928-51-8

Basic information

• Product Name: 4-Chloro-1-butanol
• Synonyms: 4-CHLORO-1-BUTANOL;4-CHLOROBUTANOL;4-CHLOROBUTANOL-1;TETRAMETHYLENE CHLOROHYDRIN;1-Butanol, 4-chloro-;4-Chlorbutan-1-ol;4-Chloro-1-butane-ol;4-chloro-1-butano
• CAS NO: 928-51-8
• Molecular Formula: C₄H₉ClO
• Molecular Weight: 108.57
• EINECS: 213-175-5
• Product Categories: omega-Chloroalkanols;omega-Functional Alkanols, Carboxylic Acids, Amines & Halides;Alcohols;Building Blocks;C2 to C6;Chemical Synthesis;Organic Building Blocks;Oxygen Compounds;API Intermediate
• Mol File: 928-51-8.mol
• Article Data: 18

Chemical Properties

• Boiling Point: 84-85 °C16 mm Hg(lit.)
• Flash Point: 97 °F
• Appearance: Clear colorless to light yellow/Liquid
• Density: 1.088 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.296mmHg at 25°C
• Refractive Index: n20/D 1.453(lit.)
• Storage Temp.: 2-8°C
• Solubility: Soluble in methanol, chloroform, and dimethyl sufoxide.
• PKA: 15.01±0.10(Predicted)
• BRN: 1731408
• CAS DataBase Reference: 4-Chloro-1-butanol(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Chloro-1-butanol(928-51-8)
• EPA Substance Registry System: 4-Chloro-1-butanol(928-51-8)

Safety Data

• Hazard Codes: Xn,C,F
• Statements: 10-22-36/37/38-20/21/22-34-40
• Safety Statements: 23-24/25-36/37/39-26-16-36/37
• RIDADR: UN 2920 8/PG 2
• WGK Germany: 3
• RTECS: EL1325000
• TSCA: Yes
• HazardClass: 3.2
• PackingGroup: III
• Hazardous Substances Data: 928-51-8(Hazardous Substances Data)

Usage

Chemical Properties

CLEAR COLOURLESS LIQUID

Uses

Different sources of media describe the Uses of 928-51-8 differently. You can refer to the following data:
1. Tetramethylene chlorohydrin is used inorganic synthesis.
2. 4-Chloro-1-butanol is employed as an internal standard in the analysis of genotoxic impurities in active pharmaceutical ingredients by GC-MS technique.
3. 4-Chloro-1-butanol was employed as an internal standard in the analysis of genotoxic impurities in active pharmaceutical ingredients by GC-MS technique.

Definition

ChEBI: A primary alcohol that is butan-1-ol substituted by a chloro group at position 4.

General Description

4-Chloro-1-butanol, an alkylating agent, is one of the genotoxic impurity in active pharmaceutical ingredients. Reaction of 4-chloro-1-butanol and Reichardt′s dye has been monitored spectrophotometrically for the determination of genotoxic impurities in pharmaceuticals.

Health Hazard

The toxicity of this compound is low. How ever, the acute toxic symptoms are those ofethylene and propylene chlorohydrins. Oralintake of this compound caused muscle con traction, gastrointestinal pain, ulceration, andliver injury in test animals.LD50 value, oral (mice): 990 mg/kgTetramethylene chlorohydrin caused tumorsin lungs in test animals. Its carcinogenicity,however, is not yet fully established.

Fire Hazard

Flammable; flash point 36°C (97°F); vapor density 3.7 (air = 1); the vapor forms an explosive mixture with air, range is not reported. Fire-extinguishing agent: “alcohol” foam; a water spray may be used to cool fire-exposed containers and to flush any spill. It decomposes to HCl and tetrahydrofuran on heating.

Safety Profile

Moderately toxic by ingestion. Questionable carcinogen with experimental neoplastigenic data. Mutation data reported. When heated to decomposition it emits toxic fumes of Cl-. See also CHLORIDES and ALCOHOLS.

Waste Disposal

Tetramethylene chlorohydrin is burned ina chemical incinerator equipped with anafterburner and scrubber.

InChI:InChI=1/C4H9ClO/c5-3-1-2-4-6/h6H,1-4H2

Synthetic route

1-chloro-4-tetrahydropyranyloxybutane (41302-05-0) → 4-Chloro-1-butanol (928-51-8)

Conditions	Yield
ammonium cerium(IV) nitrate In alkaline aq. solution; acetonitrile at 70℃; for 2h; pH=8; Decomposition;	86%

4-Chlorobutyl acetate (6962-92-1) → 4-Chloro-1-butanol (928-51-8)

Conditions	Yield
With toluene-4-sulfonic acid In methanol for 4h; Heating;	85.4%

tetrahydrofuran (109-99-9) → 4-Chloro-1-butanol (928-51-8)

Conditions	Yield
With hydrogenchloride for 5h; Heating;	82%
With hydrogenchloride Heating;	57%
With hydrogenchloride	55%

Butane-1,4-diol (110-63-4) → 4-Chloro-1-butanol (928-51-8)

Conditions	Yield
With pyridine; thionyl chloride at 80℃; for 1h;	36%
With hydrogenchloride; bismuth(III) chloride; silica gel at 80℃;
With disulfur dichloride anfangs auf dem Wasserbad, danach auf 150grad;
With pyridine; thionyl chloride at 55℃;
With thionyl chloride In chloroform for 5h; Inert atmosphere;

oxirane (75-21-8) + chloroethane (75-00-3) → 4-Chloro-1-butanol (928-51-8)

Conditions	Yield
With aluminium trichloride

tetrahydrofuran (109-99-9) → silicic acid tetrakis-(4-chloro-butyl ester) (17898-52-1) + 4-Chloro-1-butanol (928-51-8)

Conditions	Yield
With hydrogenchloride; tetrachlorosilane

trichloroacetic 4-chlorobutyl ester (84273-54-1) → 4-Chloro-1-butanol (928-51-8)

Conditions	Yield
With sodium hydroxide

3-butenyl chloride (927-73-1) → 4-chloro-2-butanol (2203-34-1) + 4-Chloro-1-butanol (928-51-8)

Conditions	Yield
(i) B2H6, THF, H2O, (ii) NaOH, H2O2; Multistep reaction;

3-butenyl chloride (927-73-1) → 4-Chloro-1-butanol (928-51-8)

Conditions	Yield
(i) bis-(2-methyl-butyl)-borane, THF, H2O, (ii) NaOH, H2O2; Multistep reaction;

1,4-dichlorobutane (110-56-5) → 4-Chloro-1-butanol (928-51-8)

Conditions	Yield
(i) SbF5, SO2, (ii) acetone, (iii) Na2CO3, MeOH; Multistep reaction;

1-chloro-4-tetrahydropyranyloxybutane (41302-05-0) → 4-Chloro-1-butanol (928-51-8) + 5-hydroxy-pentanoic acid 4-chloro-butyl ester

Conditions	Yield
With aluminum oxide; Oxone; water In methanol at 50℃; Yield given; Yields of byproduct given;

tetrahydrofuran (109-99-9) + hydrogenchloride (7647-01-0) → 4-Chloro-1-butanol (928-51-8)

oxirane (75-21-8) + aluminium trichloride (7446-70-0) + chloroethane (75-00-3) → 4-Chloro-1-butanol (928-51-8)

pyridine (110-86-1) + thionyl chloride (7719-09-7) + Butane-1,4-diol (110-63-4) → 4-Chloro-1-butanol (928-51-8)

Conditions	Yield
at 55℃;

hydrogenchloride (7647-01-0) + methanol (67-56-1) + 4-Chlorobutyl acetate (6962-92-1) → 4-Chloro-1-butanol (928-51-8)

Conditions	Yield
at 40℃;

<4-chloro--acetate → 4-Chloro-1-butanol (928-51-8)

Conditions	Yield
With hydrogenchloride; methanol at 40℃;

Butane-1,4-diol (110-63-4) + disulfur dichloride → 4-Chloro-1-butanol (928-51-8)

Conditions	Yield
zuletzt auf 150grad;

diethyl ether (60-29-7) + γ-chlorobutyric acid (627-00-9) + lithium alanate → tetrahydrofuran (109-99-9) + 4-Chloro-1-butanol (928-51-8) + butan-1-ol (71-36-3)

boron trichloride (10294-34-5) → 4-Chloro-1-butanol (928-51-8) + bis(4-chlorobutyloxy)chloroborane (98997-54-7)

1-(4-chlorobutoxy)-2,2,6,6-tetramethylpiperidine → 4-Chloro-1-butanol (928-51-8)

Conditions	Yield
With acetic acid; zinc In tetrahydrofuran for 12h; Schlenk technique; Inert atmosphere;

Butane-1,4-diol (110-63-4) → 1,3-dichlorobutane (1190-22-3) + 4-Chloro-1-butanol (928-51-8) + bis-(4-chlorobutyl)ether (6334-96-9) + 1,4-dichlorobutane (110-56-5)

Conditions	Yield
With Tributylphosphine oxide; bis(trichloromethyl) carbonate at 50 - 60℃; Reagent/catalyst; Large scale;

4-Chloro-1-butanol (928-51-8) + 2-methyldiphenylsilyl-1,3-dithiane (135746-47-3) → 4-[1-(methyl-diphenyl-silyl)-2,6-dithiacyclohexyl]-1-butanol

Conditions	Yield
With lithium diisopropyl amide In tetrahydrofuran at -78℃;	100%

4-Chloro-1-butanol (928-51-8) + aniline (62-53-3) → N-phenylpyrrolidine (4096-21-3)

Conditions	Yield
With iron(III) chloride hexahydrate	100%

3,4-dihydro-2H-pyran (110-87-2) + 4-Chloro-1-butanol (928-51-8) → 1-chloro-4-tetrahydropyranyloxybutane (41302-05-0)

Conditions	Yield
With pyridinium p-toluenesulfonate In dichloromethane at 20℃;	99%
pyridinium p-toluenesulfonate In dichloromethane for 8h; Ambient temperature;	98%
With pyridinium p-toluenesulfonate In dichloromethane for 7h; Ambient temperature;	97%

4-Chloro-1-butanol (928-51-8) + tert-butyldimethylsilyl chloride (18162-48-6) → 4-(t-butyldimethylsiloxy)-1-chlorobutane (89031-83-4)

Conditions	Yield
Stage #1: 4-Chloro-1-butanol; tert-butyldimethylsilyl chloride In dichloromethane at 0℃; for 0.5h; Inert atmosphere; Stage #2: With 1H-imidazole In dichloromethane at 0℃; for 1.5h; Inert atmosphere;	99%
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; Substitution;	93%
With 1H-imidazole In dichloromethane at 0 - 20℃; for 4h;	50%

4-Chloro-1-butanol (928-51-8) + p-toluenesulfonyl chloride (98-59-9) → 4-chlorobutyl 4-methylbenzenesulfonate (20999-32-0)

Conditions	Yield
With dmap; triethylamine In dichloromethane at 20℃; for 1.5h;	99%
With pyridine In chloroform at 0℃; for 2.5h;	85%
With pyridine at 0℃; for 2h; Inert atmosphere;	79%
With pyridine In tetrahydrofuran for 20h; Ambient temperature;	49%
With pyridine at 0℃; for 3.5h;

2-(trimethylsilyl)-1,3-dithiane (13411-42-2) + 4-Chloro-1-butanol (928-51-8) → 4-(2-Trimethylsilanyl-[1,3]dithian-2-yl)-butan-1-ol (78633-24-6)

Conditions	Yield
With lithium diisopropyl amide In tetrahydrofuran at -78℃;	99%
With lithium diisopropyl amide In tetrahydrofuran at -78℃;	97%

4-Chloro-1-butanol (928-51-8) + 2-(phenylsulfonyl)tetrahydro-2H-pyran (96754-03-9) → 1-chloro-4-tetrahydropyranyloxybutane (41302-05-0)

Conditions	Yield
With sodium hydrogencarbonate; magnesium bromide In tetrahydrofuran Ambient temperature; overnight (15-24 hrs);	97%
With sodium hydrogencarbonate; magnesium bromide In tetrahydrofuran Ambient temperature;	97%

4-Chloro-1-butanol (928-51-8) + Tetramethylammonium hydrogen carbonate (58345-96-3) → butylene carbonate (4427-94-5)

Conditions	Yield
In acetonitrile	97%

4-Chloro-1-butanol (928-51-8) + 4-nitro-benzoyl chloride (122-04-3) → δ-chlorobutyl 4-nitrobenzoate (58168-12-0)

Conditions	Yield
With triethylamine In dichloromethane at 0℃; for 2h;	96%
With triethylamine In dichloromethane at 0 - 20℃; for 2h;	96%
With triethylamine In dichloromethane at 0 - 20℃; for 2h;	96%
With triethylamine In chloroform for 18h; Ambient temperature;	68%

4-Chloro-1-butanol (928-51-8) + benzyl mesylate (55791-06-5) → [(4-chlorobutoxy)methyl]benzene (50873-93-3)

Conditions	Yield
With magnesium oxide; lithium trifluoromethanesulfonate; lithium tetrakis(pentafluorophenyl)borate In dichloromethane; cyclohexane at 20℃; for 24h;	96%

4-Chloro-1-butanol (928-51-8) + sodium thiomethoxide (5188-07-8) → 4-(methylthio)-1-butanol (20582-85-8)

Conditions	Yield
With sodium iodide In ethanol at 20℃; for 12h;	95%
In water at 25℃; for 48h;	72%
With ethanol
In water

4-Chloro-1-butanol (928-51-8) + acryloyl chloride (814-68-6) → 4-chloro-1-butanol acrylate (2206-87-3)

Conditions	Yield
With triethylamine In dichloromethane at 0℃;	95%
With triethylamine In benzene
With triethylamine In chloroform at 0℃;
With triethylamine In chloroform at 10℃; for 12h;

4-Chloro-1-butanol (928-51-8) + isobutene (115-11-7) → 1-(tert-butoxy)-4-chlorobutane (104164-65-0)

Conditions	Yield
Amberlyst H-15 In hexane	95%
With Amberlyst H-15 In hexane at 20℃; for 15h;	95%
With Amberlyst 15 In hexane at 20℃; for 8h;	95%
With sulfuric acid
Amberlyst H-15 In hexane Ambient temperature; Yield given;

4-Chloro-1-butanol (928-51-8) + L-phenylalanine (63-91-2) → L-phenylalanine 4-chlorobutyl ester hydrochloride (131326-15-3)

Conditions	Yield
With hydrogenchloride at 40℃; for 19h;	95%

4-Chloro-1-butanol (928-51-8) + 1-(4-Fluorophenyl)piperazine (2252-63-3) → 4-[4-(4-fluorophenyl)piperazin-1-yl]butan-1-ol (1156220-20-0)

Conditions	Yield
With cesium hydroxide; sodium iodide at 60℃; for 0.05h; Microwave irradiation; Neat (no solvent); chemoselective reaction;	95%

4-Chloro-1-butanol (928-51-8) + chloro-diphenylphosphine (1079-66-9) → 4-chlorobutyl diphenylphosphinite (1346017-23-9)

Conditions	Yield
With potassium carbonate In dichloromethane at -5℃; for 5h;	95%

4-Chloro-1-butanol (928-51-8) → 4-chlorobutyraldehyde (6139-84-0)

Conditions	Yield
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hydrogencarbonate; sodium bromide In dichloromethane; water at 25℃; Electrolysis; Saturated solution;	94%
With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -78℃; Swern Oxidation; Inert atmosphere;	90%
With oxalyl dichloride In dimethyl sulfoxide	85%

4-Chloro-1-butanol (928-51-8) + 1-chloro-1-methylsiletane (2351-34-0) → 1-(4-Chloro-butoxy)-1-methyl-siletane

Conditions	Yield
With urea at 50℃; for 4h;	94%

4-Chloro-1-butanol (928-51-8) + trimethylamine (75-50-3) → (4-hydroxy-butyl)-trimethyl-ammonium; chloride (125422-10-8)

Conditions	Yield
In water; acetonitrile at 70℃; for 18h; Inert atmosphere;	94%
In water for 24h; Heating / reflux;	94%
In water; acetonitrile at 70℃; for 14h;

TETRAHYDROPYRANE (142-68-7) + 4-Chloro-1-butanol (928-51-8) → 1-chloro-4-tetrahydropyranyloxybutane (41302-05-0)

Conditions	Yield
In dichloromethane at 0 - 20℃; for 2h; Inert atmosphere;	94%

1-vinylimidazole (1072-63-5) + 4-Chloro-1-butanol (928-51-8) → C9H15N2O(1+)*Cl(1-)

Conditions	Yield
In water at 80℃;	94%

4-Chloro-1-butanol (928-51-8) + sodium 1-buthanethiolate (4779-86-6) → n-butyl 4-hydroxybutyl sulfide (5331-34-0)

Conditions	Yield
In methanol for 2h; Heating;	92%

4-Chloro-1-butanol (928-51-8) + acetoacetic acid methyl ester (105-45-3) → (4'-Chloro-1'-butyl)-3-oxobutanoate (91116-20-0)

Conditions	Yield
With dmap In cyclohexane for 16h; Heating;	92%
With dmap In cyclohexane for 16h; Heating;	92%

4-Chloro-1-butanol (928-51-8) + para-thiocresol (106-45-6) → 4-(p-tolylthio)butan-1-ol (27975-48-0)

Conditions	Yield
With sodium ethanolate In ethanol at 0 - 20℃;	92%

1-methyl-1H-imidazole (616-47-7) + 4-Chloro-1-butanol (928-51-8) → 3-(4-hydroxybutyl)-1-methyl-1H-imidazol-3-ium chloride

Conditions	Yield
at 80℃; for 4h; Neat (no solvent);	92%
at 80℃; for 4h;	92%
at 80℃; for 5h;	89%
at 80℃; for 24h;

4-Chloro-1-butanol (928-51-8) + methylhydrazine (60-34-4) → 4-(1-methylhydrazinyl)butan-1-ol

Conditions	Yield
In neat liquid at 20℃; for 24h; Inert atmosphere;	92%

4-Chloro-1-butanol (928-51-8) + ethyl vinyl ether (109-92-2) → 1-Chlor-3-(1'-aethoxyaethoxy)-butan (52500-29-5)

Conditions	Yield
With dichloro-acetic acid at 0℃; for 12h; Addition;	90%
With trifluoroacetic acid for 24h; Ambient temperature;	86%
With toluene-4-sulfonic acid at 0℃; for 1.5h;	67%

4-Chloro-1-butanol (928-51-8) + sodium thioethylate (811-51-8) → 4-(ethylthio)-1-butanol (18721-62-5)

Conditions	Yield
	90%

4-Chloro-1-butanol (928-51-8) + trifluoroacetic anhydride (407-25-0) → 4-chlorobutanol-1-trifluoromethanesulfonate (103935-55-3)

Conditions	Yield
With dmap; potassium carbonate In dichloromethane at -50℃; for 1h;	90%

1-(2-Methoxyphenyl)piperazine (35386-24-4) + 4-Chloro-1-butanol (928-51-8) → 4-[4-(2-methoxyphenyl)piperazin-1-yl]butan-1-ol (40004-65-7)

Conditions	Yield
With cesium hydroxide; sodium iodide at 55℃; for 1h; Microwave irradiation; Neat (no solvent); chemoselective reaction;	90%

Upstream product

• 75-21-8 oxirane 
• 75-00-3 chloroethane 
• 84273-54-1 trichloroacetic 4-chlorobutyl ester 
• 6962-92-1 4-Chlorobutyl acetate 
• 41302-05-0 1-chloro-4-tetrahydropyranyloxybutane 
• 60-29-7 diethyl ether 
• 627-00-9 γ-chlorobutyric acid 
• 110-63-4 Butane-1,4-diol 
• 10294-34-5 boron trichloride 
• 7647-01-0 hydrogenchloride 
• 67-56-1 methanol 
• 110-86-1 pyridine 
• 7719-09-7 thionyl chloride 
• 7446-70-0 aluminium trichloride 

Downstream Products

• 4672-11-1 4-piperidin-1-yl-butan-1-ol 
• 41302-05-0 1-chloro-4-tetrahydropyranyloxybutane 
• 92493-12-4 4-(4-phenyl-piperazin-1-yl)-butan-1-ol 
• 20582-85-8 4-(methylthio)-1-butanol 
• 109-99-9 tetrahydrofuran 
• 123-75-1 pyrrolidine 
• 6940-78-9 4-chlorobutyl bromide 
• 627-00-9 γ-chlorobutyric acid 
• 13325-10-5 4-Aminobutanol 
• 79448-06-9 4,4’-azanediylbis(butan-1-ol) 
• 14970-83-3 4-Mercapto-1-butanol 
• 84157-94-8 4-hydroxybutylhydrazine 
• 6334-96-9 bis-(4-chlorobutyl)ether 
• 26978-64-3 4-hydroxy-butane-1-sulfonic acid 

Relevant articles and documents

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