7529-22-8

Basic information

• Product Name: 4-Methylmorpholine N-oxide
• Synonyms: 4-methyl-morpholin4-oxide;Morpholine, 4-methyl-, 4-oxide;Morpholine,4-methyl-,4-oxide;N-Methylmorpholine oxide;4-METHYLMORPHOLINE N-OXIDE;4-METHYLMORPHOLINE 4-OXIDE;N-METHYLMORPHOLINE 4-OXIDE;NMO
• CAS NO: 7529-22-8
• Molecular Formula: C₅H₁₁NO₂
• Molecular Weight: 117.15
• EINECS: 231-391-8
• Product Categories: Heterocycles;Aromatic Morpholines;Oxidation;Synthetic Organic Chemistry;Heterocycles, Metabolites & Impurities, Pharmaceuticals, Intermediates & Fine Chemicals
• Mol File: 7529-22-8.mol
• Article Data: 36

Chemical Properties

• Melting Point: 180-184 °C(lit.)
• Boiling Point: 118-119°C
• Flash Point: 118-119°C
• Appearance: Clear colorless to yellow/Liquid
• Density: 1,14 g/cm3
• Vapor Pressure: 1.41hPa at 20℃
• Refractive Index: n20/D 1.43
• Storage Temp.: 2-8°C
• Solubility: DMSO (Soluble), Methanol (Slightly)
• PKA: 4.93±0.20(Predicted)
• Water Solubility: Soluble in water, methanol, ethanol, acetone, ethers and dimethylsulfoxide.
• Stability: Hygroscopic
• BRN: 507437
• CAS DataBase Reference: 4-Methylmorpholine N-oxide(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Methylmorpholine N-oxide(7529-22-8)
• EPA Substance Registry System: 4-Methylmorpholine N-oxide(7529-22-8)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36/37
• WGK Germany: 1
• TSCA: Yes
• Hazardous Substances Data: 7529-22-8(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 7529-22-8 differently. You can refer to the following data:
1. 4-Methylmorpholine N-Oxide is a metabolite of Morpholine (M723725). N-Methylmorpholine N-Oxide is commonly used to dissolve cellulose as well as in the dissolution of of scleroproteins.
2. 4-Methylmorpholine N-oxide acts as a non-metallic catalyst for the cyanosilylation of ketones. It is also employed as a co-oxidant for Sharpless asymmetric dihydroxylation in ionic liquids. It serves as a solvent in the Lyocell process to produce tencel fiber. Further, it is used in the preparation of aldehydes from primary alcohols in the presence of tetrapropylammonium perruthenate.
3. Non-metallic catalyst for the cyanosilylation of ketones. Co-oxidant for Sharpless asymmetric dihydroxylation in ionic liquids.

General Description

4-Methylmorpholine?N-oxide is an organic compound used as a co-oxidant along with OsO4 and ruthenates in organic synthesis. In recent studies, it has been used as a catalyst in silylcyanation of aldehydes and ketones. Lyocell, a regenerated cellulose fiber, can be prepared using 4-methylmorpholine?N-oxide in an eco-friendly manner.

Flammability and Explosibility

Flammable

Purification Methods

When the oxide is dried for 2-3hours at high vacuum, it dehydrates. Add MeOH to the oxide and distil off the solvent under vacuum until the temperature is ca 95o. Then add Me2CO at reflux and cool to 20o. The crystals are filtered off, washed with Me2CO and dried. The degree of hydration may vary and may be important for the desired reactions. [van Rheenan et al. Tetrahedron Lett 1973 1076, Schneider & Hanze US Pat 2 769 823; see also Sharpless et al. Tetrahedron Lett 2503 1976.]

InChI:InChI=1/C5H11NO2/c1-6(7)2-4-8-5-3-6/h2-5H2,1H3

Synthetic route

4-methyl-morpholine (109-02-4) → 4-methylmorpholine N-oxide (7529-22-8)

Conditions	Yield
With 4-hydroperoxy-5-ethyl-3-methyllumiflavine In tert-butyl alcohol at 30℃; Rate constant;	100%
With carbon dioxide; phosphoric acid; dihydrogen peroxide under 7500.75 Torr; for 0.133333h; Reagent/catalyst; Pressure; Time; Autoclave;	100%
With dihydrogen peroxide; benzonitrile; Mg-Al-O-t-Bu HT (Catalyst B) In methanol; water at 65℃; for 0.5h; Product distribution / selectivity;	98%

4-methyl-morpholine (109-02-4) + 3-bromo-4,5-dihydro-5-hydroperoxy-4,4-dimethyl-3,5-diphenyl-3H-pyrazole (76847-41-1) → 3-bromo-4,5-dihydro-5-hydroxy-4,4-dimethyl-3,5-diphenyl-3H-pyrazole (76847-42-2) + 4-methylmorpholine N-oxide (7529-22-8)

Conditions	Yield
In chloroform-d1 at 34℃; Rate constant;	A n/a B 95 % Spectr.

4-methyl-morpholine (109-02-4) + cis-3-bromo-4,5-dihydro-5-hydroperoxy-4,4-dimethyl-3,5-diphenyl-3H-pyrazole (72229-10-8) → 4-methylmorpholine N-oxide (7529-22-8)

Conditions	Yield
In chloroform at 34℃; Rate constant; Mechanism; other α-azo hydroperoxides; oxidation of other amines, PhS, and olefins; var. solvents, deuterium isotope effect;

4-methyl-morpholine (109-02-4) + C17H16(2)HBrN2O2 (107743-45-3) → 4-methylmorpholine N-oxide (7529-22-8)

Conditions	Yield
In chloroform at 34℃; Rate constant; Mechanism; other α-azo hydroperoxides; oxidation of other amines, Ph2S, and olefins; var. solvent, deuterium isotope effect;

4-[6-hydroxy-2,7,8-trimethyl-2-(4,8,12-trimethyl-tridecyl)-chroman-5-ylmethyl]-4-methyl-morpholin-4-ium; iodide → 4-methylmorpholine N-oxide (7529-22-8)

Conditions	Yield
With sodium percarbonate In hexane; dichloromethane; acetonitrile at 50℃; for 1h; Substitution; Oxidation;

2a-(4-Pentenyl)-2a,3,4,5-tetrahydrobenz[cd]indole-2(1H)-one (201609-30-5) + 4-methylmorpholine N-oxide (7529-22-8) → 2a-(3-Formylpropyl)-2a,3,4,5-tetrahydrobenz[cd]indole-2(1H)-one (201609-31-6)

Conditions	Yield
With sodium periodate; osmium(VIII) oxide In 1,4-dioxane; water	100%

4-methylmorpholine N-oxide (7529-22-8) + N-[4-nitro-2-phenylbenzoyl]-methionine methyl ester (180977-02-0) → 4-Nitro-2-phenylbenzoyl-[1'(S)-ethoxycarbonyl-3'-methylsulfonyl]propyl amide

Conditions	Yield
With osmium(VIII) oxide In water; acetone; tert-butyl alcohol	100%

4-methylmorpholine N-oxide (7529-22-8) + dimethyl sulfate (77-78-1) → N-methoxy-N-methylmorpholinium methyl sulfate

Conditions	Yield
In acetonitrile	100%

diethyl sulfate (64-67-5) + 4-methylmorpholine N-oxide (7529-22-8) → N-ethoxy-N-methylmorpholinium ethyl sulfate

Conditions	Yield
In acetonitrile for 24h;	100%

2,6-anhydro-3-azido-1,4-di-O-benzyl-3,5-dideoxy-D-arabino-hex-5-enitol + 4-methylmorpholine N-oxide (7529-22-8) → 4-azido-4-deoxy-3,6-di-O-benzyl-D-galactopyranose

Conditions	Yield
Stage #1: 2,6-anhydro-3-azido-1,4-di-O-benzyl-3,5-dideoxy-D-arabino-hex-5-enitol With osmium(VIII) oxide; water In tetrahydrofuran; tert-butyl alcohol at 20℃; for 0.5h; Stage #2: 4-methylmorpholine N-oxide In tetrahydrofuran; tert-butyl alcohol for 28.5h;	100%

C18H32GeN2SSi + 4-methylmorpholine N-oxide (7529-22-8) → C18H32GeN2OSSi

Conditions	Yield
In tetrahydrofuran at 20℃; for 12h;	97%

Resin-OsO4 + Hydroquinidine 1,4-phthalazinediyl diether (DHQD)2PHAL + Resin-OsO4(0.01 eq wt) + (E)-1,2-diphenyl-ethene (103-30-0) + 4-methylmorpholine N-oxide (7529-22-8) → (R,R)-hydroxybenzoin (52340-78-0)

Conditions	Yield
In water; acetone	96%
In water; acetone	96%

(E)-1,2-diphenyl-ethene (103-30-0) + 4-methylmorpholine N-oxide (7529-22-8) → (R,R)-hydroxybenzoin (52340-78-0)

Conditions	Yield
In water; acetone	96%

tert-butyl N-(4-hydroxycyclohexyl)carbamate (224309-64-2) + tetrapropylammonium perruthennate (114615-82-6) + 4-methylmorpholine N-oxide (7529-22-8) → N-(tert-butoxycarbonyl)-4-aminocyclohexanone (179321-49-4)

Conditions	Yield
molecular sieves In dichloromethane; ethyl acetate	96%

trismethyluranium (69517-44-8) + 4-methylmorpholine N-oxide (7529-22-8) → C19H57N3OSi6U

Conditions	Yield
In diethyl ether at -21℃; for 0.5h; Inert atmosphere;	96%

benzyl cyclopent-3-enyl(methyl)carbamate + 4-methylmorpholine N-oxide (7529-22-8) → benzyl (1S,3R,4S)-3,4-dihydroxycyclopentyl(methyl)carbamate (1225384-36-0) + C14H19NO4

Conditions	Yield
With osmium(VIII) oxide In water; acetone; tert-butyl alcohol at 20℃;	A 96% B n/a

sodium tetraphenyl borate (143-66-8) + 4-methylmorpholine N-oxide (7529-22-8) → C24H20B(1-)*C5H12NO2(1+)

Conditions	Yield
With acetic acid In water at 20℃; for 0.25h;	96%

7-(6-exo-(methoxymethoxy)-3-phenyl-3a-(1-phenylvinyl)-1,3a,4,5,6,6a-hexahydropentalen-2-yl)heptan-1-ol + 4-methylmorpholine N-oxide (7529-22-8) → C32H40O4

Conditions	Yield
With tetrapropylammonium perruthennate In water; acetonitrile	96%

1,4-diaza-bicyclo[2.2.2]octane (280-57-9) + 4-methylmorpholine N-oxide (7529-22-8) + N-{3-[[4-(allyloxy)benzyl](benzyl)amino]-2-methylphenyl}methanesulfonamide (448953-11-5) → N-(3-{benzyl[4-(2,3-dihydroxypropoxy)benzyl]amino}-2-methylphenyl)methanesulfonamide

Conditions	Yield
With sodium hydrogen sulfate; osmium(VIII) oxide In water; ethyl acetate; acetone; tert-butyl alcohol	95%

C33H38GeN2OSi + 4-methylmorpholine N-oxide (7529-22-8) → C66H76Ge2N4O4Si2

Conditions	Yield
In tetrahydrofuran at 20℃; for 18h;	95%

tetrapropylammonium perruthennate (114615-82-6) + 4-methylmorpholine N-oxide (7529-22-8) + (4S)-4-(2-methyl-3(RS)-hydroxybut-2-yl)-2,2-dimethyl[1,3]dioxane (220367-72-6) → (4S)-4-(2-methyl-3-oxobut-2-yl)-2,2-dimethyl[1,3]dioxane (220367-71-5)

Conditions	Yield
molecular sieve In dichloromethane	94.5%

1-(9-Decenyl)-3,7-dimethylxanthine (156918-57-9) + 4-methylmorpholine N-oxide (7529-22-8) → 1-(9',10'-dihydroxydecyl)-3,7-dimethylxanthine

Conditions	Yield
With osmium(VIII) oxide In water; acetone; tert-butyl alcohol	93%

1-(9-Decenyl)-3,7-dimethylxanthine (156918-57-9) + 4-methylmorpholine N-oxide (7529-22-8) → 1-(9',10'-dihydroxydecyl)-3,7-dimethylxanthine (156918-13-7) + 1-(7-acetoxy-8-bromooctyl)3,7-dimethylxanthine (159431-48-8)

Conditions	Yield
In water; acetone; tert-butyl alcohol	A 93% B n/a

C33H38GeN2OSSi + 4-methylmorpholine N-oxide (7529-22-8) → C66H76Ge2N4O4Si2

Conditions	Yield
In tetrahydrofuran at 20℃; for 12h;	93%

4-methylmorpholine N-oxide (7529-22-8) + 6,6-Dimethyloct-1-yn-7-en-4-ol (379228-74-7) → C11H16O2

Conditions	Yield
Stage #1: 6,6-Dimethyloct-1-yn-7-en-4-ol With dicobalt octacarbonyl In dichloromethane at 20℃; for 4h; Stage #2: 4-methylmorpholine N-oxide In dichloromethane at 0℃; for 4h; Temperature;	92.4%

Upstream product

• 109-02-4 4-methyl-morpholine 
• 76847-41-1 3-bromo-4,5-dihydro-5-hydroperoxy-4,4-dimethyl-3,5-diphenyl-3H-pyrazole 
• 72229-10-8 cis-3-bromo-4,5-dihydro-5-hydroperoxy-4,4-dimethyl-3,5-diphenyl-3H-pyrazole 
• 107743-45-3 C₁₇H₁₆⁽²⁾HBrN₂O₂ 

Downstream Products

• 106476-34-0 1-morpholino-2-(benzylamino)propane 
• 109-02-4 4-methyl-morpholine 
• 87177-56-8 4-hydroxy-3-morpholin-4-ylmethylbenzoic acid methyl ester 
• 110-91-8 morpholine 
• 312329-68-3 1-hexanoyl-3,4-dimethyl-4-(3-formylphenyl)piperidine 
• 365462-71-1 ethyl 4-formyl-3-nitrobenzoate 
• 312329-48-9 1-Hexyl-3,4-dimethyl-4-(3-(1,2-dihydroxyethyl)phenyl)-piperidine 
• 247566-80-9 5-nitro-2-(4-oxocyclohexylamino)-N-(1,3-benzodioxol-5-ylmethyl)benzamide 
• 263397-88-2 (-)-2(R),3(S)-methano-3-(3,5-diisopropylphenyl)-pentanal 
• 17159-79-4 ethyl 4-oxocyclohexane-1-carboxylate 
• 252017-94-0 (R)-N-[2-Chloro-4-(thien-2-ylmethylsulphonyl)phenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide 
• 242459-55-8 4-(3-[1-(1H-benzo[d]imidazol-2-ylsulfonyl)-2-piperidyl]-1,2,4-oxadiazol-5-ylmethoxy)benzaldehyde 
• 330936-13-5 (2R,3S)-3,5,7,3',4'-pentakis(benzyloxy)flavan-4-one 
• 41959-26-6 2-benzyl-2-azabicyclo[2.2.2]octan-6-one 

Relevant articles and documents

A concise synthesis of N-(trideuteromethyl)morpholine-N-oxide monohydrate

An efficient synthesis of N-(trideuteromethyl)morpholine N-oxide monohydrate (3) is described. The procedure applies the tocopheryl protecting group, and makes use of sodium percarbonate as the oxidant and water donor, thus avoiding both the troublesome direct alkylation of morpholine and the unsuitable oxidation by aqueous hydrogen peroxide. Overall yields of purified material range above 90%.

Preparation method for N-methylmorpholine-N-oxide (NMMO)

The invention provides a preparation method for N-methylmorpholine-N-oxide (NMMO). The method comprises the following steps: (1) adding a nanocrystalline metal oxide into N-methylmorpholine(NMM), mixing and stirring to enable the nanocrystalline metal oxide to be uniformly mixed with the NMM; (2) dropwise adding a hydrogen peroxide solution into mixed liquid of the NMM and a catalyst; (3) raising the temperature to accelerate the reaction process; (4) performing filtering and reduced pressure distillation on a solution prepared in (3) to obtain a required NMMO solution. The method for preparing the NMMO provided by the invention has the advantages of fast reaction rate, low reaction temperature, few by-products and the like.

Comparison of riboflavin-derived flavinium salts applied to catalytic H2O2 oxidations

A series of flavinium salts, 5-ethylisoalloxazinium, 5-ethylalloxazinium, and 1,10-ethylene-bridged alloxazinium triflates, were prepared from commercially available riboflavin. This study presents a comparison between their optical and redox properties, and their catalytic activity in H2O2 oxidations of sulfide, tertiary amine, and cyclobutanone. Reflecting the difference between the π-conjugated ring structures, the flavinium salts displayed very different redox properties, with reduction potentials in the order of: 5-ethylisoalloxazinium > 5-ethylalloxazinium > 1,10-ethylene-bridged alloxazinium. A comparison of their catalytic activity revealed that 5-ethylisoalloxazinium triflate specifically oxidises sulfide and cyclobutanone, and 5-ethylalloxazinium triflate smoothly oxidises tertiary amine. 1,10-Bridged alloxazinium triflate, which can be readily obtained from riboflavin in large quantities, showed moderate catalytic activity for the H2O2 oxidation of sulfide and cyclobutanone.