83-72-7

Basic information

• Product Name: 2-Hydroxy-1,4-naphoquinone
• Synonyms: 1,4-Naphthalenedione,2-hydroxy-;1,4-Naphthoquinone, 2-hydroxy-;2-Hydroxy-1,4-naphthalenedione;2-hydroxy-4-naphthalenedione;2-hydroxy-4-naphthoquinone;2-Hydroxynaphthoquinone;4-Naphthalenedione,2-hydroxy-1;C.I. Natural Orange 6
• CAS NO: 83-72-7
• Molecular Formula: C₁₀H₆O₃
• Molecular Weight: 174.15
• EINECS: 201-496-3
• Product Categories: Intermediates of Dyes and Pigments;Anthraquinones, Hydroquinones and Quinones;Inhibitors;Pyridines
• Mol File: 83-72-7.mol
• Article Data: 60

Chemical Properties

• Melting Point: 192-195 °C (dec.)(lit.)
• Boiling Point: 265.11°C (rough estimate)
• Flash Point: 173.572 °C
• Appearance: Yellow/Crystalline Powder
• Density: 1.2346 (rough estimate)
• Refractive Index: 1.5036 (estimate)
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: Acetonitrile (Slightly), Chloroform (Slightly), Methanol (Slightly)
• PKA: 4.31±0.10(Predicted)
• Water Solubility: 2 g/L (20 ºC)
• Stability: Stable. Combustible. Incompatible with strong oxidizing agents.
• Merck: 14,5393
• BRN: 1565260
• CAS DataBase Reference: 2-Hydroxy-1,4-naphoquinone(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Hydroxy-1,4-naphoquinone(83-72-7)
• EPA Substance Registry System: 2-Hydroxy-1,4-naphoquinone(83-72-7)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 36/37/38-68-36-22
• Safety Statements: 26-37/39-36/37/39-36
• WGK Germany: 3
• RTECS: QL8200000
• TSCA: Yes
• Hazardous Substances Data: 83-72-7(Hazardous Substances Data)

Usage

Description

Lawsone [CAS: 83-72-7] (CI Natural Orange 6; CI 75420), also known as henna and isojuglone, occurs in the shrub henna (Lawsone alba). In England, the plant is known as Egyptian privet. The dye was extracted from the leaves of the plant, using sodium bicarbonate, and the extracts used to dye protein fibers an orange shade. Henna is probably the oldest cosmetic known. The ancient Egyptians used it as a hair dye and for staining fingernails. It is said that Mohammed dyed his beard with henna. Lawsone has been identified as 2-hydroxy-1,4-naphthoquinone. It has been synthesized by the Thiele acetylation of 1,4-naphthoquinone followed by hydrolysis and oxidation.

Chemical Propterties

2-Hydroxy-1,4-naphthoquinone (HNQ, C10H6O3) is also called Lawsone, which is a white cubic crystal. Its melting point is 192-195 oC, and flash point is 192 oC. The solubility of HNQ is 2 g/L in water at 20 oC. It is stable, but it is combustible and incompatible with strong oxidizing agents.

Application

2-Hydroxy-1,4-naphthoquinone(HNQ) is the principal natural dye ingredient contained at 1.0-1.4% in the leaves of Henna (Lawsonia inermis). It is an ancient red-orange dye. Henna has been used for more than 4000 years not only as a hair dye, but also as a body paint and tattoo dye. Today, semi-permanent hair dyes containing Henna as well as its pure dye ingredient HNQ are widely used and have become increasingly popular due to their natural origin.

Biological Toxicity

2-Hydroxy-1,4-naphoquinone(HNQ) was reported to be a weak bacterial mutagen for Salmonella typhimurium strain TA98 or was more clearly mutagenic for strain TA 2637, both in the presence of metabolic activation. HNQ was unable to induce sex-linked recessive lethal mutations in Drosophila melanogaster. The available data suggest that the use of Henna or 2-Hydroxy-1,4-naphoquinone(HNQ) for hair dyeing presents no or negligible risk of genotoxicity to the consumer.

Chemical Properties

Yellow crystal powder

History

Lawsone (CI Natural Orange 6; CI 75420), also known as henna and isojuglone, occurs in the shrub henna (Lawsone alba). In England, the plant is known as Egyptian privet. The dye was extracted from the leaves of the plant, using sodium bicarbonate, and the extracts used to dye protein fibers an orange shade. Henna is probably the oldest cosmetic known. The ancient Egyptians used it as a hair dye and for staining fingernails. It is said that Mohammed dyed his beard with henna. Lawsone has been identified as 2-hydroxy-1,4-naphthoquinone. It has been synthesized by the Thiele acetylation of 1,4-naphthoquinone followed by hydrolysis and oxidation.

Uses

Different sources of media describe the Uses of 83-72-7 differently. You can refer to the following data:
1. 2-Hydroxy-1,4-naphthoquinone is used for preparing decorative hair and skin dyes. 2-Hydroxy-1,4-naphthoquinone also demonstrates antimicrobial and antioxidant effects. It also suppress the formation of hydrogen peroxide and superoxide radical anion by aldehyde oxidase-catalyzed reactions.
2. antifungal, sunscreen, antibacterial, antineoplastic
3. An antimicrobial antioxidant dye isolated from Henna.

Definition

A coloring principle obtained from dried leaves of certain tropical plants (North Africa, India).

Synthesis Reference(s)

The Journal of Organic Chemistry, 53, p. 808, 1988 DOI: 10.1021/jo00239a023Tetrahedron Letters, 25, p. 533, 1984 DOI: 10.1016/S0040-4039(00)99930-1

General Description

Yellow prisms or yellow powder.

Air & Water Reactions

Insoluble in water.

Reactivity Profile

Phenols, such as 2-Hydroxy-1,4-naphoquinone, do not behave as organic alcohols, as one might guess from the presence of a hydroxyl (-OH) group in their structure. Instead, they react as weak organic acids. Phenols and cresols are much weaker as acids than common carboxylic acids (phenol has Ka = 1.3 x 10^[-10]). These materials are incompatible with strong reducing substances such as hydrides, nitrides, alkali metals, and sulfides. Flammable gas (H2) is often generated, and the heat of the reaction may ignite the gas. Heat is also generated by the acid-base reaction between phenols and bases. Such heating may initiate polymerization of the organic compound. Phenols are sulfonated very readily (for example, by concentrated sulfuric acid at room temperature). The reactions generate heat. Phenols are also nitrated very rapidly, even by dilute nitric acid. Nitrated phenols often explode when heated. Many of them form metal salts that tend toward detonation by rather mild shock.

Health Hazard

ACUTE/CHRONIC HAZARDS: 2-Hydroxy-1,4-naphoquinone may be absorbed through the skin and can cause skin irritation.

Fire Hazard

Flash point data for 2-Hydroxy-1,4-naphoquinone are not available but 2-Hydroxy-1,4-naphoquinone is probably combustible.

Contact allergens

Henna, prepared by powdering the dried leaves of henna plant (Lawsonia inermis L.), is used for coloring and conditioning hair and nails, particularly by Muslims or Hindus. It contains Lawsone, which very rarely induces contact allergy. Most dermatitis caused by “black henna” is due to PPD and derivatives

Purification Methods

Crystallise Lawsone B from *C6H6 or AcOH (m 192.5o, 195-196o). It sublimes in a vacuum (m 194o). It has UV with max at 455nm (aqueous NaOH). [Beilstein 8 H 300, 8 I 635, 8 II 344, 8 III 2543, 8 IV 2360.]

InChI:InChI=1/C10H6O3/c11-8-5-9(12)10(13)7-4-2-1-3-6(7)8/h1-5,12H

Synthetic route

2-hydroxy-3-iodonaphthalene-1,4-dione (35135-38-7) → 2-Hydroxy-1,4-naphthoquinone (83-72-7)

Conditions	Yield
With hydrogen iodide In dichloromethane at 20℃;	100%

morpholine (110-91-8) + sodium 1,2-naphthoquinone-4-sulfonate (521-24-4) → 2-Hydroxy-1,4-naphthoquinone (83-72-7) + 4-morpholinonaphthalene-1,2-dione (4569-83-9) + disodium 2-hydroxy-1-oxo-1,4-dihydro-4,4-naphthalenedisulfonate

Conditions	Yield
pH=8;	A n/a B 99% C n/a

1,2,4-triacetyloxynaphthalene (1785-67-7) → 2-Hydroxy-1,4-naphthoquinone (83-72-7)

Conditions	Yield
Stage #1: 1,2,4-triacetyloxynaphthalene With hydrogenchloride In methanol; water at 70℃; for 1h; Stage #2: With dihydrogen peroxide In water at 20℃;	91.6%
Stage #1: 1,2,4-triacetyloxynaphthalene With hydrogenchloride In methanol; water for 1h; Reflux; Stage #2: With dihydrogen peroxide In methanol; water	91.6%
With sodium hydroxide; air

2-methoxy-1,4-naphthoquinone (2348-82-5) → 2-Hydroxy-1,4-naphthoquinone (83-72-7)

Conditions	Yield
With aluminum (III) chloride In dichloromethane at 40℃; for 3h;	91%
With aluminum (III) chloride; dichloromethane at -5 - 40℃; for 3h;	87.1%

2-(N-phenylsulfinamoyl)-1,4-naphthoquinone → 2-Hydroxy-1,4-naphthoquinone (83-72-7)

Conditions	Yield
With hydrogenchloride for 1h; Heating;	90%

2-hydroxy-1,4-dimethoxynaphthalene (74097-20-4) → 2-Hydroxy-1,4-naphthoquinone (83-72-7) + 4-methoxy-1,2-naphthoquinone (18916-57-9)

Conditions	Yield
With ammonium cerium(IV) nitrate; water In acetonitrile Yield given;	A n/a B 87%
With ammonium cerium(IV) nitrate; water In acetonitrile Yields of byproduct given;	A n/a B 87%

2--1,4-naphthoquinone → 2-Hydroxy-1,4-naphthoquinone (83-72-7)

Conditions	Yield
With hydrogenchloride for 1h; Heating;	86%

methyl 1,4-dihydro-1,4-dioxo-3-(1-pyrrolidinyl)-2-naphthoate (159495-45-1) → 2-Hydroxy-1,4-naphthoquinone (83-72-7)

Conditions	Yield
With hydrogenchloride In methanol; water at 100℃; for 5h;	83.3%

1,2-Dihydroxynaphthalene (574-00-5) → 2-Hydroxy-1,4-naphthoquinone (83-72-7)

Conditions	Yield
With KO2 In pyridine; toluene at -10℃; for 6h;	80%
With KO2 In pyridine; toluene at -10℃; for 6h; Mechanism; oxidation of other dihydroxynaphthalenes in heterogeneous aprotic media;	80%
With crown-ether In pyridine; toluene for 0.0833333h;	60%
With potassium superoxide; tetraethylammonium bromide In N,N-dimethyl-formamide at 20℃;	56%
With alkaline solution; oxygen

1,3-dihydroxynaphthalene (132-86-5) → 2-Hydroxy-1,4-naphthoquinone (83-72-7)

Conditions	Yield
With zirconium phosphate; phthalocyanine[Fe(3+)]; oxygen In acetone at 20℃; for 6h;	80%
With oxygen In 1,4-dioxane; water at 20℃; for 6h;	79%
With crown-ether In pyridine; toluene for 0.0833333h;	60%

4-o-nitrophenylthio-1,2-naphthoquinone (108732-56-5) → 2-Hydroxy-1,4-naphthoquinone (83-72-7) + 2-nitrothiophenol (4875-10-9)

Conditions	Yield
With sodium hydroxide In ethanol; water for 0.0333333h;	A 80% B n/a

[1,4]naphthoquinone (130-15-4) → 2-Hydroxy-1,4-naphthoquinone (83-72-7)

Conditions	Yield
Stage #1: [1,4]naphthoquinone With sulfuric acid In acetic anhydride Cooling with ice; Stage #2: With methanol; sodium methylate for 4h; Cooling with ice;	70%
With air
Multi-step reaction with 3 steps 1: ZnCl2 / 50 - 60 °C 2: alcohol; hydrochloric acid 3: ice; sulfuric acid; dichromate / 0 °C View Scheme

3,4-dihydronaphthalene-1(2H)-one (529-34-0) → 2-Hydroxy-1,4-naphthoquinone (83-72-7)

Conditions	Yield
With potassium tert-butylate; oxygen In tert-butyl alcohol for 2h;	70%
With 18-crown-6 ether; superoxyde de potassium In tetrahydrofuran for 5h; Ambient temperature;	63.8%
With potassium tert-butylate In tert-butyl alcohol at 20℃; under 760.051 Torr; for 2h;	50%

3,4-Dimethoxy-1-naphthol (70477-38-2) → 2-Hydroxy-1,4-naphthoquinone (83-72-7) + 3,4-Dimethoxy-2-(3,4-dimethoxy-1-naphthyloxy)-1(2H)-naphthalinon (88381-94-6)

Conditions	Yield
With sodium hydroxide; potassium hexacyanoferrate(III) In water	A n/a B 65%

2-(2,2-diphenylethyl)-2,3-dihydro-2,3-epoxy-1,4-naphthoquinone (74954-83-9) → 1,1-Diphenylethylene (530-48-3) + 2-Hydroxy-1,4-naphthoquinone (83-72-7) + (3aR,8aS)-3a-Hydroxy-3,3-diphenyl-2,3,3a,8a-tetrahydro-cyclopenta[a]indene-1,8-dione (81847-43-0) + C24H18O3 (74954-90-8)

Conditions	Yield
In benzene Quantum yield; Irradiation; other solvent;	A 4% B 5% C 30% D 65%

2-t-butyldimethylsilyloxy-5-formyl-6-hydroxy-2-m-methoxyphenyl-2,3-dihydronaphtho<1,2-b><1,4>dioxin → 2-Hydroxy-1,4-naphthoquinone (83-72-7) + 1-(3-Methoxyphenyl)ethanone (586-37-8)

Conditions	Yield
With hydrogenchloride; iron(III) chloride In ethanol for 3.5h; Heating;	A 63% B 36%

1,4-dimethoxynaphthalene-2-carbaldehyde (75965-83-2) → 2-Hydroxy-1,4-naphthoquinone (83-72-7) + 2-hydroxy-1,4-dimethoxynaphthalene (74097-20-4) + 1,4-dimethoxynaphthalene-2-carboxylic acid (78265-13-1)

Conditions	Yield
With selenium(IV) oxide; dihydrogen peroxide In tetrahydrofuran for 96h; Heating;	A 8% B 55% C 22%

4-methoxy-aniline (104-94-9) + 3-phenyliodonio-1,2,4-trioxo-1,2,3,4-tetrahydronaphthalenide (117560-06-2) → 2-Hydroxy-1,4-naphthoquinone (83-72-7) + N-(4-methoxyphenyl)phenylamine (1208-86-2) + 2-iodo-3-phenoxy-1,4-naphthoquinone (160246-88-8) + 3-iodo-4-hydroxy-1,2-naphthoquinone (572874-62-5)

Conditions	Yield
With copper(II) bis(trifluoromethanesulfonate) In dichloromethane at 20℃;	A n/a B 43% C 16% D 35%

[14C]-58C80 (94015-46-0) → 2-Hydroxy-1,4-naphthoquinone (83-72-7) + 9-t-butyl-6b,7,8,9,10,10a-hexahydrobenzo-(b)naphtho-(2,1-d)furan-5,6-quinone + 3-t-butyl-1,2,3,4-tetrahydrobenzo(b)naphtho(2,3-d)furan-6-11-quinone (104907-54-2) + 2-hydroxy-3-(trans-4-t-butylcyclohexyl)-1,4-naphthoquinone (86790-29-6)

Conditions	Yield
With sulfuric acid at 55℃; for 40h;	A 2.7% B 35.5% C 1.1% D 40.5%

3,4-dihydronaphthalene-1(2H)-one (529-34-0) + Potassium superoxide, 18-Crown-6 → 2-Hydroxy-1,4-naphthoquinone (83-72-7) + α-naphthol (90-15-3)

Conditions	Yield
In toluene for 12h; Var.: Aliquat 336 instead of 18-Crown-6;	A 10% B 38%
In toluene for 12h; Var.: Aliquat 336 instead of 18-Crown-6;	A 30% B 6%

α-naphthol (90-15-3) + Potassium superoxide, 18-Crown-6 → 2-Hydroxy-1,4-naphthoquinone (83-72-7)

Conditions	Yield
In toluene exothermic. Var.: Aliquat 336 instead of 18-Crown-6;	34%

sodium 1,2-naphthoquinone-4-sulfonate (521-24-4) + isopropylamine (75-31-0) → 2-Hydroxy-1,4-naphthoquinone (83-72-7) + 4-(1-Methylethyl)-amino-1,2-naphthalindion (86614-18-8) + 2-Isopropylamino-4-[(E)-isopropylimino]-4H-naphthalen-1-one (86614-20-2) + 4-Hydroxy-3-[3-isopropylamino-4-oxo-4H-naphthalen-(1Z)-ylideneamino]-naphthalene-1-sulfonic acid (86614-11-1) + acetone (67-64-1)

Conditions	Yield
In water for 0.25h; Product distribution; Ambient temperature; other aliphatic amines;	A 2% B 25% C 1% D 33% E n/a

1,2,3,4-tetrahydronaphthalen-2-one (530-93-8) + Potassium superoxide, 18-Crown-6 → 2-Hydroxy-1,4-naphthoquinone (83-72-7) + 2-(2-carboxyethyl)benzoic acid (776-79-4) + β-naphthol (135-19-3)

Conditions	Yield
In toluene for 12h; Var.: Aliquat 336 instead of 18-Crown-6;	A 27% B 14% C 5%

1,4-Dihydroxynaphthalene (571-60-8) → 2-Hydroxy-1,4-naphthoquinone (83-72-7)

Conditions	Yield
With KO2 In tetrahydrofuran; toluene at -10℃; for 6h;	20%
With sodium hydroxide; H3; dihydrogen peroxide

3-aminopyrazole (1820-80-0) + sodium 1,2-naphthoquinone-4-sulfonate (521-24-4) → 2-Hydroxy-1,4-naphthoquinone (83-72-7) + N-(3-pyrazolyl)-1,4-naphthoquinone

Conditions	Yield
With hydrogenchloride Heating;	A 17% B 7%

2-Methoxynaphthalene (93-04-9) → 2-Hydroxy-1,4-naphthoquinone (83-72-7) + 2-methoxy-1,4-naphthoquinone (2348-82-5)

Conditions	Yield
With dihydrogen peroxide; methyltrioxorhenium(VII) In acetic acid at 20℃; for 3h;	A 16% B 14%

2-(2-methylpropyl)-2,3-dihydro-2,3-epoxy-1,4-naphthoquinone (73645-16-6) → 2-Hydroxy-1,4-naphthoquinone (83-72-7) + (3aS,8aS)-3a-Hydroxy-3,3-dimethyl-2,3,3a,8a-tetrahydro-cyclopenta[a]indene-1,8-dione (81847-42-9) + C14H14O3 (73645-23-5) + 9b-Hydroxy-1,1-dimethyl-1,9b-dihydro-2H-naphtho[2,1-b]furan-5-one (73645-25-7)

Conditions	Yield
In benzene Quantum yield; Irradiation; other solvent;	A 12% B n/a C 12% D 14%

3-phenyliodonio-1,2,4-trioxo-1,2,3,4-tetrahydronaphthalenide (117560-06-2) + N-4-methylphenylhydrazine (539-44-6) → 2-Hydroxy-1,4-naphthoquinone (83-72-7) + 4-Methylazobenzol (949-87-1)

Conditions	Yield
With copper(II) bis(trifluoromethanesulfonate) In dichloromethane at 20℃;	A n/a B 7%

2,3-epoxy-2,3-dihydro-1,4-naphthoquinone (15448-58-5) + furan-2,3,5(4H)-trione pyridine (1:1) → 2-Hydroxy-1,4-naphthoquinone (83-72-7)

α-naphthol (90-15-3) → 2-Hydroxy-1,4-naphthoquinone (83-72-7)

Conditions	Yield
With sodium hydroxide; H3; dihydrogen peroxide
With potassium hydroxide; H3; dihydrogen peroxide
Multi-step reaction with 2 steps 1: K2S2O8; aqueous NaOH 2: aqueous H2O2; aq. NaOH solution; H32(O2)2> View Scheme

2-Hydroxy-1,4-naphthoquinone (83-72-7) → 2-hydroxy-3-iodonaphthalene-1,4-dione (35135-38-7)

Conditions	Yield
With N-iodo-succinimide In dichloromethane for 0.333333h; Reflux;	100%
With ammonium iodide; Oxone In methanol for 1h; Reflux;	92%
With potassium carbonate; morpholine-iodine complex In water at 20℃; for 3h;	87%

2-Hydroxy-1,4-naphthoquinone (83-72-7) + p-toluidine (106-49-0) → 2-(p-toluidino)-1,4-naphthoquinone (57182-49-7)

Conditions	Yield
In neat (no solvent) at 100℃; under 750.075 Torr; for 0.05h; Microwave irradiation;	100%
With acetic acid
With ethanol

2-Hydroxy-1,4-naphthoquinone (83-72-7) + 1,2-diamino-benzene (95-54-5) → benzo[a]phenazin-5-ol (2089-82-9)

Conditions	Yield
at 70℃; for 0.25h; Product distribution; Further Variations:; Temperatures; solid-state reaction;	100%
With 1,4-diaza-bicyclo[2.2.2]octane In ethanol	91%
With acetic acid at 20℃; for 24h;	88%

2-Hydroxy-1,4-naphthoquinone (83-72-7) → 2-chloro-1,4-naphthoquinone (1010-60-2)

Conditions	Yield
With thionyl chloride Heating;	100%
With thionyl chloride for 22h; Reflux;	100%
With oxalyl dichloride; N,N-dimethyl-formamide In benzene at 50℃; for 0.75h;	95%
With thionyl chloride	94%
With thionyl chloride at 90℃; for 48h;	85%

2-Hydroxy-1,4-naphthoquinone (83-72-7) + [bis(acetoxy)iodo]benzene (3240-34-4) → 3-phenyliodonio-1,2,4-trioxo-1,2,3,4-tetrahydronaphthalenide (117560-06-2)

Conditions	Yield
In dichloromethane at 10 - 20℃; for 1h; Inert atmosphere;	100%
In chloroform at 20℃; for 5h;	91%
In chloroform at 0 - 20℃; for 5h;	89%

Benzyloxymethyl chloride (3587-60-8) + 2-Hydroxy-1,4-naphthoquinone (83-72-7) → 2-benzyloxymethoxy-1,4-naphthoquinone

Conditions	Yield
Stage #1: 2-hydroxynaphtho-1,4-quinone With potassium carbonate In N,N-dimethyl-formamide; mineral oil at 20℃; for 0.166667h; Molecular sieve; Inert atmosphere; Stage #2: Benzyloxymethyl chloride In N,N-dimethyl-formamide; mineral oil at 20℃; for 1h; Molecular sieve; Inert atmosphere; chemoselective reaction;	100%

methanol (67-56-1) + 2-Hydroxy-1,4-naphthoquinone (83-72-7) → 2-methoxy-1,4-naphthoquinone (2348-82-5)

Conditions	Yield
With sulfuric acid for 5h; Reflux;	99%
With hydrogen cation Heating;	97%
With sulfuric acid at 65℃; for 14h;	91%

ethyl 2-oxo-4-(p-chlorophenyl)but-3-enoate (133678-11-2) + 2-Hydroxy-1,4-naphthoquinone (83-72-7) → (4R)-ethyl 4-(4-chlorophenyl)-2-hydroxy-5,10-dioxo-3,4,5,10-tetrahydro-2H-benzo[g]chromene-2-carboxylate (1309979-27-8)

Conditions	Yield
With 1-(3,5-bis(trifluoromethyl)phenyl)-3-((1S,2S)-2-(piperidin-1-yl)-2,3-dihydro-1H-inden-1-yl)thiourea In 1,2-dichloro-ethane at -20℃; for 24h; Michael addition; optical yield given as %ee; enantioselective reaction;	99%
With C40H31F6N3O2 In diethyl ether at 20℃; for 4h; Michael Addition; enantioselective reaction;	97%

2-Hydroxy-1,4-naphthoquinone (83-72-7) + ethyl 2-oxo-4-(p-fluorophenyl)but-3-enoate (1375649-28-7) → (4R)-ethyl 4-(4-fluorophenyl)-2-hydroxy-5,10-dioxo-3,4,5,10-tetrahydro-2H-benzo[g]chromene-2-carboxylate (1309979-25-6)

Conditions	Yield
With 1-(3,5-bis(trifluoromethyl)phenyl)-3-((1S,2S)-2-(piperidin-1-yl)-2,3-dihydro-1H-inden-1-yl)thiourea In 1,2-dichloro-ethane at -20℃; for 24h; Michael addition; optical yield given as %ee; enantioselective reaction;	99%
With C40H31F6N3O2 In diethyl ether at 20℃; for 4h; Michael Addition; enantioselective reaction;	85%

2-Hydroxy-1,4-naphthoquinone (83-72-7) + 1-nitro-2-(4-chlorophenyl)ethylene (101671-01-6) → (R)-2-[1-(4-chlorophenyl)-2-nitroethyl]-3-hydroxy-1,4-naphthoquinone (1312990-95-6)

Conditions	Yield
With C22H26F3N3O2 In dichloromethane at 30℃; for 6h; Michael addition; optical yield given as %ee; enantioselective reaction;	99%

1H-benzimidazol-2-amine (934-32-7) + 2-Hydroxy-1,4-naphthoquinone (83-72-7) + 4-nitrobenzaldehdye (555-16-8) → 2-(((1H-benzo[d]imidazol-2-yl)amino)(4-nitrophenyl)methyl)-3-hydroxynaphthalene-1,4-dione (1259091-97-8)

Conditions	Yield
With MCM-41 In ethanol at 20℃; for 1.16667h; Green chemistry;	99%
With montmorillonite K-10 In ethanol at 20℃; for 8h;	93%
With indium(III) chloride In water for 6h; Reflux;	80%

2-aminopyridine (504-29-0) + pyrimidine-2,4,5,6(1H,3H)-tetraone (61066-33-9, 61066-34-0, 61066-35-1, 61127-23-9) + 2-Hydroxy-1,4-naphthoquinone (83-72-7) → 2-aminopyridinium 2-(5-hydroxy-2,4,6-trioxohexahydropyrimidin-5-yl)-1,3,4-trioxo-1,2,3,4-tetrahydronaphthalen-2-ide (1367747-95-2)

Conditions	Yield
In chloroform for 3.5h; Reflux;	99%

(5-methyl-pyridin-2-yl)amine (1603-41-4) + pyrimidine-2,4,5,6(1H,3H)-tetraone (61066-33-9, 61066-34-0, 61066-35-1, 61127-23-9) + 2-Hydroxy-1,4-naphthoquinone (83-72-7) → 2-amino-5-methylpyridinium 2-(5-hydroxy-2,4,6-trioxohexahydropyrimidin-5-yl)-1,3,4-trioxo-1,2,3,4-tetrahydronaphthalen-2-ide (1367748-14-8)

Conditions	Yield
In chloroform for 1h; Reflux;	99%

3-methylpyridin-2-ylamine (1603-40-3) + pyrimidine-2,4,5,6(1H,3H)-tetraone (61066-33-9, 61066-34-0, 61066-35-1, 61127-23-9) + 2-Hydroxy-1,4-naphthoquinone (83-72-7) → 2-amino-3-methylpyridinium 2-(5-hydroxy-2,4,6-trioxohexahydropyrimidin-5-yl)-1,3,4-trioxo-1,2,3,4-tetrahydronaphthalen-2-ide (1367748-05-7)

Conditions	Yield
In chloroform for 1h; Reflux;	99%

2-Hydroxy-1,4-naphthoquinone (83-72-7) + salicylaldehyde (90-02-8) + dimedone (126-81-8) → 3-(3,3-dimethyl-1-oxo-2,3,4,9-tetrahydro-1H-xanthen-9-yl)-4-hydroxynaphthalene-1,2-dione

Conditions	Yield
With L-proline In ethanol at 80℃; for 6h;	99%

2-Hydroxy-1,4-naphthoquinone (83-72-7) + (2-nitroethenyl)benzene (102-96-5) → (S)-2-(1-phenyl-2-nitroethyl)-3-hydroxynaphthalene-1,4-dione (1308657-27-3)

Conditions	Yield
With C45H40N4O5 In dichloromethane at 20℃; for 24h; Reagent/catalyst; Solvent; Michael Addition; enantioselective reaction;	99%
With C35H46N4O10S In toluene at 30℃; for 6h; Michael Addition;	96%
With hydrophobic anchor-tagged asymmetric amino thiourea In dichloromethane at 30℃; for 4h; Michael Addition; enantioselective reaction;	95%
With 1-[1-(R)-(1-naphthyl)-2,2,2-trifluoroethyl]-3-[(1S,2S)-2-(dimethylamino)cyclohexyl]thiourea In toluene at 20℃; for 24h; Michael Addition;	84%

2-Hydroxy-1,4-naphthoquinone (83-72-7) + ethyl 2-oxo-4-(p-nitrophenyl)but-3-enoate (55629-97-5, 28525-87-3) → C22H17NO8 (1460310-39-7)

Conditions	Yield
With chiral cyclohexanediamine functionalized calix[4]squaramide In dichloromethane at 25℃; Michael Addition; enantioselective reaction;	99%
With C40H31F6N3O2 In diethyl ether at 20℃; for 3h; Michael Addition; enantioselective reaction;	95%

2-Hydroxy-1,4-naphthoquinone (83-72-7) + 1-acetyl-3-(dicyanomethylene)-1,3-dihydro-2H-indol-2-one (79343-59-2) → 1′-acetyl-2-amino-2′,5,10-trioxo-5,10-dihydrospiro[benzo[g]chromene-4,3′-indoline]-3-carbonitrile (1561873-04-8)

Conditions	Yield
With C29H30F6N4OS In diethyl ether at 20℃; for 24h; Time; Concentration; Michael Addition; enantioselective reaction;	99%

2-Hydroxy-1,4-naphthoquinone (83-72-7) + C14H8ClN3O (1561873-75-3) → 1′-allyl-2-amino-4′-chloro-2′,5,10-trioxo-5,10-dihydrospiro[benzo[g]chromene-4,3′-indoline]-3-carbonitrile (1561873-11-7)

Conditions	Yield
With C29H30F6N4OS In diethyl ether at 20℃; for 3h; Michael Addition; enantioselective reaction;	99%

2-Hydroxy-1,4-naphthoquinone (83-72-7) + 2-(4-chloro-2-oxoindolin-3-ylidene)malononitrile (1332338-70-1) → 2-amino-4′-chloro-2′,5,10-trioxo-5,10-dihydrospiro[benzo[g]chromene-4,3′-indoline]-3-carbonitrile (1561872-57-8)

Conditions	Yield
With C29H30F6N4OS In diethyl ether at 20℃; for 6h; Time; Concentration; Michael Addition; enantioselective reaction;	99%

pyrrolidine (123-75-1) + 2-Hydroxy-1,4-naphthoquinone (83-72-7) + salicylaldehyde (90-02-8) → 2-hydroxy-3-((2-hydroxyphenyl)(pyrrolidin-1-yl)methyl)naphthalene-1,4-dione (1620161-62-7)

Conditions	Yield
With toluene-4-sulfonic acid In acetonitrile at 20℃; for 1.6h; Mannich Aminomethylation;	99%
In ethanol at 20℃; for 24h; Darkness;	77%

2-Hydroxy-1,4-naphthoquinone (83-72-7) + 4-methyl-benzaldehyde (104-87-0) + benzo[1,3]dioxolo-5-ylamine (14268-66-7) → 12-(4-methylphenyl)-5,10-dihydro-benzo[i][1,3]dioxolo[4,5-b]acridine-6,11-dione

Conditions	Yield
With L-proline In ethanol for 1h; Reflux; Green chemistry;	99%

N-methoxymethylisatin (50899-39-3) + 2-Hydroxy-1,4-naphthoquinone (83-72-7) + malononitrile (109-77-3) → (R)-2-amino-1'-(methoxymethyl)-2',5,10-trioxo-5,10-dihydrospiro[benzo[g]chromene-4,3'-indoline]-3-carbonitrile

Conditions	Yield
With QD-4 In toluene at 20℃; for 23h; Molecular sieve; Inert atmosphere; enantioselective reaction;	99%

2-Hydroxy-1,4-naphthoquinone (83-72-7) + 1,3-cylohexanedione (504-02-9) + propionaldehyde (123-38-6) → C19H16O4

Conditions	Yield
With silica-supported tungstic acid In neat (no solvent) at 60℃; for 0.0666667h; Sonication; Green chemistry;	99%

2-Hydroxy-1,4-naphthoquinone (83-72-7) + 1,3-cylohexanedione (504-02-9) + (4-isopropylbenzaldehyde) (122-03-2) → C26H22O4

Conditions	Yield
With silica-supported tungstic acid In neat (no solvent) at 60℃; for 0.0666667h; Sonication; Green chemistry;	99%

2-Hydroxy-1,4-naphthoquinone (83-72-7) + 2,4-difluorobenzaldehyde (1550-35-2) → C27H12F2O5

Conditions	Yield
With silica-supported tungstic acid In neat (no solvent) at 60℃; for 0.0833333h; Sonication; Green chemistry;	99%

2-Hydroxy-1,4-naphthoquinone (83-72-7) + dimedone (126-81-8) + 2-Fluorobenzaldehyde (446-52-6) → C25H19FO4

Conditions	Yield
With silica-supported tungstic acid In neat (no solvent) at 60℃; for 0.05h; Sonication; Green chemistry;	99%

2-Hydroxy-1,4-naphthoquinone (83-72-7) + 4-nitrobenzaldehdye (555-16-8) + 4-methoxy-aniline (104-94-9) → 2-hydroxy-3-(((4-methoxyphenyl)amino)(4-nitrophenyl)methyl)naphthalene-1,4-dione

Conditions	Yield
With Bi(III) immobilized on triazine dendrimer-magnetic Fe3O4 nanoparticle In ethanol at 20℃; for 0.133333h;	99%
With montmorillonite K-10 In ethanol at 20℃; for 8.25h;	83%

Upstream product

• 571-60-8 1,4-Dihydroxynaphthalene 
• 15448-58-5 2,3-epoxy-2,3-dihydro-1,4-naphthoquinone 
• 623-11-0 1-methyl-4-nitrosobenzene 
• 857994-33-3 3-acetoxy-3-methyl-naphthalene-1,2,4-trione 
• 574-00-5 1,2-Dihydroxynaphthalene 
• 1785-67-7 1,2,4-triacetyloxynaphthalene 
• 132-86-5 1,3-dihydroxynaphthalene 
• 1526-73-4 3-chloro-2-hydroxy-naphthalene-1,4-dione 
• 6628-97-3 2-(phenylamino)naphthoquinone 
• 13302-67-5 naphthalene-1,2,4-triol 
• 64-17-5 ethanol 
• 41245-70-9 1a-cyclohexyl-1a,7a-dihydronaphth<2,3b>oxirene-2,7-dione 
• 124-41-4 sodium methylate 
• 20513-06-8 2-amino-[1,4]naphthoquinone-4-imine 

Downstream Products

• 6320-30-5 2-hydroxy-3-(morpholinomethyl)naphthalene-1,4-dione 
• 125647-88-3 2-hydroxy-3-(3-phenyl-propenyl)-[1,4]naphthoquinone 
• 1785-67-7 1,2,4-triacetyloxynaphthalene 
• 1785-65-5 2-acetoxy-1,4-naphthoquinone 
• 105438-12-8 2-hydroxy-3-styryl-[1,4]naphthoquinone 
• 76309-73-4 2-cyclohexylaminomethyl-3-hydroxy-[1,4]naphthoquinone 
• 96306-50-2 3,3′-(phenylmethylene)bis(2-hydroxynaphthalene-1,4-dione) 
• 57182-49-7 2-(p-toluidino)-1,4-naphthoquinone 
• 10409-20-8 2-(4-chlorophenyl)-3-hydroxynaphthalene-1,4-dione 
• 483-55-6 phthiocol 
• 6628-97-3 2-(phenylamino)naphthoquinone 
• 29366-44-7 2-ethyl-3-hydroxy-[1,4]naphthoquinone 
• 29366-41-4 2-hydroxy-3-(prop-1-en-1-yl)naphthalene-1,4-dione 
• 75112-65-1 2-(4-nitrophenylamino)-1,4-naphthoquinone 

Relevant articles and documents

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Rhodium(II)-catalyzed reaction of 1,3-bis(diazo)indan-2-one with alcohols: Formation of unexpected 1,1-dialkoxy ketones

The rhodium(II)-catalyzed decomposition of 1,3-bis(diazo)indan-2-one (1) in boiling dichloromethane containing primary alcohols gave 1,1-dialkoxyindan-2-ones (2) in good yields without any formation of 1,3-dialkoxy derivatives.

Isoxazoles. 10. Degradation and enolization kinetics of 4- aminoisoxazolyl-1,2-naphthoquinone in basic aqueous solution

The kinetics of enolization and degradation of N-(5-methyl-4-isoxazolyl)- 4-amino-1,2-naphthoquinone (1) was investigated in aqueous solutions over a pH range of 7.30 to 12.25, at 35 °C and at constant ionic strength (μ = 0.5) using reversed-phase HPLC. Pseudo-first-order kinetics was observed throughout the pH range studied. The rate of enolization (k(e)), the keto- enol equilibrium constant (K(t)), and specific base catalysis rate constant (k(OH)) were determined. Good agreement between the theoretical pH-rate profile and the experimental data supports the proposed transformation process. The average recovery for 1 and its tautomerization product 2- hydroxy-N-(5-methyl-4-isoxazolyl)-1,4-naphthoquinone 4-imine (2) from mixtures of different composition was evaluated.

Isoxazoles. 9. Degradation kinetics of 4-(isoxazolylamino)-1,2- naphthoquinone in acidic aqueous solution

The degradation kinetics of N-(5-methyl-4-isoxazolyl)-4-amino-1,2- naphthoquinone (1) was studied in aqueous solution over a pH range of 0.65- 7.50, at 35 °C and at a constant ionic strength of 0.5. The degradation rates were determined by high-pressure liquid chromatography and were observed to follow pseudo-first-order kinetics with respect to the concentration of 1. The pH-rate profile was linear with slope -1 under acidic pH, becoming pH independent from 3.50 to 7.50. Good agreement between the theoretical pH-rate profile and the experimental data supports the proposed degradation process. The catalytic rate constants for hydrogen ion and water were k(H) = 0.901 M-1 h-1 and k(o) = 1.34 x 10-3 h-1, respectively. These data are appropriate to develop a stable dosage form of 1. The accuracy, peak sharpness, and asymmetry factor for the analytical method were determined.

Discovery of juglone and its derivatives as potent SARS-CoV-2 main proteinase inhibitors

SARS-CoV-2 as a positive-sense single-stranded RNA coronavirus caused the global outbreak of COVID-19. The main protease (Mpro) of the virus as the major enzyme processing viral polyproteins contributed to the replication and transcription of SARS-CoV-2 in host cells, and has been characterized as an attractive target in drug discovery. Herein, a set of 1,4-naphthoquinones with juglone skeleton were prepared and evaluated for the inhibitory efficacy against SARS-CoV-2 Mpro. More than half of the tested naphthoquinones could effectively inhibit the target enzyme with an inhibition rate of more than 90% at the concentration of 10 μM. In the structure-activity relationships (SARs) analysis, the characteristics of substituents and their position on juglone core scaffold were recognized as key ingredients for enzyme inhibitory activity. The most active compound, 2-acetyl-8-methoxy-1,4-naphthoquinone (15), which exhibited much higher potency in enzyme inhibitions than shikonin as the positive control, displayed an IC50 value of 72.07 ± 4.84 nM towards Mpro-mediated hydrolysis of the fluorescently labeled peptide. It fit well into the active site cavity of the enzyme by forming hydrogen bonds with adjacent amino acid residues in molecular docking studies. The results from in vitro antiviral activity evaluation demonstrated that the most potent Mpro inhibitor could significantly suppress the replication of SARS-CoV-2 in Vero E6 cells within the low micromolar concentrations, with its EC50 value of about 4.55 μM. It was non-toxic towards the host Vero E6 cells under tested concentrations. The present research work implied that juglone skeleton could be a primary template for the development of potent Mpro inhibitors.

Menadione structure-based novel coronavirus 3CL protease inhibitor

The invention discloses a menadione derivative capable of resisting novel coronavirus and medical application of the menadione derivative. The structure of the compound is shown as a formula (I), in the formula, R is a hydrogen atom, methyl, acetyl or hydroxyl, and R1 is hydrogen, methoxy, benzyloxy or benzoyloxy. The compound disclosed by the invention can inhibit the 3CL hydrolase of the 2019-nCoV novel coronavirus, and has the activity of resisting the novel coronavirus. In-vitro activity determination experiments show that the enzyme inhibition rate of part of the compounds reaches 90% or above under the concentration of 1 [mu] M, and is significantly superior to that of a positive control drug alkannin. Cell-level toxicity test experiment results show that the toxicity of menadione and the derivative thereof to host normal cells HSF is significantly lower than that of positive drugs alkannin and juglone, and part of the compounds show relatively strong anti-novel coronavirus activity in vitro, and have an important significance for the development of high-efficiency and low-toxicity new anti-novel coronavirus drugs.

Naphtho[2,3-: B] furan-4,9-dione synthesis via palladium-catalyzed reverse hydrogenolysis

A reverse hydrogenolysis process has been developed for two-site coupling of 2-hydroxy-1,4-naphthoquinones with olefins to produce naphtha[2,3-b]furan-4,9-diones and hydrogen (H2). The reaction is catalyzed by commercially available Pd/C without oxidants and hydrogen acceptors, thereby providing an intrinsically waste-free approach for the synthesis of functionalized and potentially biologically relevant naphtha[2,3-b]furan-4,9-diones.