3-Azibutanol

3-Azibutanol Property

Boiling point:

133.2±32.0℃ (760 Torr)

Density 

1.26±0.1 g/cm3 (20 ºC 760 Torr)

Flash point:

52.5±14.4℃

storage temp. 

Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

solubility 

Chloroform (Slightly), Methanol (Slightly)

form 

Oil

color 

Clear Colourless

Stability:

Light Sensitive

InChI

InChI=1S/C4H8N2O/c1-4(2-3-7)5-6-4/h7H,2-3H2,1H3

InChIKey

YXAYZDNOWMFZLL-UHFFFAOYSA-N

SMILES

N1C(C)(CCO)N=1

Safety

HS Code 

2933998090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P260Do not breathe dust/fume/gas/mist/vapours/spray.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P312Call a POISON CENTER or doctor/physician if you feel unwell.

3-Azibutanol Chemical Properties,Usage,Production

Uses

3,3-Azo-1-butanol is used in the synthesis of Itraconazole (I937500) analogues for inhibition of endothelial cell proliferation, displaying antiangiogenic and antihedgehog activity. Also used in the synthesis of anticonvulsant methoxypropionamides.

Synthesis

General procedure for the synthesis of 2-(3-methyl-3H-bisacridin-3-yl)ethanol from the compound (CAS: 409320-90-7): 4-hydroxy-2-butanone (20, 1.00 g, 11.35 mmol) was transferred to a dry flask and cooled to 0 °C under nitrogen atmosphere. A 7N methanol ammonia solution (11.2 mL, 79 mmol) was added via syringe and the reaction mixture was stirred at 0 °C for 3 h. The reaction mixture was then purified by a liquid chromatography system. A solution of hydroxylamine-O-sulfonic acid (1.476 g, 13.05 mmol) in methanol (9.7 mL) was added dropwise, followed by slow warming of the reaction mixture to room temperature and continued stirring for 16 hours. Upon completion of the reaction, the reaction mixture was filtered through a sintered glass funnel and the filtrate was transferred to a reaction vessel and cooled to 0 °C again. Triethylamine (1.58 mL, 11.35 mmol) was added, followed by the slow addition of molecular iodine (2.88 g, 11.35 mmol) in 10 equal portions until a violet/brown color of iodine persisted in the reaction vessel. The solvent was removed under reduced pressure and the crude product was purified by Kugelrohr distillation (60 °C, 1-3 Torr) to afford the 2,2-diazapropenyl intermediate as a clear oil (304 mg, 27% yield). A portion of the intermediate (300 mg, 3.00 mmol) was dissolved in anhydrous pyridine (6 mL) and cooled to 0 °C in an ice bath. To this solution was added p-toluenesulfonyl chloride (628 mg, 3.30 mmol). The reaction mixture was stirred at 0-4 °C for 24 h and then poured into a mixture of 37% v/v HCl (15 mL) and ice (80 mL). The resulting suspension was extracted three times with ether and the combined organic layers were washed sequentially with 1N HCl solution, 1N NaOH solution, water and brine. The organic extract was dried over MgSO4, filtered and concentrated under vacuum to give a clarified oil (428 mg, 15% overall yield in 3 steps), which could be used in subsequent reactions without further purification.

References

[1] Journal of Medicinal Chemistry, 2011, vol. 54, # 20, p. 7363 - 7374
[2] Patent: WO2013/36866, 2013, A1. Location in patent: Paragraph 0234; 0284
[3] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 6, p. 1538 - 1544
[4] Molecules, 2017, vol. 22, # 8,