4394-85-8

Basic information

• Product Name: N-Formylmorpholine
• Synonyms: 4-Morpholinecarbaldehyde;Formmorpholime;Morpholine, 4-formyl-;N-Formylmorfolin;4-MORPHOLINECARBOXALDEHYDE;4-FORMYLMORPHOLINE;N-FORMYLMORPHOLINE;MORPHOLINE-4-CARBOXALDEHYDE
• CAS NO: 4394-85-8
• Molecular Formula: C₅H₉NO₂
• Molecular Weight: 115.13
• EINECS: 224-518-3
• Mol File: 4394-85-8.mol
• Article Data: 215

Chemical Properties

• Melting Point: 20-23 °C(lit.)
• Boiling Point: 236-237 °C(lit.)
• Flash Point: >230 °F
• Appearance: Clear yellow/Liquid
• Density: 1.145 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.0472mmHg at 25°C
• Refractive Index: n20/D 1.485(lit.)
• Storage Temp.: 2-8°C
• Solubility: SOLUBLE
• PKA: -0.75±0.20(Predicted)
• Explosive Limit: 1.2-8.2%(V)
• Water Solubility: SOLUBLE
• Sensitive: Hygroscopic
• BRN: 110293
• CAS DataBase Reference: N-Formylmorpholine(CAS DataBase Reference)
• NIST Chemistry Reference: N-Formylmorpholine(4394-85-8)
• EPA Substance Registry System: N-Formylmorpholine(4394-85-8)

Safety Data

• Statements: 36/37/38
• Safety Statements: 23-24/25
• WGK Germany: 3
• RTECS: QD9694000
• TSCA: Yes
• Hazardous Substances Data: 4394-85-8(Hazardous Substances Data)

Usage

Chemical Properties

CLEAR YELLOW LIQUID

Uses

Different sources of media describe the Uses of 4394-85-8 differently. You can refer to the following data:
1. 4-Formylmorpholine is widely used as a solvent and extracting agent for aromatics. It is used as a scrubbing agent for acidic gases. It is employed in the preparation of adenine hydrochloride labeled with 14C, 4-(trifluoromethyl)morpholine, 3-alkyl-2-chloro-5,6-dihydrobenzaldehyde and terphenyl dialdehyde. It plays an important role in the desulfurization of natural gas, synthetic gas, flue gas and gasoline.
2. 4-Formylmorpholine has been used in the preparation of:adenine hydrochloride labelled with 14Cterphenyl dialdehyde

Synthesis Reference(s)

The Journal of Organic Chemistry, 25, p. 199, 1960 DOI: 10.1021/jo01072a012

General Description

Treatment of 4-formylmorpholine with sulphur tetrafluoride in the presence of potassium fluoride gives 4-(trifluoromethyl)morpholine in excellent yields. 4-Formylmorpholine reacts with series of 2-alkyl-2-cyclohexen-1-ones in the presence of POCl3 to give the corresponding 3-alkyl-2-chloro-5,6-dihydrobenzaldehydes and allylic alcohols (by-product).

Flammability and Explosibility

Nonflammable

InChI:InChI=1/C5H9NO2/c7-5-6-1-3-8-4-2-6/h5H,1-4H2

Synthetic route

morpholine (110-91-8) + formic acid (64-18-6) → 4-morpholinecarboxaldehyde (4394-85-8)

Conditions	Yield
With cyano-hydroxyimino-acetic acid 2,2-dimethyl-[1,3]dioxolan-4-ylmethyl ester; sodium hydrogencarbonate; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In water at 20℃; for 3h; Reagent/catalyst; Solvent;	100%
In butan-1-ol at 120℃; Solvent; Temperature;	99.35%
In ethanol at 140℃; for 24h; Solvent; Autoclave;	98%

morpholine (110-91-8) + formamide (77287-34-4, 77287-35-5, 60100-09-6) → 4-morpholinecarboxaldehyde (4394-85-8)

Conditions	Yield
With Iron(III) nitrate nonahydrate In toluene for 7h; Reflux;	100%
With water; boric acid at 100℃; for 24h;	87%
With [bis(acetoxy)iodo]benzene In neat (no solvent) at 100℃; for 0.333333h; Microwave irradiation; Green chemistry;	86%

lithium morpholide (37828-58-3) + carbon monoxide (201230-82-2) → 4-morpholinecarboxaldehyde (4394-85-8)

Conditions	Yield
With water In tetrahydrofuran at 0℃; under 759.8 Torr;	100%
In tetrahydrofuran at 0℃; Product distribution; with/without n-BuLi reag.; various inhibitors;

morpholine (110-91-8) + carbon dioxide (124-38-9) → 4-morpholinecarboxaldehyde (4394-85-8)

Conditions	Yield
With phenylsilane; 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine In tetrahydrofuran-d8 at 100℃; under 750.075 Torr; for 6h; Inert atmosphere;	100%
With C21H24N2; phenylsilane In tetrahydrofuran at 20℃; under 750.075 - 2250.23 Torr; for 0.25h; Reagent/catalyst; Solvent; Temperature; Time; Concentration; Inert atmosphere; Glovebox;	100%
With phenylsilane at 25℃; under 3750.38 Torr; for 12h; Pressure; Temperature; Autoclave;	100%

morpholine (110-91-8) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → 4-morpholinecarboxaldehyde (4394-85-8)

Conditions	Yield
With 1,2,4-Triazole; 8-quinolinol; copper(II) choride dihydrate at 150℃; Reagent/catalyst; Temperature;	98%
With zinc(II) phthalocyanine; carbon dioxide; phenylsilane at 25℃; under 3750.38 Torr; for 6h; Autoclave; chemoselective reaction;	92%
Stage #1: N,N-dimethyl-formamide With bis(2-chlorophenyl)borinic acid; acetic acid at 65℃; for 0.25h; Inert atmosphere; Stage #2: morpholine at 65℃; for 24h; Inert atmosphere;	89%

morpholine (110-91-8) + formaldehyd (50-00-0) → 4-morpholinecarboxaldehyde (4394-85-8)

Conditions	Yield
With sodium hydroxide In water at 25℃; for 6h;	97%
With potassium iodide In water Ambient temperature; electrolysis;	83%
With oxygen; sodium hydroxide In tetrahydrofuran; water at 10℃; for 23h;	75%

morpholine (110-91-8) + Isopropenyl formate (32978-00-0) → 4-morpholinecarboxaldehyde (4394-85-8)

Conditions	Yield
In ethyl acetate for 1h; Ambient temperature;	97%

4-((Z)-2-Methyl-undec-1-enyl)-morpholine → 4-morpholinecarboxaldehyde (4394-85-8) + methyl nonyl ketone (112-12-9)

Conditions	Yield
With oxygen; Cu-X zeolite In 1,2-dichloro-ethane; acetonitrile at 50℃; for 5h; Oxidation; Oxidative cleavage;	A 96% B 97%

morpholine (110-91-8) + Methyl formate (107-31-3) → 4-morpholinecarboxaldehyde (4394-85-8)

Conditions	Yield
With calcium(II) bis(trifluoromethanesulfonyl)imide In neat (no solvent) at 115℃; for 1h; Microwave irradiation; Sealed tube;	96%
With methanol at 140℃; for 16h; Reagent/catalyst;	92.7%
With 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine In toluene at 20℃; for 0.5h;	90%
With [bis({2‐[bis(propan‐2‐yl)phosphanyl]ethyl})amide](carbonyl)(hydride)iron(II) In tetrahydrofuran at 80℃; for 8h; Catalytic behavior; Mechanism; Reagent/catalyst; Schlenk technique; Sealed tube; Inert atmosphere;

morpholine (110-91-8) + carbon monoxide (201230-82-2) → 4-morpholinecarboxaldehyde (4394-85-8)

Conditions	Yield
dodecacarbonyl-triangulo-triruthenium In tetrahydrofuran at 185℃; for 24h;	95.5%
With 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine In toluene at 100℃; under 22502.3 Torr; for 20h; Autoclave;	83%
With potassium hydroxide In methanol at 110℃; under 7500.75 Torr; for 15h; Autoclave;	76%

morpholine (110-91-8) + chloroform (67-66-3) → 4-morpholinecarboxaldehyde (4394-85-8)

Conditions	Yield
With sodium ethanolate at 50℃; Riemer-Tiemann reaction; Inert atmosphere;	95%
With potassium fluoride on basic alumina In acetonitrile at 20℃; for 18h;	80%
With sodium hydroxide; tetrabutyl ammonium fluoride at 50℃; for 2.08333h;	35%

1-(4-morpholino)-2,2-diphenylethene (61253-71-2) → 4-morpholinecarboxaldehyde (4394-85-8) + benzophenone (119-61-9)

Conditions	Yield
With oxygen; copper dichloride In 1,2-dichloro-ethane; acetonitrile at 50℃; for 1h; Oxidation; Oxidative cleavage;	A 95% B 87%
With aluminum oxide; potassium permanganate; neutral In acetone for 4h; Ambient temperature;	A n/a B 75%

morpholine (110-91-8) + ammonium formate (16712-16-6, 64165-14-6, 65387-22-6, 70179-79-2, 540-69-2) → 4-morpholinecarboxaldehyde (4394-85-8)

Conditions	Yield
In acetonitrile for 10h; Formylation;	95%

morpholine (110-91-8) + carbon dioxide (124-38-9) → 4-methyl-morpholine (109-02-4) + 4-morpholinecarboxaldehyde (4394-85-8)

Conditions	Yield
With tris(2-diphenylphosphinoethyl)phosphine; hydrogen; potassium carbonate; cobalt(II) perchlorate hexahydrate In ethanol at 140℃; under 45004.5 Torr; for 24h; Catalytic behavior; Reagent/catalyst; Temperature; Autoclave; Green chemistry;	A 1% B 95%
With tris(2-diphenylphosphinoethyl)phosphine; hydrogen; potassium carbonate; cobalt(II) perchlorate hexahydrate In ethanol at 120℃; under 45004.5 Torr; for 24h; Catalytic behavior; Reagent/catalyst; Temperature; Autoclave; Green chemistry;	A 10% B 79%
With potassium phosphate; tris(2-diphenylphosphinoethyl)phosphine; hydrogen; cobalt(II) perchlorate hexahydrate In tetrahydrofuran at 140℃; under 45004.5 Torr; for 24h; Catalytic behavior; Mechanism; Time; Reagent/catalyst; Temperature; Pressure; Autoclave; Green chemistry;	A 69% B 28%
With C27H36Cl2N2Zn; phenylsilane at 100℃; for 20h;
With diphenylsilane; [(2,6-(2,4,6-Me3C6H2)2C6H3)Ge(O)(1,3,4,5-tetramethylimidazol-2-ylidene)2]Cl In [D3]acetonitrile at 50℃; under 750.075 Torr; for 3h; Time; Inert atmosphere;	A 75 %Spectr. B 21 %Spectr.

N-cyanomorpholine (1530-89-8) + acetic acid (64-19-7) → 4-morpholinecarboxaldehyde (4394-85-8) + 4-acetylmorpholine (1696-20-4)

Conditions	Yield
With zinc for 2h; Heating;	A 6% B 94%

N-cyanomorpholine (1530-89-8) → 4-morpholinecarboxaldehyde (4394-85-8) + 4-acetylmorpholine (1696-20-4)

Conditions	Yield
With acetic acid; zinc for 2h; Heating;	A 6% B 94%

4-(2-methyl-1-propenyl)morpholine (2403-55-6) → 4-morpholinecarboxaldehyde (4394-85-8) + acetone (67-64-1)

Conditions	Yield
With oxygen; Cu-X zeolite In 1,2-dichloro-ethane; acetonitrile at 50℃; for 5h; Oxidation; Oxidative cleavage;	A 93% B n/a

1,2-dimorpholylethane (1723-94-0) → 4-morpholinecarboxaldehyde (4394-85-8)

Conditions	Yield
With tris(bipyridine)ruthenium(II) dichloride hexahydrate; water; oxygen; silica gel; caesium carbonate In acetonitrile at 20℃; for 60h; Inert atmosphere; Irradiation;	93%

4-((E)-2,6-Dimethyl-hepta-1,5-dienyl)-morpholine → 4-morpholinecarboxaldehyde (4394-85-8) + 6-Methyl-hept-5-en-2-on (110-93-0)

Conditions	Yield
With aluminum oxide; potassium permanganate; neutral In acetone for 4h; Ambient temperature;	A n/a B 92%

3-(4-isopropyl)-phenyl-2-methyl-1-(4-morpholino)-1-propene → 4-morpholinecarboxaldehyde (4394-85-8) + 1-(4-isopropylphenyl)propan-2-one (7306-39-0)

Conditions	Yield
With aluminum oxide; potassium permanganate; neutral In acetone for 4h; Ambient temperature;	A n/a B 91%

morpholine (110-91-8) + formic acid ethyl ester (109-94-4) → 4-morpholinecarboxaldehyde (4394-85-8)

Conditions	Yield
With Novozyme 435 CALB In tetrahydrofuran at 20℃; Green chemistry; Enzymatic reaction;	91%
With o-toluenesulfonic acid at 55℃; for 4h;	88%
With toluene-4-sulfonic acid at 60℃; for 24h;	56%
at 65℃; for 12h; Inert atmosphere;
at 60℃; for 24h;

morpholine (110-91-8) + [((η5-C5H3)2(SiMe2)2)Ru2(μ-D)(CO)4]OSO2CF3 → 4-morpholinecarboxaldehyde (4394-85-8) + [(η5-C5H3)2(Si(CH3)2)2]Ru2(CO)4 (287097-09-0) + [(η5-C5H3)2(SiMe2)2]Ru2(CO)3(morpholine) (287097-16-9)

Conditions	Yield
With triphenylmethane In benzene-d6 Kinetics; amine was added to a soln. in C6D6 in NMR tube for 5 min (Ar); not sepd., detected by NMR spectra;	A 91% B 5% C n/a

morpholine (110-91-8) + Hex-1-en-2-yl formate (134965-38-1) → 4-morpholinecarboxaldehyde (4394-85-8)

Conditions	Yield
In ethyl acetate for 1h; Ambient temperature;	90%

4-(2-phenyl-propenyl)-morpholine (28478-27-5) → 4-morpholinecarboxaldehyde (4394-85-8) + acetophenone (98-86-2)

Conditions	Yield
With aluminum oxide; potassium permanganate; neutral In acetone for 4h; Ambient temperature;	A n/a B 90%
With aluminum oxide; potassium permanganate In acetone for 4h; Product distribution; Ambient temperature; reactions of derivatives, under var. conditions;	A n/a B 90%

4-[(1H-imidazol-1-yl)carbonyl]morpholine (93605-74-4) → 4-morpholinecarboxaldehyde (4394-85-8)

Conditions	Yield
With sodium tetrahydroborate In tetrahydrofuran; water at 20℃;	90%

4-methyl-morpholine (109-02-4) → 4-morpholinecarboxaldehyde (4394-85-8)

Conditions	Yield
With [2,2]bipyridinyl; C10H16NO; copper(II) bis(trifluoromethanesulfonate); copper(l) chloride In acetonitrile at 20℃; for 6h;	90%

4-((trimethylsilyl)methyl)morpholine (54600-30-5) → 4-morpholinecarboxaldehyde (4394-85-8)

Conditions	Yield
With copper(I) bromide In acetonitrile at 25℃; for 4h; chemoselective reaction;	86%

4-(2-methyl-undec-1-enyl)-morpholine (28478-28-6) → 4-morpholinecarboxaldehyde (4394-85-8) + methyl nonyl ketone (112-12-9)

Conditions	Yield
With aluminum oxide; potassium permanganate; neutral In acetone for 4h; Ambient temperature;	A n/a B 84%

1-(4-morpholino)-2-phenylpropene (39166-22-8) → 4-morpholinecarboxaldehyde (4394-85-8) + acetophenone (98-86-2)

Conditions	Yield
With oxygen; Cu-X zeolite In 1,2-dichloro-ethane; acetonitrile at 50℃; for 5h; Oxidation; Oxidative cleavage;	A 70% B 84%

4-morpholinecarboxaldehyde (4394-85-8) + dimethyl sulfate (77-78-1) → 4-(Methoxymethylene)-morpholinium methyl sulfate (5780-15-4)

Conditions	Yield
at 60 - 70℃; for 3h;	100%
at 70℃; for 2h;

4-morpholinecarboxaldehyde (4394-85-8) + 3-bromo-4,5-bis(trimethylsilylethynyl)toluene (350600-10-1) → 2,3-bis(trimethylsilylethynyl)-5-methylbenzaldehyde (350600-11-2)

Conditions	Yield
With sec.-butyllithium In tetrahydrofuran; diethyl ether at -78℃;	100%

2-(4-isopropoxyphenoxy)thiazole (929118-32-1) + 4-morpholinecarboxaldehyde (4394-85-8) → 2-(4-isopropoxyphenoxy)thiazole-5-carbaldehyde (929118-34-3)

Conditions	Yield
Stage #1: 2-(4-isopropoxyphenoxy)thiazole With n-butyllithium In tetrahydrofuran at -78℃; for 1.25h; Stage #2: 4-morpholinecarboxaldehyde In tetrahydrofuran at -78℃; for 4h; Further stages.;	100%

4-morpholinecarboxaldehyde (4394-85-8) → 4-thioformylmorpholine (5780-30-3)

Conditions	Yield
With Lawessons reagent In dichloromethane at 20℃; for 3h;	99%
With tetraphosphorus decasulfide In diethyl ether at 0 - 20℃; for 3h;	80%
With tetraphosphorus decasulfide	78.9%

4-morpholinecarboxaldehyde (4394-85-8) + toluene-4-sulfonamide (70-55-3) → (E)-4-methyl-N-(morpholinomethylene)benzenesulfonamide (15294-84-5)

Conditions	Yield
With diazoacetic acid ethyl ester; zinc trifluoromethanesulfonate In cyclohexane for 12h; Reflux; stereoselective reaction;	99%
With thionyl chloride In chloroform at 60℃; for 3h;	87%
With tert.-butylhydroperoxide; sodium iodide In water at 90℃; for 3h;	52%

4-morpholinecarboxaldehyde (4394-85-8) + para-chlorotoluene (106-43-4) → 4-(4-methylphenyl)morpholine (3077-16-5)

Conditions	Yield
With NHC-Pd(II)-Im; potassium tert-butylate In tetrahydrofuran at 20℃; for 6h; Inert atmosphere;	99%

4-morpholinecarboxaldehyde (4394-85-8) + chlorobenzene (108-90-7) → 4-Phenylmorpholine (92-53-5)

Conditions	Yield
With NHC-Pd(II)-Im; potassium tert-butylate In tetrahydrofuran at 20℃; for 6h; Inert atmosphere;	99%
With bis(1,5-cyclooctadiene)nickel (0); 7,9-bis(2,6-diisopropylphenyl)-7H-acenaphtho[1,2-d]imidazol-9-ium chloride; potassium tert-butylate In water; toluene at 35℃; for 10h; Glovebox; Sealed tube; Inert atmosphere;	90%

3-Chloropyridine (626-60-8) + 4-morpholinecarboxaldehyde (4394-85-8) → N-(3-pyridyl)morpholine (92670-29-6)

Conditions	Yield
With NHC-Pd(II)-Im; potassium tert-butylate In tetrahydrofuran at 20℃; for 6h; Inert atmosphere;	99%

2-chloropyridine (109-09-1) + 4-morpholinecarboxaldehyde (4394-85-8) → 4-(pyridin-2-yl)morpholine (24255-25-2)

Conditions	Yield
With NHC-Pd(II)-Im; potassium tert-butylate In tetrahydrofuran at 20℃; for 6h; Inert atmosphere;	99%

4-morpholinecarboxaldehyde (4394-85-8) + 1-chloromethyl-3-methyl-benzene (620-19-9) → 4-(3-methylbenzyl)morpholine (90754-64-6)

Conditions	Yield
With NHC-Pd(II)-Im; sodium hydroxide In water at 50℃; for 3h; Inert atmosphere; Schlenk technique;	99%
With potassium hydroxide In water at 50℃; for 3h; Green chemistry;	80%

4-morpholinecarboxaldehyde (4394-85-8) + 1-chloromethyl-2-methylbenzene (552-45-4) → 4-(2-methylbenzyl)morpholine (51180-64-4)

Conditions	Yield
With NHC-Pd(II)-Im; sodium hydroxide In water at 50℃; for 3h; Inert atmosphere; Schlenk technique;	99%
With potassium hydroxide In water at 50℃; for 3h; Green chemistry;	81%

4-morpholinecarboxaldehyde (4394-85-8) + p-methoxybenzyl chloride (824-94-2) → 4-(4-methoxy-benzyl)-morpholine (17494-29-0)

Conditions	Yield
With NHC-Pd(II)-Im; sodium hydroxide In water at 50℃; for 3h; Inert atmosphere; Schlenk technique;	99%
With potassium hydroxide In water at 80℃; for 3h; Temperature; Green chemistry;	90%

4-morpholinecarboxaldehyde (4394-85-8) + m-methoxybenzyl chloride (824-98-6) → 4-[(3-methoxyphenyl)methyl]morpholine (122439-14-9)

Conditions	Yield
With NHC-Pd(II)-Im; sodium hydroxide In water at 50℃; for 3h; Inert atmosphere; Schlenk technique;	99%
With potassium hydroxide In water at 50℃; for 3h; Green chemistry;	90%

4-morpholinecarboxaldehyde (4394-85-8) + 2-cyanobenzyl chloride (612-13-5) → 2-(morpholin-4-ylmethyl)benzonitrile (37812-33-2)

Conditions	Yield
With potassium hydroxide In water at 50℃; for 3h; Green chemistry;	99%
With NHC-Pd(II)-Im; sodium hydroxide In water at 50℃; for 3h; Inert atmosphere; Schlenk technique;	98%

4-morpholinecarboxaldehyde (4394-85-8) + m-tolyl aldehyde (620-23-5) → (3-methylphenyl)-4-morpholinylmethanethione

Conditions	Yield
With sulfur; sodium carbonate; triethylamine In water at 120℃; for 12h; Inert atmosphere; Sealed tube;	99%

4-morpholinecarboxaldehyde (4394-85-8) + 4-methoxy-benzaldehyde (123-11-5) → N-(4-methoxy-thiobenzoyl)-morpholine (6392-01-4)

Conditions	Yield
With sulfur; sodium carbonate; triethylamine In water at 120℃; for 12h; Schlenk technique; Inert atmosphere;	99%
With sulfur; sodium carbonate; triethylamine In water at 120℃; for 12h; Inert atmosphere; Sealed tube;	96%

4-morpholinecarboxaldehyde (4394-85-8) → 2-(2-chloro-4-methoxyphenoxy)-1,3-thiazole-5-carbaldehyde (946884-30-6)

Conditions	Yield
Stage #1: 2-(2-chloro-4-methoxyphenoxy)-1,3-thiazole With n-butyllithium In tetrahydrofuran; hexanes at -78℃; for 1.16667h; Stage #2: 4-morpholinecarboxaldehyde In tetrahydrofuran; hexanes at -78 - 25℃; for 1.08333h; Product distribution / selectivity;	98%

4-morpholinecarboxaldehyde (4394-85-8) + 1-chloro-3-methoxy-benzene (2845-89-8) → 4-(3-methoxyphenyl)morpholine (32040-09-8)

Conditions	Yield
With NHC-Pd(II)-Im; potassium tert-butylate In tetrahydrofuran at 20℃; for 6h; Inert atmosphere;	98%

4-morpholinecarboxaldehyde (4394-85-8) + 1-chloro-3-methylbenzene (108-41-8) → 4-m-tolylmorpholine (7025-91-4)

Conditions	Yield
With NHC-Pd(II)-Im; potassium tert-butylate In tetrahydrofuran at 20℃; for 6h; Inert atmosphere;	98%

4-morpholinecarboxaldehyde (4394-85-8) + 4-tert-butylbenzyl chloride (19692-45-6) → 4-(4-(tert-butyl)benzyl)morpholine

Conditions	Yield
With potassium hydroxide In water at 100℃; for 3h; Temperature; Green chemistry;	98%
With NHC-Pd(II)-Im; sodium hydroxide In water at 80℃; for 3h; Temperature; Inert atmosphere; Schlenk technique;	94%

4-morpholinecarboxaldehyde (4394-85-8) + 4-cyanobenzyl chloride (874-86-2) → 4-(morpholin-4-ylmethyl)benzonitrile (37812-51-4)

Conditions	Yield
With NHC-Pd(II)-Im; sodium hydroxide In water at 50℃; for 3h; Inert atmosphere; Schlenk technique;	98%
With potassium hydroxide In water at 50℃; for 3h; Green chemistry;	92%

4-morpholinecarboxaldehyde (4394-85-8) + 4-nitrobenzyl chloride (100-14-1) → 4-(4-nitrobenzyl)morpholine (6425-46-3)

Conditions	Yield
With potassium hydroxide In water at 50℃; for 3h; Green chemistry;	98%
With NHC-Pd(II)-Im; sodium hydroxide In water at 50℃; for 3h; Inert atmosphere; Schlenk technique;	97%

4-morpholinecarboxaldehyde (4394-85-8) + 1-Chloro-4-(chloromethyl)benzene (104-83-6) → 4-(4'-chloro-benzyl)morpholine (6425-43-0)

Conditions	Yield
With NHC-Pd(II)-Im; sodium hydroxide In water at 50℃; for 3h; Inert atmosphere; Schlenk technique;	98%
With potassium hydroxide In water at 80℃; for 3h; Temperature; Green chemistry;	93%

4-morpholinecarboxaldehyde (4394-85-8) + 1-chloro-2-(chloromethyl)benzene (611-19-8) → 2-(morpholinomethyl)chlorobenzene (415932-72-8)

Conditions	Yield
With NHC-Pd(II)-Im; sodium hydroxide In water at 50℃; for 3h; Inert atmosphere; Schlenk technique;	98%
With potassium hydroxide In water at 50℃; for 3h; Green chemistry;	96%

4-morpholinecarboxaldehyde (4394-85-8) + 1-Chloromethylnaphthalene (86-52-2) → 4-(naphthalene-1-ylmethyl)morpholine (2862-82-0)

Conditions	Yield
With NHC-Pd(II)-Im; sodium hydroxide In water at 50℃; for 3h; Inert atmosphere; Schlenk technique;	98%
With potassium hydroxide In water at 80℃; for 3h; Temperature; Green chemistry;	87%

4-morpholinecarboxaldehyde (4394-85-8) + 4-Methylbenzyl chloride (104-82-5) → 4-(4-methylbenzyl)morpholine (46340-40-3)

Conditions	Yield
With NHC-Pd(II)-Im; sodium hydroxide In water at 50℃; for 3h; Inert atmosphere; Schlenk technique;	98%
With potassium hydroxide In water at 80℃; for 3h; Temperature; Green chemistry;	96%

Upstream product

• 110-91-8 morpholine 
• 67-66-3 chloroform 
• 56176-55-7 1-morpholino-1-butene 
• 28478-27-5 4-(2-phenyl-propenyl)-morpholine 
• 160663-31-0 2,2-Dichloro-3-oxo-butyraldehyde 
• 53175-28-3 2-chloro-2-butenal 
• 7364-09-2 2-chloro-3,3-dimethylacrolein 
• 28478-26-4 4-(2-ethylbut-1-en-1-yl)morpholine 
• 2403-55-6 4-(2-methyl-1-propenyl)morpholine 
• 15159-40-7 4-morpholinocarbonyl chloride 
• 109-72-8 n-butyllithium 
• 598-30-1 sec.-butyllithium 
• 1571-08-0 methyl 4-formylbenzoate 
• 124-38-9 carbon dioxide 

Downstream Products

• 452-06-2 7H-purin-2-amine 
• 109-02-4 4-methyl-morpholine 
• 90437-72-2 4-methyl-2-(morpholin-4-yl)thiazole-5-carbaldehyde 
• 155600-95-6 4-((E)-2-(4-[(E)-2-(4-formylphenyl)ethenyl]phenyl)ethenyl)benzaldehyde 
• 198011-60-8 bromomethylenemorpholinium bromide 
• 220090-92-6 2-hydroxy-3-(morpholin-4-ylmethyl)-5-methylbenzaldehyde 
• 89115-20-8 4-[bis(4-methoxyphenyl)amino]benzaldehyde 
• 220996-80-5 4-bromo-2-[(trifluoromethyl)oxy]benzaldehyde 
• 110-91-8 morpholine 
• 16423-59-9 2-(morpholin-4-yl)-2-oxoacetaldehyde 
• 7560-83-0 N-Methyldicyclohexylamine 
• 163271-80-5 3-triisopropylsilyl-2-propynal 
• 295311-97-6 4-phenyl-2-(1'H-pyrrol-2'-yl)thiazole-5-carbaldehyde 
• 290348-16-2 2,2'-(1,4-phenylene)bis[4-(tert-butyl)thiazole-5-carbaldehyde] 

Relevant articles and documents

Confirmation by trapping, synthesis, and reactivity of 2,3-dehydro-N-methylmorpholine (DNMM)

The elusive 4-methyl-3,4-dihydro-2H-[1,4]oxazine (2,3-dehydro-N-methylmorpholine, DNMM, 5) was confirmed to occur as degradation product of N-methylmorpholine-N-oxide (1) by trapping with the α-tocopherol-derived ortho-quinone methide in a hetero-Diels-Alder reaction with inverse electron demand. The regioselectivity of the addition was in good agreement with DFT computational data. An authentic sample of 5 was synthesized from formmorpholide (16) via 2-methoxy-formmorpholide in 38% overall yield.

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Nickel-Catalyzed Amination of Aryl Chlorides with Amides

A nickel-catalyzed amination of aryl chlorides with diverse amides via C-N bond cleavage has been realized under mild conditions. A broad substrate scope with excellent functional group tolerance at a low catalyst loading makes the protocol powerful for synthesizing various aromatic amines. The aryl chlorides could selectively couple to the amino fragments rather than the carbonyl moieties of amides. Our protocol complements the conventional amination of aryl chlorides and expands the usage of inactive amides.

Solvent-free, Efficient Transamidation of Carboxamides with Amines Catalyzed by Recyclable Sulfated Polyborate Catalyst

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