4-hydroxybenzoic acid methyl ester

Structural formula
General
Surname	4-hydroxybenzoic acid methyl ester
other names	methyl p -hydroxybenzoate; PHB methyl ester; Methyl 4-hydroxybenzoate ( IUPAC , Ph. Eur. ); Methyl p- hydroxybenzoate; Methyl para- hydroxybenzoate; Nipagin M; METHYL PARABS ( INCI ) ; E 218;
Molecular formula	C 8 H 8 O 3
Brief description	white, almost odorless, crystalline powder
External identifiers / databases
EC number	202-785-7
ECHA InfoCard	100.002.532
PubChem	7456
Wikidata	Q229987
properties
Molar mass	152.15 g · mol -1
Physical state	firmly
density	1.361 g cm −3 (20 ° C)
Melting point	125-128 ° C
boiling point	Decomposes at 270-280 ° C
Vapor pressure	8.63 · 10 −2 Pa (50 ° C)
solubility	slightly soluble in water (2.5 g l −1 at 25 ° C); very sparingly soluble in water, slightly soluble in ethanol 96% and methanol ;
safety instructions
GHS labeling of hazardous substances	no GHS pictograms
	no GHS pictograms
H and P phrases	H: 412
	P: 273
Toxicological data	> 8000 mg kg −1 ( LD 50 , mouse , oral )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Methyl 4-hydroxybenzoate , and para -Hydroxybenzoesäuremethylester ( PHB-Methylester ), the Methylester of the aromatic carboxylic acid 4-hydroxybenzoic acid and one of the parabens . Nipagin is also used as a common name.

properties

4-Hydroxybenzoic acid methyl ester is a white, odorless, crystalline substance that has a slightly burning taste and has a weak anesthetic effect. The melting point is 126.0 ° C with a melting enthalpy of 166.5 J g ⁻¹ . The compound crystallizes in a monoclinic crystal lattice with the space group Cc . According to August, the vapor pressure function results according to ln (P) = −A / T + B (P in Pa, T in K) with A = 34.3 ± 0.3 and B = 11889 ± 92 in the temperature range from 30 ° C to 54 ° C. A molar enthalpy of sublimation of 98.8 kJ · mol ⁻¹ can be derived from the vapor pressure function . The compound dissolves little in water (2.5 g / l at 25 ° C.), but dissolves well in organic solvents such as acetone , chloroform , ethanol and ether . Phenolate (sodium methyl p-hydroxybenzoate) is formed in alkaline solutions .

Solubility in various solvents (at 25 ° C, in g / 100 g solvent)
solvent	water	Water (80 ° C)	Methanol	Ethanol	Propylene glycol	acetone	Diethyl ether	peanut oil
solubility	0.25	2.0	59	52	22nd	64	23	0.5

The methyl 4-hydroxybenzoate forms eutectically melting mixtures with other 4-hydroxybenzoic acid esters .

Eutectics for mixtures of 4-hydroxybenzoic acid esters
	Ethyl paraben	Propyl paraben	Butyl paraben
Mole fraction of methyl paraben	0.46	0.35	0.78
Eutectic melting point	88.5 ° C	77.8 ° C	59.8 ° C

use

4-Hydroxybenzoic acid methyl ester is used as a preservative, for example in shampoos , shower gels and other cosmetics as well as in liquid medicines. It is also used in research to prevent undesirable fungal growth on bacteriological agar plates .

PHB methyl ester is approved in the EU as a food additive with the number E 218 . The sodium salt ( sodium methyl p- hydroxybenzoate , E 219 ) is usually used because of its better solubility .

Health risks

4-Hydroxybenzoic acid methyl ester - like parabens in general - can cause pseudo- allergic reactions in humans, especially in asthmatics , such as B. hives or asthmatic attacks.

4-Hydroxybenzoic acid methyl ester was included in the EU's ongoing action plan ( CoRAP ) in 2012 in accordance with Regulation (EC) No. 1907/2006 (REACH) as part of substance evaluation . The effects of the substance on human health and the environment are re-evaluated and, if necessary, follow-up measures are initiated. The causes of the uptake of methyl 4-hydroxybenzoate were concerns about its classification as a CMR substance, consumer use , exposure of sensitive population groups , high (aggregated) tonnage and widespread use, as well as a potential endocrine disruptor . The re-evaluation has been running since 2014 and is carried out by France . In order to be able to reach a final assessment, further information was requested.

Occurrence

In nature, the substance plays a role as a sex attractant of the provisional bitch . It is also a natural ingredient in royal jelly from bees .

Individual evidence

↑ Entry on METHYL PARABS in the CosIng database of the EU Commission, accessed on December 28, 2019.
↑ ^a ^b ^c ^d ^e ^f Entry on methyl 4-hydroxybenzoate in the GESTIS substance database of the IFA , accessed on January 8, 2018(JavaScript required) .
↑ ^a ^b ^c ^d ^e Giordano, F .; Bettini, R .; Donini, C .; Gazzaniga, A .; Caira, MR; Zhang, GGZ; Grant, DJW: Physical properties of parabens and their mixtures: Solubility in water, thermal behavior, and crystal structures in J. Pharm. Sci. 88 (1999) 1210-1216, doi : 10.1021 / js9900452 .
↑ ^a ^b ^c Perlovich, GL; Rodionov, SV; Bauer-Brandl, A .: Thermodynamics of solubility, sublimation and solvation processes of parabens in Eur. J. Pharm. Sci. 24 (2005) 25-33, doi : 10.1016 / j.ejps.2004.09.007 .
↑ European Pharmacopoeia, 8th edition, Grundwerk 2014, p. 4078.
↑ Entry on 4-hydroxybenzoic acid methyl ester in the ChemIDplus database of the United States National Library of Medicine (NLM) .
^ Hermann PT Ammon, Curt Hunnius: Hunnius Pharmaceutical Dictionary , 2004, de Gruyter Verlag , ISBN 3-11-017475-8 .
↑ Entry on 4-hydroxybenzoates. In: Römpp Online . Georg Thieme Verlag, accessed on July 10, 2016.
↑ Markus DW Lipp: Emergency training for dentists: Prophylaxis, diagnosis, therapy , 1997, Schlütersche Verlagsgesellschaft , ISBN 3-87706-465-5 .
↑ Community rolling action plan ( CoRAP ) of the European Chemicals Agency (ECHA): Methyl 4-hydroxybenzoate , accessed on March 26, 2019.Template: CoRAP status / 2014
↑ Goodwin, M. et al. : Sex pheromones in the dog. In: Science (1979) Vol. 203, pp. 559-561; PMID 569903 ; doi : 10.1126 / science.569903 .
↑ Ishiwata et al .: Determination and confirmation of methyl p-hydroxybenzoate in royal jelly and other foods produced by the honey bee. in: Food additives & contaminants (1995) Volume 12 (2), pp. 281-285; PMID 7781824 .

[CosIng-1] Entry on METHYL PARABS in the CosIng database of the EU Commission, accessed on December 28, 2019.

[GESTIS-2] ↑ ^a ^b ^c ^d ^e ^f Entry on methyl 4-hydroxybenzoate in the GESTIS substance database of the IFA , accessed on January 8, 2018(JavaScript required) .

[Grant-3] Giordano, F .; Bettini, R .; Donini, C .; Gazzaniga, A .; Caira, MR; Zhang, GGZ; Grant, DJW: Physical properties of parabens and their mixtures: Solubility in water, thermal behavior, and crystal structures in J. Pharm. Sci. 88 (1999) 1210-1216, doi : 10.1021 / js9900452 .

[Perlovich-4] Perlovich, GL; Rodionov, SV; Bauer-Brandl, A .: Thermodynamics of solubility, sublimation and solvation processes of parabens in Eur. J. Pharm. Sci. 24 (2005) 25-33, doi : 10.1016 / j.ejps.2004.09.007 .

[EP80-5] European Pharmacopoeia, 8th edition, Grundwerk 2014, p. 4078.

[ChemIDplus-6] Entry on 4-hydroxybenzoic acid methyl ester in the ChemIDplus database of the United States National Library of Medicine (NLM) .

[7] Hermann PT Ammon, Curt Hunnius: Hunnius Pharmaceutical Dictionary , 2004, de Gruyter Verlag , ISBN 3-11-017475-8 .

[Römpp-8] Entry on 4-hydroxybenzoates. In: Römpp Online . Georg Thieme Verlag, accessed on July 10, 2016.

[9] Markus DW Lipp: Emergency training for dentists: Prophylaxis, diagnosis, therapy , 1997, Schlütersche Verlagsgesellschaft , ISBN 3-87706-465-5 .

[10] Community rolling action plan ( CoRAP ) of the European Chemicals Agency (ECHA): Methyl 4-hydroxybenzoate , accessed on March 26, 2019.Template: CoRAP status / 2014

[11] Goodwin, M. et al. : Sex pheromones in the dog. In: Science (1979) Vol. 203, pp. 559-561; PMID 569903 ; doi : 10.1126 / science.569903 .

[12] Ishiwata et al .: Determination and confirmation of methyl p-hydroxybenzoate in royal jelly and other foods produced by the honey bee. in: Food additives & contaminants (1995) Volume 12 (2), pp. 281-285; PMID 7781824 .