77-09-8 Usage
Uses
Used in Chemistry Laboratories:
Phenolphthalein is used as an acid-base indicator for acidimetric titrations, as it changes color in response to pH variations, helping to identify the endpoint of a titration process.
Used in Pharmaceutical Industry:
Phenolphthalein was previously used as a laxative due to its ability to stimulate the intestinal mucosa and constrict smooth muscles. However, its use as a laxative has been discontinued due to concerns regarding its potential carcinogenicity.
Used in Research:
Phenolphthalein can be used as an inhibitor and pH indicator in various research applications, such as studying the effects of different substances on cellular processes. It has also been shown to induce centrosome amplification and tubulin depolymerization in vitro, which can be useful in understanding the mechanisms of cell division and other biological processes.
acid–base indicator
Phenolphthalein is another weak organic acid. It is not particularly water soluble, so we generally dissolve it in aqueous ethanol. The ethanol explains the pleasant, sweet smell of phenolphthalein solutions.
Phenolphthalein is colourless and clear in acidic solutions, but imparts an intense puce pink colour in alkaline solutions of higher pH, with λ(max) = 552 nm. The coloured form of phenolphthalein contains a quinone moiety; in fact, any chromophore based on a quinone has a red colour. But if a solution is prepared at pH 7 (e.g. as determined with a pH meter), we find the phenolphthalein indicator is still colourless, and the pink colour only appears when the pH reaches 8.2. Therefore, we have a problem: the indicator has not detected neutrality, since it changes colour at too high a value of pH. in fact, only a tiny incremental addition of alkali solution is needed to substantially increase the solution pH by several pH units. In other words, a fraction of a drop of alkali solution is the only difference between pH 7 (at the true volume at neutralization) and pH 8 when the phenolphthalein changes from colourless to puce pink.
Figure 1 lists the pH changes for a series of common pH indicators. The colour changes occur over a wide range of pHs, the exact value depending on the indicator chosen. Methyl violet changes from yellow to blue as the pH increases between 0 and 1.6. At the opposite extreme, phenolphthalein responds to pH changes in the range 8.2 to 10.
Phenolphthalein molecular structure
This product can be obtained by mixing phthalic anhydride with phenol, followed by co-heating with sulfuric acid.
Phenolphthalein has its chemical name be 2- [bis- (4-hydroxyphenyl) methyl] benzoic acid. Molecular formula: C20H16O4, relative molecular mass: 318.33. The structural formula is shown in Figure 1 (in fact, it is often existed in the form of colorless lactone, see Figure 2). It appears as triclinic white to yellowish crystalline powder with the melting point of 237 ~ 259 ℃ and the relative density of 1.277 (20/4 ℃). It is easily soluble in ethanol, ether and other organic solvents, slightly soluble in water. It has a weak acidity and is almost completely presented in the molecule state even in very dilute solution. It is soluble in alkaline solution, exhibiting red color in alkaline solution, but is colorless in acidic solution. The three benzene rings in the phenolphthalein molecule are linked to the carbon atoms of a sp3 hybrid center, and there is no conjugate relationship between the benzene rings, being colorless. After coming across alkali, the lactone ring open and generate disodium salt, the central carbon atoms are transferred into the sp2 hybrid state, containing benzoquinone structure. At this time, it forms conjugated system with the three benzene rings which are red; but in excess of alkali, but it is further converted to sp3 hybrid state so that the conjugate system disappears, the color also will recede.
Phenolphthalein indicator
Phenolphthalein indicator is a commonly used acid/alkali titration indicator in analytic chemistry. Phenolphthalein, in alkaline solution, has its colorless lactone ring open to form quinone structure with the color exhibiting red. Upon coming across strong alkali, phenolphthalein can be converted into colorless carboxylate. Its color range is pH 7.0 (colorless) ~ 10.0 (red). The test solution was prepared by dissolving 1 g of 90% ethanol per liter of ethanol.
Phenolphthalein is colorless in the solution of pH below 8.5, become red at pH higher than 9. Upon excess amount of alkali and no color, the color process is as follows:
Phenolphthalein, when used as acid-alkali titration indicator, is generally used at a concentration of 1% concentration. 1 g of phenolphthalein was dissolved in 100 ml of 80% alcohol; slowly drop 0.1 mol / l sodium hydroxide to reddish (for neutralizing the small amount of acid potentially existing in alcohol). The pH range of discoloration is 8.2 to 10. It is colorless upon PH <8.2, is red upon pH> 10. The principle of color change is mainly due to that under different acid and alkali conditions, the structure of the molecule itself changes and further causes different colors. Mixing the phenolphthalein and other indicators can formulate the widely used indicator (also known as a general indicator).
Mix 1.3 grams of phenolphthalein, 0.9 grams of bromo-thymol blue, 0.4 grams of methyl red and 0.2 grams of thymol blue and dissolve in 1 liter 70% to 80% alcohol. After completely dissolving, then add some 0.1 mol / l sodium hydroxide makes it become just green before application. The advantage is that the color change with the pH changes is remarkable: red for pH = 4; orange for pH 5; yellow for pH 6, green for pH 7; cyan for pH 8; blue for pH 9; and purple for pH 10.
Different broad indicator can be formulated as needed. Phenolphthalein indicator is not only used in laboratories, but also widely used in industrial and agricultural production. In addition to being used in the pH control of the reaction and acid/alkali titration analysis during the manufacturing of chemical products, it is also used for determining the pH of the weaving in the printing and dyeing industry. This is very important for printing and dyeing processing. For example, if the mercerized cloth contains residual alkali that has not been washed, the dyeing will have no shine. However, the phenolphthalein indicator alone can only determine whether the texture of the weave is acidic or alkaline and its pH range, and can’t further determine its specific pH. The wide range of indicators used above can be clearly reflected of the acid and alkali strength in the cloth. Phenolphthalein, in medicine can also be used as laxative, because it can stimulate the peristalsis of the intestinal to promote defecation. However, it can occasionally cause allergic reactions such as dermatitis, thus should be used with attention.
Phenolphthalein test paper
Phenolphthalein test paper is one of the simple test papers commonly used in chemical analysis. It’s highly targeted. Its turns red in case of alkali, and is colorless in acid and neutral solution. To test the presence of ammonia in the air, it will be appears light red. The preparation method is simple: the filter paper is immersed in phenolphthalein solution and taken out for drying after full absorption.
Pharmacology and Toxicology
Phenolphthalein can be used for the treatment of habitual refractory constipation, mainly acting on the colon. After oral administration, it can be subject to slowly decomposition under the effect of the small intestinal alkaline fluid to form soluble sodium salt, thereby stimulating the plexus inside the intestinal wall. It directly acts on the intestinal smooth muscle and increase peristalsis, while also inhibiting the absorption of water within the intestine, so that water and electrolyte accumulates in the colon, resulting in laxative effect. It has mild effect and rarely causes intestinal cramps.
Pharmacokinetics
About 15% is absorbed after oral administration. The absorbed drugs mainly exist in the form of glucuronide to be excreted from urine or the feces, some can also be excreted to the intestine through the bile, reabsorbed in the intestine, to form intestinal - liver circulation and prolong the role time. At 4 to 8 hours after the drug administration, the patients will discharge soft stool. The excretion time for drug administration once needs 3 to 4 days. This product can also be secreted from milk.
Adverse reactions
Phenolphthalein mainly takes effect in the large intestine, leading to the formation of little amount of semi-liquid feces in 4 to 8 hours without colic. The claim regarding that the yellow phenolphthalein is three times stronger than the white version has not been proven. As a result of enterohepatic circulation, the effect of a single dose can last 3 to 4 days. This drug is an active member in a lot of laxative preparations that can be legally sold without a doctor's prescription.
Severe adverse effects are rare but can occur in excess amount. For the elderly, phenolphthalein should be hanged, because its lasting effect can cause serious depletion of water and electrolytes. In allergic patients, it can cause occur dermatitis (fixed rash, itching, burning sensation, blistering, and residual pigmentation). There are reports of fatal allergic reactions, but have not yet determined to be related with phenolphthalein. There are occasional reports of non-thrombocytopenic purpura and the occurrence of dehydration and electrolyte imbalance caused excessive diarrhea after long-term application. Phenolphthalein makes alkaline urine or feces turn pink.
Production method
It is derived from the condensation of phthalic anhydride and phenol.
World Health Organization (WHO)
Phenolphthalein has been widely used as a laxative since its
cathartic activity was first described in 1902. Because it undergoes enterohepatic
circulation it is eliminated slowly and it has been associated with adverse effects,
notably skin reactions, potassium loss and atonia. This has led to the withdrawal
of phenolphthalein from pharmaceutical preparations in several countries.
Elsewhere, it remains available, often in over-the-counter preparations.
Safety Profile
Confirmed carcinogen. US Food and Drug Administration recommends removal from laxative formulations. Moderately toxic by intraperitoneal route. Human systemic effects: changes in urine composition, gastritis, nausea or vomiting. Used in medicine as a laxative; in chemistry as an indicator. When heated to decomposition it emits acrid smoke and irritating fumes
Carcinogenicity
Phenolphthalein is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals.
Purification Methods
Dissolve it in EtOH (7mL/g), then dilute it with eight volumes of cold water, filter and heat on a water-bath to remove most of the alcohol and the phenolphthalein that precipitates is filtered off and dried in vacuo.[Beilstein 18 II 119, 18 III/1V 1945, 18/4 V 188.]
Check Digit Verification of cas no
The CAS Registry Mumber 77-09-8 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 7 and 7 respectively; the second part has 2 digits, 0 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 77-09:
(4*7)+(3*7)+(2*0)+(1*9)=58
58 % 10 = 8
So 77-09-8 is a valid CAS Registry Number.
InChI:InChI=1/C20H16O4/c21-15-9-5-13(6-10-15)19(14-7-11-16(22)12-8-14)17-3-1-2-4-18(17)20(23)24/h1-12,19,21-22H,(H,23,24)
77-09-8Relevant articles and documents
Synthesis and evaluation of intrinsic bioactivity of fluorescein and phenolphthalein derivatives
Bharathkumar, Kuruba,Durairaj, Arulappan,Mohanapriya, Raman,Obadiah, Asir,Ramanathan, Subramanian,Santhoshkumar, Palanichamy,Vasanthkumar, Samuel
, (2021/09/28)
Fluorescein and phenolphthalein derivatives have been synthesized and screened for their bioactivity via molecular docking, cytotoxicity and antioxidant studies. In molecular docking studies, the compounds 3d have exhibited better glide score and hydrogen bonding ability when docked with t-RNA Dimethylallyltransferase. Antioxidant capabilities were evaluated via DPPH and ABTS radical scavenging activity. In this screening, compound 3d exhibited better inhibition efficiency in the DPPH and ABTS methods. Cytotoxicity of the compounds was assessed by the cell sustainability assay against human cervical cancer cell line (HeLa). All the synthesized compounds exhibited cytotoxic effects against HeLa cells and compounds 3d displayed better activity (IC50) than the standard drug (doxorubicin).
NbCl5 Promoted the Efficient Synthesis of Phthalein Derivatives: Optical Characterization and Solvatochromic Effect
Moreno, Vitor Fernandes,dos Santos, Giovanny Carvalho,da Costa, Gyordanna Mayara Gaspar,Gomes, Marcelo Henrique Ayala,Silva-Filho, Luiz Carlos da
supporting information, p. 2811 - 2821 (2019/08/26)
Organic dyes derived from phthaleins have a large number of industrial applications and can be synthesized using a Lewis acid by Friedel–Crafts acylation, followed by an addition reaction to the carbonyl compound. This work aims to investigate the use of NbCl5 as a catalyst for the acylation reaction. The behavior of the phthalein derivatives in several solvents and when subjected to different pH conditions was studied. These compounds showed a color-changing effect depending on the pH and solvent, making them useful for applications as indicators. The phthaleins change their conformations depending on the condition of the medium. Photophysical studies of these compounds were carried out through their UV–Vis absorption spectra. Here, we show the umbrella-like conformation change of phthalein derivatives that depend on the solvent and the pH of the medium.
CONTINUOUS METHODS OF MANUFACTURE OF 2-ARYL-3,3-BIS(4-HYDROXYARYL)PHTHALIMIDINES, AND POLYMERS DERIVED THEREFROM
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Paragraph 0064, (2018/03/25)
A continuous method for the manufacture of a 2-aryl-3,3-bis(hydroxyaryl)phthalimidine comprising continuously heating an anhydride with a phenol in the presence of a catalyst and a first co-catalyst, to form a first reaction mixture comprising a phenolphthalein compound; precipitating the phenolphthalein compound; combining a primary arylamine with an acid catalyst and a second co-catalyst to form a second reaction mixture; adding the phenolphthalein compound to the second reaction mixture; continuously heating the second reaction mixture to provide a third reaction mixture comprising a crude phthalimidine; and treating the crude phthalimidine to remove aminophenol and purify the phthalimidine is provided.
Use of metal-accumulating plants for implementing chemical reactions
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Page/Page column 41, (2015/10/28)
The use of metal-accumulating plants for implementing chemical reactions.
USE OF COMPOSITIONS OBTAINED BY CALCINING PARTICULAR METAL-ACCUMULATING PLANTS FOR IMPLEMENTING CATALYTICAL REACTIONS
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Paragraph 0717-0721, (2016/01/25)
The use of metal-accumulating plants for implementing chemical reactions especially catalytical reactions.
New chemical markers based on phthaleins
Nekhoroshev,Nekhoroshev,Poleshchuk,Yarkova,Nekhorosheva,Gasparyan
, p. 711 - 718 (2015/08/03)
New chemical markers based on mixtures of individual phthaleins were developed. These markers are characterized by high level of secrecy in use, good transferability to contacting persons, enhanced retention on the objects marked, and reliable identification of phthaleins by expert investigation. The experimental studies of the markers obtained show that the synthesized mixture of three phthalein homologs contains the previously unknown phthalein with unsymmetrical phenolic substituents, o-cresolphenolphthalein [3-(3′-methyl-4′-hydroxyphenyl)-3-(4?-hydroxyphenyl)phthalide], which decreases the probability of the marker falsification. Quantum-chemical calculations of the reaction of the o-cresolphthalein synthesis show that the overall reaction is characterized by small positive changes in the enthalpy and Gibbs free energy, and the second and third steps occur with negative changes in the Gibbs energy. The optimum structure of the transition state was calculated.
Use of compositions obtained by calcing particular metal-accumulating plants for implementing catalytical reactions
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Page/Page column, (2014/09/03)
The invention relates to the use of compositions derived from metal-accumulating plants, wherein the metals are more particularly zinc, nickel and copper, for implementing chemical reactions especially catalytical reactions, a method for the preparation of specific Ni-containing composition, and said Ni-containing composition.
Design and performance of supported Lewis acid catalysts derived from metal contaminated biomass for Friedel-Crafts alkylation and acylation
Losfeld, Guillaume,Escande, Vincent,Vidal De La Blache, Paul,L'Huillier, Laurent,Grison, Claude
scheme or table, p. 111 - 116 (2012/09/08)
The main goal of this work was to prove the interest of metal hyperaccumulator plants in supported Lewis acid catalysis. Friedel-Crafts alkylation and acylation reveal the great catalytic activity of different plant extracts. This approach is a green solution with chemical benefits including high yield, excellent regioselectivity, small amounts of catalyst, mild conditions and concrete perspectives towards the depletion of mineral resources. The results also constitute an incentive for the development of phytoextraction programs on metal-bearing soils.
Ferric hydrogensulphate as a recyclable catalyst for the synthesis of fluorescein derivatives
Eshghi, Hossein,Mirzaie, Narges
experimental part, p. 504 - 509 (2012/07/13)
Polycondensation reactions of phenols with phthalic anhydride were carried out in the presence of ferric hydrogensulphate under melt conditions. The reactions proceeded in short reaction times by using a catalytic amount of Fe(HSO4)3 and the corresponding fluorescein derivatives were obtained in high yields. The simplicity, scale-up, along with the use of an inexpensive, non-toxic, recyclable catalyst of an environmentally benign nature, are other remarkable features of the procedure. The absorption and emission properties of these fluorescein derivatives were studied.
Identification of the catalytic residues of carboxylesterase from arthrobacter globiformis by diisopropyl fluorophosphate-labeling and site-directed mutagenesis
Nishizawa, Masako,Yabusaki, Yoshiyasu,Kanaoka, Masaharu
experimental part, p. 89 - 94 (2011/09/30)
The role of amino acid residues in the enzymatic activity of carboxylesterase from Arthrobacter globiformis was analyzed by diisopropyl fluorophosphate (DFP) labeling and site-directed mutagenesis. The electrospray ionization mass spectrometric (ESI-MS) analysis of the esterase, covalently labeled by DFP, showed stoichiometric incorporation of the inhibitor into the enzyme. The further comparison of endopeptidase-digested fragments between native and DFP-labeled esterase by fast atom bombardment mass spectrometric (FAB-MS) analysis as well as site-directed mutagenesis indicated that Ser59 in the consensus sequence Ser-X-X-Lys, which is conserved exclusively in penicillin-binding proteins and some esterases, served as a catalytic nucleophile. In addition, the results obtained from analysis of the mutants at position 62 suggested the importance of the basic amino acid side chain at this position, and suggested the significance of this residue acting directly as a general base rather than its involvement in the maintenance of the optimum hydrogenbonding network at the active site.
