Diazotization s. a. Sodium

To a cold mixture of 800 cc. of 95 per cent ethyl alcohol and 200 cc. of concentrated sulfuric acid (Note i) in a 5-I. round-bottom flask, provided with an efficient mechanical stirrer, is added 250 g. (1.33 moles) of crude 3-bromo-4-aminotoluene (p. 8). The solution is stirred and cooled to 10° and a solution of 148 g. (2.05 moles) of d.s.p. sodium nitrite in 260 cc. of water is added from a separatory funnel. During this addition, the temperature of the mixture must not be allowed to rise above 10°. After all of the nitrite solution has been added, the mixture is stirred twenty minutes longer to complete the diazotization. 

To 375 cc. (4.3 moles) of hydrochloric acid (sp. gr. 1.18) and 200 g. of ice is added 139.6 g. (1.5 moles) of aniline. The resulting solution is diazotized with a solution of 103.5 S (x-5 moles) of c. p. sodium nitrite, ice being added to the reaction mixture, as necessary, in order to keep the temperature below 50. The final volume of the diazotized solution is about 1 1. This solution is added in a slow stream from a dropping funnel to the potassium selenide solution, which is being vigorously stirred with a mechanical stirrer. When all the diazotized solution has been added, the red aqueous solution is decanted from the dark oil which forms and is heated to boiling (Note 4). It is then poured back on the oil, the mixture is well stirred (Note 5), 200 cc. of chloroform is added, and the selenium collected on a filter and washed with a little more chloroform (Note 6). After the chloroform layer is separated, the aqueous layer is again... 

Arylnaphthalenes. Arylnaphthalenes can be prepared by replacement of the amino group of naphthylamines by aryl groups. a-Phenyl-naphthalene can be prepared satisfactorily only through the stabilized diazonium salt method, but /3-phenylnaphthalene is obtained readily by several procedures. A considerable number of derivatives of /3-phenylnaphthalene have been prepared. An example is 5-nitro-6-methoxy-2-phenylnaphthalene (XII), which can be obtained in 19% yield from the nitromethoxy-/3-naphthylamine and benzene. From the reaction between diazotized /S-naphthylamine and nitrobenzene and sodium acetate, /S-(2-nitrophenyl)-naphthalene (XIII 14%) and /3-(4-nitrophenyl)-naphthalene (XIV 26%) are formed. 

Diazotization of a mixture of diamino derivatives (R,S)-22 afforded the triazolo[l,5-c]pyrimidine 23. When the reaction time and the proportion of sodium nitrite were increased, a second compound 24, resulting from a reductive deamination of the amino group [89JCS(P1)2401] was obtained (Scheme 5). 

The diazotization of amino derivatives of six-membered heteroaromatic ring systems, particularly that of aminopyridines and aminopyridine oxides, was studied in detail by Kalatzis and coworkers. Diazotization of 3-aminopyridine and its derivatives is similar to that of aromatic amines because of the formation of rather stable diazonium ions. 2- and 4-aminopyridines were considered to resist diazotization or to form mainly the corresponding hydroxy compounds. However, Kalatzis (1967 a) showed that true diazotization of these compounds proceeds in a similar way to that of the aromatic amines in 0,5-4.0 m hydrochloric, sulfuric, or perchloric acid, by mixing the solutions with aqueous sodium nitrite at 0 °C. However, the rapidly formed diazonium ion is hydrolyzed very easily within a few minutes (hydroxy-de-diazonia-tion). The diazonium ion must be used immediately after formation, e. g., for a diazo coupling reaction, or must be stabilized as the diazoate by prompt neutralization (after 45 s) to pH 10-11 with sodium hydroxide-borax buffer. All isomeric aminopyridine-1-oxides can be diazotized in the usual way (Kalatzis and Mastrokalos, 1977). The diazotization of 5-aminopyrimidines results in a complex ring opening and conversion into other heterocyclic systems (see Nemeryuk et al., 1985). 

Minka et al. have reported an absorption spectroscopic method for the determination of procaine [42]. The drug (base or hydrochloride) was determined after a diazotization coupling reaction with 0.1% 3-(l,2-dicarboxyethyl)-rhodamine solution. After addition of 20% sodium hydroxide solution, the absorbance of the red solution was obtained using a blue filter. Sample values were evaluated by means of a calibration graph, and Beer s law was obeyed over the range of 1 -10 pg/mL of procaine. 

The melting point of the />-toluenesulfonylanthranilic acid is not a good criterion of purity because the />-toluenesulfonic acid salt of anthranilic acid has about the same value. The neutral equivalents are widely different 154 for the salt and 291 for />-toluenesulfonylanthranilic acid. The compound obtained in this preparation gives a negative test for anthranilic acid on diazotization and treatment with alkaline /S-naphthol solution. The probable impurity is the sodium salt of />-toluene-sulfonylanthranilic acid. 

Workers in the dinitrophenol plant should be protected in the usual way (i.e. gloves, respirators, chMige of clothes, bath, etc.). Selection of workers hMidling dinitrophenol is also recommended since it has been shown that a great mMiy people are resistant to its toxic effects, Selection is based on 15 days medical observation of each new worker in the dinitrophenol plant, in particular in the analysis of the mine every other day. A test for the presence of Mninonitrophenols is particularly importance. Usually Denien s reaction [33] is used. According to Lazarev [31], the reaction comprises acidification of the mine with 10% sulphuric acid and diazotization with sodium nitrite, followed by shaking up the prepMed solution with an ammoniacal solution of p- naphthol. If a red colour appeMS it indicates the presence of 4-amino-2-nitrophenol in the mine, while a violet shade is evidence for the presence of 2-Mnino-4-nitrophenol. 

The diazotization/fluorodediazoniation of a-amino acids takes place with retention of configuration. Thus, when (S )-2-amino-3-cyclohexylpropionic acid (1) is treated with excess sodium nitrite in hydrogen fluoride/pyridine, (5 )-2-fluoro-3-cyclohexylpropionic acid (2) is obtained without any racemization.82... 

Dissolve 9 3 S of aniline in 30 cc of cone, hydrochloric acid and 100 cc of water. Then pieces of ice are added to the solution to reduce the temperature to 0°C. Prepare sodium nitrite solution by adding 7 2 g of sodium nitrite to 35 cc of water. Add this solution to the aniline solution slowly, and diazotization occurs. Test the solution with potassium iodide starch papers, to avoid excess of sodium nitrite solution. The point is determined by the colour change of the test paper to a slight blue. Add pieces of ice to the solution during the diazotization to keep the temperature at about 5 C. On the other hand, dissolve 15 g of sodium hyroxide in 200 cc of water and then dissolve g of fi naphthol in this... 

A colorimetric method for microdetermination of sulfonamides based on diazotization of the drug with sodium nitrite and hydrochloric acid has been reported (59). The diazonium salt is then coupled with 8-hydroxyquinoline in alkaline medium and the absorbance of the developed color measured at its maximum wavelength. A similar method involves diazotization and coupling of the sulfonamide with indole in alkaline solution to form an intense yellow azo dye which exhibits maximum absorption at 449 nm. Beer s law is obeyed over the concentration range 1-32 /ig/ml with a relative standard deviation of less than 2% (60). The reaction of sulfonamides with chloramine-T in sulfuric acid gives a yellow product which is suitable for the determination of sulfonamides in different formulations. It has an accuracy similar to that of the Bratton and Marshall method (61). 

Burgstahler et al. diazotized the sparingly soluble hydrochloride of 3,4-di-r-butylaniline at O-S", treated the filtered solution with sodium fluoroborate, and obtained the diazonium fluond>orate. This salt underwent slow solvolysis in a mixture of acetic acid — acetic anhydride with formation of the corresponding acetate. 

Sodium disulfide (or polysulflde) solution, Na S. For use in the preparation of thio-salicylic acid, the reagent is prepared by heating and stirring a mixture of 1.1 moles of Na2S-9H20, 290 ml. of water, and 1.1 moles of powdered sulfur until a brownish red solution results. A solution of 40 g. of sodium hydroxide in 100 ml. of water is added, and the solution is cooled in a salt-ice bath and stirred at 0-5° during addition of a solution of diazotized anthranilic acid. This Sandmeyer-type displacement gives a disulfide reducible to thiosalicylic acid. 

In a i-l. flask 132 g. (0.5 mole) of s-iodoanthranilic acid (p. 52) and 35 g. (0.5 mole) of sodium nitrite are dissolved in a mixture of 500 cc. of warm water and 60 cc. of 30 per cent sodium hydroxide solution. After cooling to 20 the solution is added from a dropping funnel, over a period of fifteen to twenty minutes, to a well-stirred mixture of 250 cc. of concentrated hydrochloric acid (sp. gr. 1.18) and 250 g. of ice in a 2-I. beaker more ice is added, as required, to keep the temperature below 20°. The insoluble, yellow diazonium compound separates before completion of the diazotization. After all the solution has been added from the dropping funnel, the reaction mixture is stirred for five minutes and tested for excess nitrous acid with starch-iodide paper. If required, small amounts of solid sodium nitrite are added and the test is repeated at three-minute intervals until a slight excess is definitely established. The diazonium compound is allowed to settle and as much as possible of the... 

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