56651-60-6

Basic information

• Product Name: 4-Methoxybenzyl isocyanate
• Synonyms: 4-METHOXYBENZYL ISOCYANATE;4-METHOXYBENZYL ISOCYANATE 98%;4-Methoxybenzyl isocyanate ,98%;1-(isocyanatomethyl)-4-methoxybenzene;4-Methoxybenzyl isocyanate,99%;4-methoxybenyl isocyanate;1-(Isocyanatomethyl)-4-methoxybenzene, 4-(Isocyanatomethyl)phenyl methyl ether, 4-(Isocyanatomethyl)anisole;Isocyanic acid, p-methoxybenzyl-
• CAS NO: 56651-60-6
• Molecular Formula: C₉H₉NO₂
• Molecular Weight: 163.17
• Product Categories: Isocyanates;Nitrogen Compounds;Organic Building Blocks
• Mol File: 56651-60-6.mol
• Article Data: 26

Chemical Properties

• Boiling Point: 60-66 °C0.6 mm Hg(lit.)
• Flash Point: >230 °F
• Appearance: clear colourless to yellow liquid
• Density: 1.143 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.0223mmHg at 25°C
• Refractive Index: n20/D 1.433(lit.)
• Storage Temp.: 2-8°C
• CAS DataBase Reference: 4-Methoxybenzyl isocyanate(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Methoxybenzyl isocyanate(56651-60-6)
• EPA Substance Registry System: 4-Methoxybenzyl isocyanate(56651-60-6)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 20/21/22-36/37/38-42
• Safety Statements: 26-36/37/39-37/39
• RIDADR: UN 2206PSN1B 6.1 / PGIII
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 56651-60-6(Hazardous Substances Data)

Usage

Chemical Properties

clear colourless to yellow liquid

Uses

4-Methoxybenzyl isocyanate (p-Methoxybenzyl isocyanate) may be used in the synthesis of 1-(4-methoxybenzyl)-3-{2-[(4-nitrophenyl)amino]ethyl}urea and 1-(4-methoxybenzyl)-3-{2-[(5-nitropyridin-2-yl)amino]ethyl} urea.It may be used in the multi-step synthesis of:diimidazodiazepine containing 5:7:5-fused heterocycle2-deoxy-2-ureido-D-ribo-hexulofuranosonamidebicyclic guanidine core of batzelladine A

General Description

4-Methoxybenzyl isocyanate (PMBNCO), also known as p-methoxybenzyl isocyanate, is an organic building block containing an isocyanate group. Its enthalpy of vaporization at boiling point has been reported.

InChI:InChI=1/C9H9NO2/c1-12-9-4-2-8(3-5-9)6-10-7-11/h2-5H,6H2,1H3

Synthetic route

bis(trichloromethyl) carbonate (32315-10-9) + 4-methoxy-benzylamine (2393-23-9) → 4-methoxybenzyl isocyanate (56651-60-6)

Conditions	Yield
With triethylamine In dichloromethane	100%
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at -80℃;
With sodium hydrogencarbonate In dichloromethane; water at 0℃; for 2.5h;

2-(4-methoxy-benzyloxy)-tetrahydro-pyran (18494-82-1) + tetrabutylammonium isocyanate (39139-87-2) → 4-methoxybenzyl isocyanate (56651-60-6)

Conditions	Yield
With triphenylphosphine; 2,3-dicyano-5,6-dichloro-p-benzoquinone In acetonitrile for 5h; Reflux;	98%

tetrabutylammonium isocyanate (39139-87-2) + 4-Methoxybenzyl alcohol (105-13-5) → 4-methoxybenzyl isocyanate (56651-60-6)

Conditions	Yield
With triphenylphosphine; 2,3-dicyano-5,6-dichloro-p-benzoquinone In acetonitrile at 20℃;	97%

silver cyanate (3315-16-0) + p-methoxybenzyl chloride (824-94-2) → 4-methoxybenzyl isocyanate (56651-60-6)

Conditions	Yield
In diethyl ether for 18h; Heating;	74%

phosgene (75-44-5) + N-(4-methoxybenzyl)-1,1,1-trimethylsilanamine (54965-03-6) → 4-methoxybenzyl cyanate + 4-methoxybenzyl isocyanate (56651-60-6)

Conditions	Yield
In toluene at 0℃; Title compound not separated from byproducts.;	A 7% B 58.4%

phosgene (75-44-5) + 4-methoxy-benzylamine (2393-23-9) → 4-methoxybenzyl isocyanate (56651-60-6)

Conditions	Yield
With toluene at 120℃;
With sodium hydrogencarbonate In dichloromethane; toluene at 0℃; for 3h;

phosgene (75-44-5) + 4-methoxybenzylamine hydrochloride (17061-61-9) → 4-methoxybenzyl isocyanate (56651-60-6)

Conditions	Yield
In chlorobenzene at 115℃;

(4-Methoxy-phenyl)-acetyl azide (87721-45-7) → 4-methoxybenzyl isocyanate (56651-60-6)

Conditions	Yield
In chloroform for 0.5h; Heating;
Heating; Neat (no solvent);

sodium isocyanate (917-61-3) + (4-methoxybenzyl)dimethylsulfonium (46122-80-9) → 4-Methoxybenzyl alcohol (105-13-5) + 4-methoxybenzyl cyanate + 4-methoxybenzyl isocyanate (56651-60-6)

Conditions	Yield
With sodium chloride In water-d2 at 80℃; Rate constant; Mechanism; Product distribution; other reagents;

4-Methoxyphenylacetic acid (104-01-8) → 4-methoxybenzyl isocyanate (56651-60-6)

Conditions	Yield
With diphenyl phosphoryl azide; triethylamine
Multi-step reaction with 2 steps 1: thionyl chloride 2: sodium azide / toluene / 1 h / Heating View Scheme
Multi-step reaction with 3 steps 1: oxalyl chloride, dimethylformamide / CH2Cl2 / 0.42 h 2: NaN3 / acetone; H2O / 0.5 h / 0 - 5 °C 3: CHCl3 / 0.5 h / Heating View Scheme

4-methoxyphenyl-acetic chloride (4693-91-8) → 4-methoxybenzyl isocyanate (56651-60-6)

Conditions	Yield
With sodium azide In toluene for 1h; Heating;
Multi-step reaction with 2 steps 1: NaN3 / acetone; H2O / 0.5 h / 0 - 5 °C 2: CHCl3 / 0.5 h / Heating View Scheme

4-methoxy-benzylamine (2393-23-9) → 4-methoxybenzyl isocyanate (56651-60-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 96.5 percent / H2SO4 / 2 h / Heating 2: 58.4 percent / toluene / 0 °C View Scheme

p-Methoxybenzyl bromide (2746-25-0) → 4-methoxybenzyl isocyanate (56651-60-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: AcOH; aq. NaOH 2: thionyl chloride 3: sodium azide / toluene / 1 h / Heating View Scheme

p-methoxybenzylnitrile (104-47-2) → 4-methoxybenzyl isocyanate (56651-60-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: AcOH; aq. NaOH 2: thionyl chloride 3: sodium azide / toluene / 1 h / Heating View Scheme

4-Methoxybenzyl alcohol (105-13-5) → 4-methoxybenzyl isocyanate (56651-60-6)

Conditions	Yield
Multi-step reaction with 5 steps 1: PBr3 / CH2Cl2 2: AcOH; aq. NaOH 3: thionyl chloride 4: sodium azide / toluene / 1 h / Heating View Scheme

2-(4-methoxyphenyl)acetamide (6343-93-7) → 4-methoxybenzyl isocyanate (56651-60-6)

Conditions	Yield
With [N-(p-tolylsulfonyl)imino]phenyliodinane In dichloromethane at 20℃; for 1.5h; Hofmann rearrangement; Inert atmosphere;

4-methoxy-benzylamine (2393-23-9) + trichloromethyl chloroformate (503-38-8) → 4-methoxybenzyl isocyanate (56651-60-6)

Conditions	Yield
With dmap In dichloromethane at 0 - 20℃; for 0.75h;

ethyl 3-amino-1-cyclopentyl-1H-pyrazole-4-carboxylate (791071-55-1) + 4-methoxybenzyl isocyanate (56651-60-6) → ethyl 1-cylcopentyl-3-(3-(4-methoxybenzyl)ureido)-1H-pyrazole-4-carboxylate (791071-56-2)

Conditions	Yield
With triethylamine In toluene Heating / reflux;	100%

1-(4-methoxy-benzyl)-4-nitro-1H-pyrazole-3-carboxylic acid hydrazide (896467-75-7) + 4-methoxybenzyl isocyanate (56651-60-6) → C21H22N6O6 (896467-77-9)

Conditions	Yield
In tetrahydrofuran at 0℃; for 0.166667h;	100%

(R)-2-(4-Methoxy-phenyl)-thiazolidine-4-carboxylic acid (222404-25-3) + 4-methoxybenzyl isocyanate (56651-60-6) → C20H20N2O4S (1245507-55-4)

Conditions	Yield
In tetrahydrofuran	100%

(+/-)-2-phenylpropionic acid vinyl ester (117760-33-5) + 4-methoxybenzyl isocyanate (56651-60-6) → 2-hydroxy-N-(4-methoxybenzyl)propanamide

Conditions	Yield
With lipase from Candida cylindracea In aq. phosphate buffer at 20℃; for 48h; pH=7.4; Enzymatic reaction; chemoselective reaction;	99%

1,2-benzisothiazolin-3-one (2634-33-5) + 4-methoxybenzyl isocyanate (56651-60-6) → N-(4-methoxybenzyl)benzisothiazol-3-one-2-amide (1437999-95-5)

Conditions	Yield
In tetrahydrofuran; dichloromethane for 0.5h; Reflux;	98%

tert-butyl (3R)-3-{[(4-fluorophenyl)methyl]amino}piperidine-1-carboxylate + 4-methoxybenzyl isocyanate (56651-60-6) → tert-butyl (3R)-3-{[(4-fluorophenyl)methyl]({[(4-methoxyphenyl)methyl]carbamoyl})amino}piperidine-1-carboxylate

Conditions	Yield
In dichloromethane for 20h;	96.1%

1-amino-3-methylbutane (107-85-7) + 4-methoxybenzyl isocyanate (56651-60-6) → 1-(4-methoxy-benzyl)-3-(3-methyl-butyl)-urea

Conditions	Yield
for 3h;	95%

C10H13N3O2 (1092096-40-6) + 4-methoxybenzyl isocyanate (56651-60-6) → 1-((2R,3S,3aS,9aR)-2-hydroxy-5-oxo-2,3,3a,4,5,9a-hexahydro-1H-cyclopenta[e]pyrrolo[1,2-a]pyrazin-3-yl)-3-(4-methoxybenzyl)urea (1449694-06-7)

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; for 1.33333h;	94%
In N,N-dimethyl-formamide at 20℃; for 1.33333h;	94%

4-methoxybenzyl isocyanate (56651-60-6) → C9H13N3O2

Conditions	Yield
With hydrazine hydrate In dichloromethane at 20℃; for 2h; Cooling with ice;	93%
With hydrazine hydrate In dichloromethane at 20℃; for 2h; Cooling with ice;	93%

C12H21NO6 (192219-28-6) + 4-methoxybenzyl isocyanate (56651-60-6) → C21H30N2O8 (175275-00-0)

Conditions	Yield
In acetonitrile Ambient temperature;	92%

4-methoxybenzyl isocyanate (56651-60-6) + C15H25NO6 (154014-00-3) → C21H30N2O8 (154014-01-4)

Conditions	Yield
In acetonitrile at 20℃; Addition;	92%

2',3',4',9'-tetrahydro-N,N-dimethyl-4-butyl-spiro[cyclohexane-1,1'(1'H)-pyrido[3,4-b]indol]-4-amine (1004546-45-5) + 4-methoxybenzyl isocyanate (56651-60-6) → 2',3',4',9'-tetrahydro-N,N-dimethyl-4-butyl-2'-4-methoxybenzylaminocarbonyl-spiro[cyclohexane-1,1'(1'H)-pyrido[3,4-b]indol]-4-amine (1050677-02-5)

Conditions	Yield
With triethylamine In acetonitrile for 13h; Reflux;	92%

(S)-2-azido-3-phenylpropionic acid methyl ester (116911-32-1) + 4-methoxybenzyl isocyanate (56651-60-6) → (S)-5-benzyl-N,3-bis(4-methoxybenzyl)-2,4-dioxoimidazolidine-1-carboxamide (1446141-49-6) + (R)-5-benzyl-N,3-bis(4-methoxybenzyl)-2,4-dioxoimidazolidine-1-carboxamide

Conditions	Yield
With triphenylphosphine In acetonitrile at 20℃; for 3h;	A 92% B n/a

(2S,4S,5R,6S)-6-isobutyl-2-((2R,3S)-3-isobutylaziridin-2-yl)-3-oxa-1-aza-bicyclo[3.1.0]hexan-4-ol (1215325-21-5) + 4-methoxybenzyl isocyanate (56651-60-6) → (4R,5R,6S)-4-hydroxy-6-isobutyl-3-(4-methoxybenzyl)-1,3-diazabicyclo[3.1.0]hexan-2-one (1360571-36-3)

Conditions	Yield
In 1,1,1,3',3',3'-hexafluoro-propanol; water at 20℃; 8:2 HFIPl :H2O (v/v); diastereoselective reaction;	90%

benzyl 2-azidoacetate (173601-46-2) + 4-methoxybenzyl isocyanate (56651-60-6) → N,3-diethyl-2,4-dioxoimidazolidine-1-carboxamide (1446141-56-5)

Conditions	Yield
With triphenylphosphine In acetonitrile at 20℃; for 3h;	89%

N-(2-acetylphenyl)-2-[(triphenylphosphoranylidene)amino]benzamide (947522-96-5) + 4-methoxybenzyl isocyanate (56651-60-6) → 1-(4-methoxybenzyl)-3-[2-(methylene-4H-benzo[d][1,3]oxazine-2-yl)phenyl]urea

Conditions	Yield
In toluene aza-Wittig reaction; Heating;	88%
In toluene at 20℃; Inert atmosphere; Reflux;	88%

2-(4-hydroxyphenyl)-4,5-dihydro-1,3-thiazole (90563-68-1) + 4-methoxybenzyl isocyanate (56651-60-6) → (4-methoxy)-benzylcarbamic acid 4-(4,5-dihydrothiazol-2-yl)phenyl ester (1165760-83-7)

Conditions	Yield
With triethylamine In toluene for 2.5h; Inert atmosphere; Reflux;	88%

piperidine (110-89-4) + 4-methoxybenzyl isocyanate (56651-60-6) → piperidine-1-carboxylic acid 4-methoxy-benzylamide

Conditions	Yield
for 3h;	87%

5-acetamido-7,8,9-tri-O-acetyl-2,6-anhydro-4-amino-3,4,5-trideoxy-D-glycero-D-galacto-non-2-enonic acid methyl ester (139110-70-6) + 4-methoxybenzyl isocyanate (56651-60-6) → methyl 5-acetamido-7,8,9-tri-O-acetyl-2,6-anhydro-3,4,5-trideoxy-4-(3-(4-methoxybenzyl)ureido)-D-glycero-D-galacto-non-2-enonate

Conditions	Yield
With dmap In dichloromethane at 20℃; Inert atmosphere;	87%

1-(5-nitrothiazol-2-yl)piperidin-4-amine (1601751-76-1) + 4-methoxybenzyl isocyanate (56651-60-6) → 1-(4-methoxybenzyl)-3-(1-(5-nitrothiazol-2-yl)piperidin-4-yl)urea

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 6h;	85.9%

ethyl-2-azidoacetate (637-81-0) + 4-methoxybenzyl isocyanate (56651-60-6) → N,3-bis(4-methoxybenzyl)-2,4-dioxoimidazolidine-1-carboxamide (1446141-57-6)

Conditions	Yield
With triphenylphosphine In acetonitrile at 20℃; for 3h;	85%

4-methoxybenzyl isocyanate (56651-60-6) + 2-[4-(3-hydrazinocarbonylpropyl)phenoxy]-2-methylpropionic acid tert-butyl ester (425672-62-4) → 2-(4-{N'-[(4-methoxybenzylaminocarbonyl)hydrazino]-4-oxobutyl}phenoxy)-2-methylpropionic acid tert-butyl ester

Conditions	Yield
In dichloromethane at 20℃; for 2h;	85%
In dichloromethane at 20℃; for 2h;	6.37 g

2-carbomethoxyaniline (134-20-3) + 4-methoxybenzyl isocyanate (56651-60-6) → 3-(4-methoxybenzyl)-2,4-dioxo-1,2,3,4-tetrahydroquinazoline (221539-62-4)

Conditions	Yield
With triethylamine In 1,4-dioxane at 140℃; for 0.75h; Microwave irradiation; Sealed vial;	84%
Stage #1: 2-carbomethoxyaniline; 4-methoxybenzyl isocyanate In toluene at 0 - 20℃; Stage #2: With sodium hydroxide In toluene at 70℃; for 6h;

1-aminocyclohexanecarboxylic acid benzyl ester (102373-23-9) + 4-methoxybenzyl isocyanate (56651-60-6) → 1-[3-(4-methoxy-benzyl)-ureido]-cyclohexanecarboxylic acid benzyl ester (467443-24-9)

Conditions	Yield
In chloroform at 20℃; for 3h;	83%

6-methyl-N-[3-(4-piperidinyloxy)phenyl]-4'-(trifluoromethoxy)-[1,1'-biphenyl]-2-carboxamide (871032-54-1) + 4-methoxybenzyl isocyanate (56651-60-6) → N-[(4-methoxyphenyl)methyl]-4-[3-[[[6-methyl-4'-(trifluoro-methoxy)[1,1'-biphenyl]-2-yl]carbonyl]amino]phenoxy]-1-piperidinecarboxamide

Conditions	Yield
Stage #1: 6-methyl-N-[3-(4-piperidinyloxy)phenyl]-4'-(trifluoromethoxy)-[1,1'-biphenyl]-2-carboxamide; 4-methoxybenzyl isocyanate In dichloromethane for 8h; Stage #2: In dichloromethane at 20℃;	82%

4-(4-chlorophenyl)-2-thiazolamine (2103-99-3) + 4-methoxybenzyl isocyanate (56651-60-6) → 1-(4-(4-chlorophenyl)thiazol-2-yl)-3-(4-methoxybenzyl)urea

Conditions	Yield
In tetrahydrofuran at 120℃; for 2h; Microwave irradiation;	82%

2-hydrazinyl-3-iodo-4-methylpyridine (1192744-67-4) + 4-methoxybenzyl isocyanate (56651-60-6) → C15H17IN4O2 (1345842-22-9)

Conditions	Yield
In dichloromethane at 20℃;	81%

Upstream product

• 75-44-5 phosgene 
• 2393-23-9 4-methoxy-benzylamine 
• 917-61-3 sodium isocyanate 
• 46122-80-9 (4-methoxybenzyl)dimethylsulfonium 
• 39139-87-2 tetrabutylammonium isocyanate 
• 105-13-5 4-Methoxybenzyl alcohol 
• 6343-93-7 2-(4-methoxyphenyl)acetamide 
• 503-38-8 trichloromethyl chloroformate 
• 18494-82-1 2-(4-methoxy-benzyloxy)-tetrahydro-pyran 
• 104-47-2 p-methoxybenzylnitrile 
• 2746-25-0 p-Methoxybenzyl bromide 
• 54965-03-6 N-(4-methoxybenzyl)-1,1,1-trimethylsilanamine 
• 4693-91-8 4-methoxyphenyl-acetic chloride 
• 32315-10-9 bis(trichloromethyl) carbonate 

Downstream Products

• 271598-03-9 5-amino-4-cyano-2-hydroxy-1-(4-methoxybenzyl)imidazole 
• 676997-09-4 Acetic acid (2S,3R,4S,5S,6R)-2-[(11E,13E)-(4R,5S,6S,7R,9R,16R)-4-acetoxy-5-methoxy-9,16-dimethyl-2,10-dioxo-7-(2-oxo-ethyl)-oxacyclohexadeca-11,13-dien-6-yloxy]-4-dimethylamino-5-(4-methoxy-benzylcarbamoyloxy)-6-methyl-tetrahydro-pyran-3-yl ester 
• 91467-13-9 5,5-Dichloro-3-(4-methoxy-benzyl)-oxazolidine-2,4-dione 
• 1165760-83-7 (4-methoxy)-benzylcarbamic acid 4-(4,5-dihydrothiazol-2-yl)phenyl ester 
• 1226709-88-1 C₂₅H₃₂BrN₃O₂ 
• 99075-91-9 methyl N-(4'-methoxybenzyl)carbamate 
• 1393924-23-6 C₃₈H₄₉N₃O₆ 
• 1437999-95-5 N-(4-methoxybenzyl)benzisothiazol-3-one-2-amide 
• 1401354-83-3 C₂₅H₂₉NO₄ 
• 1401354-96-8 C₂₅H₂₉NO₄ 

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