=2.5, 0.5Hz), 10.99 (1H, br).

References: [1]Patent: EP2208728,2010,A1 .Location in patent: Page/Page column 48.
[2]Australian Journal of Chemistry,1960,vol. 13,p. 95 - 102.

45
[ 320-72-9 ]
[ 106-49-0 ]
[ 50728-73-9 ]