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Chemical Structure| 928-51-8 Chemical Structure| 928-51-8

Structure of 4-Chloro-1-butanol
CAS No.: 928-51-8

Chemical Structure| 928-51-8

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Product Details of [ 928-51-8 ]

CAS No. :928-51-8
Formula : C4H9ClO
M.W : 108.57
SMILES Code : OCCCCCl
MDL No. :MFCD00002967
InChI Key :HXHGULXINZUGJX-UHFFFAOYSA-N
Pubchem ID :13569

Safety of [ 928-51-8 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H226-H290-H302-H314-H335-H351
Precautionary Statements:P210-P233-P234-P240-P241-P242-P243-P261-P264-P270-P271-P273-P280-P301+P312+P330-P301+P330+P331-P303+P361+P353-P304+P340+P310-P305+P351+P338+P310-P363-P370+P378-P390-P403+P233-P403+P235-P405-P406-P501
Class:3(8)
UN#:2924
Packing Group:

Computational Chemistry of [ 928-51-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 6
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 3
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 27.3
TPSA ?

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

20.23 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.6
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

0.85
Log Po/w (WLOGP)?

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

1.0
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.

1.16
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

1.1
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.14

Water Solubility

Log S (ESOL):?

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

-0.85
Solubility 15.3 mg/ml ; 0.141 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-0.86
Solubility 15.1 mg/ml ; 0.139 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very 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

-1.48
Solubility 3.64 mg/ml ; 0.0335 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.

-6.36 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

3.0
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)

1.55

Application In Synthesis of [ 928-51-8 ]

* 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 [ 928-51-8 ]

[ 928-51-8 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 110-91-8 ]
  • [ 928-51-8 ]
  • [ 5835-79-0 ]
YieldReaction ConditionsOperation in experiment
35% EXAMPLE 3; l -(4-Hydroxybutyl)morpholine was prepared as follows. In a 250 mL flask was mixed morpholine (65.5 g, 750 mmol), 4-chlorobutanol (27.2 g, 250 mmol), sodium iodide (3.8 g, 25 mmol) and 75 mL of dioxane. The reaction was heated to reflux. <n="76"/>After 2 days the reaction was allowed to cool to ambient temperature. Solvent was removed by rotary evaporation leaving a brown oil. The oil was dissolved in 100 mL of 2N NaOH, extracted with EtOAc and dried over Na2SO4. After filtration of the drying agent solvent was removed in vacuo leaving an orange oil. The oil was distilled (90 0C, 1 mm Hg), leaving 1 - (4-hydroxylbutyl)morpholine ( 13.9 g, 87 mmol, 35 % yield) as a colorless oil.
  • 2
  • [ 928-51-8 ]
  • [ 1813-33-8 ]
  • [ 131084-28-1 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; In tetrahydrofuran; tetrahydrofuran, ethyl bromide; EXAMPLE 17 1'-[4-[1-(4-Fluorophenyl)-5-trifluoromethylindazol-3-yl]-1-butyl]spiro]isobenzofuran-1(3H),4'-piperidine], 17a. To a suspension of magnesium turnings (135 g) in 300 ml of dry tetrahydrofuran, ethyl bromide (140 g) dissolved in 500 ml of dry tetrahydrofuran was slowly added followed by reflux for 20 min. A solution of 4-chloro-1-butanol (274 g) in 500 ml of tetrahydrofuran was added dropwise at reflux temperature. After stirring for 20 min, the Grignard solution was filtered and added portionwise to a solution of <strong>[1813-33-8]2-chloro-4-trifluoromethyl-benzonitril</strong> (200 g) in 600 ml of dry tetrahydrofuran. The reaction mixture was stirred for 16 h at room temperature followed by addition af 2N hydrochloric acid and ice. Extraction with ether, drying of the ether phase over magnesium sulfate and removal of solvent in vacuo left a viscous oil which was applied to a silica gel column (eluent:dichloromethane/ether=3:1) giving 4-(2-chloro-5-trifluoromethylbenzoyl)-1-butanol (101 g) as an oil.
  • 3
  • [ 928-51-8 ]
  • [ 14437-03-7 ]
  • 4-chlorobutyl tosylcarbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% at 100℃; for 0.333333h;Sealed tube; Microwave irradiation; General procedure: The 4-substituted methyl (phenylsulfonyl)carbamate was dissolved in the chosen alcohol (2 mL) in a microwave vial, which was closed using an aluminum open-top seal with PTFE-faced septum. The reaction mixture was heated under microwave irradiation at 100-120 oC for 20-60 min. The crude reaction mixture was concentrated under reduced pressure and the residue was purified using silica gel column chromatography to yield the desired (aryl)carbamate.
  • 4
  • [ 928-51-8 ]
  • [ 6223-83-2 ]
  • C18H15ClO3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
2.84 g With toluene-4-sulfonic acid; In toluene; at 90℃; for 5.0h;Dean-Stark; In the reaction (R-3), the compound (A-1) and the compound (B-1) were reacted to obtain a compound (C-1). Hereinafter, the compound (A-1) is sometimes described as the first raw material of the reaction (R-3) and the compound (B-1) is described as the second raw material of the reaction (R-3). 2.24 g (0.01 mol) of the compound (A-1), 3.26 g (0.03 mol) of the compound (B-1) and toluene (100 mL) were added to the flask, The contents of the flask were dissolved. Into the flask, p-toluenesulfonic acid (0.001 mol) was added. The flask was set in a Dean-Stark apparatus. The content of the flask was heated at 90 C. for 5 hours, It was refluxed while dehydrating. The content of the obtained flask was depressurized, Toluene was distilled off. Ion exchanged water was added to the mixture after distillation under reduced pressure, and the mixture was extracted with chloroform. After drying the obtained organic layer, The organic layer was depressurized and chloroform was distilled off. As a result, the compound (C-1) was obtained as a crude product. The yield of the compound (C-1) was 2.84 g, and the yield of the compound (C-1) from the compound (A-1) was 90 mol%.
  • 5
  • [ 928-51-8 ]
  • [ 381-98-6 ]
  • C8H10ClF3O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
34 g With toluene-4-sulfonic acid; In di-isopropyl ether; cyclohexene; for 12h;Dean-Stark; Reflux; In a reaction vessel equipped with a Dean-Stark apparatus, 20.0 g of a compound represented by the formula (D-6-4)28.4 g of 2-trifluoromethylacrylic acid,1.8 g of p-toluenesulfonic acid monohydrate,300 mL of cyclohexane,150 mL of diisopropyl ether was added.And heated under reflux for 12 hours while removing water.It was diluted with dichloromethane and washed sequentially with a 5% aqueous sodium hydrogen carbonate solution and brine.Purification was carried out by column chromatography (silica gel, dichloromethane)34.0 g of a compound represented by the formula (D-6-5) was obtained.
34 g With toluene-4-sulfonic acid; In di-isopropyl ether; cyclohexane; for 12h;Dean-Stark; Reflux; 20.0 g of the compound represented by the formula (I-6-10), 28.4 g of acrylic acid, 1.8 g of p-toluenesulfonic acid monohydrate, 300 mL of cyclohexane and 150 mL of diisopropyl ether were put into a reactor equipped with a Dean-Stark apparatus, and heated under reflux for 12 hours while removing water. This was diluted with dichloromethane, and washed sequentially with an aqueous solution of 5% sodium hydrogencarbonate, and salt water. Purification through column chromatography (silica gel, dichloromethane) gave 34.0 g of the compound of the formula (I-6-12).
  • 6
  • [ 5521-61-9 ]
  • [ 928-51-8 ]
  • C10H13ClN2O2 [ No CAS ]
 

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