58-27-5

Basic information

• Product Name: Menadione
• Synonyms: usafek-5185;VitaminK0;β-Methyl-1,4-naphthoquinone;Menadione (1.05793);MENADIONE, USP;MENADIONE (K3) 1000MG NEAT;(MENADIONE)VITAMIN K3, 98+% USP;VITAMIN K3(FEEDSTUFF GRADEMSB96)
• CAS NO: 58-27-5
• Molecular Formula: C11H8O2
• Molecular Weight: 172.18
• EINECS: 200-372-6
• Product Categories: Biochemistry;Vitamins;Nutritional fortification substances;Vitamins and derivatives;Vitamin Ingredients;Miscellaneous Compounds;Aromatics;Intermediates & Fine Chemicals;Pharmaceuticals;RUMENSIN;Isolabel;Other APIs;Inhibitors;feeding additive raw materials
• Mol File: 58-27-5.mol
• Article Data: 178

Chemical Properties

• Melting Point: 105-107 °C(lit.)
• Boiling Point: 262.49°C (rough estimate)
• Flash Point: 113.8 °C
• Appearance: yellow/crystalline
• Density: 1.1153 (rough estimate)
• Refractive Index: 1.5500 (estimate)
• Storage Temp.: Store at RT.
• Solubility: oil: soluble
• Water Solubility: INSOLUBLE
• Sensitive: Light Sensitive
• Stability: Stable. May be light sensitive. Incompatible with strong oxidizing agents.
• Merck: 14,5831
• BRN: 1908453
• CAS DataBase Reference: Menadione(CAS DataBase Reference)
• NIST Chemistry Reference: Menadione(58-27-5)
• EPA Substance Registry System: Menadione(58-27-5)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 22-36/37/38-43
• Safety Statements: 26-36-37/39-24
• WGK Germany: 3
• RTECS: QL9100000
• F: 8
• TSCA: Yes
• HazardClass: IRRITANT
• Hazardous Substances Data: 58-27-5(Hazardous Substances Data)

Usage

Chemical properties

It appears as white crystalline or crystalline powder, being almost odorless and hygroscopic. Its color will change in case of light. It is easily soluble in water, slightly soluble in ethanol, but insoluble in ether and benzene.

Application

Different sources of media describe the Application of 58-27-5 differently. You can refer to the following data:
1. Menadione is a good hemostatic drug, its main function is to participate in the synthesis of thrombin, promote blood coagulation, can effectively prevent bleeding diseases, and also participate in the mineralization of bones. Menadione is also an important component of feed additives, an indispensable nutrient for the growth and development of livestock, and can also be used as plant growth regulators, promoters, herbicides, etc.
2. The primary known function of vitamin K is to assist in the normal clotting of blood, but it may also play a role in normal bone calcification. It is being incorporated into cosmetic preparations, particularly those used for treating dark circles. It could also be used in acne products, and there are studies underway on its efficacy for the treatment of spider veins.

Production

Menadione is synthesized by oxidizing 2-methylnaphthalene with chromic anhydride and then reacting with sodium bisulfite.Reaction: Dissolve 2-methylnaphthalene in glacial acetic acid, stir and cool to below 40°C, slowly add a mixture of chromic anhydride and an equal amount of water, and maintain the temperature at 35-40°C. After the addition, the temperature was kept at 40 °C for 0.5 h, then heated to 70 °C for 45 min, and then heated to 85 °C for 15 min. The reactant was poured into a large amount of water, and menadione was precipitated under constant stirring. After filtering, the filter cake was repeatedly washed with water until the aqueous solution had no sour taste, and then filtered to obtain Menadione. Yield 51%.

Description

Vitamin K is a general term referring to a group of naphthoquinone derivatives required in the diet for blood clotting. Menadione is a fat-soluble vitamin that is essential for blood clotting. It is destroyed by irradiation during processing but has no appreciable loss during storage. It occurs in spinach, cabbage, liver, and wheat bran.

Chemical Properties

Bright-yellow crystals with a very faint acrid odour. Insoluble in water; soluble in benzene (1 g/10 mL), ethanol (1 g/60 mL), and vegetable oils (1g/50 mL); moderately soluble in carbon tetrachloride and chloroform. Stable in air; decomposed by sunlight; destroyed by alkalis and reducing agents.

Physical properties

Appearance: phylloquinone is a yellow oil at room temperature, but the other vitamers K are yellow crystals. Solubility: the vitamers K and MK and most forms of menadione are insoluble in water, slightly soluble in ethanol, and readily soluble in ether, chloroform, fats, and oils. Stability: the vitamers K are sensitive to light and alkali, but are relatively stable to heat and oxidizing environments.Menadione, the formal parent compound of the menaquinone series does not occur naturally but is a common synthetic form called menadione (2-methyl-1,4- naphthoquinone). This compound forms a water-soluble sodium bisulfite addition product, menadione sodium bisulfite, whose practical utility is limited by its instability in complex matrices such as feeds. However, in the presence of excess sodium bisulfite, it crystallizes as a complex with an additional mole of sodium bisulfite (i.e., menadione sodium bisulfite complex), which has greater stability, therefore, is used widely as a supplement to poultry feeds. A third water-soluble compound is menadione pyridinol bisulfite (MPB).

Originator

Kappaxin,Sterling Winthrop

Uses

Menadione is precursor to verious types of Vitamin K. It is of industrial importance as an intermediate in the synthesis of phylloquinone, and salts of its bisulfite adduct are used as stabilized forms in the animal feed industry. Commercially significant forms are menadione sodium bisulfite and menadione dimethyl pyrimidinol. Used as a micronutrient for livestock and pet foods.

Indications

Vitamin K activity is associated with several quinones, including phylloquinone (vitamin K1), menadione (vitamin K3), and a variety of menaquinones (vitamin K2). These quinones promote the synthesis of proteins that are involved in the coagulation of blood.These proteins include prothrombin, factor VII (proconvertin), factor IX (plasma thromboplastin). The vitamin K quinones are obtained from three major sources.Vitamin K is present in various plants, especially green vegetables. The menaquinones that possess vitamin K2 activity are synthesized by bacteria, particularly gram-positive organisms; the bacteria in the gut of animals produce useful quantities of this vitamin.Vitamin K3 is a chemically synthesized quinone that possesses the same activity as vitamin K1.

Definition

ChEBI: Menadione is a member of the class of 1,4-naphthoquinones that is 1,4-naphthoquinone which is substituted at position 2 by a methyl group. It is used as a nutritional supplement and for the treatment of hypoprothrombinemia. It has a role as a nutraceutical, a human urinary metabolite, an angiogenesis inhibitor, an EC 3.4.22.69 (SARS coronavirus main proteinase) inhibitor and an antineoplastic agent. It is a member of 1,4-naphthoquinones and a vitamin K.

Preparation

Menadione can be prepared by oxidizing 2-methylnaphthalene with chromic acid or hydrogen peroxide.

Brand name

Kappaxin (Sterling Winthrop); Kayquinone.

Therapeutic Function

Prothrombogenic vitamin

General Description

Menadione is a prothrombogenic compound and belongs to the Vitamin K class of compounds, which are necessary for the biosynthesis of prothrombin and other blood clotting factors. It is used as a model quinone in cell culture and in vivo investigations. It is obtained as a catabolic product of phylloquinone and circulating precursor of tissue menaquinone-4 in rats.

Hazard

Irritant to skin and mucous membranes, especially the alcoholic solution.

Biochem/physiol Actions

Menadione is an oxidative stress inducer.

Pharmacology

The typical role of vitamin K is to maintain normal blood coagulation function. Its role is related to the metabolic processes.

Clinical Use

Vitamin K deficiency results in increased bleeding time. This hypoprothrombinemia may lead to hemorrhage from the gastrointestinal tract, urinary tract, and nasal mucosa. In normal, healthy adults, deficiency is rare. The two groups at greatest risk are newborn infants and patients receiving anticoagulant therapy; hypoprothrombinemia preexists in these two groups. Any disease that causes the malabsorption of fats may lead to deficiency. Inhibition of the growth of intestinal bacteria from extended antibiotic therapy will result in decreased vitamin K synthesis and possible deficiency.

Side effects

Toxicity of vitamin K has not been well defined. Jaundice may occur in a newborn if large dosages of vitamin K are given to the mother before birth. Although kernicterus may result, this can be prevented by using vitamin K.

Safety Profile

Poison by ingestion, intraperitoneal, and subcutaneous routes. Experimental teratogenic effects. Questionable carcinogen with experimental tumorigenic data. Human mutation data reported. When heated to decomposition it emits acrid smoke and irritating fumes.

Purification Methods

Recrystallise it from 95% EtOH, or MeOH after filtration. It forms bright yellow crystals which are decomposed by light. Its solubility in EtOH is 1.7% and in *C6H6 it is 10%. It IRRITATES mucous membranes and skin. [Fieser J Biol Chem 133 391 1940, Beilstein 7 IV 2430.]

InChI:InChI=1/C11H8O2/c1-7-6-10(12)8-4-2-3-5-9(8)11(7)13/h2-6H,1H3

Synthetic route

2-methyl-1,4-naphthohydroquinone (481-85-6) → menadione (58-27-5)

Conditions	Yield
With iodate form of Amberlyst A26 In dichloromethane at 20℃; for 2h; further reagent;	100%
With sulfuric acid; sodium bromide In dichloromethane; water at 15℃; for 2.98h; Electrolysis;	99%
With carbon dioxide; oxygen In water at 35 - 60℃; under 57005.7 - 62256.2 Torr; for 0.0833333h; Autoclave;	96%

2-methylnaphthalen-1-ol (7469-77-4) → menadione (58-27-5)

Conditions	Yield
With Co(salN-Medpt); oxygen In acetonitrile for 0.5h;	100%
Stage #1: 2-methylnaphthalen-1-ol In acetonitrile at 74.84℃; Stage #2: With dihydrogen peroxide In acetonitrile for 0.75h; Reflux; chemoselective reaction;	97.3%
With sulfuric acid; dihydrogen peroxide In water at 36 - 40℃; for 6h; Temperature; Solvent; Green chemistry;	94.7%

2-Methylnaphthalene (91-57-6) → menadione (58-27-5)

Conditions	Yield
With dihydrogen peroxide; acetic acid In water at 75℃; for 5h; Product distribution / selectivity;	100%
With C69H63Cl6N3O9(3-)*1.5Cu(2+); acetic acid In water at 40 - 100℃; for 14h; Catalytic behavior; Reagent/catalyst; Temperature; Concentration;	93%
With dihydrogen peroxide; acetic acid In acetonitrile Catalytic behavior; Solvent; Reflux;	93%

2-methyl-5,6,9,10-tetrahydro-1,4-naphthoquinone → menadione (58-27-5)

Conditions	Yield
With palladium 10% on activated carbon In acetone for 24h; Reflux; Inert atmosphere;	100%
With sodium dichromate; sulfuric acid; acetic acid a) 80-90 deg C, 1 h, b) RT, 12 h;	93%
With manganese(II) bromide; copper(I) bromide In dimethyl sulfoxide at 85℃; under 600.06 Torr; for 26h; Temperature;	91.3%

C11H10O2 (92071-59-5) → menadione (58-27-5)

Conditions	Yield
With palladium 10% on activated carbon In acetone Reflux;	100%

Hykinone (130-37-0) → menadione (58-27-5)

Conditions	Yield
With sodium hydroxide In chloroform; water at 20℃; Product distribution / selectivity;	100%
With water; sodium carbonate at 25℃; for 120h; Time;

2-methyl-5,8-dihydro-1,4-naphthalenediol (3090-46-8) → menadione (58-27-5)

Conditions	Yield
With carbon dioxide; oxygen In water at 37 - 80℃; under 60756.1 - 69757 Torr; for 0.125h; Pressure; Temperature; Autoclave;	98.4%
With lithium perchlorate In acetonitrile; tert-butyl alcohol at 16 - 18℃; for 8.6h; electrolysis on Pt electrodes;	94%
With chromium(VI) oxide; acetic acid at 20℃;

2-methyl-5,6,7,8-tetrahydronaphthalene-1,4-diol (16368-80-2) → menadione (58-27-5)

Conditions	Yield
With carbon dioxide; oxygen In water at 37 - 80℃; under 58505.9 - 72007.2 Torr; for 0.111111h; Autoclave;	95.7%

1,4-dimethoxy-2-methylnaphthalene (53772-19-3) → menadione (58-27-5)

Conditions	Yield
With ammonium cerium(IV) nitrate In acetonitrile at 20℃; for 0.166667h; Oxidation; Demethylation;	94%
With bis-[(trifluoroacetoxy)iodo]benzene In methanol; water at 20℃; for 0.5h;	92%
With tert.-butylhydroperoxide; poly(bis-1,2-phenylene) diselenide In tert-butyl alcohol at 80℃; for 12h;	90%
With ammonium persulfate; silver nitrate In water; acetonitrile for 18h; Ambient temperature;	56%

phthalic acid dimethyl ester (131-11-3) + tert-butyl 3-cyanobutanoate → menadione (58-27-5)

Conditions	Yield
Stage #1: phthalic acid dimethyl ester; tert-butyl 3-cyanobutanoate With potassium tert-butylate In toluene at 100 - 105℃; for 3h; Green chemistry; Stage #2: With sodium hydroxide In water; toluene at 20 - 30℃; for 3h; Green chemistry; Stage #3: With hydrogenchloride In water; toluene at 60℃; for 3h; pH=2 - 2.5; Green chemistry;	92.3%

di-tert-butyliminoxyl (33802-06-1) + 2-methyl-1,4-napthohydroquinone → menadione (58-27-5)

Conditions	Yield
	92%

phthalic acid di(tert-butyl)ester (30448-43-2) + tert-butyl 3-cyanobutanoate → menadione (58-27-5)

Conditions	Yield
Stage #1: phthalic acid di(tert-butyl)ester; tert-butyl 3-cyanobutanoate With potassium tert-butylate In toluene at 100 - 105℃; for 3h; Green chemistry; Stage #2: With sodium hydroxide In water; toluene at 20 - 30℃; for 3h; Green chemistry; Stage #3: With hydrogenchloride In water; toluene at 60℃; for 3h; pH=2 - 2.5; Green chemistry;	91.9%

phthalic acid di(tert-butyl)ester (30448-43-2) + C8H13NO2 → menadione (58-27-5)

Conditions	Yield
Stage #1: phthalic acid di(tert-butyl)ester; C8H13NO2 With potassium tert-butylate In 5,5-dimethyl-1,3-cyclohexadiene at 100 - 105℃; for 3h; Green chemistry; Stage #2: With sodium hydroxide In 5,5-dimethyl-1,3-cyclohexadiene; water at 20 - 30℃; for 3h; Green chemistry; Stage #3: With hydrogenchloride In 5,5-dimethyl-1,3-cyclohexadiene; water at 60℃; for 3h; pH=2 - 2.5; Green chemistry;	91.9%

phthalic acid dimethyl ester (131-11-3) + methyl 3-cyanobutanoate → menadione (58-27-5)

Conditions	Yield
Stage #1: phthalic acid dimethyl ester; methyl 3-cyanobutanoate With sodium methylate In methanol; toluene at 90 - 100℃; for 3h; Green chemistry; Stage #2: With sodium hydroxide In water; toluene at 20 - 30℃; for 3h; Green chemistry; Stage #3: With hydrogenchloride In water; toluene at 60℃; for 3h; pH=2 - 2.5; Green chemistry;	90.7%

2-methyl-5,8-dihydro-1,4-naphthoquinone (82654-73-7) → menadione (58-27-5)

Conditions	Yield
With lithium perchlorate In acetonitrile at 16 - 17℃; for 3.2h; electrolysis on Pt electrodes;	90%

dimethyl sulfoxide (67-68-5) + [1,4]naphthoquinone (130-15-4) → menadione (58-27-5)

Conditions	Yield
In tert-butyl alcohol for 12h; Methylation; UV-irradiation;	90%

rac-ethyl 3-cyanobutanoate (22584-00-5) + phthalic acid dimethyl ester (131-11-3) → menadione (58-27-5)

Conditions	Yield
Stage #1: rac-ethyl 3-cyanobutanoate; phthalic acid dimethyl ester With sodium ethanolate In methanol; toluene at 90 - 100℃; for 3h; Green chemistry; Stage #2: With sodium hydroxide In water; toluene at 20 - 30℃; for 3h; Green chemistry; Stage #3: With hydrogenchloride In water; toluene at 60℃; for 3h; pH=2 - 2.5; Green chemistry;	89%

phthalic acid dimethyl ester (131-11-3) + C8H13NO2 → menadione (58-27-5)

Conditions	Yield
Stage #1: phthalic acid dimethyl ester; C8H13NO2 With sodium methylate In methanol; chlorobenzene at 90 - 100℃; for 3h; Green chemistry; Stage #2: With sodium hydroxide In water; chlorobenzene at 20 - 30℃; for 3h; Green chemistry; Stage #3: With hydrogenchloride In water; chlorobenzene at 60℃; for 3h; pH=2 - 2.5; Green chemistry;	88.3%

2-methylnaphthalen-1-ol (7469-77-4) + lead(IV) tetraacetate (546-67-8) → menadione (58-27-5) + 2-acetoxy-2-methylnaphthalen-1(2H)-one (76274-21-0)

Conditions	Yield
In benzene Ambient temperature;	A 3% B 88%

Diethyl phthalate (84-66-2) + methyl 3-cyanobutanoate → menadione (58-27-5)

Conditions	Yield
Stage #1: Diethyl phthalate; methyl 3-cyanobutanoate With sodium ethanolate In methanol; toluene at 90 - 100℃; for 3h; Green chemistry; Stage #2: With sodium hydroxide In water; toluene at 20 - 30℃; for 3h; Green chemistry; Stage #3: With hydrogenchloride In water; toluene at 60℃; for 3h; pH=2 - 2.5; Green chemistry;	87.8%

1-acetoxy-1,3-butadiene (1515-76-0) + 2-methylbenzene-1,4-diol (95-71-6) → menadione (58-27-5)

Conditions	Yield
With oxygen In dimethyl sulfoxide at 55℃; for 24h; pH=4.5; Reagent/catalyst; Enzymatic reaction;	85.8%

3-methylene-1,2,3,4-tetrahydronaphthalen-1-ol → menadione (58-27-5)

Conditions	Yield
With pyridinium chlorochromate In dichloromethane at 20℃; for 5h;	81%

2-Methylnaphthalene (91-57-6) → 6-methyl-1,4-naphthoquinone (605-93-6) + menadione (58-27-5)

Conditions	Yield
With sulfuric acid; dihydrogen peroxide; acetic anhydride; acetic acid at 60℃; for 6.33333h; Product distribution / selectivity;	A n/a B 80%
With perchloric acid; dihydrogen peroxide; acetic anhydride; acetic acid at 60℃; for 6.33333h; Product distribution / selectivity;	A n/a B 80%
With phosphoric acid; dihydrogen peroxide; acetic anhydride; acetic acid at 60℃; for 6.33333h; Product distribution / selectivity;	A n/a B 75%

2-Hydroxy-1,4-naphthoquinone (83-72-7) + dimethyl sulfoxide (67-68-5) → menadione (58-27-5) + 2,3-dimethyl-5-hydroxy-1,4-naphthoquinone (80596-51-6)

Conditions	Yield
With copper(II) sulfate at 50℃; for 2h;	A 60% B 80%

1-acetoxybuta-1,3-diene (1515-76-0, 35694-19-0, 35694-20-3) + 2-methylbenzene-1,4-diol (95-71-6) → menadione (58-27-5)

Conditions	Yield
With laccase In acetate buffer at 55℃; for 24h; pH=4.5; Diels-Alder reaction;	75%

2-methylnaphthalen-1-ol (7469-77-4) → menadione (58-27-5) + 2-acetoxy-2-methylnaphthalen-1(2H)-one (76274-21-0)

Conditions	Yield
With lead(IV) acetate In acetonitrile Ambient temperature;	A 16% B 74%

2-methylnaphthalen-1-ol (7469-77-4) → phthiocol (483-55-6) + menadione (58-27-5)

Conditions	Yield
With dihydrogen peroxide; methyltrioxorhenium(VII) In acetic acid at 20℃; for 2h;	A 6% B 74%

3-methylnaphthalen-1-ol (13615-40-2) → menadione (58-27-5)

Conditions	Yield
With salcomine; oxygen In N,N-dimethyl-formamide for 3h; Ambient temperature;	70%
With salcomine; oxygen In N,N-dimethyl-formamide for 3h;	64%

(1S*,2S*)-2-methyl-1,2-dihydronaphthalen-1-ol → menadione (58-27-5) + 3,3′-dimethyl-1,1′-binaphthalenyl-4,4′-diol (107866-11-5)

Conditions	Yield
With Jones reagent (excess) In acetone at 0℃;	A n/a B 68%

3-oxo-1,3-dihydroisobenzofuran-1-carbonitrile (27613-27-0) + methacrylic acid methyl ester (80-62-6) → menadione (58-27-5)

Conditions	Yield
Stage #1: 3-oxo-1,3-dihydroisobenzofuran-1-carbonitrile With lithium tert-butoxide In tetrahydrofuran at -78 - -60℃; for 0.416667h; Inert atmosphere; Stage #2: methacrylic acid methyl ester In tetrahydrofuran at -78 - 20℃; Inert atmosphere;	64%

menadione (58-27-5) → 2,3-epoxy-2-methyl-2,3-dihydro-1,4-naphthoquinone (15448-59-6, 61840-91-3, 82864-14-0, 105016-62-4)

Conditions	Yield
With dihydrogen peroxide; β‐cyclodextrin In water at 25℃; for 96h; pH 9; other reagents (t-BuOOH, NaOCl, PhC(CH3)2OOH), MCPBA), other solvents (DMF, DMSO), addition of base (NaOH, NaHCO3, Na2CO3);	100%
With dihydrogen peroxide; β‐cyclodextrin; alpha cyclodextrin In water at 25℃; for 96h; Product distribution; pH 9; other oxidizing agents (t-BuOOH, NaOCl, PhC(CH3)2OOH), MCPBA); other solvents (DMF, DMSO), addition of base (NaOH, Na2CO3, NaHCO3); enantioselectivity (up to 40percent ee by NMR); same reaction with further naphthoquinones;	100%
With lithium hydroxide; tetrabutylammomium bromide; dihydrogen peroxide In toluene at 15 - 25℃; for 0.416667h; Epoxidation; ultrasonic irradiation;	100%

menadione (58-27-5) → 2-methyl-1,4-naphthohydroquinone (481-85-6)

Conditions	Yield
With sodium dithionite In diethyl ether; water	100%
With sodium dithionite In diethyl ether; water at 20℃;	100%
With sodium dithionite In diethyl ether; water	100%

Isopropenyl acetate (108-22-5) + menadione (58-27-5) → Acetic acid (1S,2aR,8aR)-1,8a-dimethyl-3,8-dioxo-1,2,2a,3,8,8a-hexahydro-cyclobuta[b]naphthalen-1-yl ester (75858-24-1)

Conditions	Yield
In benzene for 1h; Irradiation;	100%

menadione (58-27-5) + prenylindium sesquiiodide → 2,3-dihydro-2-methyl-2-(3-methyl-but-2-enyl)-1,4-naphthoquinone (74785-15-2)

Conditions	Yield
In N,N-dimethyl-formamide at -23℃; for 3h;	100%

Ge[N(C(CH3)3)(Si(CH3)3)]2 + menadione (58-27-5) → Ge(N(Si(CH3)3)C(CH3)3)2OC6H(CH3)(CH(CH)2CH)O

Conditions	Yield
In tetrahydrofuran (Ar); stirring (1 h, -78°C); soln. filtn. off, drying (vac.); elem. anal.;	100%

1-hexene (592-41-6) + 1-iodo-2,2,3,3,4,4,5,5,5-nonafluorobutane (423-39-2) + menadione (58-27-5) → 2-(1-butyl-3,3,4,4,5,5,6,6,6-nonafluoro-hexyl)-3-methyl-[1,4]naphthoquinone

Conditions	Yield
With dibenzoyl peroxide In acetic acid for 4h; Heating;	99%

1-(4-bromo-phenyl)-5-oxo-pyrrolidine-3-carboxylic acid hydrazide + menadione (58-27-5) → N'-(3-methyl-4-oxo-1,4-dihydronaphthalen-1-ylidene)-1-(4-bromophenyl)-5-oxopyrrolidine-3-carbohydrazide (1342800-33-2)

Conditions	Yield
With hydrogenchloride In water; isopropyl alcohol for 19h; Reflux;	99%

menadione (58-27-5) + 2,3-dimethyl-buta-1,3-diene (513-81-5) → 2,3,4a-trimethyl-1,4,4a,9a-tetrahydro-anthraquinone

Conditions	Yield
With tetradecafluorohexane; lithium perfluorooctane sulfonate In water at 25℃; for 72h; Diels-Alder reaction;	98%

1-iodo-2,2,3,3,4,4,5,5,5-nonafluorobutane (423-39-2) + menadione (58-27-5) → 2-methyl-3-nonafluorobutyl-[1,4]naphthoquinone

Conditions	Yield
With dibenzoyl peroxide In acetic acid for 4h; Heating;	98%

menadione (58-27-5) → (2S,3R)-2,3-epoxy-2-methyl-1,4-naphthoquinone

Conditions	Yield
With tert.-butylhydroperoxide; C49H63Cl6N7O2*ClH; potassium hydroxide In tert-butyl methyl ether; water at 0℃; for 0.5h; enantioselective reaction;	98%
With sodium hypochlorite; diphenylether; Cinchona alkaloid phase-transfer catalyst In chlorobenzene at -10℃;

C12H15N3O2 (956593-14-9) + menadione (58-27-5) → N'-(3-methyl-4-oxo-1,4-dihydronaphthalen-1-ylidene)-1-(3-methylphenyl)-5-oxopyrrolidine-3-carbohydrazide (1342800-28-5)

Conditions	Yield
With hydrogenchloride In water; isopropyl alcohol for 19h; Reflux;	98%

menadione (58-27-5) + 1,3-dihydro-imidazole-2-thione (872-35-5) → 2-(1H-imidazole-2-ylthio)-3-methylnaphthalene-1,4-dione (1449761-93-6)

Conditions	Yield
In methanol at 20℃; for 8h;	98%

menadione (58-27-5) + 2-(5,7-dimethyl-3,4-dihydronaphthalen-1(2H)-ylidene)acetaldehyde → C25H22O2

Conditions	Yield
With (2S)-2-{diphenyl[(trimethylsilyl)oxy]methyl}pyrrolidine; benzoic acid In chloroform at 20℃; for 20h;	98%

menadione (58-27-5) + dimethyl sulfate (77-78-1) → 1,4-dimethoxy-2-methylnaphthalene (53772-19-3)

Conditions	Yield
Stage #1: menadione With palladium on activated charcoal; hydrogen In methanol for 6h; Stage #2: dimethyl sulfate With sodium methylate In methanol at 50℃; for 0.333333h; Inert atmosphere;	97.1%
Stage #1: menadione With hydrogenchloride; tin(ll) chloride In ethanol at 20℃; for 0.5h; Stage #2: dimethyl sulfate With potassium hydroxide In ethanol; acetone at 60℃; for 2h;	73%
Stage #1: menadione With hydrogenchloride; tin(ll) chloride In ethanol at 20℃; Stage #2: dimethyl sulfate With potassium hydroxide In acetone at 60℃;
Stage #1: menadione With hydrogenchloride; tin(ll) chloride In ethanol at 40℃; for 0.166667h; Stage #2: dimethyl sulfate With potassium hydroxide In acetone at 20℃; for 2.5h; Further stages.;
Stage #1: menadione With sodium dithionite In ethyl acetate at 20℃; for 0.5h; Stage #2: dimethyl sulfate With sodium methylate In isopropyl alcohol at 63℃; for 0.5h;

menadione (58-27-5) → (5aS,5bR,11aS,11bR)-5a,11a-Dimethyl-5a,5b,11a,11b-tetrahydro-dibenzo[b,h]biphenylene-5,6,11,12-tetraone

Conditions	Yield
2,4,6-tri(4-pyridyl)-1,3,5-triazine In water-d2 at 20℃; for 3h; Irradiation;	96%

1-(4-chlorophenyl)-5-oxopyrrolidin-3-carbohydrazide + menadione (58-27-5) → N'-(3-methyl-4-oxo-1,4-dihydronaphthalen-1-ylidene)-1-(4-chlorophenyl)-5-oxopyrrolidine-3-carbohydrazide (1342800-34-3)

Conditions	Yield
With hydrogenchloride In water; isopropyl alcohol for 19h; Reflux;	96%

menadione (58-27-5) + cyclobutanone oxime ester → 4-(3-methyl-1,4-dioxo-1,4-dihydro-naphthalen-2-yl)-3-phenyl-butyronitrile

Conditions	Yield
With (1,2-dimethoxyethane)dichloronickel(II); bathophenanthroline In acetonitrile at 100℃; for 6h; Sealed tube; Inert atmosphere;	96%

menadione (58-27-5) → 2-bromo-3-methyl-[1,4]naphthoquinone (3129-39-3)

Conditions	Yield
With aluminum oxide; bromine for 2h; Ambient temperature; other reagents: iodine monobromide, acetic acid;	95%
With N-chloro-succinimide; copper(II) chloride monohydrate In acetonitrile at 82℃; for 4h; regioselective reaction;	95.9%
Stage #1: menadione With bromine In dichloromethane at 25℃; for 1h; Stage #2: With pyridine In dichloromethane at 25℃; for 12h;	93%

formaldehyd (50-00-0) + menadione (58-27-5) → 2-(chloromethyl)-3-methylnaphthalene-1,4-dione (31599-79-8)

Conditions	Yield
With hydrogenchloride; acetic acid at 20℃;	95%
With hydrogenchloride; acetic acid	87%
With hydrogenchloride In water; acetic acid at 60 - 65℃; for 0.5h;	86%

Upstream product

• 186581-53-3 diazomethane 
• 481-85-6 2-methyl-1,4-naphthohydroquinone 
• 7469-77-4 2-methylnaphthalen-1-ol 
• 83-70-5 vitamin K₅ 
• 6325-58-2 3-(1,4-dihydro-2-methyl-1,4-dioxo-naphthalen-3-yl-thio)propionic acid 
• 64648-85-7 2-Bromo-3-Methyl-1,1,4,4-tetramethoxy-1,4-dihydronaphthalene 
• 943232-38-0 (7R,11R)-3,7,11,15-tetramethyl-2-hexadecenyl bromide 
• 64-19-7 acetic acid 
• 130-15-4 [1,4]naphthoquinone 
• 91-57-6 2-Methylnaphthalene 
• 67-68-5 dimethyl sulfoxide 
• 67-64-1 acetone 
• 53772-19-3 1,4-dimethoxy-2-methylnaphthalene 
• 23177-71-1 2-methyl-1,4-naphthoquinone radical anion 

Downstream Products

• 59962-61-7 2-(4-methoxyphenyl)-3-methylnaphthalene-1,4-dione 
• 2593-55-7 2-methyl-3-methylthio-1,4-naphthoquinone 
• 6325-58-2 3-(1,4-dihydro-2-methyl-1,4-dioxo-naphthalen-3-yl-thio)propionic acid 
• 70691-68-8 3-methyl-2-(phenylthio)-1,4-naphthoquinone 
• 26269-05-6 2-amino-4-methyl-naphtho[1,2-d]thiazol-5-ol 
• 101959-62-0 2-[2-(4-Bromo-phenyl)-2-oxo-ethyl]-3-methyl-[1,4]naphthoquinone 
• 579-10-2 N-acetyl-N-methylaniline 
• 78236-98-3 2-[2,2-Bis-(methyl-phenyl-amino)-vinyl]-3-methyl-[1,4]naphthoquinone 
• 81466-98-0 2-<(3-acetylphenyl)imino>-1,2-dihydro-5-hydroxy-1,4-dimethylnaphtho<1,2-d>thiazole 
• 54812-04-3 2‐cyclohexyl‐3‐methylnaphthalene‐1,4‐dione 
• 116425-06-0 2-methyl-3-(2’-phenylethyl)-1,4-naphthoquinone 
• 88007-98-1 2-methyl-3-(2-oxo-2-phenylethyl)naphthalene-1,4-dione 
• 92-52-4 biphenyl 
• 92-52-4 biphenyl 

Relevant articles and documents

A new metal-free access to vitamin K3

2-Methylnaphthalene is oxidized in about 80% yield with 7-9/1 regioselectivity to 2-methyl-1,4-naphthoquinone by hydrogen peroxide with a strong mineral acid as the catalyst. No (transition) metal catalyst is required for this transformation.

An Experimental Test of the Competition Correction for Charge Capture from the Matrix in Intermolecular Electron Tunnelling Reactions

Further experimental tests have been made of a previously presented method to correct for competition for charge capture from the matrix in intermolecular electron transfer (ET) reactions in rigid media.The method is based on a two-step tunnelling model which takes into account the correlation between matrix charge capture and intermolecular electron transfer.The goal is to obtain reliable intermolecular ET rates as a function of distance from measurements on rigid solutions containing two randomly distributed solutes.The method should yield the same rate vs. distance function for different donor solute concentrations.Good agreement was obtained by applying the competition correction to pulse radiolysis data for the reaction of the biphenyl anion with 2-methyl-1,4-naphthoquinone in 2-methyltetrahydrofuran (MTHF) at 77 K for donor:acceptor solute concentration ratios of 20:1 to 2:1.Worse agreement was obtained for the reaction of biphenyl anion with phenanthrene in MTHF, in which case the reaction is slow, and its energetics are substantially influenced by solvation.For such slow reactions, accurate measurements of intermolecular ET rates require donor:acceptor solute concentration ratios such that the donor solute captures most of the matrix charges.It was observed that some biphenyl cations are produced by direct ionizations and are stable in frozen MTHF.

Selective synthesis of vitamin K3 over mesoporous NbSBA-15 catalysts synthesized by an efficient hydrothermal method

Well hexagonally ordered NbSBA-15 catalysts synthesized by an efficient hydrothermal method were used, for the first time, for the selective synthesis of vitamin K3 by liquid-phase oxidation of 2-methyl-1-naphthol (2MN1-OH) under various reaction conditions. The recyclable NbSBA-15 catalysts were also reused to find their catalytic activities. To investigate the leaching of non-framework niobium species on the surface of silica networks, the results of original and recyclable NbSBA-15 catalysts were correlated and compared. To find an optimum condition for the selective synthesis of vitamin K3, the washed NbSBA-15(2.2pH) was extensively used in this reaction with various reaction parameters such as temperature, time and ratios of reactant (2M1N-OH to H2O2), and the obtained results were also demonstrated. Additionally, the liquid-phase oxidation of 2M1N-OH was carried out with different solvents to find the best solvent with a good catalytic activity. Based on the all catalytic studies, the vitamin K3 selectivity (97.3%) is higher in NbSBA-15(2.2pH) than that of other NbSBA-15 catalysts, and the NbSBA-15(2.2pH) is found to be a highly active and eco-friendly heterogeneous catalyst for the selective synthesis of vitamin K3.

Manganese(II) naphthenate as effective catalyst for the clean oxidation of 2-methylnaphthalene by hydrogen peroxide

Oxidation of 2-methylnaphthalene (2-MN) with aqueous hydrogen peroxide was conducted in acetic acid. The epoxidation pathway was investigated by increasing the CH3CO3H content and adding manganese(II) naphthenate (MnPc) as catalyst. 2-Methyl-1,4-naphthoquinone was obtained in 75.6% conversion and with 80.0% selectivity under the latter conditions. A probable mechanism in which MnPc catalyzes the oxidation of 2-MN by hydrogen peroxide in acetic acid is proposed. Springer Science+Business Media B.V. 2012.

OXIDATION OF 2-METHYLNAPHTHALENE TO 2-METHYL-1,4-NAPHTHOQUINONE WITH HYDROGEN PEROXIDE IN THE PRESENCE OF Pd(II)-POLYSTYRENE SULFONIC ACID RESIN

The oxidation of 2-methylnaphthalene was carried out in acetic acid with aqueous(60percent) hydrogen peroxide in the presence of Pd(II)-polystyrene sulfonic acid resin. 2-Methyl-1,4-naphthoquinone was obtained in a yield of 50 to 60percent at 50 deg C for 8 h.The catalysts recovered by the filtration were reusable.

Phase-transfer oxidation of 2-methyl-1-naphthol into 2-methyl-1,4-naphthoquinone in the presence of vanadomolybdophosphoric heteropolyacids

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Liquid phase oxidation of 2-methylnaphthalene to 2-methyl-1,4- naphthoquinone over lanthanum doped MCM-41

Liquid phase oxidation of 2-methylnaphthalene was carried out under mild reaction conditions over lanthanum doped MCM-41 using aqueous hydrogen peroxide (30%) as oxidant and acetic acid as solvent without adding any initiator. The catalyst exhibited very high substrate conversion (95.8%) and reasonable product (2-methyl-1,4-naphthoquinone) selectivity (69.3%) under mild condition. Fast hot catalyst filtration experiment proved that the catalyst acted as a heterogeneous one and it can be reused two times without losing its activity to a greater extent. A possible mechanism was proposed.

Metalloporphyrin-catalyzed oxidation of 2-methylnaphthalene to vitamin K3 and 6-methyl-1,4-naphthoquinone by potassium monopersulfate in aqueous solution

The metalloporphyrin-catalyzed oxidation of 2-methylnaphthalene (1) by potassium monopersulfate produced mainly two naphthoquinones: 2-methyl-1,4-naphthoquinone (2) (menadione or vitamin K3) and 6-methyl-1,4-naphthoquinone (3). In aqueous solution and at room temperature in the presence of 5 mol % of the water-soluble metalloporphyrins MnTPPS or FeTMPS, 2-methylnaphthalene was quantitatively oxidized to quinones 2 and 3. Based on experiments performed in 18O-labeled water and according to the 'redox tautomerism' mechanism previously described for such catalysts, the oxidation to quinones is proposed to be mainly due to a cytochrome P-450-type oxygenation reaction (oxygen atom transfer), rather than a peroxidase-type oxidation (electron transfer).

Different Solid Forms of Vitamin K3and Their Effect on the Chemical Stability

MSB, the commercially available form of vitamin K3, has been widely applied in medicine, the nutrition industry, and livestock feed for decades. However, undesired degradation in an alkaline environment significantly decreases its efficacy and limits its application. Herein, polymorphism screening was performed on MSB to obtain solid forms with improved chemical stability. Two new solid forms were discovered, including form A and HB. Their crystal structures were elucidated by single crystal X-ray diffraction, and these forms were adequately characterized by powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, and dynamic vapor sorption. The transformation relationships between these solid forms were fully discussed. Single-crystal-to-single-crystal transformation behavior was also detected by X-ray diffraction and hot-stage microscopy. The chemical stability in an alkaline environment of the newly discovered forms was investigated and compared with that of the marketed form. It was found that form A significantly alleviates the degradation of MSB. This gratifying chemical stability may be attributed to its compact packing pattern and the molecular conformation advantage.

Fabrication, characterization and structure activity relationship of Co and Mn encapsulated on magnetic nanocomposite and its application in one-pot tandem synthesis of various tetrazoles and vitamin K3

Considering the importance of vitamin K3 in commercial pet foods, veterinary medicines, poultry, and some swine feed and also tetrazole derivatives in pharmacy, medicine, chemistry, petroleum, and military industry, design efficient catalytic systems are desirable. Herein, four magnetic nanocomposites (MNCs) of cobalt and manganese using metformin, 3-aminopropyltrimethoxysilane (L1) and 2-aminoethyl-3-aminopropyltrimethoxysilane (L2) were designed and constructed as an efficient and controllable catalytic system. The synthesized nanocomposites fully characterized by FT-IR, AAS, ICP-OES, BET, CHN elemental analysis, SEM, TEM, DLS, EDX, TGA, VSM, and XPS spectroscopy. The well-prepared magnetically recoverable nanocomposites were used in the synthesis of a wide derivatives of α-hydrazino tetrazoles (α-HyT), ferrocenyltetrazoles (FcT), arylaminotetrazoles (ArAT) and also vitamin K3. Besides, the effect of operating parameters, such as the amount of catalyst, nature of solvent, temperature and reaction time, metal nature, chain length and hydrophobicity properties of linkers, was studied in the catalytic efficiency of synthesized nanocatalysts. The best catalytic results were obtained in the following order: FS-L2-Met@Co(II) > FS-L2-Met@Mn(II) > FS-L1-Met@Co(II) > FS-L1-Met@Mn(II) due to their structural characteristics. In addition to high TOF, these magnetic nanocomposites are superior in easy, inexpensive, and commercially preparation, keeping the structural and magnetic characteristics, easy magnetically separation from the reaction medium, short reaction time, mild reaction condition, easy work-up, and reusability without any metal leaching in six runs. Graphical abstract: [Figure not available: see fulltext.]

Preparation method of menadione sodium hydrogen sulfite

The invention provides a preparation method of menadione sodium hydrogen sulfite. The preparation method comprises the following steps of: by taking alpha-methyl-gamma-butyrolactone and benzene as raw materials, preparing 2-methyl-3, 4-dihydro-1 (2H)-naphthalenone through Friedel-Crafts reaction; carrying out halogenation reaction on the 2-methyl-3, 4-dihydro-1 (2H)-naphthalenone and a halogenation reagent at the ortho position of carbonyl, and carrying out alkali elimination to prepare 2-methyl-1-naphthol; oxidizing the 2-methyl-1-naphthol through air to obtain 2-methyl-1, 4-naphthoquinone; and carrying out addition reaction on the 2-methyl-1, 4-naphthoquinone and sodium hydrogen sulfite to prepare the menadione sodium hydrogen sulfite. According to the method, the raw materials are cheap, easily available and low in cost; the process operation is safe, simple and convenient, less process wastewater is generated, and the method is green and environment-friendly; and the stability of the raw materials and intermediate products is high, high reaction activity and selectivity are high, reaction conditions are easy to realize, side reactions are few, the purity and yield of the product are high, and industrial production of the menadione sodium bisulfite can be facilitated.

PHOTOOXIDATION OF PHENOLIC COMPOUNDS

The present invention relates to the photooxidation of phenolic compounds to the respective quinoid compounds using methylene blue as photosensitizer in a solvent mixture of water and alcohols using light of the high wavelength range of the visible spectrum.