1820-81-1

Basic information

• Product Name: 5-Chlorouracil
• Synonyms: TIMTEC-BB SBB004103;2,4(1H,3H)-Pyrimidinedione,5-chloro-;2,4-Pyrimidinediol,5-chloro-;3h)-pyrimidinedione,5-chloro-4(1h;5-Chlor-2,4-dihydroxypyrimidin;5-Chloro-1H-pyrimidine-2,4-dione;5-Chloro-2,4-pyrimidinedione;5-chloro-uraci
• CAS NO: 1820-81-1
• Molecular Formula: C₄H₃ClN₂O₂
• Molecular Weight: 146.53
• EINECS: 217-339-7
• Product Categories: PYRIMIDINE;Pyridines, Pyrimidines, Purines and Pteredines;Pyrimidine series;Heterocyclic Compounds;Biochemistry;Nucleobases and their analogs;Nucleosides, Nucleotides & Related Reagents;Nucleic acids;Bases & Related Reagents;Heterocycles;Nucleotides
• Mol File: 1820-81-1.mol
• Article Data: 15

Chemical Properties

• Melting Point: >300 °C(lit.)
• Boiling Point: 413.6 °C at 760 mmHg
• Flash Point: 203.9 °C
• Appearance: white to light beige crystalline powder
• Density: 1.6838 (rough estimate)
• Vapor Pressure: 1.98E-07mmHg at 25°C
• Refractive Index: 1.6550 (estimate)
• Storage Temp.: Refrigerator
• Solubility: 1 M NH4OH: soluble50mg/mL
• PKA: 6.77±0.10(Predicted)
• Water Solubility: 2.501g/L(25 oC)
• BRN: 127173
• CAS DataBase Reference: 5-Chlorouracil(CAS DataBase Reference)
• NIST Chemistry Reference: 5-Chlorouracil(1820-81-1)
• EPA Substance Registry System: 5-Chlorouracil(1820-81-1)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 22-24/25-36-26
• WGK Germany: 3
• RTECS: YQ9410000
• Hazardous Substances Data: 1820-81-1(Hazardous Substances Data)

Usage

Chemical Properties

white to light beige crystalline powder

Uses

Different sources of media describe the Uses of 1820-81-1 differently. You can refer to the following data:
1. 5-Chlorouracil was used as a control in resazurin-based cytotoxicity assay for screening of cytotoxicity in hepatocytes and liver cell lines.
2. 5-Chlorouracil can be used for the experimental and clinical treatment of neoplastic and viral diseases.

Definition

ChEBI: An organochlorine compound consisting of uracil having an chloro substituent at the 5-position.

General Description

The shape resonance spectra of 5-chlorouracil, obtained from fixed-nuclei elastic scattering calculations by the Schwinger multichannel method with pseudopotentials, was studied.

Purification Methods

It recrystallises from hot H2O (4g/500mL) using charcoal. [McOmie et al. J Chem Soc 3478 1955, West & Barrett J Am Chem Soc 76 3146 1954, Beilstein 24 III/IV 1231.]

InChI:InChI=1/C4H3ClN2O2/c5-2-1-6-4(9)7-3(2)8/h1H,(H2,6,7,8,9)

Synthetic route

uracil (66-22-8) → 5-chlorouracil (1820-81-1)

Conditions	Yield
With 1,2-Dichloro-3-iodobenzene In water; acetic acid at 80℃; for 0.25h;	92%
With hydrogenchloride; ammonium cerium(IV) nitrate In methanol at 70℃; for 5.5h;	82%
With sodium hydrogencarbonate; lithium chloride In acetonitrile Ambient temperature; electrolysis (Pt electrodes, SCE reference, LiClO4 as supporting electrolyte);	77%
With potassium phosphate; potassium chloride; dihydrogen peroxide; chloroperoxidase pH 3;	7%

5-chloro-2,4-dimethoxypyrimidine (123551-49-5) → 5-chlorouracil (1820-81-1)

Conditions	Yield
With hydrogenchloride	69%

5-methoxycarbonyluracil → 5-chlorouracil (1820-81-1)

Conditions	Yield
With hydrogenchloride; chlorine In water for 16h; Heating;	63%

uracil (66-22-8) → 5-chlorouracil (1820-81-1) + 5,5-dichloro-6-hydroxy-5,6-dihydrouracil (2072-83-5)

Conditions	Yield
With sodium persulfate; water; sodium chloride In acetic acid at 100 - 105℃;	A 20% B 53%
With sodium persulfate; water; sodium chloride In acetic acid at 100 - 105℃;	A 20% B 53%

5-chloro-6-hydroxy-5-methoxycarbonyl-5,6-dihydrouracil (65906-87-8) → 5-chlorouracil (1820-81-1)

Conditions	Yield
With hydrogenchloride In water for 15h; Heating;	27%
In hydrogenchloride

N-chloro-succinimide (128-09-6) + acetic anhydride (108-24-7) + acetic acid (64-19-7) + uracil (66-22-8) → 5-chlorouracil (1820-81-1)

N-chloro-succinimide (128-09-6) + uracil (66-22-8) → 5-chlorouracil (1820-81-1)

2-ethylmercapto-5-chloro-3H-pyrimidin-4-one (106146-79-6) → 5-chlorouracil (1820-81-1)

Conditions	Yield
With hydrogenchloride

1-α-D-arabinopyranosyl-5-chloro-1H-pyrimidine-2,4-dione → 5-chlorouracil (1820-81-1)

Conditions	Yield
With hydrogenchloride

1-acetyl-1H-pyrimidine-2,4-dione (40338-28-1) → 5-chlorouracil (1820-81-1)

Conditions	Yield
Yield given. Multistep reaction;

5-Chloro-6-hydroxyamino-dihydro-pyrimidine-2,4-dione → 5-chlorouracil (1820-81-1)

Conditions	Yield
With hydroxylamine at 25℃; Equilibrium constant; var. pH;

(+-)-5,5-dichloro-6-methoxy-dihydro-pyrimidine-2,4-dione → 5-chlorouracil (1820-81-1)

Conditions	Yield
With hydrogenchloride; tin

5.5-dichloro-4-oxy-dihydrouracil → 5-chlorouracil (1820-81-1)

Conditions	Yield
With hydrogenchloride; tin

uracil (66-22-8) → 5-chlorouracil (1820-81-1) + 5.5-dichloro-4-oxy-dihydrouracil

Conditions	Yield
With chlorine

5-chloro-2'-deoxyuridine (50-90-8) → 5-chlorouracil (1820-81-1)

Conditions	Yield
With phosphate buffer; thymidine phosphorylase from Escherichia coli at 37℃; pH=7; Enzyme kinetics; Further Variations:; concentration of reagent;

methyl 2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (42821-92-1) → 5-chlorouracil (1820-81-1)

Conditions	Yield
With hydrogenchloride In water

5-chlorouracil (1820-81-1) → C4H4ClN2O2 (65094-55-5)

Conditions	Yield
With H2SO4 glasses Product distribution; Irradiation;	100%

chloro-trimethyl-silane (75-77-4) + 5-chlorouracil (1820-81-1) → 5-chloro-2,4-bis-O-trimethylsilyluracil (58990-53-7)

Conditions	Yield
With 1,1,1,3,3,3-hexamethyl-disilazane Ambient temperature;	99%

5-chlorouracil (1820-81-1) + sodium thiophenolate (930-69-8) → 5-(phenylsulfanyl)-2,4(1H,3H)-pyrimidinedione (1137-90-2)

Conditions	Yield
In N,N,N,N,N,N-hexamethylphosphoric triamide at 150℃; for 0.0833333h; microwave irradiation;	97%

5-chlorouracil (1820-81-1) + ethyl acrylate (140-88-5) → 3-(5-chloro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)propionic acid ethyl ester (1370413-72-1)

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 60℃; Aza-Micheal reaction;	96%

5-chlorouracil (1820-81-1) → 2,4,5-trichloropyrimidine (5750-76-5)

Conditions	Yield
With phosphorus pentachloride; trichlorophosphate Neat (no solvent); Heating / reflux;	95%
With phosgene; Triphenylphosphine oxide In nitrobenzene at -5 - 125℃; for 0.833333h; Inert atmosphere;	93%
With N,N-diethylaniline; trichlorophosphate at 110℃; for 24h;	81%

5-chlorouracil (1820-81-1) + 1,1,1,3,3,3-hexamethyl-disilazane (999-97-3) → 5-chloro-2,4-bis-O-trimethylsilyluracil (58990-53-7)

Conditions	Yield
With ammonium sulfate for 5h; Heating;	95%
With chloro-trimethyl-silane Heating;
With ammonium sulfate for 3h; Heating;

5-chlorouracil (1820-81-1) + acrylic acid methyl ester (292638-85-8) → 3-(5-chloro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)propionic acid methyl ester (1256346-76-5)

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 60℃; for 4h; Michael Addition;	95%
With triethylamine In N,N-dimethyl-formamide at 20℃; Michael-type addition; regioselective reaction;	88%

5-chlorouracil (1820-81-1) + acrylic acid n-butyl ester (141-32-2) → 3-(5-chloro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)propionic acid butyl ester (1370413-75-4)

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 60℃; Aza-Micheal reaction;	95%

5-chlorouracil (1820-81-1) + 1-chloro-2,4-dinitro-benzene (97-00-7) → 1-(2,4-dinitro-phenyl)-5-chloro-1H-pyrimidine-2,4-dione

Conditions	Yield
With zinc(II) oxide at 130℃; for 0.1h; Ionic liquid; Microwave irradiation;	92%

5-chlorouracil (1820-81-1) → 5-Chloro-4-thiouracil (63331-62-4)

Conditions	Yield
With diphosphorus pentasulfide; sodium hydrogencarbonate In diethylene glycol dimethyl ether at 110℃; for 3h;	90%

5-chlorouracil (1820-81-1) + α-D-glucopyranose peracetylate (604-68-2) → 5-chloro-1-(2,3,4,6-tetra-O-acetyl-β-D-gluco-hexopyranosyl)uracil (379218-39-0)

Conditions	Yield
Stage #1: 5-chlorouracil With 1,1,1,3,3,3-hexamethyl-disilazane; saccharin In acetonitrile for 3h; Heating; Stage #2: α-D-glucopyranose peracetylate With trimethylsilyl trifluoromethanesulfonate In acetonitrile at 20 - 85℃;	90%

5-chlorouracil (1820-81-1) + benzylamine (100-46-9) → 5-(benzylamino)dihydropyrimidine-2,4(1H,3H)-dione (28485-19-0)

Conditions	Yield
at 150℃; for 0.333333h; microwave irradiation;	88%

5-chlorouracil (1820-81-1) + 1,8-diazabicyclo[5.4.0]undec-7-ene (6674-22-2) → 2,3,4,6,7,8,9,10-octahydro-pyrimido[1,2-a]azepine; compound with 5-chloro-1H-pyrimidine-2,4-dione

Conditions	Yield
In acetonitrile at 20℃;	87%

5-chlorouracil (1820-81-1) + adenosine (58-61-7) → C4H3ClN2O2*C10H13N5O4 (1369492-08-9)

Conditions	Yield
In ethanol; chloroform; water for 8h; Reflux;	84%

5-chlorouracil (1820-81-1) + [Zn(OH)(hydrotris(3-tert-butyl-5-isopropyl-1-pyrazolyl)borate)] → [Zn(hydrotris(3-tert-butyl-5-isopropyl-1-pyrazolyl)borate)(5-chlorouracilate)]

Conditions	Yield
In methanol; dichloromethane (N2); using Schlenk techniques; addn. of suspn. of 5-chlorouracil in methanol to soln. of Zn(HB(Me3CC3HN2CHMe2)3)(OH) in CH2Cl2; stirring overnight; filtration, evapn. of solvent, drying under vac., elem. anal.;	81%

5-chlorouracil (1820-81-1) + N-hydroxy-4-methylbenzenecarboximidoyl chloride (36288-37-6) → 6-chloro-3-(p-tolyl)-5H-[1,2,4]oxadiazolo[4,5-a]pyrimidin-5-one

Conditions	Yield
With dmap In 1,4-dioxane for 5h; Reflux;	80%

5-chlorouracil (1820-81-1) + trimethylsilyl trifluoromethanesulfonate (27607-77-8) + 3,4,6-tris-O-tert-butyldimethylsilyl-1,2-anhydro-α-D-glucopyranose (121654-00-0) → 1-[3′,4′,6′-tri-O-(tert-butyldimethylsilyl)-2-O-trimethylsilyl-β-D-glucopyranosyl]-5-chloro-2,4(1H,3H)-pyrimidinedione

Conditions	Yield
Stage #1: 5-chlorouracil With 1,1,1,3,3,3-hexamethyl-disilazane at 120℃; for 1.5h; Inert atmosphere; Stage #2: trimethylsilyl trifluoromethanesulfonate; 3,4,6-tris-O-tert-butyldimethylsilyl-1,2-anhydro-α-D-glucopyranose at 60℃; for 3h; Inert atmosphere;	80%

5-chlorouracil (1820-81-1) + 4-ethyl-N-hydroxybenzene-1-carboximidoyl chloride (61946-91-6) → 6-chloro-3-(4-ethylphenyl)-5H-[1,2,4]oxadiazolo[4,5-a]pyrimidin-5-one

Conditions	Yield
With dmap In 1,4-dioxane for 5h; Reflux;	79%

5-chlorouracil (1820-81-1) + trimethylsilyl trifluoromethanesulfonate (27607-77-8) + 1,2-anhydro-3,4,6-tri-O-benzyl-β-D-mannopyranose (74372-90-0, 112289-38-0, 135202-48-1, 148888-66-8, 71696-32-7) → 1-[3′,4′,6′-tri-O-(benzyl)-2-O-trimethylsilyl-glucopyranosyl]-5-chloro-2,4(1H,3H)-pyrimidinedione

Conditions	Yield
Stage #1: 5-chlorouracil With 1,1,1,3,3,3-hexamethyl-disilazane at 120℃; for 1.5h; Inert atmosphere; Stage #2: trimethylsilyl trifluoromethanesulfonate; 1,2-anhydro-3,4,6-tri-O-benzyl-β-D-mannopyranose at 60℃; for 3h; Inert atmosphere;	79%

1,2,3,5-tetra-O-acetyl-3-C-ethynyl-D-ribo-pentofuranose (848644-37-1) + 5-chlorouracil (1820-81-1) → 1-[2,3,5-tri-O-acetyl-3-C-ethynyl-β-D-ribo-pentofuranosyl]-5-chlorouracil (848644-41-7)

Conditions	Yield
With N,O-bis-(trimethylsilyl)-acetamide; trimethylsilyl trifluoromethanesulfonate In acetonitrile at 50℃; for 29h;	78%

5-chlorouracil (1820-81-1) + acrylonitrile (107-13-1) → C7H6ClN3O2

Conditions	Yield
With triethylamine In water at 100℃; for 0.0833333h; Michael addition; microwave irradiation;	78%

5-chlorouracil (1820-81-1) + (bromomethyl)pentafluorobenzene (1765-40-8) → N1,N3-bis(pentafluorobenzyl)-5-chlorouracil

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In methanol at 42℃; for 2h;	77%

5-chlorouracil (1820-81-1) + chromium chloride hexahydrate + His (4998-57-6) → Cr(3+)*C4H2N2O2Cl(1-)*C6H8N3O2(1-)*H2O*Cl(1-) = Cr(C4H2N2O2Cl)(C6H8N3O2)(H2O)Cl (203308-39-8)

Conditions	Yield
With triethyl formate; aq. NaOH In ethanol; water addn. aq. histidine to pptd. (pH 5-6, aq. NaOH) suspn. of metal/5-chlorouracil complex in ethanol; pptn. on concn. and ether addn., drying (vac., 50°C); elem. anal.;	75%

5-chlorouracil (1820-81-1) + allyl bromide (106-95-6) → N-allyl 5-chlorouracil

Conditions	Yield
With sodium hydroxide In water at 100℃; for 0.166667h; Microwave irradiation; regioselective reaction;	75%

5-chlorouracil (1820-81-1) → 5-chloro-6-deuteropyrimidine-2,4(1H,3H)-dione

Conditions	Yield
With [D]-sodium hydroxide; sodium In water-d2 at 0 - 120℃; Inert atmosphere;	75%

5-chlorouracil (1820-81-1) + 4-Fluoronitrobenzene (350-46-9) → 5-chloro-1-(4-nitro-phenyl)-1H-pyrimidine-2,4-dione

Conditions	Yield
Stage #1: 5-chlorouracil With potassium carbonate In dimethyl sulfoxide at 80℃; for 0.5h; Stage #2: 4-Fluoronitrobenzene In dimethyl sulfoxide at 70 - 80℃;	74%

5-chlorouracil (1820-81-1) + thiophenol (108-98-5) → 5-(phenylsulfanyl)-2,4(1H,3H)-pyrimidinedione (1137-90-2)

Conditions	Yield
With potassium carbonate In ethylene glycol at 130 - 140℃; for 2h;	71%

iron(III) chloride hexahydrate + 5-chlorouracil (1820-81-1) + His (4998-57-6) → Fe(3+)*C4H2N2O2Cl(1-)*C6H8N3O2(1-)*H2O*Cl(1-) = Fe(C4H2N2O2Cl)(C6H8N3O2)(H2O)Cl (203308-40-1)

Conditions	Yield
With triethyl formate; aq. NaOH In ethanol; water addn. aq. histidine to pptd. (pH 5-6, aq. NaOH) suspn. of metal/5-chlorouracil complex in ethanol; pptn. on concn. and ether addn., drying (vac., 50°C); elem. anal.;	70%

5-chlorouracil (1820-81-1) + chromium chloride hexahydrate → Cr(3+)*C4H2N2O2Cl(1-)*OH(1-)*Cl(1-) = Cr(C4H2N2O2Cl)(OH)Cl

Conditions	Yield
With triethyl orthoformate In ethanol refluxing (2-3 h); pptn. (pH 5-6, aq. NaOH), washing (ethanol), drying (vac., 50°C);elem. anal.;	70%

Upstream product

• 128-09-6 N-chloro-succinimide 
• 108-24-7 acetic anhydride 
• 64-19-7 acetic acid 
• 66-22-8 uracil 
• 106146-79-6 2-ethylmercapto-5-chloro-3H-pyrimidin-4-one 
• 40338-28-1 1-acetyl-1H-pyrimidine-2,4-dione 
• 123551-49-5 5-chloro-2,4-dimethoxypyrimidine 
• 65906-87-8 5-chloro-6-hydroxy-5-methoxycarbonyl-5,6-dihydrouracil 
• 50-90-8 5-chloro-2'-deoxyuridine 
• 42821-92-1 methyl 2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate 
• 858781-45-0 5-bromo-5-chloro-6-hydroxy-dihydro-pyrimidine-2,4-dione 
• 64-17-5 ethanol 
• 7647-01-0 hydrogenchloride 
• 2072-83-5 5,5-dichloro-6-hydroxy-5,6-dihydrouracil 

Downstream Products

• 5750-76-5 2,4,5-trichloropyrimidine 
• 58990-53-7 5-chloro-2,4-bis-O-trimethylsilyluracil 
• 85236-94-8 3'-amino-2',3'-dideoxy-5-chlorouridine 
• 63331-62-4 5-Chloro-4-thiouracil 
• 120-89-8 parabanic acid 
• 19186-12-0 dihydro-6-hydroxypyrimidine-2,4,5(3H)-trione 
• 1137-90-2 5-(phenylsulfanyl)-2,4(1H,3H)-pyrimidinedione 
• 70291-89-3 5-(phenylselanyl)pyrimidine-2,4(1H,3H)-dione 
• 28485-19-0 5-(benzylamino)dihydropyrimidine-2,4(1H,3H)-dione 
• 1226569-83-0 C₁₂H₉ClN₂O₃ 
• 1228040-71-8 methyl 3-(5-chloro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-(tritylamino)propanoate 
• 214687-03-3 3-benzoyl-5-chloropyrimidine-2,4(1H,3H)-dione 

Relevant articles and documents

IODO- AND CHLORODEMERCURATION OF 5,5'-MERCURIBISURACILS

The direct C mercuration in the 5 position of 1-acetyluracil by means of mercury(II) trifluoroacetate in anhydrous acetonitrile is described.The intermediately formed 1-acetyl-5-trifluoroacetoxymercuriuracil, without isolation, was subjected to symmetrization by the action of potassium iodide.The acetyl groups were then readily split out by the action of water.The resulting 5,5'-mercuribisuracil (50percent yield) forms 5-iodo- or 5-chlorouracil in 93percent or 72percent yields, respectively, under the influence of an aqueous KI3 solution or excess pure liquid S2Cl2.

Chloroperoxidase Catalyzed Halogenation of Pyrimidine Bases

Treatment of uracil or cytosine with H2O2 and potassium halides in the presence of chloroperoxidase in potassium phosphate buffer solution at pH 3.0 resulted in halogenation of the substrates, whereas no reaction occured on thymine by a similar treatment.

4'-substituted nucleosides

Nucleosides compounds of Formula I: STR1 wherein B is a purine or a pyrimidine; X and X' are H; Y is H; Y' is OH, F or H; or Y' and X' together makes a bond; Z is STR2 where n is zero, one, two or three; or Y' and Z together form a cyclic phosphate ester; Z' is --CN, --CH3, CH2 N3 or --CH2 J, where J is a halogen atom; or Z' and Y' together are --CH2 O--; and pharmaceutically acceptable esters, ethers, amides, N-acyl moieties and salts thereof.

Cerium(IV)-Mediated Halogenation at C-5 of Uracil Derivatives

Treatment of protected uracil nucleosides 1 or 2 with elemental iodine or metal halogenides and ceric ammonium nitrate (CAN) at 80 deg C gave the corresponding protected 5-halouracil nucleosides 3a-f in excellent yields.Treatment of the resulting crude 3a-f with 0.1 M NaOMe/MeOH at ambient temperature gave the corresponding 5-halouridines 4a-f in high overall yields from 1 or 2.Further, 5-halouraciles 9a-f were prepared in good yields by treatment of 1,3-dimethyluracil (7) or uracil (8) with elemental iodine, metal halogenides, or hydrochloric acid and CAN.Halouridines 4a-e also were obtained in good yields by treatment of unprotected uracil nucleosides 5 or 6 with halogen sources as above and CAN.