7529-22-8

Usage

Uses

Used in Textile Industry:
4-Methylmorpholine N-oxide is used as a solvent in the Lyocell process for producing Tencel fiber, an eco-friendly and sustainable material derived from wood pulp.
Used in Chemical Synthesis:
4-Methylmorpholine N-oxide acts as a non-metallic catalyst for the cyanosilylation of ketones, facilitating the formation of valuable chemical intermediates.
Used in Organic Synthesis:
It is employed as a co-oxidant for Sharpless asymmetric dihydroxylation in ionic liquids, a reaction that is crucial for the synthesis of complex organic molecules.
Used in Aldehyde Preparation:
4-Methylmorpholine N-oxide is used in the preparation of aldehydes from primary alcohols in the presence of tetrapropylammonium perruthenate, a reaction that is essential for the synthesis of various organic compounds.

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 
• 50-00-0 formaldehyd 
• 60460-70-0 4-bromo-2-(N-morpholinyl)methylphenol 
• 4727-98-4 1,1,3,3-tetrabenzoylpropane 
• 27438-39-7 2-hydroxy-1-(N-morpholinomethyl)naphthalene 
• 4438-01-1 2-(morpholinomethyl)phenol 
• 1723-94-0 1,2-dimorpholylethane 
• 6320-30-5 2-hydroxy-3-(morpholinomethyl)naphthalene-1,4-dione 
• 861430-63-9 2(S)-{[7-(4-tert-Butyl-phenoxy)-1-cyclopentylmethyl-isoquinoline-3-carbonyl]-amino}-3-[5-(1,2-dihydroxy-ethyl)-thiophen-2-yl]-propionic acid methyl ester 
• 864961-62-6 5-isobutyrylthiophene-3-sulfonic acid [2-(4-fluorophenyl)ethyl]-methyl-amide 
• 137076-22-3 tert butyl 4-formylpiperidine-1-carboxylate 

Relevant academic research and scientific papers

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%.

PRODUCTION OF AN AMINE OXIDE BY OXIDATION OF A TERTIARY AMINE

A method for producing an amine oxide by oxidation of a tertiary amine in a reactor under continuous introduction of tertiary amine in a reaction fluid and export of amine oxide, wherein a suitable surface-to-volume ratio and/or a suitable flow speed with corresponding surface/volume loads are selected in the continuous process. The reaction fluid is usually reacted in the reactor with a laminar flow.

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.

Optimized preparation method of N-methylmorpholine-N-oxide

The invention belongs to the technical field of chemical synthesis, and particularly relates to an optimized preparation method of N-methylmorpholine-N-oxide. The N-methylmorpholine-N-oxide (NMMO) isan organic solvent in a cellulose spinning process. The synthesis methods commonly used in the field mainly comprise a hydrogen peroxide peroxidation method and a molecular oxygen-aldehyde catalytic oxidation method; wherein the hydrogen peroxide method is widely applied due to the advantages of mild reaction conditions, high product quality and the like, and catalysts commonly used in the conventional hydrogen peroxide catalysis method comprise basic ion exchange resin, copper hydroxide, manganese dioxide, quaternary ammonium salt compounds and the like; however, these catalysts have higher requirements on the reaction conditions. Researches show that when titanium dioxide is used as a catalyst, the temperature for preparing N-methylmorpholine-N-oxide can be reduced, the yield of N-methylmorpholine-N-oxide is greatly increased, the reaction temperature is only 40 DEG C, and the yield can be increased to 90%; so that the production energy consumption is reduced, and the method has goodindustrial production and popularization significance.

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.

Novel low viscous, green and amphiphilic N-oxides/phenylacetic acid based Deep Eutectic Solvents

Four novel Deep Eutectic Solvents (DESs) were prepared by mixing phenylacetic acid (which is a natural molecule present in honey) with amine N-oxides, which are molecules easily biodegradable in nature. Three of these N-oxides are amphiphilic. The novel DESs have very low freezing points (from ??34?°C to 20?°C) and they have very low viscosity, much lower than the most common and used DES in literature so far (choline chloride/urea mixture). The conductivity values resulted low and the ionicity analysis showed these DESs to be “super ionic”. Their polarity resulted high enough and it can be compared with other commonly used solvents or ionic liquids.

Renewable waste rice husk grafted oxo-vanadium catalyst for oxidation of tertiary amines to N-oxides

Low cost renewable waste rice husks (RH) have been used as a support for grafting of an oxo-vanadium Schiff base via covalent attachment for the oxidation of tertiary amines to N-oxide. The synthesis of the desired RH grafted oxo-vanadium complex involves prior functionalization of the RH support with amino-propyltrimethoxysilane (APTMS) followed by its reaction with salicylaldehyde to get an RH-functionalized Schiff base which subsequently reacted with vanadyl sulphate to get the targeted oxo-vanadium catalyst. The synthesized catalyst was found to be an efficient heterogeneous catalyst and afforded an excellent yield of corresponding N-oxides via oxidation of tertiary amines with hydrogen peroxide as an oxidant. Furthermore, the synthesized catalyst was found to be quite stable and showed consistent activity for five runs without any loss in activity.

Selectivity Modulation of the Ley–Griffith TPAP Oxidation with N-Oxide Salts

A wide variety of novel non-hygroscopic N-oxide tetraphenylborate salts were synthesized and evaluated as co-oxidants in the Ley–Griffith (TPAP) oxidation of benzylic and allylic alcohols under non-anhydrous conditions. The novel DABCOO·TPB (2:1) salt was herein unearthed as a viable competitor to the first-generation NMO·TPB (2:1) salt, but more importantly gave increased performance under oxidative competition. X-ray crystal structure analysis and NMR spectroscopy revealed that depending on the crystallization conditions 1:1, 2:1 or 3:2 N-oxide–tetraphenylborate salts could be formed.

Toward chemistry-based design of the simplest metalloenzyme-like catalyst that works efficiently in water

Enzymes exhibit overwhelmingly superior catalysis compared with artificial catalysts. Current strategies to rival enzymatic catalysis require unmodified or minimally modified structures of active sites, gigantic molecular weight, and sometimes the use of harsh conditions such as extremely low temperatures in organic solvents. Herein, we describe a design of small molecules that act as the simplest metalloenzyme-like catalysts that can function in water, without mimicking enzyme structures. These artificial catalysts efficiently promoted enantioselective directtype aldol reactions using aqueous formaldehyde. The reactions followed Michaelis-Menten kinetics, and heat-resistant asymmetric environments were constructed in water.

2,2,2-Trifluoroacetophenone as an organocatalyst for the oxidation of tertiary amines and azines to N-oxides

A cheap, mild and environmentally friendly oxidation of tertiary amines and azines to the corresponding Noxides is reported by using polyfluoroalkyl ketones as efficient organocatalysts. 2,2,2-Trifluoroacetophenone was identified as the optimum catalyst for the oxidation of aliphatic tertiary amines and azines. This oxidation is chemoselective and proceeds in high-to-quantitative yields utilizing 10 mol% of the catalyst and H2O2 as the oxidant.