Phthalein reaction

NOTE. It is not expected that a student xvill attempt to memorise all the colour tests given in Part III. He might for example be expected to know the Phthalein Reaction for phenol itself (p. 339). Details of the divergence from the standard result are recorded primarily for reference, so that a student will not be diverted from his line of investigation if he observes that a suspected phenol does not respond exactly to the standard colour changes. 

Phthalein reaction. Place in a dry test-tube about 0 2 g. of the phenol and an equal quantity of phthalic anhydride (or acid), moisten with 2 drops (not more) of cone. H2SO4 and gently fuse together for about 1 minute. Allow to cool somewhat, and then add 10% NaOH solution in excess. 

Phthalein reaction. Fuse together carefully in a dry test-tube a few crystals of phthalic acid or of a phthalate and an equal quantity of ph tol moistened with 2 drops of cone. H2SO4. Cool, dissolve in water and add NaOH solution in excess the bright red colour of phenolphthalein in alkaline solution is produced. 

Phthalimide 233 Ill (i) Hot aniline gives phthal-anil, 205. (ii) Gives the fluorescein and phthalein reactions. (Pages 54, 55.) (iii) Phthalimidomethyl derivative, 144. ... 

Special reactions — — — Fluores- cein Iodoform (KI + NaClO) FeSO, + H.O, + NaOH violet — — — (a) Fluores- cein W Phthalein —... 

Irreversible reaction of [18] iodine with acetylsalicylic acid, aethaverine, amidopyrine, ascorbic acid, benzo-caine, quinine, dihydrocodeine, fluorescein, glycine, hydrocortisone acetate, isoni-azid, metamizole, papaverine, paracetamol, phenacetin, phenol-phthalein, piperazine, resorcinol, salicylic acid, salicylamide, sulfaguanidine, thymol, triethanolamine, tris buffer detection by reaction chromatography... 

The reaction of phthalyl chloride with benzene, leading to phthalo-phenone, the parent substance of the phthaleins ... 

The process is reversible and therefore provides an easily visible method for measuring pH change in the range of 8.5-9.0. The ionisation reactions of sulfophthaleins follow a similar pathway. Substitution in the phenolic rings of the phthaleins and sulfophthaleins provides a variety of coloured dianions, which change colour over different ranges of pH (see section 1.4.2.1). 

Completion of the run, after 30-40 hours, is indicated when a few drops of the solution show an alkaline reaction to phenol-phthalein. No harm is done if the electrolysis is carried a few hours beyond this point however, after excessively long periods, formation of polymeric material lowers the yield and renders purification of the product rather troublesome. 

Reactions are quenched by the addition of ethanol, which not only attenuates enzyme action but also facilitates solubilization of the fatty acids during subsequent titration to yield sodium salts (the presence of Ca2+ or Mg2+ can interfere in the assay by forming fatty acid soaps recalcitrant to titration). One will note a clearing of the titration vessel as titration progresses, even though the ethanol-quenched subsample may initially be turbid because of insoluble fatty acids. The choice of a thymol-phthalein end-point (pH 9.3 to 10.5) indicator is essential to ensure the complete titration of all fatty acids, in view of the relative high pKa values for oleic acid noted earlier. 

Reaction IV. (a) Action of Dehydrating Agents on a Mixture of an Aromatic Hydrocarbon and an Aromatic Alcohol. (B., 6, 964.)—This reaction, which was discovered by Baeyer, gains importance from its similarity to the methods used in preparing such substances as phenol-phthalein and fluorescein (see pp. 107, 385). 

Reaction XXIX. (a) Condensation of a Phenol with Phthalic Anhydride to form a Phthalein. (A., 183, 1 202, 68.)—The phthaleins result from the condensation of phthalic anhydride (1 mol.) with phenols (2 mols.) on heating with dehydrating agents—sulphuric acid, fused zinc chloride (to 120°) or anhydrous oxalic acid (to 115°). These compounds are particularly important some are dyes of great technical value. The simplest representative of the class is phenolphthalein. 

Reaction XXIX. (b) Condensation of a Phenol with Phthalic Anhydride to a derivative of Anthraquinone. (A., 212, 10.)—When equimole-cular quantities of phthalic anhydride and a phenol react at 180° in the presence of cone, sulphuric acid, the product is not a phthalein, but the action takes a different course, and a derivative of anthraquinone is obtained. 

M. D. Alexander, "Reactions of the Alkali Metals with Water A Novel Demonstration/ J. Chem. Educ., Vol. 69,1992,418. The reaction of sodium metal with water to produce an aqueous solution of sodium hydroxide and hydrogen gas is performed at the interface between paint thinner and the more dense water. Periodically, bubbles of hydrogen gas carry the sodium metal into the organic layer, temporarily stopping the reaction. The presence of the aqueous layer is shown by a phenol-phthalein indicator color change. 

Solubility in water. Determine the solubility of 1.0 g of the sample in water. If in doubt as to whether a portion of the mixture dissolves, remove the supernatant liquid with a dropper and evaporate to dryness on a water bath. Determine the reaction of the aqueous solution or suspension to litmus and to phenol-phthalein. 

Seventy grams (1.0 mol) of dry finely powdered hydroxyl-amine hydrochloride and 0.01 to 0.02 g. of solid phenol-phthalein are placed in the flask. One hundred milliliters of butyl alcohol is added and after 10 minutes of preliminary stirring, the butoxide solution is introduced at such a rate that the pink color of the indicator never predominates. After about 2.5 hours, the end point of the reaction is just exceeded. To discharge the pink color, a small quantity of hydroxylamine hydrochloride is introduced in the flask, and stirring is continued until the solution becomes colorless. 

The procedure usually is unsuitable for tertiary alcohols since the reaction with phthalic anhydride or succinic anhydride either fails or results in dehydration of the alcohol. A few tertiary alkyl phthalates, however, have been prepared and resolved by first converting the alcohols to sodium or potassium salts and allowing these to react79 80 with phthalic anhydride. This modification has been applied successfully to dUa- and /S-santalols81 and cB-linalool.81 As already mentioned, glycols cannot be resolved by this procedure because they form polymeric esters when heated with phthalic or succinic anhydride. Phenols also usually form phthaleins or other condensation products instead of simple acid esters. 

Phthalein type dyes have been prepared from 2,3-dicarboxypyrazine by heating with phenols or aromatic amines and zinc chloride. For example, compound (25) was obtained with resorcinol (1353). Efforts to prepare 2,6-diaminopyrazine through a Curtius-Schmidt reaction on 2-acetamido-6-carboxypyrazine (with sodium azide, sulfuric acid, and trichloroacetic acid) proved unsuccessful (434). The preparation of bicyclic heterocyles from 2-amino-3-carboxypyrazines has been described in Section VIII. 1D(6). 

Now when phthalophenone is hydrolyzed with alkalies it yields mono-carboxy tri-phenyl carbinol which on reduction yields mono-carbozy tri-phenyl methane and this by loss of carbon dioxide yields tri-phenyl methane. This means that phthalophenone is a lactone inner anhydride of mono-carboxy tri-phenyl carbinol and a true tri-phenyl methane derivative as shown in the reactions below. Now, also, phthalophenone by nitrating yields a di-nitro compound which by reduction yields a di-amino derivative and this by the diazo reaction has the two amino groups replaced by hydroxyls. The result is phenol phthalein, which is therefore also a lactone inner anhydride of mono-carboxy di-hydroxy tri-phenyl carbinol. All of these relationships may be represented by the following ... 

In a related phthalein dye, however, this condition is fully met. The dye fluorescein is resorcinol phthalein and is made from phthalic anhydride or phthalyl chloride and resorcinol just as phenol phthalein is made from phthalic anhydride and phenol (p. 750). These relationships may be expressed as follows writing the final dye salt both as a tri-phenyl methane derivative (B) and as a pyronine (C). The reactions are exactly analogous to those given for the preparation of phenolphthalein and its dye salt (p. 750), some of the intermediate steps being omitted in the present case. 

E) Preparation of Thymolphthalein. Prepare the reaction mixture, following the same procedure as in section (D). Use 6 g of th3unol, 3.7 g of phthalic anhydride, and 3-4 g of zinc chloride. Heat for 8 hours at 105-110°. Cool, and add 20 ml of a mixtme of equal parts of ether and benzene. Provide the tube with a micro condenser, and reflux in the water bath for fifteen minutes to dissolve the unreacted th3unol. Cool, and decant the solvent. Add 30 ml of methanol, heat to dissolve the phthalein, and pour the hot extract into a beaker. Repeat the extraction with 10-15 ml of alcohol. The residue consists of zinc chloride. Save it for future reference, if the yield of the phthalein is low. Add to the alcohohc extract water in small amounts until precipitation begins, and then cool. After an hour filter the crystals of thymolphthalein. If the product is colored, dissolve in the minimum amount of hot alcohol and precipitate by slow addition of water. 

On treating with energetic dehydrating agents, most phthaleins are converted into anthraquinone derivatives, one molecule of phenol being split off during the reaction [63]. 

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