1076-38-6|4-Hydroxycoumarin| Ambeed

4-Hydroxycoumarin, a coumarin derivative, is one of the most versatile heterocyclic scaffolds and is frequently applied in the synthesis of various organic compounds. 4-Hydroxycoumarin possesses both electrophilic and nucleophilic properties. 4-Hydroxycoumarin derivatives are employed as the anticoagulant, antibacterial, antifungal, antiviral, antitumor, antiprotozoal, insecticidal, antimycobacterial, antimutagenic, antioxidant, anti-inflammatory agents, HIV protease inhibitors and tyrosine kinase inhibitors.

Synonyms: Benzotetronic Acid; NSC 11889; 4-Coumarinol

4.5 *For Research Use Only !

{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]} Purity: {[proInfo.pro_purity]}

Change View

Size	Price	VIP Price	US Stock	Global Stock	In Stock
{[ item.pr_size ]}		Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

{[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

Quality Control of 4-Hydroxycoumarin Purity: 98% SDS Specification

COA

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

NMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

CNMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

HPLC

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

LC-MS

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

1-2 Day Shipping
High Quality
Technical Support

Product Details of 4-Hydroxycoumarin

CAS No. :	1076-38-6
Formula :	C₉H₆O₃
M.W :	162.14
SMILES Code :	O=C1OC2=C(C=CC=C2)C(O)=C1
Synonyms :	Benzotetronic Acid; NSC 11889; 4-Coumarinol
MDL No. :	MFCD00006856
InChI Key :	VXIXUWQIVKSKSA-UHFFFAOYSA-N
Pubchem ID :	54682930

Safety of 4-Hydroxycoumarin

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

Application In Synthesis of 4-Hydroxycoumarin

* 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 [ 1076-38-6 ]

[ 1076-38-6 ] Synthesis Path-Downstream 1~35

1
[ 110-86-1 ]
[ 1076-38-6 ]
[ 1080-12-2 ]
[ 84245-27-2 ]

References: [1]Journal of the American Chemical Society,1944,vol. 66,p. 902,905.

2
[ 1123-93-9 ]
[ 50-00-0 ]
[ 1076-38-6 ]
[ 7759-57-1 ]

References: [1]Journal of the Chemical Society. Perkin transactions I,1966,vol. 20,p. 1790 - 1792.

3
[ 1076-38-6 ]
[ 4865-84-3 ]

Yield	Reaction Conditions	Operation in experiment
96%		Example 1: 100 gms 4-hydroxy coumarin is added to hydroxy 1 amine solution in water (from 200 gms Hydroxylamine Hydrochloride and 1200 ml 10% sodium carbonate solution ) at room temperature. pH of the reaction mass maintained in the range of 4.5 to 5.5. Reaction mass is warmed to 40 0C and maintained at 40-45 0C for 12 hours till the reaction completes . Reaction mass is cooled to 10 0C and pH of the mass is adjusted to 1 to 1.5 with dilute hydrochloric acid. Precipitated l,2-Benzisoxazole-3-acetic acid is cooled to 0-5 Cand maintained at 0-5 C for lhour and isolated and dried at 60-700C.Dry weight : 105 gms ( 96% by theory on 4-Hydroxy coumarin, 1.05 wt/wt)HPLC purity : 99.68%, Oxime impurity :0.16%. Melting point: 125-126 0C. Percentage of formation of product and impurity at various pH ranges and temperatures recorded in the table below ( process same as example 1)
93.3%		Example 2: *?10% sodium hydroxide solution ( 450 ml) is added to the aqueous Hydroxylamine hydrochloride solution ( 200 gms in 500 ml water) till the pH of the mass is around 5.0. At room temperature. 100 gms 4-hydroxy coumarin is added to above solution at room temperature. Reaction mass is warmed to 40 C and maintained at 40-45 0C for 12 hours till the reaction completes. Reaction mass is colled to 10 0C and pH of the mass is adjusted to 1 to 1.5 with dilute hydrochloric acid. Precipitated l,-benzisoxazole-3acetic acid is cooled further to 0-5 0C and maintained at 0-5 0C for 1 hour, isolated by filtration and dried at 60-70 0C.Dry weight : 102 gms ( 93.3 % on theory on 4-Hydroxy coumarin, 1.04 Wt/Wt) <n="6"/>HPLC purity : 99.86% Oxime impurity: 0.06%
62%	With hydroxylamine hydrochloride; sodium acetate; In methanol; at 25 - 70℃; for 6 - 7h;	Step (1) Preparation of 1,2-benzisoxazol-3yl-acetic acid. Hydroxyl amine hydrochloride (750.0 g, 10.80 mol) was added to a stirred solution of 4-Hydroxy coumarin (500 g, 3.086 mol) in methanol (5.0 liters) at 25-30 C. Sodium acetate (885.0 g, 10.80 mol) was added to the above solution lot wise in half an hour. The reaction mass was stirred at 25-30 C. for half an hour, heated to reflux (65-70 C.) and maintained at reflux for 5-6 hours. After completion of the reaction (by TLC), methanol was distilled under vacuum (<50 C.). After complete removal of methanol, 7.0 liters of water was added to the residue and the resulting solution was cooled to 10-15 C. The pH of the reaction mass was adjusted to 2-3 with 50% HCl and stirred the reaction for one hour at 10-15 C. The solid obtained was filtered and washed with 2.0 lit of water. The solid was dried at 55-60 C. till LOD reached <1.0%; N. Wt 410.0 g., Yield 62%, Purity 99% by HPLC.

40%	With hydroxylamine hydrochloride; sodium hydrogencarbonate; In methanol; at 65℃; for 15h;Inert atmosphere;	To a solution of 4-hydroxycoumarin 7 (10.0 g, 61.7 mmol) in methanol (100 mL), was added NH2OH.HCl (15.0 g, 216 mmol, 3.5 eq) and NaHCO3 (18.1 g, 216 mmol, 3.5 eq). The resulting mixture was refluxed for 15 hours at 65 oC. The completion of reaction was checked by TLC using pet. ether : ethyl acetate (1:1). After completion of reaction, excess of methanol was distilled off under vacuum to give residue. The residue was dissolved in 10% NaHCO3 solution (500 mL) and filtered to remove insoluble impurities. The filtrate was acidified with conc. HCl till pH 2. The solid obtained was filtered and washed with hot 5% ethyl acetate in pet ether to give 1,2-benzisoxazol-3-acetic acid 8 as a white solid (Yield = 40 %, M. P.: 122oC).
		Example 3:Mixture of 4-hydroxy coumarin (100 Kg), 10% aqueous sodium carbonate solution (1200 Lts) and hydroxylamine hydrochloride ( 200 Kgs) stirred for 0.5 hour at 20-25 0C and pH around 4.5 to 5.5 for uniform solution. Reaction mass was warmed to 40 0C and maintained at 40-45 0C and pH 4.5 to 5.5 for 20-24 hours till the reaction completes.Reaction mass pH adjusted to 1.0 to 1.5 with dilute hydrochloric acid below 10 0C. Precipitated l,2-benzisoxazole-3tauacetic acid is further cooled to 0-5 C, maintained for one hour at 0-5 C, isolated by centrifuging and dried at 60-700C.Dry weight: 105 Kgs . LOD ( at 105C for 4 hours ) : 0.35%. Oxime impurity: 0.27%. Melting point : 124-1260C.
	With hydroxylamine hydrochloride; triethylamine;	Preparation of 2-(l ,2-benzoxazol-3-yl)ethanol 2)2OHReaction of 4-hydroxycoumarin with hydroxylamine hydrochloride in presence of trielhylamine (TEA) gives l ,2-benzoxazol-3-ylacetic acid (WO 02/070495) which after esterification is reduced to the corresponding alcohol, using lithium aluminium hydride, to give the title compound; NMR (300 MHz, CDC13) delta 3.04 (br s, 1 H), 3.24 (t, J = 6.0 Hz, 2H), 4. 1 3 (I, ./ = .5.7 Hz, 2H), 7.30-7.35 (m, 2H), 7.57 (br s, 2H), 7.69 (d, J = 7.8 Hz, 1 H).

References: [1]Patent: WO2008/26217,2008,A1 .Location in patent: Page/Page column 4; 5-6.
[2]Patent: WO2008/26217,2008,A1 .Location in patent: Page/Page column 4-5.
[3]European Journal of Medicinal Chemistry,2009,vol. 44,p. 2828 - 2833.
[4]Patent: US2006/84814,2006,A1 .Location in patent: Page/Page column 3; 4.
[5]Journal of Medicinal Chemistry,2003,vol. 46,p. 5428 - 5436.
[6]Synthetic Communications,2018,vol. 48,p. 2877 - 2887.
[7]Journal of Heterocyclic Chemistry,1969,vol. 6,p. 279 - 283.
[8]Phytochemistry,1993,vol. 32,p. 777 - 780.
[9]Agricultural and Biological Chemistry,1985,vol. 49,p. 3563 - 3568.
[10]Patent: WO2008/26217,2008,A1 .Location in patent: Page/Page column 5.
[11]Patent: WO2011/138657,2011,A1 .Location in patent: Page/Page column 51.

4
[ 1076-38-6 ]
[ 21834-92-4 ]
[ 132356-41-3 ]

References: [1]Helvetica Chimica Acta,1990,vol. 73,p. 1865 - 1878.

5
[ 1076-38-6 ]
[ 14615-72-6 ]
3,3'-(3,5-dibenzyloxybenzylidene)-bis-(4-hydroxycoumarin) [ No CAS ]

References: [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 242 - 249.
[2]Zeitschrift fur Physikalische Chemie,2016,vol. 230,p. 97 - 110.

6
[ 1076-38-6 ]
[ 463-49-0 ]
[ 156150-67-3 ]
3-{2-[3-chloro-4-fluorophenyl]prop-2-en-1-yl}-4-hydroxy-2H-chromen-2-one [ No CAS ]

References: [1]Tetrahedron,2004,vol. 60,p. 3359 - 3373.

7
[ 1076-38-6 ]
[ 1196-29-8 ]
[ 4865-84-3 ]

Yield	Reaction Conditions	Operation in experiment
	With methanol; hydroxylamine hydrochloride; sodium methylate; for 5 - 10h;Heating / reflux;	EXAMPLE 1; 1, 2-Benisoxazole-3-acetica acid; Methanolic solution of 4-Hydroxycoumarin (59 Kg, 314.19 moles) is refluxed with hydroxylamine hydrochloride (75.98 Kg, 1093.23 moles) and sodium methoxide 26.18% w/v solution (225. 38 Ltr, 1092.27 mole) for 5 to 10 hours. After the said time inorganic solid is filtered off and filtrate containing 1, 2-Bezisoxazole-3-acetic acid in methanol is concentrated to afford solid which is made alkaline with sodium bicarbonate and extracted with diethyl ether. In ether extract 2-hydroxyacetophenone oxime is found, which is discarded. By further acidification of aqueous layer with 2N hydrochloric acid, 1, 2-Benzisoxazole-3-acetic acid (49. 18 Kg) is obtained as a crystalline solid with melting point 122 to 124 C and having HPLC purity about 95 to 98%

References: [1]Patent: WO2005/44808,2005,A1 .Location in patent: Page/Page column 9.

8
[ 1076-38-6 ]
[ 139-33-3 ]
[ 4865-84-3 ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 1 1) A mixture of hydroxylamine sulfate (43 g), water (113 ml) and a 25% aqueous sodium hydroxide solution (57 ml) is stirred, and thereto are added 4-hydroxycoumarin (21 g) and ethylenediamine-tetraacetic acid disodium salt dihydrate (0.4 g), and the mixture is stirred with heating at 84 C. to 86 C. for 4 hours. The reaction mixture is cooled, and thereto are added 1,2-dichloroethane (30 ml) and water (43 ml), and the mixture is stirred. The 1,2-dichloroethane layer is removed, and the pH value thereof is adjusted to pH 1-2 with 62.5% sulfuric acid. The mixture is extracted twice with 1,2-dichloroethane (120 ml and 10 ml) to give a mixture of 1,2-benzisoxazole-3-acetic acid and 1,2-dichloroethane. The purity of 1,2-benzisoxazole-3-acetic acid in this mixture is 98%.; EXAMPLE 2 A mixture of hydroxylamine sulfate (344.0 g), water (904 ml) and a 25% aqueous sodium hydroxide solution (456 ml) is stirred, and thereto are added 4-hydroxycoumarin (168.0 g) and ethylenediaminetetraacetic acid disodium salt dihydrate (3.2 g), and the mixture is stirred with heating at 84 C.-86 C. for 4 hours. The reaction mixture is cooled, and thereto is added 1,2-dichloroethane (240 ml). The mixture is stirred, and the aqueous layer is collected. The pH value of the aqueous layer is adjusted to pH 1-2 with 25% sulfuric acid, and the precipitated crystals are collected by filtration, washed with water, and dried with air at 60 C. for 15 hours to give 1,2-benzisoxazole-3-acetic acid (170.4 g).

References: [1]Patent: US2005/215796,2005,A1 .Location in patent: Page/Page column 3.

9
[ 1076-38-6 ]
[ 2145-27-9 ]
[ 66233-72-5 ]
[ 4865-84-3 ]

Yield	Reaction Conditions	Operation in experiment
	With hydroxylamine hydrochloride; sodium methylate; In methanol; sodium bicarbonate;	EXAMPLE 9 Preparation of 6-Fluoro-1,2-benzisoxazole-3-acetic acid STR70 A solution of sodium methoxide (22.3 g, 0.412 mol) in methanol is added to a solution of hydroxylamine hydrochloride (30.4 g, 0.438 mol) in methanol. The resultant mixture is stirred at room temperature for 30 minutes and filtered. The filtrate is added to a refluxing solution of 7-fluoro-4-hydroxycoumarin (18.5 g, 0.103 mol) in methanol. The reaction mixture is refluxed overnight and concentrated in vacuo to obtain a yellow solid. A solution of the solid in a sodium hydrogen carbonate solution is washed with ether and acidified with 6N hydrochloric acid. The resultant precipitate is filtered and dried to give a solid which is recrystallized from water to give the title product as a beige solid, mp 132-133 C. Using essentially the same procedure, but substituting 4-hydroxycoumarin for 7-fluoro-4-hydroxycoumarin, 1,2-benzisoxazole-3-acetic acid is obtained as an off-white solid, mp 123-127 C.

References: [1]Patent: US5484763,1996,A .

10
[ 1076-38-6 ]
[ 28785-06-0 ]
[ 109-77-3 ]
C₂₂H₁₈N₂O₃ [ No CAS ]

References: [1]Tetrahedron,2010,vol. 66,p. 5637 - 5641.

11
[ 1076-38-6 ]
[ 399-25-7 ]
[ 1296198-83-8 ]

Yield	Reaction Conditions	Operation in experiment
85%	With water; at 30℃; for 9h;Inert atmosphere; Sonication;	General procedure: A mixture of 4-hydroxycoumarin (10) (1 mmol) and β-nitrostyrene (11) (1.2 mmol) was suspended in 5 mL of water in a 20 mL vial. The vial was placed into the ultrasonic bath (Branson Ultrasonics, Ultrasonic bath Model 3010R-DTH, 50 kHz frequency) at 30 C for the specific time mentioned in Table 2. The progress of the reaction was monitored by TLC. After completion of the reaction, the resulting solid product was filtered and washed with water (2×10 mL) and n-hexane (5×10 mL). Then solid was dried under vacuum to obtain the product (12a-n) in almost pure form in exellent yields (83-94%).

References: [1]Tetrahedron,2011,vol. 67,p. 2870 - 2877.

12
[ 119-84-6 ]
[ 1076-38-6 ]
[ 2669-94-5 ]
[ 495-78-3 ]
[ 1318928-52-7 ]
[ 1481-92-1 ]
[ 20349-89-7 ]

References: [1]ARKIVOC,2011,vol. 2011,p. 170 - 181.

13
[ 1076-38-6 ]
[ 615-67-8 ]
[ 1351158-88-7 ]

References: [1]Journal of Organic Chemistry,2012,vol. 77,p. 445 - 459.

14
[ 1076-38-6 ]
[ 42906-19-4 ]
3,3'-(4-di-p-tolyl-aminobenzylidene)bis-(4-hydroxycoumarin) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With piperidine; In ethanol; at 20℃; for 4h;	General procedure: DBH was synthesized according to a previous report [14]. Amixture of 4-(di-p-tolyl-amino)-benzaldehyde (10 mmol) and 4-hydroxycoumarin (20 mmol) was dissolved in 100 mL of EtOH. Afew drops of piperidine were added, and the mixture was stirredfor 4 h at room temperature. After reaction completion as determinedby TLC, water was added until precipitation occurred. Afterfiltering the precipitates, they were sequentially washed with icecooledwater and ethanol and then dried under a vacuum. 3,3'-(4-Di-p-tolyl-amino-benzylidene)-bis-(4-hydroxycoumarin) (DBH): m.p. 213-214 °C. IR(KBr pellet cm-1): 3440, 2350, 1653, 1604, 1560, 1344, 1095, 761 cm-1. 1H NMR (CDCl3, delta, ppm): 11.584(s, 1H), 11.301(s, 1H), 8.014-8.085(m, 2H), 7.616-7.658(m, 2H), 7.411-7.431(d, 4H), 6.992-7.076(m, 12H), 6.067(s, 1H), 2.315(s, 6H). HRMS (ESI+): m/z: calcd for C39H29NO6: 630.1887 [M + Na+]; found: 630.1879.

References: [1]Journal of Molecular Structure,2014,vol. 1075,p. 509 - 514.

15
[ 700-06-1 ]
[ 1076-38-6 ]
[ 109-77-3 ]
2-amino-4-(1H-indol-3-yl)-5-oxo-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile [ No CAS ]