4-Methylpyrimidine

4-Methylpyrimidine Property

Melting point:

32°C

Boiling point:

141-142 °C (lit.)

Density 

1.031 g/mL at 25 °C (lit.)

refractive index 

n20/D 1.496(lit.)

Flash point:

105 °F

storage temp. 

Inert atmosphere,Room Temperature

solubility 

soluble in Chloroform, Methanol

pka

2.02±0.10(Predicted)

form 

Liquid

color 

Clear colorless to slightly yellow

Water Solubility 

miscible

BRN 

105781

CAS DataBase Reference

3438-46-8(CAS DataBase Reference)

NIST Chemistry Reference

Pyrimidine, 4-methyl-(3438-46-8)

EPA Substance Registry System

Pyrimidine, 4-methyl- (3438-46-8)

Safety

Hazard Codes 

T,F,Xi

Risk Statements 

10-61

Safety Statements 

16-53-45

RIDADR 

UN 1993 3/PG 3

WGK Germany 

3

TSCA 

Yes

HazardClass 

3

PackingGroup 

III

HS Code 

29335995

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H226Flammable liquid and vapour

Precautionary statements

P210Keep away from heat/sparks/open flames/hot surfaces. — No smoking.

P240Ground/bond container and receiving equipment.

P241Use explosion-proof electrical/ventilating/lighting/…/equipment.

P303+P361+P353IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.

4-Methylpyrimidine Chemical Properties,Usage,Production

Chemical Properties

Light Yellow Oil

Uses

4-Methylpyrimidine was used in the synthesis of crystalline trans-[RuCl(3)(NO)L(2)] complexes. 4-Methylpyrimidine was also used to bridge dinuclear oxovanadium(IV) complexes.

Synthesis Reference(s)

Tetrahedron Letters, 29, p. 6853, 1988 DOI: 10.1016/S0040-4039(00)88458-0

Synthesis

The general procedure for the synthesis of 4-methylpyrimidine, methanol and ammonium formate from 4,4-dimethoxy-2-butanone and the compound (CAS:77287-34-4) is as follows: 272 g (6.0 mol) of formamide was added to a dry double-shelled glass reactor, which was heated to 190 °C (bottom temperature) under continuous stirring. Over a period of 3 h, 209 g (1.5 mol) of 4,4-dimethoxy-2-butanone of 95% purity was slowly added via a peristaltic pump. At the same time, 342 g of yellow reaction fraction, mainly composed of methanol, water, 4-methylpyrimidine, and ammonium formate, was collected via a simple jacketed lift tube and a descending temperature-controlled cooler. When the addition was complete, the head temperature dropped rapidly to about 158 °C and the reaction was then continued for 30 min. Care was taken to avoid excessive cooling to prevent precipitation of the by-product ammonium formate (about 15 g) in the gas space or on the cooling side. At the recommended rate of addition of 4,4-dimethoxy-2-butanone, salts in the distillate enter the receiver. During the reaction, the bath temperature is maintained at 215-220°C, the bottom temperature is 188-196°C, and the head temperature is raised to about 158°C. Salt Removal: Prior to the removal of the reaction water, the ammonium salts in the reject fraction must be removed to avoid their sublimation in the gas space and mixing into the final product fraction (2-3%). The reaction distillate (342 g) was placed in a flask and heated in the laboratory with a 125°C radiator, controlling the bottom temperature to no more than 60°C (oil bath to 68°C), and the head temperature was raised to about 39°C for 1.5 h to release about 15 g of ammonium salt. After separation of the salt, 327 g of the mixture remained, containing primarily 4-methylpyrimidine, water, and methanol, with 34-36 mass% 4-methylpyrimidine and about 12% water. Water separation and distillation: to remove water from the mixture containing 4-methylpyrimidine (~34%), water (~12%) and methanol, 250 g of trimethyl orthoformate (TMOF, 2.35 mol) was added to 327 g of the mixture and stirred for 30 min at room temperature. This was followed by atmospheric pressure low boiling point distillation (reflux ratio 5:1) using a 60 cm packed column (filled with Moltifill packing, 10° or Boden). The bath temperature was increased from 89°C to 160°C, the bottom temperature was increased from 69°C to 126°C, and the head temperature was decreased from 34°C to 65°C (fraction 1, ~340 g). The target product was distilled in the same column at 80 mbar. During the first stage, the bath temperature was increased from 96°C to about 120°C, the bottom temperature was increased from 66°C to 81°C, and the head temperature was increased from 31°C to 69°C (fraction 2, about 16 g). In the main fraction collection stage (bath temperature 122-162 °C, bottom temperature 80-128 °C, head temperature 69-72 °C), the same method was used to collect the front and back fractions (~35 g), resulting in ~111 g of 4-methylpyrimidine with >99% CC purity (Fraction 3, main run) in 79% yield.

References

[1] Patent: EP1457489, 2004, A1. Location in patent: Page 3