596-27-0

Basic information

• Product Name: o-Cresolphthalein
• Synonyms: 3,3-bis(4-hydroxy-3-methylphenyl)-(3H)-Isobenzofuranone;3,3-bis(4-hydroxy-3-methylphenyl)-1(3h)-isobenzofuranon;3,3-Bis(4-hydroxy-3-methylphenyl)-1-(3H)-iso-benzofuranone;3,3-bis(4-hydroxy-3-methylphenyl)-1(3h)-isobenzofuranone;3’,3’’-dimethyl-phenolphthalei;cresolphthalein;Di-o-Cresolphthalide;o-Cresolphalein
• CAS NO: 596-27-0
• Molecular Formula: C₂₂H₁₈O₄
• Molecular Weight: 346.38
• EINECS: 209-881-8
• Product Categories: Analytical Chemistry;Indicator (pH);pH Indicators;CTitration;Indicators;pH Indicators - Solids;Stains and Dyes;Stains&Dyes, A to;Phthalein
• Mol File: 596-27-0.mol

Chemical Properties

• Melting Point: 223-225 °C
• Boiling Point: 401.12°C (rough estimate)
• Flash Point: 198.8 °C
• Appearance: Clear colorless/powder
• Density: 1.1425 (rough estimate)
• Vapor Pressure: 6.29E-13mmHg at 25°C
• Refractive Index: 1.4400 (estimate)
• Solubility: Solubility Slightly soluble in water; soluble in ethanol
• PKA: 9.40(at 25℃)
• Water Solubility: slightly soluble
• Merck: 14,2576
• BRN: 310554
• CAS DataBase Reference: o-Cresolphthalein(CAS DataBase Reference)
• NIST Chemistry Reference: o-Cresolphthalein(596-27-0)
• EPA Substance Registry System: o-Cresolphthalein(596-27-0)

Safety Data

• Hazard Codes: Xn
• Statements: 40-36/37/38-20/21/22
• Safety Statements: 36/37-36-26
• RIDADR: 1170
• WGK Germany: 3
• RTECS: SM8390000
• TSCA: Yes
• Hazardous Substances Data: 596-27-0(Hazardous Substances Data)

Usage

Uses

Used in Analytical Chemistry:
o-Cresolphthalein is used as an analytical reagent, particularly as a pH indicator. It changes color from colorless to red within the pH range of 8.2 to 9.8, making it a valuable tool for monitoring the acidity or alkalinity of solutions in laboratories.
Used in Calcification Assays:
In the field of biological research, o-Cresolphthalein has been utilized as a component in calcifying media for calcification assays. This application aids in the study of mineralization processes and the formation of calcium-containing structures in biological systems.
Used in Industrial Processes:
Although not explicitly mentioned in the provided materials, o-Cresolphthalein may also find use in various industrial processes where its color-changing properties can be employed for quality control, monitoring chemical reactions, or indicating the completion of certain processes.

Biochem/physiol Actions

o-Cresolphthalein is a reversible pH indicator. The kinetics of the reverse pathway (red-purple to colorless) is slow, thereby making it an appropriate molecule to check flow patterns in ducts with corrugated walls. It is also used for the colorimetric determination of calcium content via the o-cresolphthalein complexone method. Binding of calcium to o-cresolphthalein, in the presence of alkaline conditions (pH 10-12), results in the formation of a red complex with an absorbance at 570-575nm.

InChI:InChI=1/C22H18O4/c1-13-11-15(7-9-19(13)23)22(16-8-10-20(24)14(2)12-16)18-6-4-3-5-17(18)21(25)26-22/h3-12,23-24H,1-2H3

Synthetic route

phthalic anhydride (85-44-9) + ortho-cresol (95-48-7) → o-cresolphthalein (596-27-0)

Conditions	Yield
With methanesulfonic acid at 90℃; for 5h;	92%
With tin(IV) chloride at 120 - 125℃;
With zinc(II) chloride at 125℃;
With sulfuric acid at 120℃;
With methanesulfonic acid at 100℃; for 20h; Product distribution / selectivity;

phthalic anhydride (85-44-9) + ortho-cresol (95-48-7) + phenol (108-95-2) → phenolphthalein (77-09-8) + [3-(3'-methyl-4'-hydroxyphenyl)-3-(4''-hydroxyphenyl)phthalide] (854-76-2) + o-cresolphthalein (596-27-0)

Conditions	Yield
Stage #1: ortho-cresol; phenol With zinc(II) chloride In nitrobenzene at 50 - 60℃; Stage #2: phthalic anhydride With zinc(II) chloride In nitrobenzene at 120 - 130℃; for 4h; Overall yield = 34 %; Overall yield = 5.9 g;

o-cresolphthalein (596-27-0) + aniline (62-53-3) → 2-phenyl-3,3-bis(4-hydroxy-3-methylphenyl)phthalimidine (1315322-06-5)

Conditions	Yield
With hydrogenchloride In water at 155 - 165℃; for 20h;	95%

o-cresolphthalein (596-27-0) + iminodiacetic acid (142-73-4) → ortho-cresolphthalein (2411-89-4)

Conditions	Yield
With sodium hydroxide; formaldehyd

o-cresolphthalein (596-27-0) → 4,4'-dihydroxy-3,3'-dimethyl-benzophenone (94323-02-1)

Conditions	Yield
With potassium hydroxide at 260 - 265℃;

phthalic anhydride (85-44-9) + sulfuric acid (7664-93-9) + o-cresolphthalein (596-27-0) → 3-hydroxy-2-methylanthraquinone (17241-40-6)

o-cresolphthalein (596-27-0) + zinc dust + alkali → 2-(4,4'-dihydroxy-3,3'-dimethyl-benzhydryl)-benzoic acid (602-49-3)

o-cresolphthalein (596-27-0) + alkali + hydroxylamine hydrochloride → 2-oxy-3.3-bis-<4-oxy-3-methyl-phenyl>-phthalimidyne

1-methyl-4-nitrosobenzene (623-11-0) + o-cresolphthalein (596-27-0) + aqueous toluene-4-diazonium-chloride → 2-(3-methyl-4-hydroxybenzoyl)benzoic acid (51671-72-8) + 2-Methyl-4,6-bis-p-tolylazo-phenol + 3-(4-hydroxy-3-methyl-phenyl)-3-(4-hydroxy-3-methyl-5-p-tolylazo-phenyl)-phthalide

ethanol (64-17-5) + o-cresolphthalein (596-27-0) + mercury(II) diacetate (1600-27-7) + acetic acid (64-19-7) → 5'.5''(?)-bis-acetoxymercuri-3'.3''-dimethyl-phenolphthalein

ethanol (64-17-5) + o-cresolphthalein (596-27-0) + bromine (7726-95-6) + acetic acid (64-19-7) → 5'-bromo-4'-oxy-3'-methyl-benzophenone-carboxylic acid-(2)

ethanol (64-17-5) + o-cresolphthalein (596-27-0) + bromine (7726-95-6) → dibromo-o-cresolphthalein

sulfuric acid (7664-93-9) + o-cresolphthalein (596-27-0) + nitric acid (7697-37-2) → dinitro-o-cresolphthalein

diethyl ether (60-29-7) + o-cresolphthalein (596-27-0) + cis-nitrous acid (7782-77-6) → dinitro-o-cresolphthalein

o-cresolphthalein (596-27-0) → 4-hydroxy-4'-methoxy-3,3'-dimethyl-benzophenone (79002-05-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: KOH / 260 - 265 °C 2: methanol. sodium methylate View Scheme

o-cresolphthalein (596-27-0) → 4,4'-dimethoxy-3,3'-dimethylbenzophenone (116413-55-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: KOH / 260 - 265 °C 2: methanol. sodium methylate View Scheme

o-cresolphthalein (596-27-0) → 4,4'-dimethoxy-3,3'-dimethyl-benzophenone oxime (855287-64-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: KOH / 260 - 265 °C 2: methanol. sodium methylate View Scheme

o-cresolphthalein (596-27-0) → 4,4'-diacetoxy-3,3'-dimethyl-benzophenone (136338-48-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: KOH / 260 - 265 °C 2: acetic acid; sulfuric acid View Scheme

butanoic acid anhydride (106-31-0) + o-cresolphthalein (596-27-0) → o-cresophtalein dibutyl ester

Conditions	Yield
methanesulfonic acid In xylene Heating / reflux;

o-cresolphthalein (596-27-0) + aniline (62-53-3) → 2-phenyl-3,3-bis(4-cyanato-3-methylphenyl)phthalimidine (1315322-07-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: hydrogenchloride / water / 20 h / 155 - 165 °C 2.1: triethylamine / dichloromethane / 20 °C / cooling in an ice bath 2.2: 0 °C View Scheme

Upstream product

• 85-44-9 phthalic anhydride 
• 95-48-7 ortho-cresol 
• 108-95-2 phenol 

Downstream Products

• 2411-89-4 ortho-cresolphthalein 
• 94323-02-1 4,4'-dihydroxy-3,3'-dimethyl-benzophenone 
• 17241-40-6 3-hydroxy-2-methylanthraquinone 
• 602-49-3 2-(4,4'-dihydroxy-3,3'-dimethyl-benzhydryl)-benzoic acid 
• 51671-72-8 2-(3-methyl-4-hydroxybenzoyl)benzoic acid 
• 79002-05-4 4-hydroxy-4'-methoxy-3,3'-dimethyl-benzophenone 
• 116413-55-9 4,4'-dimethoxy-3,3'-dimethylbenzophenone 
• 855287-64-8 4,4'-dimethoxy-3,3'-dimethyl-benzophenone oxime 
• 136338-48-2 4,4'-diacetoxy-3,3'-dimethyl-benzophenone 
• 1315322-06-5 2-phenyl-3,3-bis(4-hydroxy-3-methylphenyl)phthalimidine 
• 1315322-07-6 2-phenyl-3,3-bis(4-cyanato-3-methylphenyl)phthalimidine 

Relevant articles and documents

New chemical markers based on phthaleins

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.

A facile synthesis of phthalein indicator dyes

The use of methanesulfonic acid offers a novel and highly efficient method for the synthesis of phthalein indicator dyes in excellent yields on an industrial scale.

AROMATIC ESTERS FOR MARKING OR TAGGING ORGANIC PRODUCTS

A compound represented by formula I is used as a marker for organic products. wherein Ar1 and Ar2 each independently represent a substituted or unsubstituted phenylene group or a substituted or unsubstituted naphthylene group; R1 represents a straight or branched chain alkyl group having 1 to 22 carbon atoms; R2 represents a hydrogen atom or a group of the formula C(O)R4 where R4 is a hydrogen atom or a straight or branched chain alkyl group having 1 to 22 carbon atoms; and R3 represents a hydrogen atom, a straight or branched chain alkyl group having 1 to 12 carbon atoms, a straight or branched chain alkoxy group having 1 to 12 carbon atoms, a hydroxyl group, or a substituted or unsubstituted phenyl group or a substituted or unsubstituted naphthyl group; and Z represents a hydrogen atom or a group of atoms that combine with Ar2 or R3 to form a lactone ring.