7-HYDROXYCOUMARIN-4-ACETIC ACID

7-HYDROXYCOUMARIN-4-ACETIC ACID Property

Melting point:

212 °C (dec.) (lit.)

Boiling point:

523.5±50.0 °C(Predicted)

Density 

1.511±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

solubility 

DMF: soluble

form 

Crystalline Powder

pka

4.24±0.10(Predicted)

color 

Off-white to pale yellow

λmax

326nm(MeOH)(lit.)

BRN 

204777

InChI

InChI=1S/C11H8O5/c12-7-1-2-8-6(3-10(13)14)4-11(15)16-9(8)5-7/h1-2,4-5,12H,3H2,(H,13,14)

InChIKey

BNHPMQBVNXMPDU-UHFFFAOYSA-N

SMILES

C1(=O)OC2=CC(O)=CC=C2C(CC(O)=O)=C1

CAS DataBase Reference

6950-82-9(CAS DataBase Reference)

Safety

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26-36

WGK Germany 

3

F 

8

HS Code 

29322985

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.

7-HYDROXYCOUMARIN-4-ACETIC ACID Chemical Properties,Usage,Production

Uses

Fluorogenic substrate

Uses

7-Hydroxycoumarinyl-4-acetic acid was used in the synthesis of novel and specific enzyme substrates for Maroteaux-Lamy (MPS VI) and Morquio A (MPS IVA) diseases. It was also employed as ionic liquid matrice for MALDI-TOF MS of proteins, peptides and carbohydrates.

Uses

7-Hydroxycoumarin-4-acetic acid is a fluorescence label but can also be used as pH-indicator.

Synthesis

GENERAL METHODS: Coumarin-4-acetic acid is a known compound (Manware et al., 2008). The reaction conditions for this compound were modified and optimized (Method A) to synthesize the analogues 2a-2f. These analogues were also synthesized by microwave-assisted methods (Method B). Method A: A mixture of citric acid (0.02 mol) and concentrated sulfuric acid (0.03 mol) was stirred at room temperature for 30 min. The mixture was placed in a boiling water bath to remove carbon monoxide (note: this needs to be done in a fume hood). Once the release of CO gas slowed down, the flask was removed from the water bath and left to stand for 15 minutes or until no more CO bubbles were produced in the reaction mixture. The reaction mixture was cooled to 10 °C and (un)substituted phenol (0.02 mol), pre-cooled to 10 °C, was added dropwise. The reaction mixture was stirred at room temperature for 48 h and then decanted onto ice. The precipitate was filtered and dissolved in saturated sodium bicarbonate solution. The solution was acidified to give intermediates 2a-2f. Method B: A mixture of citric acid (0.02 mol), concentrated sulfuric acid (0.03 mol), and (un)substituted phenol (0.02 mol) was placed in a microwave reactor and heated at 10% power for 4 min. The reaction mixture was poured onto crushed ice and processed according to the subsequent steps of Method A to obtain the target product. Yield of 7-hydroxycoumarin-4-acetic acid (2a): 67% for Method A and 78% for Method B; melting point: 170°C; IR (FT-IR) νmax (cm?1): 3210 (Ar C-H), 2924 (Al C-H), 1710 (C=O), 1701 (lactone C=O), 1458 (C=C), 1130 (C-O) , 1290 (C-OH); 1H-NMR (DMSO-d6, 400 MHz): δ 11.08 (1H, s, COOH), 7.41-6.98 (2H, m, H-5 and H-6), 6.69-6.23 (2H, m, H-8 and H-3), 4.93 (1H, dd, OH), 3.02-2.89 (2H, m , CH2); 13C-NMR (DMSO-d6, 100 MHz): δ 171.5 (C=O), 160.2 (C-2), 112.5 (C-3), 152.4 (C-4), 150.5 (C-8a), 135.2 (C-6), 124.8 (C-5), 122.9 (C-7), 120.1 (C-4a ), 104.1 (C-8), 37.0 (-CH2). HRMS (+ESI) [M+H]+: 221.0445 (calculated value), 221.0464 (measured value).

References

[1] Medicinal Chemistry Research, 2018, vol. 27, # 1, p. 61 - 71
[2] Tetrahedron Letters, 2012, vol. 53, # 48, p. 6598 - 6601,4
[3] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 23, p. 5732 - 5735
[4] Journal of the Chemical Society, 1950, p. 170,172
[5] Journal of the American Chemical Society, 1950, vol. 72, p. 3987,3989