1696-20-4

Basic information

• Product Name: N-Acetylmorpholine
• Synonyms: N-ACETYLMORPHOLINE;MORPHOLINE, 4-ACETYL-;4-ACETYLMORPHOLINE;Acetylmorpholine;4-acetyl-morpholin;N-1-Acetyl morpholine;N-Acetylmorfolin;N-Aetylmorpholine
• CAS NO: 1696-20-4
• Molecular Formula: C₆H₁₁NO₂
• Molecular Weight: 129.16
• EINECS: 216-913-4
• Product Categories: Building Blocks;Heterocyclic Building Blocks;Morpholines
• Mol File: 1696-20-4.mol

Chemical Properties

• Melting Point: 14 °C(lit.)
• Boiling Point: 240-245 °C
• Flash Point: >230 °F
• Appearance: Clear colourless to very slightly yellow liquid
• Density: 1.116 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.0159mmHg at 25°C
• Refractive Index: n20/D 1.483(lit.)
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: -0.72±0.20(Predicted)
• Water Solubility: MISCIBLE
• BRN: 111971
• CAS DataBase Reference: N-Acetylmorpholine(CAS DataBase Reference)
• NIST Chemistry Reference: N-Acetylmorpholine(1696-20-4)
• EPA Substance Registry System: N-Acetylmorpholine(1696-20-4)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 36-62-43
• Safety Statements: 26-36-39-36/37
• WGK Germany: 1
• RTECS: QD7000000
• TSCA: Yes
• Hazardous Substances Data: 1696-20-4(Hazardous Substances Data)

Usage

Uses

Used in Pesticide Industry:
N-Acetylmorpholine is used as a crucial intermediate for the production of agricultural fungicides. Its primary applications are in the synthesis of enoylmorpholine and flumorpholine, which are important fungicides used to protect crops from fungal infections and diseases.
The compound's role in the creation of these fungicides highlights its importance in the agricultural industry, as it contributes to the development of products that ensure the health and productivity of crops.

Flammability and Explosibility

Nonflammable

Purification Methods

Distil it through an 8inch Fenske (glass helices packing, p 11) column with a manual take-off head. Purify it by fractional distillation. The hydrobromide has m 172-175o. [Brace J Am Chem Soc 75 357 1953, deBenneville et al. J Org Chem 21 1072 1956, Beilstein 27 III/IV 274.]

InChI:InChI=1/C6H11NO2/c1-6(8)7-2-4-9-5-3-7/h2-5H2,1H3

Upstream product

• 110-91-8 morpholine 
• 108-24-7 acetic anhydride 
• 64-19-7 acetic acid 
• 75-05-8 acetonitrile 
• 918-00-3 1,1,1-trichloroacetone 
• 934-87-2 S-phenyl thioacetate 
• 94340-39-3 4-(1-Cyano-1-carboethoxy)methylene-7-acetyl-4,7-dihydrothieno<2,3-b>pyridine 
• 6291-16-3 1-deoxy-1-morpholino-D-fructose 
• 14212-87-4 1,1-bis(N-morpholinyl)ethylene 
• 141-97-9 ethyl acetoacetate 
• 105-56-6 ethyl 2-cyanoacetate 
• 2227-79-4 benzenecarbothioamide 
• 123-54-6 acetylacetone 
• 109-77-3 malononitrile 

Downstream Products

• 72311-85-4 4-(3-hydroxy-3,3-diphenyl-propionyl)-morpholine 
• 5421-70-5 Adipinsaeure-morpholid 
• 77873-72-4 3-methoxy-N-acetylmorpholine 
• 17123-83-0 N-(phenylacetyl)morpholine 
• 14135-68-3 1-morpholino-2,2-diphenylethanone 
• 121290-13-9 (E)-4-Morpholin-4-yl-4-p-tolyl-3-trifluoromethanesulfonyl-but-3-en-2-one 
• 66646-99-9 1-(2-hydroxyphenyl)-3-(morpholin-4-yl)propane-1,3-dione 

Relevant articles and documents

Heterocyclic Deformations from Molecular Enlargement

The ease of distortion of saturated nitrogen heterocycles has been examined by progressively increasing the bulk of the substituent at nitrogen.The heterocycles included the pharmacophoric piperidine and morpholine six-membered rings, as well as the five-membered oxazolidine ring.Response to increased bulk of substitution was intended to be a crude model for distortions within the drug-receptor complex.Substitution at nitrogen included methyl, (1-adamantyl)methyl, and 6-substituted β-cyclodextrin within a tetrahedral series, and acetyl and (1-adamantyl)carbonyl within a trigonal series.With methyl and acetyl serving as standards for the undistorted rings, we have found that the NCH2CH2X dihedral angle within all three heterocycles is decreased anly by about 1 deg on introduction of adamantyl groups.In agreement with this flattening distortion, the barrier to ring reversal of the piperidine is decreased by 1.4 kcal/mol on replacement of N-methyl by N-adamantylmethyl.The β-cyclodextrin ring imposes a much more severe distortion, as this same dihedral angle in the piperidine and morpholine rings decreases 5-6 deg.The barrier to rotation about the amide bond decreases 5-6 kcal/mol in all three heterocycles on going from acetyl to adamantylcarbonyl.These studies show that the response of these heterocycles to incresed steric bulk of N substitution is a flatter and hence more flexible ring.

Synthesis of 4-Vinylmorpholine Based on Acetylene

It has been shown that from the possible methods for the synthesis of 4-vinylmorpholine, the vinylation of morpholine with acetylene remains acceptable. A technologically accessible method for vinylation of morpholine with acetylene at atmospheric pressure was developed.

Electrophilic Sulfonium-Promoted Peptide and Protein Amidation in Aqueous Media

A novel amidation strategy using electrophilic sulfonium, which is soluble and stable in aqueous conditions, was developed. The sulfoniums could activate thioacid and carboxyl acid to efficiently react with amines to afford amides. This method enables applications in amidation in both aqueous media and solid-phase peptide synthesis, peptide/protein modifications, and reactive lysines of a proteome at pH 10 with activity-based protein profiling. A peptide ligand-directed labeling of the USP7-UBL2 domain was also performed using this method.

A CO2-Catalyzed Transamidation Reaction

Transamidation reactions are often mediated by reactive substrates in the presence of overstoichiometric activating reagents and/or transition metal catalysts. Here we report the use of CO2as a traceless catalyst: in the presence of catalytic amounts of CO2, transamidation reactions were accelerated with primary, secondary, and tertiary amide donors. Various amine nucleophiles including amino acid derivatives were tolerated, showcasing the utility of transamidation in peptide modification and polymer degradation (e.g., Nylon-6,6). In particular,N,O-dimethylhydroxyl amides (Weinreb amides) displayed a distinct reactivity in the CO2-catalyzed transamidation versus a N2atmosphere. Comparative Hammett studies and kinetic analysis were conducted to elucidate the catalytic activation mechanism of molecular CO2, which was supported by DFT calculations. We attributed the positive effect of CO2in the transamidation reaction to the stabilization of tetrahedral intermediates by covalent binding to the electrophilic CO2

N-acetylation of amines in continuous-flow with acetonitrile—no need for hazardous and toxic carboxylic acid derivatives

A continuous-flow acetylation reaction was developed, applying cheap and safe reagent, acetonitrile as acetylation agent and alumina as catalyst. The method developed utilizes milder reagent than those used conventionally. The reaction was tested on various aromatic and aliphatic amines with good conversion. The catalyst showed excellent reusability and a scale-up was also carried out. Furthermore, a drug substance (paracetamol) was also synthesized with good conversion and yield.

IrIII-Catalyzed direct syntheses of amides and esters using nitriles as acid equivalents: A photochemical pathway

An unprecedented IrIII[df(CF3)ppy]2(dtbbpy)PF6-catalyzed simple photochemical process for direct addition of amines and alcohols to the relatively less reactive nitrile triple bond is described herein. Various amides and esters are synthesized as the reaction products, with nitriles being the acid equivalents. A mini-library of different types of amides and esters is made using this mild and efficient process, which uses only 1 mol% of photocatalyst under visible light irradiation (λ = 445 nm). The reaction strategy is also efficient for gram-scale synthesis.

Direct amide formation in a continuous-flow system mediated by carbon disulfide

Amide bonds are ubiquitous in nature. They can be found in proteins, peptides, alkaloids, etc. and they are used in various synthetic drugs too. Amide bonds are mainly made by the use of (i) hazardous carboxylic acid derivatives or (ii) expensive coupling agents. Both ways make the synthetic technology less atom economic. We report a direct flow-based synthesis of amides. The developed approach is prominently simple and various aliphatic and aromatic amides were synthetized with excellent yields. The reaction in itself is carried out in acetonitrile, which is considered as a less problematic dipolar aprotic solvent. The used coupling agent, carbon disulfide, is widely available and has a low price. The utilized heterogeneous Lewis acid, alumina, is a sustainable material and it can be utilized multiple times. The technology is considerably robust and shows excellent reusability and easy scale-up is carried out without the need of any intensive purification protocols.

Preparation method for N-acetylmorpholine

The invention provides a preparation method for N-acetylmorpholine. The method comprises the following steps: performing a reaction on morpholine and ethyl acetate in a reactor, wherein the reaction temperature is 140-160 DEG C, the reaction time is 6-10 h, and the reaction pressure is normal pressure; and at the same time, performing a synthetic reaction under the condition of an ionic liquid catalyst to obtain crude N-acetylmorpholine, performing dealcoholization treatment on the crude N-acetylmorpholine, performing dehydration treatment, separating the morpholine, and performing rectification to obtain the N-acetylmorpholine fine product. The process provided by the invention is efficient, economical, harmless, safe, environmentally friendly, energy-saving and emission-reducing, and prepares the high-purity N-acetylmorpholine product.

Environmentally benign decarboxylative: N-, O-, and S-Acetylations and acylations

An operationally simple and general method for acetylation and acylation of a wide variety of substrates (amines, alcohols, phenols, thiols, and hydrazones) has been reported. Meldrum's acid and its derivatives have been used as an air-stable, non-volatile, cost-effective, and easy to handle acetylating/acylating agent. Easily separable byproducts (CO2 and acetone) allowed the isolation of analytically pure acetylated products without the requirement of work-up and any chromatography. This journal is

Phenysilane and Silicon Tetraacetate: Versatile Promotors for Amide Synthesis

Phenylsilane was reevaluated as a useful coupling reagent for amide synthesis. At room temperature, a wide range of amides and peptides were obtained in good to excellent yields (up to 99 %). For the first time, Weinreb amides synthesis mediated by a hydrosilane were also documented. Comparative experiments with various acetoxysilanes suggested the involvement of a phenyl-triacyloxysilane. From this mechanistic study, silicon tetraacetate was shown as an efficient amine acylating agent.