2- hydroquinone

Hydroquinone is usually more effective when utilized in combination with other agents such as topical retinoids alone or topical retinoids and topical steroids (see Table 14.1). The addition of a weak topical steroid reduces the irritant effect of hydroquinone, but the treat- 

Azelaic acid is a non-phenolic derivative (1,7-hep tanedicarboxylic acid) used at concentration of 10-20% twice a day to treat melasma with minimal side effects (allergic reactions). It acts to disturb the tyrosinase synthesis and can be used as a bleaching agent in patients sensitive to hydroquinone. Better results are obtained if a glycolic acid cream is applied sequentially to azelaic acid treatment. 

Hydroquinone inhibits melanin production when applied to the skin. The effect is reversible by exposure to ultraviolet light. 

Hydroquinone in a 2 percent solution is used in many skin-lightening creams and gels to remove freckles, age spots, and other hyper-pigmented areas of the skin. 

Since sunlight reverses the effect, a sunscreen is usually mixed into the preparation. 

Hydroquinone (Quinol, hydroquinol, p-diphenol, dihydroxybenzene, 1,4-benzenediol) 

Therapeutic Function Depigmentor Chemical Name 1,4-Benzenedlol Common Name Quinol Structural Formula  

In one epidemiological study, no significant increase in cancer incidence was found for individuals residing downwind from two natural gas refineries that emit primarily sulfur compounds, including hydrogen sulfide.  

Hydrogen sulfide was not mutagenic in Ames assays with or without metabolic activation.  

The odor is offensive and characterized as rotten eggs with a threshold ranging from 

0005 to 0.13 ppm it is unreliable as a warning signal because the gas exerts a paralyzing effect on the olfactory apparatus above 150 ppm at these concentrations the odor has been characterized as sickeningly sweet.  

The 2003 ACGIH threshold limit valuetime-weighted average (TLV-TWA) is 10 ppm (14mg/m ) with a short-term excursion limit (STEL)/ceiling of 15 ppm (21 mg/m ). 

Sample preparation Filter (Amicon Centrifree) whole blood while centrifuging at 3° at 3000 g for 1 h, inject a 100 LL aliquot of the ultrafiltrate. 

Column 170 x 4.6 5 xm Supelcosil LC-18 Mobile phase 50 mM pH 4.5 formate buffer Flow rate 1 Injection volume 100 

Detector Radioactivity ( C) UV (wavelength not specified, other papers have recommended 220-280) 

Deisinger, P.J. English, J.C. Bioavailability and metabolism of hydroquinone after intratracheal instillation in male rats, Drug Metab.Dispos., 1999, 27, 442-448. 

---

CgH,oN20. Colourless crystalline solid, m.p. 121 °C. Made by reacting phenylhydrazine with ethyl acrylate to obtain the hydrazide which cyclizes to the product. Its major commercial importance is as a photographic developing agent, being used particularly in conjunction with hydroquinone. 

Phenof 0-, m- and p-cresof catechof resorcinol hydroquinone (and other nuclear-substituted phenols) 1- and 2-naphthol. 

Action of bromine water. To a concentrated aqueous solution of the phenol or to the phenol itself, add bromine water gradually. At first the bromine is decolorised and then on adding an excess a white or yellowish-white precipitate of a polybromo-derivative is produced with all except catechol, hydroquinone, i- and 2 naphthol. 

On adding i drop of bromine water to catechol, a deep red coloration is produced immediately. On gradually adding bromine water to a solution of hydroquinone, a deep red coloration is produced, followed by the separation of deep green crystals which then dissolve giving a yellow solution, i- and 2-Naphthol will decolorise hromine water, but usually no precipitate of the bromo compound can be obtained. 

To a cold aqueous solution of benzoquinone, add 1 drop of sulphurous acid solution (SOj-water) the solution turns deep green-brown owing to the intermediate formation of quinhydrone, CeH402,CeIl4(0H)2. Now add excess of sulphurous acid the solution becomes colourless owing to the formation of hydroquinone. Add a few drops of FeClj solution the reaction is reversed and the deep yellow colour (distinct from that of FeCl ) is restored. 

A mixture of equal parts of cottonseed oil and castor oil, containing about 1 per cent, of hydroquinone as an anti oxidant, is a useful bath liquid which can be heated up to about 250°. 

About 0-1 per cent, of hydroquinone should be added as a stabiliser since n-hexaldehyde exhibits a great tendency to polymerise. To obtain perfectly pure n-/iexaldehyde, treat the 21 g. of the product with a solution of 42 g. of sodium bisulphite in 125 ml. of water and shake much bisulphite derivative will separate. Steam distil the suspension of the bisulphite compound until about 50 ml. of distillate have been collected this will remove any non-aldehydic impurities together with a little aldehyde. Cool the residual aldehyde bisulphite solution to 40-50 , and add slowly a solution of 32 g. of sodium bicarbonate in 80 ml. of water, and remove the free aldehyde by steam distillation. Separate the upper layer of n-hexaldehyde, wash it with a little water, dry with anhydrous magnesium sulphate and distil the pure aldehyde passes over at 128-128-5°. 

Dihydroxyacetophenone (II) can be prepared in good yield by heating hydroquinone diacetate (I) in the presence of 3-3 mols of aluminium chloride, Hydroquinone cannot be acylated by the Eriedel-Crafts method. 

Dihydroxyacetophenone. Finely powder a mixture of 40 g. of dry hydroquinone diacetate (1) and 87 g. of anhydrous aluminium chloride in a glass mortar and introduce it into a 500 ml. round-bottomed flask, fitted with an air condenser protected by a calcium chloride tube and connected to a gas absorption trap (Fig. II, 8, 1). Immerse the flask in an oil bath and heat slowly so that the temperature reaches 110-120° at the end of about 30 minutes the evolution of hydrogen chloride then hegins. Raise the temperature slowly to 160-165° and maintain this temperature for 3 hours. Remove the flask from the oil bath and allow to cool. Add 280 g. of crushed ice followed by 20 ml. of concentrated hydrochloric acid in order to decompose the excess of aluminium chloride. Filter the resulting solid with suction and wash it with two 80 ml. portions of cold water. Recrystallise the crude product from 200 ml. of 95 per cent, ethanol. The 3 ield of pure 2 5-dihydroxyacetophenone, m.p. 202-203°, is 23 g. 

I) Hydroquinone dIacetate may be prepared as follows. Add I drop of concentrated sulphuric acid to a mixture of 55 g. of hydroquinone and 103 g. (05-5 ml.) of A.R. acetic anhydride in a 500 ml. conical flask. Stir the mixture gently by hand it warms up rapidly and the hydroquinone dissolves. After 5 minutes, pour the clear solution on to 400 ml. of crushed ice. Alter with suction and wash with 500 ml. of water. Recrystallise the solid from 50 cent, ethanol by weight (ca. 400 ml. are required). The yield of pure hydroquinone diacetate, m.p. 122°, is 89 g. 

Benzaldehyde is easily oxidised by atmospheric oxygon giving, ultimately, benzoic acid. This auto-oxidation is considerably influenced by catalysts tiiose are considered to react with the unstable peroxide complexes which are the initial products of the oxidation. Catalysts which inhibit or retard auto-oxidation are termed anti-oxidants, and those that accelerate auto-oxidation are called pro-oxidants. Anti-oxidants find important applications in preserving many organic compounds, e.g., acrolein. For benzaldehyde, hydroquinone or catechol (considerably loss than U-1 per cent, is sufficient) are excellent anti-oxidants. 

Benzoquinone ( quinone ) is obtained as the end product of the oxidation of aniline by acid dichromate solution. Industrially, the crude product is reduced with sulphur dioxide to hydroquinone, and the latter is oxidised either with dichromate mixture or in very dilute sulphuric acid solution with sodium chlorate in the presence of a little vanadium pentoxide as catalyst. For the preparation in the laboratory, it is best to oxidise the inexpensive hydroquinone with chromic acid or with sodium chlorate in the presence of vanadium pent-oxide. Naphthalene may be converted into 1 4-naphthoquinone by oxidation with chromic acid. 

When a solution of, say, 1 g. of hydroquinone in 4 ml. of rectified spirit is poured into a solution of 1 g. of quinone in 30 ml. of water, qulnhydrone C,HA.C,H (0H)3, a complex of equimolecular amounts of the two components, is formed as dark green crystals having a gfistening metallic lustre, m.p. 172°. In solution, it is largely dissociated into quinone and hydroquinone. Quinhydrone is more conveniently prepared by the partial oxidation of hydroquinone with a solution of iron alum. 

Method 1. Cool a solution of 33 g. of hydroquinone in 150 ml. of 60 per cent, acetic acid contained in a 600 ml. beaker to below 5° in an ice bath. Dissolve 42 g. of chromic anhydride in 70 ml. of water, and add 30 ml. of glacial acetic acid. By means of a separatory funnel with bent stem and supported over the beaker, add the chromic anhydride solution... 

Dissolve 100 g. of iron alum (ferric ammonium sulphate) in 300 ml. of water at 65°, Pour the solution, with stirring, into a solution of 25 g. of hydroquinone in 100 ml, of water contained in a 600 ml. beaker. The quinhydrone is precipitated in fine needles. Cool the mixture in ice, filter with suction, and wash three or four times with cold water. Dry in the air between filter paper. The yield of quinhydrone, m.p, 172°, is 15 g. It contains a trace of iron, but this has no influence upon the e.m.f, of the quinhydrone electrode provided that the washing of the crude material has been thorough. The quinhydrone should be stored in a tightly-Btoppered bottle. 

Sulphurous acid produces a similar result, but some hydroquinone sulphonic acid is simultaneously produced. 

Reduction to hydroquinone. Dissolve, or suspend, 0-5 g. of the quinone in 5 ml. of ether or benzene and shake vigorously with a solution of 1 0 g. of sodium hydrosulphite (Na2S204) in 10 ml. of N sodium hydroxide until the colour of the quinone has disappeared. Separate the alkaline solution of the hydroquinone, cool it in ice, and acidify with concentrated hydrochloric acid. Collect the product (extract with ether, if necessary) and recrystalhse it from alcohol or water. 

In a 250 ml. distilling flask (1) place 122 g. (119 ml.) of p-phenylethyl alcohol and 40 g. of sodium hydroxide peUets (or 56 g. of potassium hydroxide). Heat is evolved. Warm gently until bubbles commence to form and the mixture separates into two sharply-defined layers. Distil slowly water, etc. passes over first accompamed by the gradual dis appearance of the upper phase. FinaUy the styrene passes over at 140 160° (mainly 150°) coUect this separately in a receiver containing about 0 1 g. of hydroquinone. Dry the distillate with a httle anhydrous calcium chloride or magnesium sulphate, and then distil under reduced pressure (2). C oUect the pure styrene at 42-43°/18 mm. The 3rield is 80 g. Add about 0-2 g. of hydroquinone (anti-oxidant) if it is desired to keep the phenylethylene. 

Phenylethylene boils at 145-146° at atmospheric pressure, but the high temperature causes a considerable loss by polymerisation. It has been stated that the addition of about 0-1 per cent, by weight of hydroquinone considerably reduces the extent of polymerisation at atmospheric pressure. 

If the compound to be tested is insoluble in water, it should be brought into solution by the addition of a little dioxan. Alcohols and some methyl ketones frequently react slowly in such cases it is advisable to employ a large excess (4-5 fold) of the relatively unstable reagent (3NaOI -> NaI03 -f- 2NaI). Quinones and hydroquinones also give the iodoform reaction. 

Krypton clathrates have been prepared with hydroquinone and phenol. 85Kr has found recent application in chemical analysis. By imbedding the isotope in various solids, kryptonates are formed. The activity of these kryptonates is sensitive to chemical reactions at the surface. Estimates of the concentration of reactants are therefore made possible. Krypton is used in certain photographic flash lamps for high-speed photography. Uses thus far have been limited because of its high cost. Krypton gas presently costs about 30/1. 

In order to make these oxidative reactions of 1,3-dienes catalytic, several reoxidants are used. In general, a stoichiometric amount of benzoquinone is used. Furthermore, Fe-phthalocyanine complex or Co-salen complex is used to reoxidize hydroquinone to benzoquinone. Also, it was found that the reaction is faster and stereoselectivity is higher when (phenylsulflnyl)benzoquinone (383) is used owing to coordination of the sulfinyl group to Pd, Thus the reaction can be carried out using catalytic amounts of PdfOAcji and (arylsulfinyl)benzoquinone in the presence of the Fe or Co complex under an oxygen atmosphere[320]. Oxidative dicyanation of butadiene takes place to give l,4-dicyano-2-butene(384) (40%) and l,2-dicyano-3-butene (385)[32l]. 

---