Methyl 4,6-dichloronicotinate Chemical Properties

Melting point:

41-43°

Boiling point:

260.0±35.0 °C(Predicted)

Density 

1.426±0.06 g/cm3(Predicted)

storage temp. 

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

form 

Solid

pka

-1.24±0.10(Predicted)

color 

White to Almost white

InChI

InChI=1S/C7H5Cl2NO2/c1-12-7(11)4-3-10-6(9)2-5(4)8/h2-3H,1H3

InChIKey

JEJMDUMJSZTJTI-UHFFFAOYSA-N

SMILES

C1=NC(Cl)=CC(Cl)=C1C(OC)=O

CAS DataBase Reference

65973-52-6

Safety Information

Hazard Codes 

Xn

Risk Statements 

22

Safety Statements 

24/25

HazardClass 

IRRITANT

HS Code 

29339900

Methyl 4,6-dichloronicotinate Usage And Synthesis

Uses

Methyl 4,6-dichloronicotinate could be used to synthesize 4,6-dichloronicotinic acid. Specifically, to a solution of methyl 4,6-dichloronicotinate in a mixture of THF (400 mL), MeOH (100 mL), and H2O (100 mL), a solution of NaOH (10 g) in 40 mL H2O was added. The mixture was stirred for 40 min at room temperature. Then, the solvents were reduced and acidified with concentrated HCl to a pH of about 2. It was extracted using a mixture of Et2O/EtOAc, and the organic layer was dried with Na2SO4. The solvents were removed, and the residue was dried in vacuo to obtain 4,6-dichloronicotinic acid as a white solid (12.3 g, 69% yield).

Synthesis

The general procedure for the synthesis of methyl 4,6-dichloronicotinate from methyl 4,6-dihydroxynicotinate was as follows: to a solution of methyl 4,6-dihydroxynicotinate (900 g, 5.3 mol) in phosphoryl chloride (4000 mL) was added N,N-diethylaniline (1035 mL, 6.4 mol). The reaction mixture was heated to 120 °C and maintained for 2 h, followed by cooling to room temperature. The reaction mixture was concentrated under vacuum and poured slowly into ice in batches. The mixture was extracted with ethyl acetate (2×). The organic extracts were combined, dried with anhydrous sodium sulfate and subsequently concentrated under vacuum. Purification of the crude product by rapid chromatography on silica gel (solvent gradient: 0% to 5% petroleum ether solution of ethyl acetate) afforded methyl 4,6-dichloronicotinate (400 g, 42% yield).LCMS (ESI) [M + H] = 206.1; 1H NMR (400 MHz, DMSO-d6) δ 8.84 (s, 1H), 7.98 (s, 1H) 3.90 (s, 3H).

References

[1] Patent: US2012/184562, 2012, A1. Location in patent: Page/Page column 6; 17
[2] Patent: US2006/217417, 2006, A1. Location in patent: Page/Page column 12
[3] Patent: WO2008/89459, 2008, A1. Location in patent: Page/Page column 60-61
[4] Journal of the Chinese Chemical Society, 2016, vol. 63, # 9, p. 758 - 769
[5] ACS Medicinal Chemistry Letters, 2014, vol. 5, # 7, p. 787 - 792

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