O-TRITYLHYDROXYLAMINE

O-TRITYLHYDROXYLAMINE Property

Melting point:

79-81 °C (lit.)

Boiling point:

443.2±44.0 °C(Predicted)

Density 

1.133

storage temp. 

Keep in dark place,Inert atmosphere,2-8°C

solubility 

soluble in Methanol

form 

powder to crystal

pka

3.10±0.70(Predicted)

color 

White to Orange to Green

BRN 

1983917

InChIKey

NZFHJBSDSXDUAO-UHFFFAOYSA-N

CAS DataBase Reference

31938-11-1

Safety

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26-37/39

WGK Germany 

3

F 

10

HS Code 

2928.00.2500

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

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P271Use only outdoors or in a well-ventilated area.

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

P302+P352IF ON SKIN: wash with plenty of soap and water.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

O-TRITYLHYDROXYLAMINE Chemical Properties,Usage,Production

Chemical Properties

White to off-white powder

Uses

O-Tritylhydroxylamine may be used in the preparation of 8-azido-O-trityloctahydroxamate and 9-azido-O-tritylnonahydroxamate. It may be used in the synthesis of Simian virus nuclear localization peptide (NLS)-histone deacetylase (HDAC) inhibitor conjugates.

Synthesis

The general procedure for the synthesis of O-tritylhydroxylamine from N-trityloxyphthalimide was as follows: triethylamine (6.0 mL, 43.1 mmol) was added slowly and dropwise over 5 min to dichloromethane (55 mL) containing N-hydroxyphthalimide (6.42 g, 39.4 mmol) and triphthaloyl chloride (10.01 g, 35.8 mmol) in a in a stirred solution. The reaction mixture was stirred continuously for 1 h at room temperature and then poured into water (100 mL) to terminate the reaction. The organic layer was separated, washed sequentially with water (2 x 100 mL) and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to afford N-(triphenylmethoxy)phthalimide (white foamy solid, 15.54 g). The intermediate was dissolved directly in a solvent mixture of chloroform (320 mL) and methanol (32 mL) without further purification, followed by slow dropwise addition of hydrazine hydrate (5.2 mL, 165.5 mmol). The reaction mixture was stirred for 2 h and poured into water (400 mL). The organic layer was separated, washed with water (2 x 300 mL) and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (silica gel 100 g, eluent: hexane-ethyl acetate, 9:1, ca. 1 L) to afford the target product, O-trityl hydroxylamine (8.92 g, 90% yield, based on triphthaloyl chloride calculations): white crystals with melting point of 85-86 °C (recrystallized from hexane); 1H NMR (400 MHz, CDCl3) δ. 7.47-7.43 (m, 6H, aromatic H), 7.37-7.26 (m, 9H, aromatic H), 4.95 (br s, 2H, NH); 13C NMR (100 MHz, CDCl3) δ: 143.2, 128.8, 127.8, 127.2, 90.8.

References

[1] Journal of Organic Chemistry, 2004, vol. 69, # 18, p. 5926 - 5933
[2] Angewandte Chemie - International Edition, 2014, vol. 53, # 1, p. 324 - 328
[3] Angew. Chem., 2014, vol. 126, # 1, p. 337,1
[4] Journal of Magnetic Resonance (1969-1992), 1987, vol. 75, # 1, p. 63 - 72
[5] Acta Poloniae Pharmaceutica - Drug Research, 2009, vol. 66, # 6, p. 671 - 680