2516-34-9

Basic information

• Product Name: Cyclobutylamine
• Synonyms: AURORA KA-7608;CYCLOBUTYLAMINE;AMINOCYCLOBUTANE;Cyclobutanamine;1-Cyclobutanamine;Cyclobutane-1-amine;Cyclobutylamine,98%;Cyclobutylamine,Aminocyclobutane
• CAS NO: 2516-34-9
• Molecular Formula: C₄H₉N
• Molecular Weight: 71.12096
• EINECS: 219-736-0
• Product Categories: cyclic compounds;Amines and Anilines;Cyclobutanes & Cyclobutenes;Simple 4-Membered Ring Compounds;Imidazoles ,Homopiperidines
• Mol File: 2516-34-9.mol

Chemical Properties

• Melting Point: 133-135.5 °C(Solv: ligroine (8032-32-4); dichloromethane (75-09-2))
• Boiling Point: 81.5 °C752 mm Hg(lit.)
• Flash Point: 24 °F
• Appearance: Clear colorless to light yellow/Liquid
• Density: 0.833 g/mL at 25 °C(lit.)
• Vapor Pressure: 81.9mmHg at 25°C
• Refractive Index: n20/D 1.437(lit.)
• Storage Temp.: Refrigerator (+4°C)
• PKA: 10.80±0.20(Predicted)
• Water Solubility: slightly soluble
• Sensitive: Hygroscopic
• BRN: 2069297
• CAS DataBase Reference: Cyclobutylamine(CAS DataBase Reference)
• NIST Chemistry Reference: Cyclobutylamine(2516-34-9)
• EPA Substance Registry System: Cyclobutylamine(2516-34-9)

Safety Data

• Hazard Codes: F,C,Xi
• Statements: 11-34-20/21/22-36/37/38
• Safety Statements: 16-26-36/37/39-45-33-7/9
• RIDADR: UN 2733 3/PG 2
• WGK Germany: 3
• HazardClass: 3
• PackingGroup: II
• Hazardous Substances Data: 2516-34-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Cyclobutylamine is used as a substrate for the microwave-assisted synthesis of 7-azaindoles from dihalopyridines. This application is significant in the development of new pharmaceutical compounds with potential therapeutic properties.
Used in Chemical Synthesis:
Cyclobutylamine is also used as a reactant in the preparation of imidazo[1,2-b]pyridazine derivatives. These derivatives are known to be selective and orally available Mps1 (TTK) kinase inhibitors, which are important in the field of medicinal chemistry and drug development.

Preparation

The preparation of cyclobutylamine from cyclobutanecarboxylic acid and hydrazoic acid has been reported previously. Cyclobutylamine has also been prepared by the Hofmann-type rearrangement of cyclobutanecarboxamide. More recently it has been prepared in 82–87% overall yield from cyclobutanecarboxamide by oxidative rearrangement with lead tetraacetate or iodosobenzene diacetate.Synthesis of cyclobutylamine

Purification Methods

It has been purified by steam distillation. The aqueous distillate (e.g. 2L) is acidified with 3N HCl (90mL) and evaporated to dryness in a vacuum. The hydrochloride is treated with a few mL of H2O, cooled in ice and a slush of KOH pellets ground in a little H2O is added slowly in portions and keeping the solution very cold. The amine separates as an oil from the strongly alkaline solution. The oil is collected, dried over solid KOH and distilled using a vacuum jacketed Vigreux column (p 11) and protected from CO2 using a soda lime tube. The fraction boiling at 79-83o is collected, dried over solid KOH for 2days and redistilled over a few pellets of KOH (b 80.5-81.5o). Best distil in a dry N2 atmosphere. The purity can be checked by GLC using a polyethylene glycol on Teflon column at 72o, 15 psi, flow rate of 102 mL/min of He. The sample can appear homogeneous but because of tailing it is not possible to tell if H2O is present. The NMR in CCl4 should show no signals less than 1 ppm from TMS. The hydrochloride has a multiplet at ca 1.5-2.6ppm (H 2,2,4,3,3,4,4), a quintet at 3.8 ppm (H 1) and a singlet at 4.75 for NH2 [Roberts & Chambers J Am Chem Soc 73 2509 1951]. The benzenesulfonamide has m 85-86o (from aqueous MeOH) and the benzoyl derivative has m 120.6-121.6o. [Roberts & Mazur J Am Chem Soc 73 2509 1951, Iffland et al. J Am Chem Soc 75 4044 1953, Werner & Casanova Jr Org Synth Coll Vol V 273 1973, Beilstein 12 IV 3.]

InChI:InChI=1/C4H9N/c5-4-2-1-3-4/h4H,1-3,5H2/p+1

Upstream product

• 1503-98-6 cyclobutyl amide 
• 7726-95-6 bromine 
• 16887-00-6 chloride 
• 1191-95-3 cyclobutanone 
• 77317-97-6 1-Cyclobutanecarbohydroxamic acid 
• 2972-05-6 cyclobutanone oxime 
• 56700-66-4 tert-butyl cyclobutylcarbamate 
• 2625-41-4 nitrocyclobutane 
• 3721-95-7 Cyclobutanecarboxylic acid 

Downstream Products

• 23794-59-4 C₂₂H₂₇N₃O₅S 
• 70457-88-4 N-acetyl-N-(3-chloro-benzoyl)-cyclobutyl-amine 
• 1191-95-3 cyclobutanone 
• 110-15-6 succinic acid 
• 390407-92-8 4-(2-cyclobutylamino-1-hydroxy-ethyl)-benzonitrile 
• 390407-90-6 3-(2-cyclobutylamino-1-hydroxy-ethyl)-benzonitrile 
• 1027033-26-6 (5-chloro-3-cyclobutylamino-2-oxo-6-phenyl-2H-pyrazin-1-yl)-acetic acid benzyl ester 
• 1026812-22-5 [6-(3-bromo-phenyl)-5-chloro-3-cyclobutylamino-2-oxo-2H-pyrazin-1-yl]-acetic acid benzyl ester 
• 862388-12-3 ((1S)-1-benzyl-3-cyclobutylamino-2-hydroxy-3-oxopropyl)carbamic acid 1,1-dimethylethyl ester 

Relevant articles and documents

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Synthesis method of cyclobutylamine

The invention discloses a synthesis method of cyclobutylamine. The synthesis method comprises the following steps: S1, respectively adding cyclobutanone, an organic solvent, a catalyst and ammonia gasinto an autoclave while stirring; and S2, introducing hydrogen into the autoclave, and reacting the mixture for 12-36 h, with the pressure of the introduced hydrogen being maintained at 20-30 atm, and the reaction temperature being controlled to be 0-100 DEG C. According to the synthesis method, raw materials are easy to obtain, synthesis conditions are mild, special safety measures are not needed, and industrial production is facilitated.

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