4426-11-3

Basic information

• Product Name: Cyanocyclobutane
• Synonyms: CYCLOBUTANECARBONITRILE;Cyanocyclobutane;Cyclobutyl cyanide;Cyanocyclobutane~Cyclobutyl cyanide;Cyclobutanecarbonitrile,97%;Cyclobutanecarbonitrile - C5653
• CAS NO: 4426-11-3
• Molecular Formula: C₅H₇N
• Molecular Weight: 81.12
• EINECS: 224-606-1
• Mol File: 4426-11-3.mol
• Article Data: 10

Chemical Properties

• Boiling Point: 144-146°C
• Flash Point: 42°C
• Appearance: Colorless liquid
• Density: 0,868 g/cm3
• Refractive Index: 1.4325
• Storage Temp.: 2-8°C
• Water Solubility: Slightly soluble in water.
• BRN: 2037573
• CAS DataBase Reference: Cyanocyclobutane(CAS DataBase Reference)
• NIST Chemistry Reference: Cyanocyclobutane(4426-11-3)
• EPA Substance Registry System: Cyanocyclobutane(4426-11-3)

Safety Data

• Hazard Codes: T
• Statements: 11-20/21/22-36-25
• Safety Statements: 3/7-9-16-36/37/39-45-26
• RIDADR: 3275
• HazardClass: 6.1
• PackingGroup: II
• Hazardous Substances Data: 4426-11-3(Hazardous Substances Data)

Usage

Chemical Properties

Colorless pure liquid

Uses

It is used for research or analysis use only, as pharmaceutical intermediate.

Application

Cyclobutanecarbonitrile is a highly polluting and highly toxic coating material, which has been banned in many countries in marine antifouling coatings.

InChI:InChI=1/C5H7N/c6-4-5-2-1-3-5/h5H,1-3H2

Synthetic route

δ-chlorovaleronitrile (6280-87-1) → cyclobutanecarbonitrile (4426-11-3) + 1-chloro-4,8-dicyanooctane

Conditions	Yield
With sodium hydroxide; tetrabutyl-ammonium chloride In tetrahydrofuran at 67℃; for 6h; Rate constant;	A 90% B 10 % Chromat.
With sodium hydroxide; tetrabutyl-ammonium chloride In tetrahydrofuran at 67℃; for 6h;	A 90% B 10 % Chromat.

5-bromopentan-1-nitrile (5414-21-1) → cyclobutanecarbonitrile (4426-11-3)

Conditions	Yield
With oxygen; tetraethylammonium perchlorate In N,N-dimethyl-formamide at 20℃; electroreduction at -1.1 V;	72%
With sodium hydroxide; tetrabutyl-ammonium chloride In tetrahydrofuran at 67℃; for 3h; Rate constant;
With N,N-Dimethylamino acetonitrile
With sodium hydroxide; tetrabutyl-ammonium chloride In tetrahydrofuran at 67℃; for 3h; Yield given;

Dimethyl-dithiocarbamic acid 1-cyano-cyclobutyl ester (61540-42-9) → cyclobutanecarbonitrile (4426-11-3)

Conditions	Yield
With 2,2'-azobis(isobutyronitrile); tri-n-butyl-tin hydride In benzene at 80℃; for 5h;	71%

isocyanate de chlorosulfonyle (1189-71-5) + Cyclobutanecarboxylic acid (3721-95-7) → cyclobutanecarbonitrile (4426-11-3)

Conditions	Yield
In dichloromethane; N,N-dimethyl-formamide	66.5%

δ-chlorovaleronitrile (6280-87-1) → cyclobutanecarbonitrile (4426-11-3)

Conditions	Yield
With sodium amide
With lithium diethylamide In N,N,N,N,N,N-hexamethylphosphoric triamide at -70℃;

cyclobutyl amide (1503-98-6) → cyclobutanecarbonitrile (4426-11-3)

Conditions	Yield
With phosphorus pentoxide durch Destillation;
With phosphorus pentoxide
With phosphorus pentoxide at 255℃; for 1h; Temperature;

1-cyanocyclobutane-1-carboxylic acid (30491-91-9) → cyclobutanecarbonitrile (4426-11-3)

1-cyanobicyclo<1.1.0>butane (16955-35-4) → cyclobutanecarbonitrile (4426-11-3) + trans-1-cyano-2-methylcyclopropane (6142-59-2, 26343-62-4, 26343-63-5, 62279-41-8, 62279-42-9)

Conditions	Yield
Yield given. Multistep reaction;

1-Benzenesulfonyl-cyclobutanecarbonitrile → cyclobutanecarbonitrile (4426-11-3)

Conditions	Yield
With magnesium; mercury dichloride In tetrahydrofuran; methanol for 2h; 0 deg C to r.t.;

sodium cyanide (143-33-9) + 1,4-dichlorobutane (110-56-5) → hexanedinitrile (111-69-3) + δ-chlorovaleronitrile (6280-87-1) + cyclobutanecarbonitrile (4426-11-3)

Conditions	Yield
With sodium hydroxide; tetrabutylammomium bromide In tetrahydrofuran for 3h; Heating; Yield given. Yields of byproduct given;

1-cyanocyclobutane-1-carboxylic acid (30491-91-9) → carbon dioxide (124-38-9) + cyclobutanecarbonitrile (4426-11-3)

Conditions	Yield
at 160℃;

Cyclobutanecarboxylic acid (3721-95-7) → cyclobutanecarbonitrile (4426-11-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: SOCl2 2: NH4OH 3: P2O5 View Scheme
Multi-step reaction with 3 steps 1: SOCl2 2: aq. NH3 3: P2O5 View Scheme
Multi-step reaction with 2 steps 1: ammonia / 0.5 h / 130 °C 2: phosphorus pentoxide / 1 h / 255 °C View Scheme

cyclobutane-1,1'-dicarboxylic acid (5445-51-2) → cyclobutanecarbonitrile (4426-11-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: Heating 2: SOCl2 3: NH4OH 4: P2O5 View Scheme

diethyl cyclobutane-1,1-dicarboxylate (3779-29-1) → cyclobutanecarbonitrile (4426-11-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: H3O+ 2: Heating 3: SOCl2 4: NH4OH 5: P2O5 View Scheme

Cyclobutanecarbonyl chloride (5006-22-4) → cyclobutanecarbonitrile (4426-11-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: NH4OH 2: P2O5 View Scheme
Multi-step reaction with 2 steps 1: aq. NH3 2: P2O5 View Scheme

C9H15NO2Si → cyclobutanecarbonitrile (4426-11-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: lithium borohydride / diethyl ether / 5.75 h / 20 °C / Inert atmosphere 2: 2,6-dimethylpyridine / dichloromethane / -10 - 20 °C 3: 2,6-dimethylpyridine / 20 °C View Scheme

1-(cyano)-2-(trimethylsilyl)cyclopropylmethanol → cyclobutanecarbonitrile (4426-11-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 2,6-dimethylpyridine / dichloromethane / -10 - 20 °C 2: 2,6-dimethylpyridine / 20 °C View Scheme

tetradeuterioacetic acid (1186-52-3) + C9H14F3NO3SSi → cyclobutanecarbonitrile (4426-11-3) + C10H14(2)H3NO2Si + C10H14(2)H3NO2Si

Conditions	Yield
With 2,6-dimethylpyridine at 20℃; Kinetics;	A 47 %Spectr. B 46 %Spectr. C 7 %Spectr.

N,N'-(ethane-1,2-diyl)dicyclobutanecarboxamide + acetonitrile (75-05-8) → cyclobutyl amide (1503-98-6) + cyclobutanecarbonitrile (4426-11-3)

Conditions	Yield
With lithium perchlorate at 40℃; for 0.5h; Electrolysis;

cyclobutanecarbonitrile (4426-11-3) + methyl 2-amino-5-methoxybenzoate (2475-80-1) → 2-cyclobutyl-7-methoxyquinazolin-4-ol (1448676-71-8)

Conditions	Yield
With hydrogenchloride In 1,4-dioxane at 100℃; for 15h; Inert atmosphere;	98%

bromochlorobenzene (106-39-8) + cyclobutanecarbonitrile (4426-11-3) → 1-(4-chlorophenyl)cyclobutanecarbonitrile (28049-61-8)

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; lithium hexamethyldisilazane In tetrahydrofuran at 80℃; for 3h; Inert atmosphere;	96%

cyclobutanecarbonitrile (4426-11-3) + prenyl bromide (870-63-3) → 1-(3-methylbut-2-enyl)cyclobutanecarbonitrile (1228309-45-2)

Conditions	Yield
With n-butyllithium; ammonium chloride; diisopropylamine In tetrahydrofuran	95%

tert-butyl 5-bromoindoline-1-carboxylate (261732-38-1) + cyclobutanecarbonitrile (4426-11-3) → C18H22N2O2

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); lithium hexamethyldisilazane; nixantphos In tetrahydrofuran at 80℃; for 18h;	95%

6-bromo-1H-indazole (79762-54-2) + cyclobutanecarbonitrile (4426-11-3) → 1-(1H-indazol-6-yl)cyclobutane-1-carbonitrile

Conditions	Yield
With N-Xantphos Pd G4; lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 0.25h; Inert atmosphere; Sealed tube;	91%

p-benzyloxyphenylbromide (6793-92-6) + cyclobutanecarbonitrile (4426-11-3) → 1-(4-(benzyloxy)phenyl)cyclobutanecarbonitrile (626603-28-9)

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; lithium hexamethyldisilazane In tetrahydrofuran at 80℃; for 3h; Inert atmosphere;	80%

cyclobutanecarbonitrile (4426-11-3) + methyl 2-amino-4-methoxybenzoate (50413-30-4) → 2-cyclobutyl-6-methoxyquinazolin-4-ol (1448676-68-3)

Conditions	Yield
With hydrogenchloride In 1,4-dioxane at 100℃; for 15h; Inert atmosphere;	79%

((1,2-bis(diisopropylphosphino)ethane)NiH)2 (130777-67-2) + cyclobutanecarbonitrile (4426-11-3) → [(1,2-bis(diisopropylphosphino)ethane)Ni(η2-cyclobutyl cyanide)] (834880-39-6)

Conditions	Yield
In tetrahydrofuran byproducts: H2; under N2 atm. ((dippe)NiH)2 and cyclobutyl cyanide in THF were mixed at room temp. and stirred for 15 min; solvent was evapd., residue was recrystd. from hexane (cold dry ice - acetone bath) and dried in vacuo for 2 h; elem. anal.;	76%

2,4,6-trichloropyridine (16063-69-7) + cyclobutanecarbonitrile (4426-11-3) → 1-(2,6-dichloro-4-pyridyl)cyclobutanecarbonitrile

Conditions	Yield
With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 1h; Inert atmosphere;	76%

cyclobutanecarbonitrile (4426-11-3) + N,N-dibenzyl-3,5-dibromoaniline → 1,1'-(5-(dibenzylamino)-1,3-phenylene)bis(cyclobutane-1-carbonitrile)

Conditions	Yield
Stage #1: cyclobutanecarbonitrile; N,N-dibenzyl-3,5-dibromoaniline With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In tetrahydrofuran for 0.25h; Inert atmosphere; Stage #2: With lithium hexamethyldisilazane In tetrahydrofuran at 80℃; for 1.5h;	75%

cyclobutanecarbonitrile (4426-11-3) + 2-Iodobenzyl bromide (40400-13-3) → 1-(2-iodobenzyl)cyclobutanecarbonitrile (495414-03-4)

Conditions	Yield
Stage #1: cyclobutanecarbonitrile With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78℃; for 1h; Stage #2: 2-Iodobenzyl bromide In tetrahydrofuran; hexane at -78 - 20℃; Further stages.;	74%

cyclobutanecarbonitrile (4426-11-3) + 2-carbomethoxyaniline (134-20-3) → 4-hydroxy-3-cyclobutylquinazoline (496867-71-1)

Conditions	Yield
With hydrogenchloride In 1,4-dioxane at 100℃; for 15h; Inert atmosphere;	73%

methyl 6-aminobenzo[d][1,3]dioxole-5-carboxylate (40680-63-5) + cyclobutanecarbonitrile (4426-11-3) → 6-cyclobutyl-[1,3]dioxolo[4,5-g]quinazolin-8-ol (1448676-75-2)

Conditions	Yield
With hydrogenchloride In 1,4-dioxane at 100℃; for 15h; Inert atmosphere;	71%

3-bromo-2-(phenylmethoxy)pyridine (52200-49-4) + cyclobutanecarbonitrile (4426-11-3) → 1-(2-(benzyloxy)pyridin-3-yl)cyclobutanecarbonitrile

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; lithium hexamethyldisilazane In tetrahydrofuran at 80℃; for 3h; Inert atmosphere;	71%

cyclobutanecarbonitrile (4426-11-3) + 2-fluoro-4-(trifluoromethyl) Pyridine → 1-[4-(trifluoromethyl)pyridin-2-yl]cyclobutanecarbonitrile (1432492-69-7)

Conditions	Yield
With potassium hexamethylsilazane In toluene at 20℃; for 72h;	64.8%
With potassium hexamethylsilazane In toluene at 20℃; for 72h;	64.8%

Cyclopentyl bromide (137-43-9) + cyclobutanecarbonitrile (4426-11-3) → 1-cyclopentylcyclobutanecarbonitrile (1432492-80-2)

Conditions	Yield
Stage #1: cyclobutanecarbonitrile With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.666667h; Stage #2: Cyclopentyl bromide In tetrahydrofuran; N,N,N,N,N,N-hexamethylphosphoric triamide at 20℃; for 3h;	62.3%
Stage #1: cyclobutanecarbonitrile With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.666667h; Stage #2: Cyclopentyl bromide With N,N,N,N,N,N-hexamethylphosphoric triamide In tetrahydrofuran at 20℃; for 3h;	62.3%

cyclobutanecarbonitrile (4426-11-3) + allyl bromide (106-95-6) → 1-allylcyclobutanecarbonitrile

Conditions	Yield
Stage #1: cyclobutanecarbonitrile With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78℃; for 0.833333h; Inert atmosphere; Stage #2: allyl bromide In tetrahydrofuran; hexane at -78 - 20℃; Inert atmosphere;	61%
Stage #1: cyclobutanecarbonitrile With lithium diisopropyl amide In tetrahydrofuran at -78 - 0℃; for 1h; Inert atmosphere; Stage #2: allyl bromide In tetrahydrofuran at -78 - 20℃; Inert atmosphere;

Upstream product

• 1503-98-6 cyclobutyl amide 
• 30491-91-9 1-cyanocyclobutane-1-carboxylic acid 
• 5414-21-1 5-bromopentan-1-nitrile 
• 61540-42-9 Dimethyl-dithiocarbamic acid 1-cyano-cyclobutyl ester 
• 1189-71-5 isocyanate de chlorosulfonyle 
• 3721-95-7 Cyclobutanecarboxylic acid 
• 75-05-8 acetonitrile 
• 1186-52-3 tetradeuterioacetic acid 
• 5006-22-4 Cyclobutanecarbonyl chloride 
• 3779-29-1 diethyl cyclobutane-1,1-dicarboxylate 
• 5445-51-2 cyclobutane-1,1'-dicarboxylic acid 
• 143-33-9 sodium cyanide 
• 110-56-5 1,4-dichlorobutane 
• 6280-87-1 δ-chlorovaleronitrile 

Downstream Products

• 28049-61-8 1-(4-chlorophenyl)cyclobutanecarbonitrile 
• 495414-03-4 1-(2-iodobenzyl)cyclobutanecarbonitrile 
• 71690-89-6 cyclobutanecarboximidamide hydrochloride 
• 913473-12-8 1-{4-[2-(cyclopropylmethoxy)ethyl]benzyl}cyclobutanecarbonitrile 
• 913473-28-6 1-[4-(2-hydroxyethyl)benzyl]cyclobutanecarbonitrile 
• 485828-81-7 1-(5-bromopyridin-2-yl)cyclobutane-1-carbonitrile 
• 74205-10-0 1-(2-methoxyphenyl)cyclobutane-1-carbonitrile 
• 5006-22-4 Cyclobutanecarbonyl chloride 
• 25774-35-0 cyclobutanecarboxylic anhydride 
• 14924-53-9 ethyl cyclobutylcarboxylate 
• 259729-89-0 [1-[1-(4-Chloro-phenyl)-cyclobutyl]-meth-(E)-ylidene]-methyl-amine 

Relevant articles and documents

The cyclopropylcarbinyl route to γ-silyl carbocations

The mesylate derivative of cis-1-hydroxymethyl-2-trimethylsilylcyclopropane has been prepared, along with a number of related mesylates and triflates with substituents on the 1-position. These substrates all solvolyze in CD3CO2D to give products derived from cyclopropylcarbinyl cations that undergo further rearrangement to give 3-trimethylsilylcyclobutyl cations. These 3-trimethylsilylcyclobutyl cations are stabilized by a long-range rear lobe interaction with the γ-trimethylsilyl group. When the substituent is electron-withdrawing (CF3, CN, or CO2CH3), significant amounts of bicyclobutane products are formed. The bicyclobutanes are a result of γ-trimethylsilyl elimination from the cationic intermediate that has an unusually long calculated Si-C bond. The solvolysis chemistry of mesylate and triflate derivatives of trans-1-hydroxymethyl-2-trimethylsilylcyclopropane and 1-substituted analogs can be quite different since these substrates do not generally lead to 3-trimethylsilylcyclobutyl cations.

Corresponding amine nitrile and method of manufacturing thereof

The invention relates to a manufacturing method of nitrile. Compared with the prior art, the manufacturing method has the characteristics of significantly reduced using amount of an ammonia source, low environmental pressure, low energy consumption, low production cost, high purity and yield of a nitrile product and the like, and nitrile with a more complex structure can be obtained. The invention also relates to a method for manufacturing corresponding amine from nitrile.

Two-Carbon Elongation/Annulation of Alcohols to Nitriles

Alcohols were replaced by a two-carbon nitrile unit in good to excellent yields via dehydrative alkylation with (phenylsulfonyl)acetonitrile under modified Mitsunobu conditions followed by desulfonylation using magnesium.Diols and haloalcohols furnished cycloalkylnitriles.