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Chemical Structure| 10421-85-9 Chemical Structure| 10421-85-9

Structure of 10421-85-9

Chemical Structure| 10421-85-9

2-Chloromandelic acid

CAS No.: 10421-85-9

4.5 *For Research Use Only !

Cat. No.: A173070 Purity: 97%

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Product Details of [ 10421-85-9 ]

CAS No. :10421-85-9
Formula : C8H7ClO3
M.W : 186.59
SMILES Code : C1=C(C(C(O)=O)O)C(=CC=C1)Cl
MDL No. :MFCD00084962
InChI Key :RWOLDZZTBNYTMS-UHFFFAOYSA-N
Pubchem ID :97720

Safety of [ 10421-85-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 10421-85-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 44.16
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

57.53 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.13
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

1.62
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

1.13
Log Po/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.

1.37
Log Po/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

1.4
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.33

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-2.26
Solubility 1.04 mg/ml ; 0.00555 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.

-2.44
Solubility 0.677 mg/ml ; 0.00363 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

-1.86
Solubility 2.56 mg/ml ; 0.0137 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.

-6.29 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

1.0
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)

1.98

Application In Synthesis of [ 10421-85-9 ]

* 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 [ 10421-85-9 ]

[ 10421-85-9 ] Synthesis Path-Downstream   1~32

  • 1
  • [ 67-56-1 ]
  • [ 10421-85-9 ]
  • [ 156276-21-0 ]
YieldReaction ConditionsOperation in experiment
97% With sulfuric acid; at 60℃; General procedure: A few drops of conc. H2SO4 were added to a stirred solution of mandelic acid 6a (4.56 g, 29 mmol) in methanol (50 ml). The reaction was refluxed for 3 hours, after which the solvent was removed and the residue dissolved in ethyl acetate (25 ml). The product was washed with a 10% aqueous K2CO3 solution (2 x 50 ml) and then with brine (2 x 50 ml). The organic layer was dried (MgSO4) and reduced to give the title compound as a white crystalline solid,
With hydrogenchloride; In water; at 75℃; for 3.0h; Example 1. Preparing of racemic alkyl 2-chloromandelate[30][31] 2g of racemic <strong>[10421-85-9]2-chloromandelic acid</strong> was added to 40ml of methanol and 35 % HCl solution. The reaction was carried out at 75 0C for 3 hours. The reaction mixture was neutralized and racemic methyl 2-chloromandelate was gained by solvent extraction and distillation under reduced pressure. Racemic ethyl 2-chloromandelate and butyl <n="5"/>2-chloromandelate were synthesized using ethanol or buthanol, respectively instead of methanol. And the products were confirmed by nuclear magnetic resonance(Burker, Model DRS300).[32] Methyl 2-chloromandelate [33] 1H-NMR(CDCl , 300MHz) delta(ppm) = 3.76(s, 3H), 5.57(s, IH), 7.27(m, 2H), 7.39(m, 2H)[34] Ethyl 2-chloromandelate [35] 1H-NMR(CDCl , 300MHz) delta(ppm) = 1.21(t, 3H), 4.21(m, 2H), 5.54(s, IH), 7.27(m, 2H), 7.38(m, 2H)[36] Butyl 2-chloromandelate [37] 1H-NMR(CDCl , 300MHz) delta(ppm) = 0.83(t, 3H), 1.23(m, 2H), 1.54(m, 2H), 4.16(t, 2H), 5.56(s, IH), 7.25(m, 2H), 7.38(m, 2H)
With sulfuric acid; magnesium sulfate;Reflux; To a stirring solution of 1000 g racemic o-chloromandelic acid dissolved in 1 L methanol were added 120 g MgSO4 and 10 ml H2SO4. The mixture was refluxed with agitation until o-chloromandelic acid was completely consumed (as monitored by TLC). After cooled to room temperature, MgSO4, and methanol were removed by filtration and rotary evaporation. Then the mixture was neutralized by saturated Na2CO3 solution and dried over anhydrous Na2SO4 to give racemic CMM. To a stirring solution of 800 g CMM dissolved in 2 L CH2Cl2 and pre-cooled at 0-10oC was added Jones reagent which was prepared by adding grinded Cr2O3 powder (530 g) into stirring concentrated H2SO4 (460 ml) followed by diluting with water to 2 L. The progress of the reaction was monitored by TLC analysis till the reaction was completed. The organic layer was separated and washed with saturated Na2CO3 solution, dried over anhydrous Na2SO4 and evaporated to give CBFM as pale yellow oil with an isolated yield of 82%. 1H NMR (CDCl3, 400 MHz): delta/ppm: 3.96 (3H, s, OCH3), 7.41-7.46 (2H, m, Ar-H), 7.51-7.54 (1H, m, Ar-H), 7.75-7.78 (1H, m, Ar-H); 13C NMR (CDCl3, 100 MHz): delta/ppm: 53.9, 127.9, 131.2, 132.2, 133.9, 134.5, 135.0, 164.1, 186.9.
With toluene-4-sulfonic acid; In toluene; for 2.0h;Reflux; General procedure: A mixture of mandelic acid(12 mmol), alcohol (1.5 eq) , TsOH (500 mg) and toluene(20mL) wasrefluxed for 2 h. The resultant mixture was diluted with NaHCO3(sat.aq.)(3X10mL) and water( 2X10mL) and dried over Na2SO4.Flash chromatography on silica gel (eluent: ethyl acetate/petroleum ether =6:1) gave the correspondingracemic mandelate ester.
With sulfuric acid; at 80℃; for 3.0h; Example 3. Preparing racemic 2-chloro-2-(2-chloro phenyl)acetic acid alkyl ester(ld, Ie, If); [52][53] 3g of <strong>[10421-85-9]2-chloromandelic acid</strong> was dissolved into 40 ml of methanol and after adding88 D of HSO , the mixture was heated and stirred at 80 0C for 3 hours. After removing solvent, water and ethyl acetate were added, then NaOH was added for neutralization. The product was extracted and distilled under reduced pressure. 2.1 ml of sulfonyl chloride was added to the previously produced substance and after 12 hours of stirring at 65 0C, solvent was removed. 2-chloro-2-(2-chloro phenyl)acetic acid methyl ester was prepared by adding water and ethyl acetate and washing 3 times. Furthermore, by using ethanol and butanol instead of methanol, 2-chloro-2-(2-chloro phenyl)acetic acid ethyl ester and 2-chloro-2-(2-chloro phenyl)acetic acid butyl ester were prepared respectively.[54] 2-chloro-2-(2-chloro phenyl)acetic acid methyl ester(ld):[55] 1H-NMRQOOMHz) delta(ppm) = 3.79(s, IH), 5.88(s, IH), 7.31(m,2H), 7.40(m,lH),7.63(m, IH)[56][57] 2-chloro-2-(2-chloro phenyl)acetic acid ethyl ester(le):[58] 1H-NMRQOOMHz) delta(ppm) = 1.26(t, 3H, J=14.1 Hz), 4.25(m, IH), 5.86(s, IH),7.32(m, 2H), 7.40(m, IH), 7.63(m, IH)[59][60] 2-chloro-2-(2-chloro phenyl)aceetic acid butyl ester(lf) :[61] 1H-NMRQOOMHz) delta(ppm) = O.88(t, 3H, J=14.4 Hz), 1.3 l(m, 2H), 1.61(m, 2H),4.19(t, 2H, J=13.5 Hz), 5.87(s, IH), 7.32(m, 2H), 7.40(m, IH), 7.63(m, IH)

  • 3
  • [ 13312-84-0 ]
  • [ 10421-85-9 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; water; In 1,4-dioxane; for 6.0h;Reflux; General procedure: A mixture of cyanohydrin (14 mmol), 37% HCl (5mL) and dioxane (10 mL) was refluxed for 6 h. The resultant mixture was dilutedwith water (10mL) and extracted with ethyl acetate (3X10mL).The pH value of the organic phase was adjusted to pH=2 with NaHCO3(sat.aq.). The aqueous phase was extracted with ethyl acetate (3X10mL).Thecombined organic phase was washed with brine (3×10 mL) and dried over Na2SO4. Flash chromatographyon silica gel (eluent: ethyl acetate/petroleum ether =2:1) gave the corresponding racemicmandelic acid
  • 5
  • [ 10421-85-9 ]
  • [ 80173-43-9 ]
  • 6
  • [ 10421-85-9 ]
  • [ 75-36-5 ]
  • [ 178437-75-7 ]
  • 8
  • [ 10421-85-9 ]
  • [ 77-78-1 ]
  • [ 35599-96-3 ]
  • 9
  • [ 64-17-5 ]
  • [ 10421-85-9 ]
  • [ 62123-75-5 ]
  • 10
  • [ 10421-85-9 ]
  • [ 10421-85-9 ]
YieldReaction ConditionsOperation in experiment
53% General procedure: A mixture of 1.52g (10mmol) racemic mandelic acid MA, 0.27g (2.5mmol) of Na2CO3, and 0.80g (5.0mmol) of (R)-(-)-3-(aminomethyl)-5-methylhexanoic acid (R)-PREG was dissolved in 6.1mL of hot water. The crystalline diastereomeric salt appeared by gradually cooling down the solution to 26C and was then separated from the mother liquor by filtration after 15min. In order to decompose the diastereomer, a mixture of 1.9mL of 25% aqueous ammonia and 2.0mL of water was added to the crystals. Next, 0.70g (4.4mmol) of crystalline (R)-(-)-3-(aminomethyl)-5-methylhexanoic acid (R)-PREG was filtered off after 3h of crystallization time, after which 1.5mL of 37% hydrochloric acid was added to the mother liquor to afford 0.43g (56%) of (R)-(-)-mandelic acid (R)-MA with an eeD of 80% that was separated from the mother liquor after 2h of crystallization (Table 2, entry 1).
  • 12
  • [ 10421-85-9 ]
  • [ 64-04-0 ]
  • [ 132274-47-6 ]
  • 13
  • [ 10421-85-9 ]
  • [ 156-41-2 ]
  • [ 132274-48-7 ]
  • 14
  • [ 591-50-4 ]
  • [ 10421-85-9 ]
  • 1-(2-chlorophenyl)-1-(4-iodophenyl)acetic acid [ No CAS ]
  • 15
  • [ 10421-85-9 ]
  • [ 70918-95-5 ]
  • (2-Chloro-phenyl)-(1-isopropyl-1H-benzoimidazol-2-yl)-methanol [ No CAS ]
  • 16
  • phosphoric acid (2-chloro-phenyl)-dicyano-methyl ester diethyl ester [ No CAS ]
  • [ 10421-85-9 ]
  • 17
  • [ 13011-88-6 ]
  • periodic acid [ No CAS ]
  • [ 10421-85-9 ]
  • [ 144-62-7 ]
  • 18
  • [ 13011-88-6 ]
  • alkaline aqueous sodium hypoiodite solution [ No CAS ]
  • [ 10421-85-9 ]
  • [ 144-62-7 ]
YieldReaction ConditionsOperation in experiment
Substitution in the procedure of example 2 for the D-(-)-2-formyloxy-2-phenylacetyl chloride used therein of an equimolar quantity of monosubstituted D-(-)-2-formyloxy-2-phenylacetyl chloride prepared from the following monosubstituted D-mandelic acids: D-2-chloro-mandelic acid; D-3-chloro-mandelic acid, D-4-chloro-mandelic acid, D-2-bromo-mandelic acid, D-3-bromo-mandelic acid, D-4-bromo-mandelic acid, D-2-fluoro-mandelic acid, D-3-fluoro-mandelic acid, D-4-fluoro-mandelic acid, ...
Substitution in the procedure of example 2 for the D-(-)-2-formyloxy-2-phenylacetyl chloride used therein of an equimolar quantity of a D-mandelic acid carboxyanhydride prepared from the following D-mandelic acids by treating the mandelic acid with phosgene as described supra. D-2-chloro-mandelic acid, D-3-chloro-mandelic acid, D-4-chloro-mandelic acid, D-2-bromo-mandelic acid, D-3-bromo-mandelic acid, D-4-bromo-mandelic acid, D-2-fluoro-mandelic acid, D-3-fluoro-mandelic acid, D-4-fluoro-mandelic acid, ...
Substitution for the D-mandelic acid carboxyanhydride in the procedure of Example 1 of an equimolar weight of the carboxyanhydrides prepared in similar fashion from the monosubstituted D-mandelic acids D-2-chloro-mandelic acid, D-3-chloro-mandelic acid, D-4-chloro-mandelic acid, D-2-bromo-mandelic acid, D-3-bromo-mandelic acid, D-4-bromo-mandelic acid, D-2-fluoro-mandelic acid, D-3-fluoro-mandelic acid, D-4-fluoro-mandelic acid, ...
Substitution for the D-mandelic acid carboxyanhydride in the procedure of Example 10 of an equimolar weight of the carboxyanhydrides prepared in similar fashion from the monosubstituted D-mandelic acids D-2-chloro-mandelic acid, D-3-chloro-mandelic acid, D-4-chloro-mandelic acid, D-2-bromo-mandelic acid, D-3-bromo-mandelic acid, D-4-bromo-mandelic acid, D-2-fluoro-mandelic acid, D-3-fluoro-mandelic acid, D-4-fluoro-mandelic acid, ...
Substitution of the D-mandelic acid carboxyanhydride in the procedure of Example 1 of an equimolar weight of the carboxyanhydrides prepared in similar fashion from the monosubstituted D-mandelic acids D-2-chloro-mandelic acid, D-3-chloro-mandelic acid, D-4-chloro-mandelic acid, D-2-bromo-mandelic acid, D-3-bromo-mandelic acid, D-4-bromo-mandelic acid, D-2-fluoro-mandelic acid, D-3-fluoro-mandelic acid, D-4-fluoro-mandelic acid, ...

  • 21
  • [ 75-25-2 ]
  • [ 89-98-5 ]
  • [ 10421-85-9 ]
  • 22
  • [ 10421-85-9 ]
  • [ 503-38-8 ]
  • 5-(2-chloro-phenyl)-[1,3]dioxolane-2,4-dione [ No CAS ]
  • 23
  • [ 10421-85-9 ]
  • [ 89-98-5 ]
  • [ 118-91-2 ]
  • 25
  • [ 10421-85-9 ]
  • [ 181039-78-1 ]
  • 26
  • [ 10421-85-9 ]
  • [ 181039-77-0 ]
  • 27
  • [ 10421-85-9 ]
  • (RS)-(2-chlorophenyl)-[2-cyano-5-(pyridin-4-ylmethoxy)-phenoxy]acetic acid [ No CAS ]
  • 28
  • [ 10421-85-9 ]
  • (RS)-(2-chlorophenyl)-[2-cyano-5-(thien-3-ylmethoxy)-phenoxy]acetic acid [ No CAS ]
  • 29
  • [ 10421-85-9 ]
  • [ 181039-80-5 ]
  • 30
  • [ 10421-85-9 ]
  • [ 181040-28-8 ]
  • 31
  • [ 10421-85-9 ]
  • [ 181039-85-0 ]
  • 32
  • [ 10421-85-9 ]
  • (RS)-(2-chlorophenyl)-[2-cyano-5-(pyridazin-4-yl-methoxy)phenoxy]acetic acid [ No CAS ]
 

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Technical Information

Categories

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