541-59-3

Basic information

• Product Name: Maleimide
• Synonyms: 3-Pyrroline-2,5-dione;Maleic imide;maleicimide;Maleinimide;MALEIMIDE;MALEIC ACID IMIDE;ASISCHEM S97810;1h-pyrrole-2,5-dione
• CAS NO: 541-59-3
• Molecular Formula: C₄H₃NO₂
• Molecular Weight: 97.07
• EINECS: 208-787-4
• Product Categories: Heterocycles series;Heterocycles;Miscellaneous Reagents;Building Blocks;Carbonyl Compounds;Chemical Synthesis;Cyclic Imides;Organic Building Blocks;MTS & Sulfhydryl Active Reagents
• Mol File: 541-59-3.mol
• Article Data: 51

Chemical Properties

• Melting Point: 91-93 °C(lit.)
• Boiling Point: 97-103°C 5mm
• Flash Point: 97-103°C/5mm
• Appearance: White to slightly yellow/Fine Crystalline Powder
• Density: 1,2493 g/cm3
• Refractive Index: 1.4543 (estimate)
• Storage Temp.: Refrigerator
• Solubility: soluble in Methanol
• PKA: 8.52±0.20(Predicted)
• Water Solubility: SOLUBLE
• BRN: 106910
• CAS DataBase Reference: Maleimide(CAS DataBase Reference)
• NIST Chemistry Reference: Maleimide(541-59-3)
• EPA Substance Registry System: Maleimide(541-59-3)

Safety Data

• Hazard Codes: T,C
• Statements: 25-34-43-36/37/38-36
• Safety Statements: 26-36/37/39-45-37/39-28A-7/9
• RIDADR: UN 2923 8/PG 2
• WGK Germany: 3
• RTECS: ON4800000
• TSCA: Yes
• HazardClass: 8
• PackingGroup: III
• Hazardous Substances Data: 541-59-3(Hazardous Substances Data)

Usage

Chemical Properties

slight yellow crystalline powder

Uses

Different sources of media describe the Uses of 541-59-3 differently. You can refer to the following data:
1. Rhodium-catalyzed conjugate arylation with arylboronic acids.1
2. Reacts quantitatively with sulfhydryl groups.Maleimide is used to immobilize the bovine serum albumin-boronic acid conjugates in association with silica beads. Its nanoparticle surface favors the conjugation with cell penetration peptides. It is involved in Rhodium-catalyzed conjugate arylation with arylboronic acids. It is actively involved in Michael additions and Diels-Alder reactions by the addition across the double bond. It acts as crosslinking reagents in polymer chemistry.

Definition

ChEBI: A cyclic dicarboximide in which the two carboacyl groups on nitrogen together with the nitogen itself form a 1H-pyrrole-2,5-dione structure.

General Description

Maleimide (2,5-Pyrroledione) is a new nanoparticle surface functional group which favors easy conjugation with cell penetration peptides. The conjugation is enabled via click chemistry to preserve its biofunctions.

Hazard

A poison.

Safety Profile

Poison by intraperitoneal and intravenous routes. An experimental teratogen. Experimental reproductive effects. When heated to decomposition it emits toxic fumes of NOx.

Purification Methods

Purify it by sublimation in a vacuum. The UV has max at 216 and 280nm in EtOH. [de Wolf & van de Straete Bull Soc Chim Belg 44 288 1935, UV: Rondestvedt et al. J Am Chem Soc 78 6115 1956, IR: Chiorboli & Mirone Ann Chim (Rome) 42 681 1952, Beilstein 21/10 V 3.]

InChI:InChI=1/C4H3NO2/c6-3-1-2-4(7)5-3/h1-2H,(H,5,6,7)

Synthetic route

maleic anhydride (108-31-6) + nickel diacetate (373-02-4, 14998-37-9, 33025-09-1, 94044-50-5, 98268-31-6) → maleiimide (541-59-3)

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide	97%

maleic anhydride (108-31-6) → maleiimide (541-59-3)

Conditions	Yield
With formamide In neat (no solvent) for 0.5h; Reagent/catalyst; Milling; Heating; Green chemistry;	93%
With 2-butenedioic acid at 100℃; for 20h; Inert atmosphere;	65%
In methanol; o-xylene

O-t-butylmaleimide (79901-70-5) → maleiimide (541-59-3) + isobutene (115-11-7)

Conditions	Yield
In chloroform-d1 Product distribution; Irradiation; photochemical reactivity;	A 83% B n/a

O-i-propylmaleimide (79887-86-8) → maleiimide (541-59-3)

Conditions	Yield
In chloroform-d1 Product distribution; Irradiation; photochemical reactivity;	80%

N-methoxycarbonylmaleimide (55750-48-6) → maleiimide (541-59-3)

Conditions	Yield
With sodium hydrogencarbonate	60%

1-hydroxy-pyrrolidine-2,5-dione (6066-82-6) + isomaleimide → maleiimide (541-59-3)

Conditions	Yield
In acetonitrile	36%

methanol (67-56-1) + meso-5,10,15,20-tetra(3-hydroxyphenyl)porphine (22112-79-4) → maleiimide (541-59-3) + methyl 3-hydroxybenzoate (19438-10-9) + 5-(3,4-benzoquinonyl)-10,15,20-tris(3-hydroxyphenyl)porphyrin

Conditions	Yield
With air for 140h; Product distribution; Photolysis;	A 1.1% B 2.5% C 5%

methanol (67-56-1) + temoporfin → maleiimide (541-59-3) + Succinimide (123-56-8) + methyl 3-hydroxybenzoate (19438-10-9) + 5-[1-[5-(3-Hydroxy-benzoyl)-1H-pyrrol-2-yl]-1-(3-hydroxy-phenyl)-meth-(Z)-ylidene]-1,5-dihydro-pyrrol-2-one

Conditions	Yield
With air; water for 23h; Product distribution; Photolysis;	A 1.2% B 0.6% C 1.5% D n/a

Succinimide (123-56-8) → maleiimide (541-59-3)

Conditions	Yield
With iodine; oxygen; silica gel at 500 - 700℃;

pyrrole (109-97-7) → maleiimide (541-59-3)

Conditions	Yield
With chromium(III) oxide; sulfuric acid
With sodium dichromate; sulfuric acid; water

N-carbamoylmaleimide (3345-50-4) → maleiimide (541-59-3)

Conditions	Yield
With triethylamine In ethyl acetate for 2h; Reflux; Large scale;	Ca. 40 kg
With N,N-dimethyl-formamide
With zinc(II) chloride at 145℃;
at 180℃; under 4 Torr;

2,5-dioxo-2,5-dihydro-pyrrole-1-carboxylic acid tert-butylamide (99362-76-2) → maleiimide (541-59-3)

Conditions	Yield
With 1,2-dichloro-benzene; zinc(II) chloride at 102 - 111℃; under 100 Torr;
at 120℃; under 100 Torr;

maleamide (928-01-8) + (E)-3-Ureido-but-2-enoic acid ethyl ester (5435-44-9, 22243-66-9) → maleiimide (541-59-3)

Conditions	Yield
beim Erhitzen im Vakuum;

maleamide (928-01-8) → maleiimide (541-59-3)

Conditions	Yield
With zinc(II) chloride im Vakuum;

N-phenylcarbamylmaleimide (62898-86-6) → maleiimide (541-59-3)

Conditions	Yield
at 150℃; under 3 Torr;

5,10,15,20,22,24-hexahydro-5,5,10,10,15,15,20,20-octamethyl-21H,23H-porphine (4475-42-7) + chromium(lll) acetate (1066-30-4) → maleiimide (541-59-3)

chromium(lll) acetate (1066-30-4) + 5,5,10,10,15,15-Hexamethyl-bilinogen (453549-35-4) → maleiimide (541-59-3)

N-Bromosuccinimide (128-08-5) + tetra-N-butylammonium salt of succinimide (74830-30-1) → maleiimide (541-59-3) + Succinimide (123-56-8)

Conditions	Yield
In acetonitrile at 35℃; Product distribution; Rate constant; also with lithium and sodium salts of succinimide; NMR monitoring; other solvent, other reaction temperature; light emission characteristics of the reaction in the presence of maleinimide (at 25.0 deg C);

4-methyl-3a,4,7,7a-tetrahydro-isoindole-1,3-dione → maleiimide (541-59-3)

Conditions	Yield
With quartz at 550℃; under 2 Torr;

Boscan 9K3 crude oil (Cretaceous, W.Venezuela) of fraction 2 → maleiimide (541-59-3)

Conditions	Yield
With chromium(VI) oxide In dichloromethane; sulfuric acid; trifluoroacetic acid

meso-5,10,15,20-tetraethyl-meso-5,10,15,20-tetramethylcalix[4]pyrrole (407630-16-4) + acetic acid (64-19-7) + chromic acid → maleiimide (541-59-3)

Conditions	Yield
bei Raumtemperatur; methylethyl ketone-pyrrole of melting point 149.5-150.5 degree;

pyrrole (109-97-7) + Cr2O3-H2SO4 → maleiimide (541-59-3)

malamide → maleiimide (541-59-3)

Conditions	Yield
With phosphorus pentoxide under 15 Torr;

pyrrole black → maleiimide (541-59-3)

Conditions	Yield
With chromium(III) oxide; sulfuric acid

maleamide (928-01-8) + P2O5 → maleiimide (541-59-3)

Conditions	Yield
under 10 - 15 Torr;

bromomaleic anhydride (5926-51-2) + 2,4-Dimethoxybenzylamine (20781-20-8) → maleiimide (541-59-3)

Conditions	Yield
In acetic acid
In acetic acid

maleiimide (541-59-3) → Succinimide (123-56-8)

Conditions	Yield
With acetic anhydride; zinc In toluene at 40 - 86℃; for 48h; Inert atmosphere; chemoselective reaction;	100%
With sulfuric acid In water for 5h; Electrochemical reaction; Flow reactor; chemoselective reaction;	96%
With palladium diacetate; 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane In dichloromethane at 25℃; for 12h; Sealed tube; Inert atmosphere; chemoselective reaction;	96%

maleiimide (541-59-3) + bis-(2,4-dimethyl-oxazol-5-yl)-methyl-amine (67864-96-4) → 1-[(2,4-Dimethyl-oxazol-5-yl)-methyl-amino]-7,9-dimethyl-10-oxa-4,8-diaza-tricyclo[5.2.1.02,6]dec-8-ene-3,5-dione (84440-26-6)

Conditions	Yield
In diethyl ether at 20℃; for 120h;	100%

maleiimide (541-59-3) + bis-(2,4-dimethyl-oxazol-5-yl)-propyl-amine (67864-94-2) → 1-[(2,4-Dimethyl-oxazol-5-yl)-propyl-amino]-7,9-dimethyl-10-oxa-4,8-diaza-tricyclo[5.2.1.02,6]dec-8-ene-3,5-dione (75213-80-8)

Conditions	Yield
In diethyl ether at 20℃; for 120h;	100%

maleiimide (541-59-3) + bis-(4-ethyl-2-methyl-oxazol-5-yl)-propyl-amine (67864-97-5) → 9-Ethyl-1-[(4-ethyl-2-methyl-oxazol-5-yl)-propyl-amino]-7-methyl-10-oxa-4,8-diaza-tricyclo[5.2.1.02,6]dec-8-ene-3,5-dione (75213-81-9)

Conditions	Yield
In diethyl ether at 20℃; for 120h;	100%

maleiimide (541-59-3) + sodium isopropanethiolate (20607-43-6) → 3-(isopropylthio)pyrrolidine-2,5-dione

Conditions	Yield
With 2-propanethiol In tetrahydrofuran for 1h; Ambient temperature;	100%

maleiimide (541-59-3) + sodium tert-butyl thiolate (29364-29-2) → 3-(tert-butylthio)pyrrolidine-2,5-dione

Conditions	Yield
With 2-methylpropan-2-thiol In tetrahydrofuran for 1h; Ambient temperature;	100%

maleiimide (541-59-3) + sodium benzylmercaptide (3492-64-6) → 3-(benzylthio)pyrrolidine-2,5-dione

Conditions	Yield
With phenylmethanethiol In tetrahydrofuran for 1h; Ambient temperature;	100%

maleiimide (541-59-3) → 2,7-diaza-bicyclo[3.5.0.0(5,9)]decantetra-1,3,6,8-one (4415-88-7)

Conditions	Yield
In acetonitrile for 1h; Irradiation;	100%
In tetrachloromethane Product distribution; Quantum yield; Ambient temperature; Irradiation; Effect of concentration on the quantum yield is studied;	95%
In 1,1,2-Trichloro-1,2,2-trifluoroethane Product distribution; Quantum yield; Ambient temperature; Irradiation; Effect of wavelength of irradiation on quantum yield is studied;	95%
In various solvent(s) Kinetics; laser flash photolysis;
In acetonitrile for 24h; Inert atmosphere; Irradiation;

maleiimide (541-59-3) + 3-METHOXYBENZYLAMINE (5071-96-5) → 3-(3-Methoxy-benzylamino)-pyrrolidine-2,5-dione (188295-14-9)

Conditions	Yield
In ethyl acetate for 20h; Ambient temperature;	100%

maleiimide (541-59-3) + methyl chloroformate (79-22-1) → N-methoxycarbonylmaleimide (55750-48-6)

Conditions	Yield
With 4-methyl-morpholine In ethyl acetate	100%
Stage #1: maleiimide With 4-methyl-morpholine In ethyl acetate at 0℃; for 0.166667h; Stage #2: methyl chloroformate In ethyl acetate at 20℃; for 1h;	99%
With 4-methyl-morpholine In ethyl acetate at 0℃; for 0.5h;	98%

maleiimide (541-59-3) + tert-butyl-dimethyl-[1-methylene-3-(2-nitro-phenyl)-allyloxy]-silane (287920-04-1) → (3aS,4S,7aR)-6-(tert-Butyl-dimethyl-silanyloxy)-4-(2-nitro-phenyl)-3a,4,7,7a-tetrahydro-isoindole-1,3-dione

Conditions	Yield
In benzene at 20℃; for 72h; Cycloaddition; Diels-Alder reaction;	100%
In toluene at 20℃; Diels-Alder reaction;	96%

maleiimide (541-59-3) + triphenylphosphine (603-35-0) → triphenylphosphoranylidene succinimide (18092-16-5, 28118-79-8)

Conditions	Yield
In acetone for 1h; Reflux;	100%
In acetone for 1h; Product distribution / selectivity; Reflux;	100%
In acetone for 1h; Heating;	94%

maleiimide (541-59-3) + 9-acetylanthracene (784-04-3) → 1-acetyldibenzo[e.h]bicyclo[2.2.2]octane-2,3-dicarboximide (312504-18-0)

Conditions	Yield
In benzene for 1.5h; Heating;	100%

furan (110-00-9) + maleiimide (541-59-3) → 3,6-epoxy-1,2,3,6-tetrahydrophthalimide (6253-28-7, 19878-26-3, 42074-03-3)

Conditions	Yield
In diethyl ether Diels-Alder reaction;	100%
In diethyl ether at 100℃; for 8h; Autoclave;	99%
In diethyl ether at 100℃; Inert atmosphere; Sealed tube;	99%

maleiimide (541-59-3) + 8,8-di(methoxymethyl)-2,3,3,5-tetramethylbicyclo[4.3.0]nona-1,5-diene → 8,8-di(methoxymethyl)-2,5,10,10-tetramethyltricyclo[4.3.2.0]undeca-1(6)-ene-3,4-dicarboximide

Conditions	Yield
In ethyl acetate for 36h; Heating;	100%

3-(5-methyl-1H-indol-3-yl)-1H-2,5-dihydro-pyrrol-2-one (916981-12-9) + maleiimide (541-59-3) → 10-methyl-2H,5H,7H-1,3,3a,3b,4,6,6a,11c-octahydro-dipyrrolo[3,4-a:3,4-c]carbazole-1,4,6-trione (916981-23-2)

Conditions	Yield
In xylene for 72h; Diels-Alder reaction; Heating;	100%

maleiimide (541-59-3) + cyclohexa-1,3-diene (1165952-91-9) → 4-aza-tricyclo[5.2.2.02,6]undec-8-ene-3,5-dione

Conditions	Yield
In toluene for 4h; Diels-Alder reaction; Heating;	100%

maleiimide (541-59-3) → 3-pyrrolin-2-one (4031-15-6)

Conditions	Yield
With trifluorormethanesulfonic acid; cyclohexane; antimony pentafluoride at 25℃; for 0.166667h;	100%

maleiimide (541-59-3) + 5-(4-methoxyphenyl)-2-phenyl-2H-tetrazole (20433-10-7) → (3aSR,6aSR)-3-(4-methoxyphenyl)-1-phenyl-1,6a-dihydropyrrolo[3,4-c]pyrazole-4,6(3aH,5H)-dione

Conditions	Yield
In ethyl acetate for 2h; UV-irradiation;	100%

maleiimide (541-59-3) + 5-[2-(2-chlorophenyl)vinyl]-1-(3-methoxypropyl)-1H-pyrrole-2-carboxylic acid ethyl ester → 4-(2-chlorophenyl)-6-(3-methoxypropyl)-1,3-dioxo-1,2,3,3a,4,5,6,8b-octahydro-2,6-diaza-as-indacene-7-carboxylic acid ethyl ester (869105-20-4)

Conditions	Yield
at 180 - 210℃; for 6h;	100%

maleiimide (541-59-3) + (2-aminoethanethiolato-N,S)bis(1,2-diaminoethane)cobalt(III) perchlorate → [(en)2Co(S(CHCONHCOCH2)CH2CH2NH2)](ClO4)3

Conditions

Yield

With H(1+) In perchloric acid aq. HClO4; to the soln. of Co-compd. in aq. HClO4 was added an org. compd.; after 1-2 h the soln. was dild. with H2O; the react. mixt. was absorbed onto an ion-exchange column; washing with aq. HClO4, elution with NaClO4 (pH 2);; Ba(NO3)2 and K2SO4 were added; KClO4 and BaSO4 were removed by fitration; the soln. was condensed by rotoevapn. at 30°C and was filtered; addn. of HClO4, standing overnight at 8°C; recrystn. from HClO4, cooling for 4 h at the same temp.;;

100%

maleiimide (541-59-3) + 2-amino-1-benzylamine (4403-69-4) → 3-(2-amino-benzylamino)-pyrrolidine-2,5-dione (940055-59-4)

Conditions	Yield
In ethyl acetate at 20 - 50℃; for 20 - 70h;	100%

maleiimide (541-59-3) + N-[(tert-butoxy)carbonyl]-L-cysteine methyl ester (172749-96-1) → N-Boc-Cys(Succ)-OMe (1201191-35-6)

Conditions	Yield
In methanol for 0.0166667h;	100%
In methanol for 0.0166667h;	100%

maleiimide (541-59-3) + vinyl acetate (108-05-4) → 1-vinyl-1H-pyrrole-2,5-dione (7685-94-1)

Conditions	Yield
With lithium chloride; palladium dichloride at 80℃; for 23h; Microwave irradiation; Sealed tube;	100%
With lithium chloride; palladium dichloride at 80℃; for 23h; Sealed tube; Inert atmosphere;	100%
With lithium chloride; palladium dichloride at 80℃; for 23h; Microwave irradiation; Sealed tube;	100%

maleiimide (541-59-3) + 1-amino-2-propene (107-11-9) → C7H8N2O2

Conditions	Yield
Stage #1: maleiimide With bromine In chloroform Reflux; Stage #2: 1-amino-2-propene In acetonitrile at 20℃;	100%

maleiimide (541-59-3) + C12H13NO2 → C16H16N2O4

Conditions	Yield
With C49H33N2O3P*CHF3O3S; C49H33N2O3P In toluene at -40℃; Reagent/catalyst; Diels-Alder Cycloaddition; stereoselective reaction;	100%

furan (110-00-9) + maleiimide (541-59-3) → (3aR,4R,7S,7aS)-3a,4,7,7a-tetrahydro-1H-4,7-epoxyisoindole-1,3(2H)-dione (19878-26-3)

Conditions	Yield
In diethyl ether at 100℃; for 8h; Autoclave;	99%
In toluene at 100℃; for 8h; Autoclave;	99%
In toluene at 100℃; for 8h; Autoclave;	99%

furan (110-00-9) + maleiimide (541-59-3) → exo-7-oxabicyclo[2.2.1]hept-4-ene-2,3-dicarboximide (6253-28-7, 19878-26-3, 42074-03-3)

Conditions	Yield
In 1,4-dioxane; 1,2-dichloro-ethane at 90℃; for 24h; Diels-Alder reaction;	99%
In diethyl ether at 100℃; for 8h; Autoclave;	99%
In toluene at 110℃; for 48h; Inert atmosphere;	91%

maleiimide (541-59-3) + [3-(benzyloxy)phenyl]methanamine (104566-43-0) → 3-N-[(3-benzyloxyphenyl)methyl]aminopyrrolidine-2,5-dione (188295-15-0)

Conditions	Yield
In ethyl acetate for 20h; Ambient temperature;	99%

maleiimide (541-59-3) + 1,3-diphenylisobenzofuran (5471-63-6) → C24H17NO3

Conditions	Yield
In chloroform Ambient temperature;	99%

Upstream product

• 123-56-8 Succinimide 
• 109-97-7 pyrrole 
• 3345-50-4 N-carbamoylmaleimide 
• 99362-76-2 2,5-dioxo-2,5-dihydro-pyrrole-1-carboxylic acid tert-butylamide 
• 928-01-8 maleamide 
• 5435-44-9 (E)-3-Ureido-but-2-enoic acid ethyl ester 
• 62898-86-6 N-phenylcarbamylmaleimide 
• 4475-42-7 5,10,15,20,22,24-hexahydro-5,5,10,10,15,15,20,20-octamethyl-21H,23H-porphine 
• 1066-30-4 chromium(lll) acetate 
• 453549-35-4 5,5,10,10,15,15-Hexamethyl-bilinogen 
• 128-08-5 N-Bromosuccinimide 
• 74830-30-1 tetra-N-butylammonium salt of succinimide 
• 79901-70-5 O-t-butylmaleimide 
• 79887-86-8 O-i-propylmaleimide 

Downstream Products

• 110-17-8 (2E)-but-2-enedioic acid 
• 160724-73-2 C₂₀H₂₁NO₂ 
• 135205-68-4 N-cyanomaleimide 
• 6253-28-7 exo-7-oxabicyclo[2.2.1]hept-4-ene-2,3-dicarboximide 
• 105495-02-1 7-Hydroxy-4-methyl-6-(4-nitro-phenyl)-pyrrolo[3,4-c]pyridine-1,3-dione 

Relevant articles and documents

Preparation method of maleimide

The invention provides a preparation method of maleimide, which comprises the following steps: S1, reacting maleic anhydride with p-methoxybenzylamine to generate 3-(4-methoxybenzylamino) acrylic acid; step S2, enabling the 3-(4-methoxybenzyl carbamoyl) acrylic acid to react with acetic anhydride, so as to generate 1-(4-methoxybenzyl) maleimide; and S3, removing the 1-(4-methoxybenzyl) group from the 1-(4-methoxybenzyl) maleimide under the action of an oxidizing agent, so as to generate the maleimide. The preparation method provided by the embodiment of the invention has the advantages of short experimental route, high raw material safety, strong experimental operability and suitability for industrial production.

METHOD OF PRODUCING MALEIMIDE

PROBLEM TO BE SOLVED: To provide a method of producing an aliphatic maleimide using substantially no solvent capable of avoiding various problems caused by solvent vapor, and securing good environmental compatibility where the A-MI obtained by the method is useful as a laminate material, an encapsulating material, an electrically insulating material, a conductive paste, an adhesive, a tackiness agent, a structural material and the like. SOLUTION: The method of producing an aliphatic maleimide comprises reacting an aliphatic amine with more than 1.2 equivalent of maleic anhydride and/or maleic acid to 1 equivalent of the aliphatic amine using no solvent substantially. SELECTED DRAWING: None COPYRIGHT: (C)2020,JPOandINPIT

Cp?Co(III)-Catalyzed C-H Alkylation with Maleimides Using Weakly Coordinating Carbonyl Directing Groups

A novel protocol for ortho-C-H alkylation of aromatic and heteroaromatic ketones and esters under Cp?Co(III) catalysis has been developed for the first time. The reaction proceeds through initial cyclometalation via weak chelation-assisted C-H bond activation, followed by coordination of activated alkene, insertion between Co-C, and protodemetalation.