2,5-Dibromopyrimidine Chemical Properties

Melting point:

83.0 to 87.0 °C

Boiling point:

316.6±34.0 °C(Predicted)

Density 

2?+-.0.06 g/cm3(Predicted)

storage temp. 

under inert gas (nitrogen or Argon) at 2-8°C

solubility 

soluble in Methanol

form 

powder to crystal

pka

-2.97±0.22(Predicted)

color 

White to Almost white

InChI

InChI=1S/C4H2Br2N2/c5-3-1-7-4(6)8-2-3/h1-2H

InChIKey

XAHITOJPIWZJHD-UHFFFAOYSA-N

SMILES

C1(Br)=NC=C(Br)C=N1

CAS DataBase Reference

32779-37-6

Safety Information

Hazard Codes 

Xn

Risk Statements 

22-41-36/37/38

Safety Statements 

26-39-36/37/39

WGK Germany 

3

HS Code 

29335990

2,5-Dibromopyrimidine Usage And Synthesis

Chemical Properties

Off-White crystal

Uses

2,5-Dibromopyrimidine is a pyrimidine compound with two reactive groups, bromine atoms, at the 2 and 5 positions. It is used as a raw material for the synthesis of many compounds or pharmaceutical intermediates.

Synthesis

General procedure for the synthesis of 2,5-dibromopyrimidines from 2-amino-5-bromopyrimidines: Scheme 1. Preparation of the related pyran(mi)dihalides A-H. The key steps include: (a) Reaction using N-bromosuccinimide (NBS) and ammonium acetate (NH4OAc) in acetonitrile (MeCN) at room temperature for 5 min in 85-90% yield of pyridine (pyr); quantitative yield of pyrimidine (pym); (b) Pyridine: 1-12 h reflux reaction in acetonitrile with aldehyde (RCHO) and sodium cyanoborohydride (Na(CN)BH3) (82% yield, R = C5Hn); pyrimidine: overnight reaction at room temperature in tetrahydrofuran (THF) using sodium hydride (NaH) and alkyl halide (R1) (85% yield, R = Me); (c) Pyridine in 77-83% yield; pyrimidine in 30-40% yield using trimethylbenzylammonium bromide (Me3(Bn)NBr) and tert-butylnitrite (t-BuONO) in dibromomethane (CH2Br2), room temperature reaction overnight; (d) Pyrimidine: 80-85% yield in dichloromethane (CH2Cl2) using hydriodic acid (HI), reacted at 0 °C; (e) i. In water (H2O), using sodium hydroxide (NaOH) and bromine (Br2), reacted at room temperature in 50-60% yield; ii. In phosphorus oxychloride (POCl3) and diethylaniline (PhNEt2), reacted at reflux for 4 hrs in 75-85% yield; iii. In dichloromethane (DCM), using hydriodic acid (HI), reacted at 0°C in 80-85% yield; (f) in alcohol (ROH), using sodium (Na), 1-12 h reaction at room temperature, quantitative yield; (g) Overnight reaction at room temperature using alkyl zinc iodide (RZnI) and dichlorobis(triphenylphosphine)palladium (Cl2Pd(PPh3)2) in N,N-dimethylformamide (DMF)/tetrahydrofuran (THF) in 72% (R = C6H13) yield of pyridine (bromo-substituted) and 81% (R = C6H13) yield of pyrimidine (iodo-substituted); (h) Quantitative yields in acetonitrile using alkynes, cuprous iodide (CuI), dichlorobis(triphenylphosphine)palladium, and triethylamine (Et3N), reacted for 1-12 h at room temperature. Pyrimidinyl bromides were prepared in a similar manner starting from the bromination of 2-aminopyrimidine. N-alkylation could not be achieved by reductive amination (probably due to the reduced nucleophilicity of the amine), but was achieved using sodium hydride and appropriate alkyl halides (B). Non-aqueous diazotization/halogenated deoxidation was used to prepare 5-bromo-2-halogenated pyrimidines, but in reduced yield relative to a similar reaction with 2-aminopyridine (again, possibly due to reduced nucleophilicity of the amine group). Alternatively, the 2-pyrimidinone can be used as a precursor to 5-bromo-2-halogenopyrimidines (Lutz, F.; Kawasaki, T.; Soai, K. Tetrahedron-Asymmetry 2006, 17, 486) or as a substrate for alkylation, yielding 5-bromo-2-alkoxypyrimidines (D) (Kokatla, H.P. Lakshman, M.K. Org. Lett. 2010, 12, 4478). Introduction of an alkynyl substituent at the 2-position (carried out satisfactorily under Sonogashira conditions), but alkylation using Negishi conditions was non-selective. Since bromine was competitively removed upon reduction of 2-alkynylpyrimidinyl bromides (F) to the corresponding 2-alkylpyrimidinyl bromides (H), we turned to 5-bromo-2-iodopyrimidines as precursors for the cross-coupling reaction, with significantly improved selectivity and yield.

References

[1] Journal of Organic Chemistry, 2012, vol. 77, # 16, p. 6908 - 6916
[2] Patent: WO2012/162818, 2012, A1. Location in patent: Page/Page column 45-46
[3] Journal of Organic Chemistry, 2008, vol. 73, # 23, p. 9326 - 9333

2,5-Dibromopyrimidine(32779-37-6)Related Product Information

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