Phenolphthalein - Wikipedia

pH indicator that turns pink in basic solution This article is about Phenolphthalein. For other related dyes in the phthalein family, see Phthalein dye. Phenolphthalein

Names
Preferred IUPAC name 3,3-Bis(4-hydroxyphenyl)-2-benzofuran-1(3H)-one
Other names 3,3-Bis(4-hydroxyphenyl)isobenzofuran-1(3H)-one
Identifiers
CAS Number	77-09-8 Y
3D model (JSmol)	Interactive image
ChEMBL	ChEMBL63857 Y
ChemSpider	4600 Y
DrugBank	DB04824 N
ECHA InfoCard	100.000.914
KEGG	D05456 Y
PubChem CID	4764
UNII	6QK969R2IF N
CompTox Dashboard (EPA)	DTXSID0021125
InChI InChI=1S/C20H14O4/c21-15-9-5-13(6-10-15)20(14-7-11-16(22)12-8-14)18-4-2-1-3-17(18)19(23)24-20/h1-12,21-22H YKey: KJFMBFZCATUALV-UHFFFAOYSA-N Y InChI=1/C20H14O4/c21-15-9-5-13(6-10-15)20(14-7-11-16(22)12-8-14)18-4-2-1-3-17(18)19(23)24-20/h1-12,21-22HKey: KJFMBFZCATUALV-UHFFFAOYAH
SMILES O=C1OC(C2=C1C=CC=C2)(C3=CC=C(C=C3)O[H])C4=CC=C(C=C4)O[H]
Properties
Chemical formula	C20H14O4
Molar mass	318.328 g·mol−1
Appearance	White powder
Density	1.277 g/cm3 (32 °C (90 °F))
Melting point	258–263 °C (496–505 °F; 531–536 K)[1]
Solubility in water	400 mg/l
Solubility in other solvents	Insoluble in benzene and hexane; very soluble in ethanol and ether; slightly soluble in DMSO
UV-vis (λmax)	552 nm (1st) 374 nm (2nd)[1]
Pharmacology
ATC code	A06AB04 (WHO)
Hazards
GHS labelling:
Pictograms	[1]
Signal word	Danger
Hazard statements	H341, H350, H361[1]
Precautionary statements	P201, P281, P308+P313[1]
NFPA 704 (fire diamond)	2 3 0
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). N verify (what is YN ?) Infobox references

Chemical compound

Phenolphthalein (/fɛˈnɒl(f)θəliːn/[citation needed] feh-NOL(F)-thə-leen) is a chemical compound with the formula C20H14O4 and is often written as "HIn", "HPh", "phph" or simply "Ph" in shorthand notation. Phenolphthalein is often used as an indicator in acid–base titrations. For this application, it turns colorless in acidic solutions and pink in basic solutions. It belongs to the class of dyes known as phthalein dyes.

Phenolphthalein is slightly soluble in water and usually is dissolved in alcohols in experiments. It is a weak acid, which can lose H+ ions in solution. The nonionized phenolphthalein molecule is colorless and the double deprotonated phenolphthalein ion is fuchsia. Further proton loss in higher pH occurs slowly and leads to a colorless form. Phenolphthalein ion in concentrated sulfuric acid is orange red due to sulfonation.[2]

Uses

[edit]

pH indicator

[edit]

Phenolphthalein (pH indicator)
below pH 8.3	above pH 10.0
8.3	⇌	10.0

Phenolphthalein's common use is as an indicator in acid-base titrations. It also serves as a component of universal indicator, together with methyl red, bromothymol blue, and thymol blue.[3]

Phenolphthalein adopts different forms in aqueous solution depending on the pH of the solution.[4][2][5][6] Inconsistency exists in the literature about hydrated forms of the compounds and the color of sulfuric acid. Wittke reported in 1983 that it exists in protonated form (H3In+) under strongly acidic conditions, providing an orange coloration. However, a later paper suggested that this color is due to sulfonation to phenolsulfonphthalein.[2]

The lactone form (H2In) is colorless between strongly acidic and slightly basic conditions. The doubly deprotonated (In2-) phenolate form (the anion form of phenol) gives the familiar pink color. In strongly basic solutions, phenolphthalein is converted to its In(OH)3− form, and its pink color undergoes a rather slow fading reaction[6] and becomes completely colorless when pH is greater than 13.

The pKa values of phenolphthalein were found to be 9.05, 9.50 and 12 while those of phenolsulfonphthalein are 1.2 and 7.70.[2]

Species	H3In+	H2In	In2−	In(OH)3−
Structure
Model
pH	<−1 in H2SO4[4]	0–8.3	8.3–10.0[7]	>12
Conditions	strongly acidic	acidic or near-neutral	basic	strongly basic
Color	orange	colorless	pink to fuchsia	colorless
Image

An animation of the pH-dependent reaction mechanism: H3In+ → H2In → In2− → In(OH)3−

Carbonation of concrete

[edit]

Phenolphthalein's pH sensitivity is exploited in other applications: concrete has naturally high pH due to the calcium hydroxide formed when Portland cement reacts with water. As the concrete reacts with carbon dioxide in the atmosphere, pH decreases to 8.5–9. When a 1% phenolphthalein solution is applied to normal concrete, it turns bright pink. However, if it remains colorless, it shows that the concrete has undergone carbonation. In a similar application, some spackling used to repair holes in drywall contains phenolphthalein. When applied, the basic spackling material retains a pink color; when the spackling has cured by reaction with atmospheric carbon dioxide, the pink color fades.[8]

Education

[edit]

In a highly basic solution, phenolphthalein's slow change from pink to colorless as it is converted to its Ph(OH)3− form is used in chemistry classes for the study of reaction kinetics.

Entertainment

[edit]

Phenolphthalein is used in toys, for example as a component of disappearing inks, or disappearing dye on the "Hollywood Hair" Barbie hair. In the ink, it is mixed with sodium hydroxide, which reacts with carbon dioxide in the air. This reaction leads to the pH falling below the color change threshold as hydrogen ions are released by the reaction:

OH−(aq) + CO2(g) → CO2−3(aq) + H+(aq).

To develop the hair and "magic" graphical patterns, the ink is sprayed with a solution of hydroxide, which leads to the appearance of the hidden graphics by the same mechanism described above for color change in alkaline solution. The pattern will eventually disappear again because of the reaction with carbon dioxide. Thymolphthalein is used for the same purpose and in the same way, when a blue color is desired.[9]

Detection of blood

[edit] Main article: Kastle-Meyer test

A reduced form of phenolphthalein, phenolphthalin, which is colorless, is used in a test to identify substances thought to contain blood, commonly known as the Kastle–Meyer test. A dry sample is collected with a swab or filter paper. A few drops of alcohol, then a few drops of phenolphthalein, and finally a few drops of hydrogen peroxide are dripped onto the sample. If the sample contains hemoglobin, it will turn pink immediately upon addition of the peroxide, because of the generation of phenolphthalein. A positive test indicates the sample contains hemoglobin and, therefore, is likely blood. A false positive can result from the presence of substances with catalytic activity similar to hemoglobin. This test is not destructive to the sample; it can be kept and used in further tests. This test has the same reaction with blood from any animal whose blood contains hemoglobin, including almost all vertebrates; further testing would be required to determine whether it originated from a human.

Laxative

[edit] See also: Phenol red

Phenolphthalein has been used for over a century as a laxative, but is now being removed from over-the-counter laxatives[10] over concerns of carcinogenicity.[11][12] Laxative products formerly containing phenolphthalein have often been reformulated with alternative active ingredients: Feen-a-Mint[13] switched to bisacodyl, and Ex-Lax[14] was switched to a senna extract.

Thymolphthalein is a related laxative made from thymol.

Despite concerns regarding its carcinogenicity based on rodent studies, the use of phenolphthalein as a laxative is unlikely to cause ovarian cancer.[15] Some studies suggest a weak association with colon cancer, while others show none at all.[16]

Phenolphthalein is described as a stimulant laxative.[16] In addition, it has been found to inhibit human cellular calcium influx via store-operated calcium entry (SOCE, see Calcium release activated channel § Structure) in vivo. This is effected by its inhibiting thrombin and thapsigargin, two activators of SOCE that increase intracellular free calcium.[17]

Phenolphthalein has been added to the European Chemicals Agency's candidate list for substance of very high concern (SVHC).[18] It is on the IARC group 2B list for substances "possibly carcinogenic to humans".[19]

The discovery of phenolphthalein's laxative effect was due to an attempt by the Hungarian government to label[clarification needed] genuine local white wine with the substance in 1900. Phenolphthalein did not change the taste of the wine and would change color when a base is added, making it a good label in principle. However, it was found that ingestion of the substance led to diarrhea. Max Kiss, a Hungarian-born pharmacist residing in New York, heard about the news and launched Ex-Lax in 1906.[20][19]

Synthesis

[edit]

Phenolphthalein can be synthesized by condensation of phthalic anhydride with two equivalents of phenol under acidic conditions. It was discovered in 1871 by Adolf von Baeyer.[21][22][23]

See also

[edit]

• Bromothymol blue
• Litmus
• Methyl orange
• pH indicator
• Universal indicator

References

[edit]

1. ^ a b c d e "Phenolphthalein". Archived from the original on 8 November 2015. Retrieved 7 October 2014.
2. ^ a b c d Tamura, Zenzo (December 1996). "Spectrophotometric Analysis of the Relationship between Dissociation and Coloration, and of the Structural Formulas of Phenolphthalein in Aqueous Solution". Analytical Sciences. 12 (6): 927–930. doi:10.2116/analsci.12.927.
3. ^ "Universal Indicator". ISCID Encyclopedia of Science and Philosophy. Archived from the original on September 25, 2006.
4. ^ a b Wittke, Georg (1 March 1983). "Reactions of phenolphthalein at various pH values". Journal of Chemical Education. 60 (3): 239. Bibcode:1983JChEd..60..239W. doi:10.1021/ed060p239. ISSN 0021-9584.
5. ^ Abdel-Hamid, Refat (1 September 1998). "The Adsorption Behavior of Phenolphthalein at a Mercury Electrode in Water-Ethanol Solutions". Monatshefte für Chemie - Chemical Monthly. 129 (8): 817–826. doi:10.1007/PL00013491. S2CID 92339258.
6. ^ a b Kunimoto, Ko-Ki (February 2001). "Molecular structure and vibrational spectra of phenolphthalein and its dianion". Spectrochimica Acta Part A. 57 (2): 265–271. Bibcode:2001AcSpA..57..265K. doi:10.1016/S1386-1425(00)00371-1. PMID 11206560.
7. ^ Rathod, Balraj B.; Murthy, Sahana; Bandyopadhyay, Subhajit (20 February 2019). "Is this Solution Pink Enough? A Smartphone Tutor to Resolve the Eternal Question in Phenolphthalein-Based Titration". Journal of Chemical Education. 96 (3): 486–494. Bibcode:2019JChEd..96..486R. doi:10.1021/acs.jchemed.8b00708. S2CID 104475433.
8. ^ US 6531528, Ronald D. Kurp, "Ready to use spackle/repair product containing dryness indicator", published 2003-03-11, assigned to Dap Products Inc. 
9. ^ "Toystore" (PDF). Archived (PDF) from the original on 2021-07-02. Retrieved 2022-02-22.
10. ^ Spiller, H. A.; Winter, M. L.; Weber, J. A.; Krenzelok, E. P.; Anderson, D. L.; Ryan, M. L. (May 2003). "Skin Breakdown and Blisters from Senna-Containing Laxatives in Young Children". The Annals of Pharmacotherapy. 37 (5): 636–639. doi:10.1345/aph.1C439. PMID 12708936. S2CID 31837142.
11. ^ Dunnick, J. K.; Hailey, J. R. (1996). "Phenolphthalein Exposure Causes Multiple Carcinogenic Effects in Experimental Model Systems" (PDF). Cancer Research. 56 (21): 4922–4926. PMID 8895745. Archived (PDF) from the original on 2022-02-17. Retrieved 2022-02-22.
12. ^ Tice, R. R.; Furedi-Machacek, M.; Satterfield, D.; Udumudi, A.; Vasquez, M.; Dunnick, J. K. (1998). "Measurement of Micronucleated Erythrocytes and DNA Damage during Chronic Ingestion of Phenolphthalein in Transgenic Female Mice Heterozygous for the p53 Gene". Environmental and Molecular Mutagenesis. 31 (2): 113–124. doi:10.1002/(SICI)1098-2280(1998)31:2<113::AID-EM3>3.0.CO;2-N. PMID 9544189. S2CID 36550267.
13. ^ "Phenolphthalein". DrugBank. Archived from the original on 2020-08-06. Retrieved 2020-04-25.
14. ^ Stolberg, Sheryl Gay (August 30, 1997). "3 Versions of Ex-Lax Are Recalled After F.D.A. Proposes Ban on Ingredient". The New York Times. Archived from the original on May 7, 2021. Retrieved April 25, 2020.
15. ^ Cooper, G. S.; Longnecker, M. P.; Peters, R. K. (2004). "Ovarian Cancer Risk and Use of Phenolphthalein-Containing Laxatives". Pharmacoepidemiology and Drug Safety. 13 (1): 35–39. doi:10.1002/pds.824. PMID 14971121. S2CID 24783082. Archived from the original on 2022-01-26. Retrieved 2019-06-26.
16. ^ a b "Other pharmaceutical agents.". IARC monographs on the evaluation of carcinogenic risks to humans. Vol. 76. International Agency for Research on Cancer. 2000. pp. 345–486. PMC 7196975. PMID 11000977.
17. ^ Dobrydneva, Y.; Wilson, E.; Abelt, C. J.; Blackmore, P. F. (2009). "Phenolphthalein as a Prototype Drug for a Group of Structurally Related Calcium Channel Blockers in Human Platelets". Journal of Cardiovascular Pharmacology. 53 (3): 231–240. doi:10.1097/FJC.0b013e31819b5494. PMID 19247192. S2CID 21833487.
18. ^ "Phenolphthalein - Substance Information - ECHA". echa.europa.eu. Archived from the original on 2018-06-12. Retrieved 2017-11-06.
19. ^ a b Arney, Kat (2018-10-25). "Phenolphthalein". Chemistry World.
20. ^ May, Paul. "Phenolphthalein - Molecule of the Month - March 2022 (HTML version)". www.chm.bris.ac.uk.
21. ^ Baeyer, A. (1871). "Ueber eine neue Klasse von Farbstoffen". Berichte der Deutschen Chemischen Gesellschaft. 4 (2): 555–558. doi:10.1002/cber.18710040209. Archived from the original on 2021-02-14. Retrieved 2020-09-02.
22. ^ Baeyer, A. (1871). "Ueber die Phenolfarbstoffe". Berichte der Deutschen Chemischen Gesellschaft. 4 (2): 658–665. doi:10.1002/cber.18710040247. Archived from the original on 2021-10-11. Retrieved 2019-06-26.
23. ^ Baeyer, A. (1871). "Ueber die Phenolfarbstoffe". Polytechnisches Journal. 201 (89): 358–362. Archived from the original on 2021-10-11. Retrieved 2022-02-22.
24. ^ Max Hubacher, U.S. patent 2,192,485 (1940 to Ex Lax Inc)

External links

[edit] Wikimedia Commons has media related to Phenolphthalein.

• Page on different titration indicators, including phenolphthalein

v t e Drugs for constipation (laxatives and cathartics) (A06)
Stool softeners	Docusate
Stimulant laxatives	Bisacodyl Bisoxatin Cascara Castor oil Dantron Oxyphenisatine Phenolphthalein Senna glycosides Sodium picosulfate
Bulk-forming laxatives	Dietary fiber Ethulose Ispaghula Methylcellulose Polycarbophil calcium Sterculia Triticum Syrup of figs
Lubricant laxatives	Liquid paraffin Mineral oil
Osmotic laxatives	Lactitol Lactulose Laminarid Magnesium carbonate Magnesium citrate Magnesium hydroxide (milk of magnesia) Magnesium oxide Magnesium peroxide Magnesium sulfate Mannitol Pentaerythritol Polyethylene glycol (macrogol) Sodium phosphate Sodium sulfate Sodium tartrate Sorbitol
Enemas	Bisacodyl Dantron Glycerol Oil Sodium laurilsulfate Sodium lauryl sulfoacetate Sodium phosphate Sorbitol
Opioid antagonists	Naloxone (Oxycodone/naloxone) PAMORAs Alvimopan Axelopran Bevenopran Methylnaltrexone Naldemedine Naloxegol
Others	Linaclotide Lubiprostone Oxyphenisatine Plecanatide Prucalopride Tegaserod Tenapanor Ulimorelin

v t e Purine receptor modulators
Receptor(ligands)	P0 (adenine) Agonists: 8-Aminoadenine Adenine P1(adenosine) Agonists: 2-(1-Hexynyl)-N-methyladenosine 2-Cl-IB-MECA 2-Chloroadenosine 2'-MeCCPA 4'-O-β-D-Glucosyl-9-O-(6''-deoxysaccharosyl)olivil 5'-N-ethylcarboxamidoadenosine Adenosine ADP AMP Apadenoson ATL-146e ATP BAY 60–6583 Binodenoson Capadenoson CCPA CGS-21680 CP-532,903 CV-1808 Evodenoson GR 79236 HENECA LUF-5835 LUF-5845 N6-Cyclopentyladenosine Namodenoson NECA Neladenoson dalanate Piclidenoson Regadenoson SDZ WAG 994 Selodenoson Sonedenoson Tecadenoson Trabodenoson UK-432,097 Antagonists: 3-Chlorostyrylcaffeine (CSC) 7-Methylxanthine 8-Chlorotheophylline 8-Phenyl-1,3-dipropylxanthine 8-Phenyltheophylline Acefylline Aminophylline ATL-444 AZD-4635 Bamifylline Cafedrine Caffeine Caffeine citrate Cartazolate CGH-2466 CGS-15943 Choline theophyllinate Ciforadenant CPX CVT-6883 Dimethazan DMPX DPCPX Dyphylline Enprofylline Etazolate Etrumadenant Fenethylline IBMX Imaradenant Inupadenant ISAM-140 ISAM-R316 Isovaleric acid Istradefylline KF-26777 Lu AA41063 Lu AA47070 MRE3008F20 MRS-1191 MRS-1220 MRS-1334 MRS-1523 MRS-1706 MRS-1754 MRS-3777 MSX-2 MSX-3 MSX-4 Muvadenant Paraxanthine Pentoxifylline Preladenant Propentofylline Proxyphylline PSB-10 PSB-11 PSB-36 PSB-603 PSB-788 PSB-1115 PSB-1901 Reversine Rolofylline SCH-442,416 SCH-58261 Sipagladenant Taminadenant Theacrine Theobromine Theodrenaline Theophylline Tozadenant Tracazolate Vipadenant VUF-5574 ZM-241,385 P2(nucleotide) P2X(ATPTooltip Adenosine triphosphate) Agonists: 2-Me-SATP α,β-Me-ATP Adenosine ADP AMP Ap4A Ap5A ATP ATPγS BzATP Cibacron blue CTP D-β,γ-Me-ATP GTP HT-AMP Ivermectin L-β,γ-Me-ATP MRS-2219 PAPET-ATP UTP Zinc Antagonists: 5-BDBD A-317491 A-438079 A-740003 A-804598 A-839977 AF-353 AZ-10606120 AZ-11645373 BBG Calcium Calmidazolium Chelerythrine Copper Emodin (Rheum officinale) Evans blue Gefapixant GW-791343 HMA Ip5I isoPPADS JNJ-47965567 KN-04 KN-62 Magnesium MRS-2159 NF-023 NF-110 NF-157 NF-279 NF-449 Opiranserin (VVZ-149) Oxidized-ATP Phenol Red Phenolphthalein PPADS PPNDS PSB-12062 Puerarin (Radix puerariae) Purotoxin 1 RB-2 Ro 0437626 Ro 51 RO-3 Sodium ferulate (Angelica sinensis, Ligusticum wallichii) Suramin TC-P 262 Tetramethylpyrazine (ligustrazine) (Ligusticum wallichii) TNP-ATP Zinc P2Y Agonists: 2-Me-SADP 2-Me-SATP 2-Thio-UTP 5-Br-UDP 5-OMe-UDP α,β-Me-ATP Adenosine ADP ADPβS Ap3A AR-C 67085MX ATP ATPγS CTP dATP Denufosol Diquafosol IDP ITP INS-365 INS-37217 MRS-2365 MRS-2690 MRS-2693 MRS-2768 MRS-2957 MRS-4062 NF-546 PAPET-ATP PSB-0474 PSB-1114 UDP UDPβS UDP-galactose UDP-glucose UDP-N-acetylglucosamine Up3U UTP UTPγS Antagonists: 2-Me-SAMP A3P5PS AMPαS Ap4A AR-C 66096 AR-C 67085MX AR-C 69931MX AR-C 118925XX ATP BzATP C1330-7 Cangrelor Clopidogrel Elinogrel Ip5I MRS-2179 MRS-2211 MRS-2279 MRS-2395 MRS-2500 MRS-2578 NF-157 NF-340 PIT PPADS Prasugrel PSB-0739 RB-2 Regrelor Suramin Ticagrelor Ticlopidine UDP
Transporter(blockers)	CNTsTooltip Concentrative nucleoside transporters 6-Hydroxy-7-methoxyflavone Adenosine dMeThPmR Estradiol KGO-2142 KGO-2173 MeThPmR Phloridzin Progesterone ENTsTooltip Equilibrative nucleoside transporters Barbiturates Benzodiazepines Cilostazol Dilazep Dipyridamole Estradiol Ethanol Hexobendine NBMPR Pentoxifylline Progesterone Propentofylline PMATTooltip Plasma membrane monoamine transporter Decynium-22
Enzyme(inhibitors)	XOTooltip Xanthine oxidase Allopurinol Amflutizole Benzbromarone Caffeic acid Cinnamaldehyde Cinnamomum osmophloeum Febuxostat Myo-inositol Kaempferol Myricetin Niraxostat Oxipurinol Phytic acid Pistacia integerrima Propolis Quercetin Tisopurine Topiroxostat Others Aminopterin Azathioprine Methotrexate Mycophenolic acid Pemetrexed Pralatrexate Many others
Others	Precursors: Adenine Adenosine AMP ADP ATP Cytosine Cytidine CMP CDP CTP Guanine Guanosine GMP GDP GTP Hypoxanthine Inosine IMP IDP ITP Ribose Uracil Uridine UMP UDP UTP Others: Chrysophanol (rhubarb)
See also: Receptor/signaling modulators