4-(Trifluoromethyl)cinnamic acid Chemical Properties

Melting point:

231-233 °C(lit.)

Boiling point:

279.2±35.0 °C(Predicted)

Density 

1.3275 (estimate)

storage temp. 

Sealed in dry,Room Temperature

solubility 

Soluble in Chloroform,Dichloromethane,Ethyl Acetate,DMSO,Acetone,etc.

form 

powder to crystal

pka

4.21±0.10(Predicted)

color 

White to Almost white

BRN 

2452800

InChI

InChI=1S/C10H7F3O2/c11-10(12,13)8-4-1-7(2-5-8)3-6-9(14)15/h1-6H,(H,14,15)/b6-3+

InChIKey

ANRMAUMHJREENI-ZZXKWVIFSA-N

SMILES

C(O)(=O)/C=C/C1=CC=C(C(F)(F)F)C=C1

CAS DataBase Reference

16642-92-5(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26-37/39

WGK Germany 

3

HazardClass 

IRRITANT

HS Code 

29163990

MSDS

• Language:English Provider:SigmaAldrich
• Language:English Provider:ACROS
• Language:English Provider:ALFA

4-(Trifluoromethyl)cinnamic acid Usage And Synthesis

Chemical Properties

white crystalline powder

Uses

trans-4-(Trifluoromethyl)cinnamic acid has been employed as internal standard for the determination of A77 1726 (2-cyano-3-hydroxy-N-[4-(trifluoromethyl)phenyl]-2-butenamide) in plasma by HPLC.

Definition

ChEBI: (E)-4-(trifluoromethyl)cinnamic acid is a member of the class of (trifluoromethyl)benzenes consisting of trans-cinnamic acid having a trifluoromethyl substituent at the para-position. It is a member of cinnamic acids and a member of (trifluoromethyl)benzenes. It is functionally related to a trans-cinnamic acid.

Synthesis

Step A. Synthesis of (E)-4-trifluoromethylcinnamic acid 1. In 30 mL of pyridine, 4-trifluoromethylbenzaldehyde (7.7 mL, 57.7 mmol), malonic acid (12.0 g, 115.4 mmol), and piperidine (0.567 μL, 5.75 mmol) were mixed, and the reaction was stirred for 18 hr at 70°C. 2. After completion of the reaction, the reaction solution was cooled to room temperature, water (300 mL) was added, and the pH was adjusted to 4 with concentrated hydrochloric acid (litmus paper test), and a precipitate was precipitated. 3. The solid product was collected by filtration and washed with water until the filtrate was neutral. 4. The solid product was dried under vacuum to obtain (E)-4-trifluoromethylcinnamic acid in white powder form (10a, 11.2 g, 90% yield). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 12.60 (bs, 1H), 7.92 (d, 2H, J = 8.2 Hz), 7.77 (d, 2H, J = 8.2 Hz), 7.66 (d, 1H, J = 16.0 Hz), 6.70 (d, 1H, J = 16.0 Hz). Step B. Amplified synthesis of (E)-4-trifluoromethylcinnamic acid 1. In a 2L four-necked round-bottomed flask equipped with an air condenser, an argon inlet, a mechanical stirrer, a thermocouple, and a stopper, 4-trifluoromethylbenzaldehyde (250 g, 196.2 mL, 1.44 mol), malonic acid (302.6 g, 2.87 mol), and pyridine (750 mL) were added. 2. The reaction was initially exothermic to 38-40 °C and maintained for 30 min. Piperidine (14.202 mL, 143.58 mmol) was then added, again exothermic, and the temperature rose to 42 °C after about 10 min. 3. After stirring for 30 minutes, the reaction was heated to 60 °C for 18 hours (overnight). 4. Confirm completion of the reaction by TLC, cool to about 40 °C, slowly add water (2 L to prevent freezing of the reaction mixture), continue to cool to room temperature, and dilute to a total volume of 6 L with additional water. 5. Adjust pH to 2.0-3.0 with concentrated hydrochloric acid (~675-700mL), stir for 30 minutes, filter to collect white solid. 6. Wash the filter cake with water until the filtrate is neutral (pH ca. 5.5-6, water consumption ca. 2.5 L), air dry in a Brinell's funnel for 2 hr, then dry in a vacuum oven at 60 °C overnight to obtain (E)-4-trifluoromethylcinnamic acid in the form of a white solid (10a, 300.5 g, 96% yield).

References

[1] European Journal of Medicinal Chemistry, 2018, vol. 149, p. 56 - 68
[2] Patent: US2007/259936, 2007, A1. Location in patent: Page/Page column 166-167; 171
[3] Journal of Medicinal Chemistry, 2015, vol. 58, # 9, p. 3859 - 3874
[4] Molecular Crystals and Liquid Crystals, 2010, vol. 528, p. 138 - 146
[5] Tetrahedron Letters, 2011, vol. 52, # 38, p. 4906 - 4910

4-(Trifluoromethyl)cinnamic acid(16642-92-5)Related Product Information

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