Phenolphthalein

“ Fig. 98.—a, Sample of filtered meat extract or nutrient gelatine to which phenolphthalein has been added. The medium is acid, as evidenced by the unaltered colour of the sample. b, The same neutralised by the addition of n/10 NaOH. The production of this faint rose-pink colour indicates that the "end-point," or neutral point to phenolphthalein, has been reached. If such a sample is cooled down to say 30° or 20° C., the colour will be found to become more distinct and decidedly deeper and brighter, resembling that shown in c. c, Also if, after the end-point is reached, a further 0.5 c.c. ”

“ Phenolphthalein, on the other hand, should be, as it is, the best of the common indicators for use with weak acids. For, since it is itself a weak acid, it is very little dissociated, and its nearly undissociated, colorless molecules are promptly formed as soon as there is any free acid (that is, free H^{+} ions) in the solution. This indicator cannot, however, be successfully used with weak bases, even ammonium hydroxide; for, since it is weak acid, the salts which it forms with weak alkalies are easily hydrolyzed, and as a consequence of this hydrolysis the change of color is not sharp. ”

“ The drug also has a definite market value and the pure substance in the form of powder, tablets or pills could not be sold at a price greatly in excess of the market value. Thus manufacturers, from business policy, add to it other drugs. There are now on the market numerous more or less secret and “fancy” preparations of phenolphthalein for which a price is charged out of all proportion to the value of the preparation. ”

“ Therefore this number increases with the dilution, and the larger the figure after the PH, the less acid the solution is.
Most saprophytic organisms and many parasitic ones grow within a wide range of H ion concentration so that titration with phenolphthalein gives sufficient accuracy for media for such organisms. On the other hand, many organisms grow within a very narrow range of H ion concentration, hence accurate standardization to a definite H ion concentration is necessary. ”

“ The liquid is then filtered into a large flask, the residue on the filter is well washed with water, the filtrate quite cooled, phenolphthalein is added and the fluid exactly neutralised with a dilute (2 to 3 per cent.) solution of alkali. Twenty-five c.c. of a 10 per cent. caustic soda solution, which must be accurately standardised upon normal acid, are then pipetted into the liquid, which is heated to boiling for ten minutes to saponify the triacetin, and the excess of alkali is then titrated back with normal acid. One c.c. of normal acid corresponds to .03067 grm. of glycerine. ”

“ A drop of phenolphthalein is now added, a little water, and the acidity determined by titration with deci-normal baryta solution, and the baryta solution taken calculated as oleic acid.
~Combined Fatty Acid.~ About 30 grms. of the glycerine are placed in a flask, and to it is added about half a grm. of caustic soda in solution. The mixture is heated for ten minutes at 150° C. After cooling some pure ether is added to it, and enough dilute H_{2}SO_{4} to render it distinctly acid. It is well shaken. All the fatty acids go into the ether. ”

“ Physicians should remember that the promoters of Purgen are simply introducing a chemical well known to laboratory workers for the last twenty years, which has been recognized as an aperient for at least seven years, and which can be purchased for 40 cents an ounce, whereas an ounce of phenolphthalein in the form of Purgen will cost $3.20 wholesale. The enthusiastic praise of the remedy, found in the advertising circulars, should be subjected to critical judgment on account of its source and motives. ”

“ Soerensen has worked out a method on this basis for the determination of different amino acids, and for tracing the course of hydrolysis of albuminous matters.
Instead of using phenolphthalein as an indicator, the electrometric apparatus of Sand (see p. 76) is employed. 50 c.c. of the filtered puer liquor are put into a beaker, the hydrogen electrode is immersed in the liquor, and the potential difference (P.D.) observed; this gives the hydrogen ion concentration of the solution. 10 c.c. of neutral formaldehyde solution (40 per cent.) ”

“ The choice is not altogether arbitrary, for experiments have shown that some are more suitable for acidimetry, while others are only applicable in alkalimetry; moreover, the strength of the acids and bases employed may exert a considerable influence on the behaviour of the indicator.
The following are well-known synthetic indicators: hacmoid, obtained from resorcin and sodium nitrite, resembles litmus. Phenolphthalein, obtained by condensing phenol with phthalic anhydride, is colourless both in acid and in neutral solution, but intensely red in the presence of alkali ”

“ Pipet a sample aliquot estimated to contain 0.5 to 2.5 μg CN - into a 25-mL volumetric flask. Alternately, to cover an unknown sample concentration range, pipet 0.5-, 1.00-, and 3.00-mL aliquots into separate 25-mL vol. flasks for each field sample. Larger or smaller aliquots may be taken, based on prior knowledge of expected analyte level. Pipet 0.5 mL 0.1 N NaOH into a 25-mL volumetric flask for reagent blank. Add one drop phenolphthalein solution to each standard or sample. NOTE: Add a little deionized-distilled water to increase volume for easier mixing. ”

“ A colorless liquid, which may become reddish.
Dosage: 0.05 Cc. or 1 minim (U.S.P.) .
Unguentum Phenolis (Ung. Phenol.) , Ointment of Phenol, U.S.P. (Ointment of Carbolic Acid) .—Liquefied phenol (2.25%) in ointment.
Phenol Iodatum (Phenol Iodat.) , Iodized Phenol, N.F. (Acidum Carbolicum Iodatum, N.F. III) .—Iodine (20%) and phenol (60%) in glycerin.
*Phenolphthaleinum (Phenolphthal.) , Phenolphthalein, U.S.P.
White or nearly white, odorless, tasteless powder. Almost insoluble in water; soluble in alcohol (1:13) .
Action and Uses: Mild but efficient cathartic. ”

“ Phenazone is an isomer of phenazine, to which it bears the same relation that plienanthrene bears to anthracene. It is formed by reducing diortho-dinitrodiphenyl with sodium amalgam and methyl alcohol, or by heating diphenylene-ortho-dihydrazine with hydrochloric acid to 150° C. It crystallizes in needles which melt at 156° C. Potassium permanganate oxidizes it to pyridazine tetracarboxylic acid. ”

“ The phenols of naphthalene are called naphthols—they bear the same relationship to naphthalene that carbolic acid bears to benzene. Owing to the structure of the naphthalene molecule there are two isomeric naphthols, whereas there is only one phenol. ”

“ Phenol dissolves readily in concentrated sulphuric acid, a mixture of phenol-ortho- and -para-sulphonic acids being formed. These acids may be separated by conversion into their potassium salts, which are then fractionally crystallized, the potassium salt of the para-acid separating first. The ortho-acid, in the form of its aqueous solution, is sometimes used as an antiseptic, under the name of aseptol. A thiophenol, C6H5SH, is known, and is prepared by the action of phosphorus pentasulphide on phenol, or by distilling a mixture of sodium benzene sulphonate and potassium sulphydrate. ”

“ For the purpose of condensing phenol with formaldehyde, it is not essential to first convert the phenol into the water-soluble phenolsulphonic acid, since it is possible to convert the condensation products of phenol and its derivatives, which are soluble in alkali, into water-soluble form by either heating the condensation products with concentrated solutions of formaldehyde and neutral sulphites, or by dissolving the condensation products in alkali and inducing reaction by means of formaldehyde bisulphite. ”

“ A phenol, e.g. crude cresylic acid, is heated with the equivalent amount of sulphuric acid for a few hours to 100°-210° C., cooled, and formaldehyde added slowly whilst cooling and stirring, in the proportion of one molecule of formaldehyde to 2 molecules of phenol. The free mineral acid is neutralized, and the resulting product is the syntan "Neradol." By this procedure only water-soluble products are obtained, but an alternative process is to heat the phenols in slightly acid solution, and then to render soluble the resinous products obtained by treating with sulphuric acid. ”

“ Several compounds related to phenacetin have been introduced into medicine. Triphenin is propylphenetidin, lactophenin is lactylphenetidin, pyrantin is para-ethoxyphenyl succinimide, EtO·C6H4·N [CO·CH2] 2, salophen or saliphenin is salicylphenetidin, amygdophenin is mandelylphenetidin. In addition, several other derivatives have been suggested which have a greater solubility than phenacetin, e.g. phesin, which is the sodium salt of phenacetin sulphonic acid, apolysin and citrophen (citrophenin) , which are citric acid derivatives of para-phenetidin, &c. ”

“ They are all absolutely false. Phenalgin is not synthetic; it is not a chemical compound; it is not the only ammoniated phenylacetamide, or the only acetanilid mixture containing carbonate of ammonium—​and it is most positively toxic.
In one place it is stated that Dr. Cyrus Edson
Employed his great facilities for chemical research and opportunities for chemical experiment for the purpose of producing a formula for a combination of stimulant ammonia of coal-tar origin (sic) and chemically pure phenylacetamide, also a coal-tar product ... which he named phenalgin, or ammoniated phenylacetamide. ”

“ Prior to the afternoon recess, Doctor, we were discussing the phenol problem. Now, in this connection, did you at any time propose experiments to be conducted at Buchenwald concerning the tolerance of serum or sera containing phenol? That is, did you propose that in 1942 or 1943 at any time?
Defendant Mrugowsky: No. No such suggestions were made and they were not necessary, because in Germany every serum contains phenol. In the German serum industry there is no serum produced without phenol. I am speaking of the sera for therapeutic purposes, not vaccines. ”

“ In Merck’s Archives, page 11, we are told in an advertisement on ‘Phenalgin’ that it ‘is a compound of peculiar character which cannot be ex­tem­por­an­eous­ly made from powdered drug’ and ‘our process of manufacturing tablets is coincident with the manufacture of Phenalgin and is the result of a long series of careful experiments by which we are able to produce tablets of Phenalgin in a friable condition without losing any of its volatile constituents or undergoing chemical changes from heat or moisture’! ”

“ If a hydroxyl is substituted for a hydrogen atom in the aromatic hydrocarbons, the action of sulphuric acid is greatly facilitated; thus, by merely mixing phenol with sulphuric acid, the sulphonic acid is at once formed, whereby, in the cold, o-phenolsulphonic acid prevails which on heating for some time to 100°-110° C. is completely converted into p-phenolsulphonic acid. In the absence of free sulphuric acid the conversion of o- into p-phenolsulphonic acid is brought about by heating the aqueous solution. ”

“ In Germany all serums which are obtained from animals, mostly horses, are mixed with 0.5 percent of phenol and carbolic acid—in order to preserve them—i. e., to 400 cubic centimeters I added a concentration of two cubic centimeters of phenol acid. This amount is, of course, far above the tolerance of human beings. Carbolic acid is one of the strongest acids we possess. When treating people with gas gangrene serums a number of deaths occurred. We discussed whether we were dealing with cases of serum death, resulting from the serum, or whether death was caused by the phenol added. ”

“ With picric acid it forms a sparingly soluble picrate, which melts at 145° C. On the condition of phenanthrene in alcoholic solution see R. Behrend, Zeit. phys. Chem., 1892, 9, p. 405; 10, p. 265. Chromic acid oxidizes phenanthrene, first to phenanthiene-quinone, and then to diphenic acid, HO2C·C6H4·C6H4·CO2H.
Phenanthrene-quinone, [C6H4] 2 [CO] 2, crystallizes in orange needles which melt at 198° C. It possesses the characteristic properties of a diketone, forming crystalline derivatives with sodium bisulphite and a dioxime with hydroxylamine. It is non-volatile in steam, and is odourless. ”

“ Phenol is another of the multitudes of substances obtainable from coal-tar; it can be prepared from aniline by the action of nitrous acid, and can be shown to be benzene with one hydrogen atom replaced by hydroxyl. If one of the adjacent hydrogen atoms of phenol is replaced by carboxyl, salicylic acid is produced; and in the presence of a suitable dehydrating agent salicylic acid reacts with phenol and phenyl salicylate, known as salol, is formed. ”

“ Chemical Analysis.—Carbolic acid may be separated from mixture with organic substances by distillation with dilute sulphuric acid, from urine by agitation with ether. Bromine water, as recommended by Landolt, gives a bulky yellowish precipitate of tribromo-phenol. The precipitate should then be collected, well washed, and gently warmed in a test tube with sodium-amalgam and water. The liquid poured into a dish and acidulated, will, if phenol be present, give the characteristic odour of that substance, and it may be seen floating in the liquid as an oily fluid. ”

“ Phenol dissolves, and forms a clear mixture. Were any phenol present in the wood creosote, the increase in the volume of the glycerine solution, if in a graduated tube, would distinctly indicate the percentage of phenol present.
4. Solubility in benzine. Wood creosote entirely soluble. Phenol is insoluble.
5. A 1 per cent, solution of wood creosote. Take of this 10 cubic centimeters, add 1 drop of a test solution of ferric chloride; an evanescent blue color is formed, passing quickly into a red color. Phenol gives a permanent blue color. ”