Diazonium ethers

When a solution of a diazonium compound in absolute methanol is boiled, the chief product is the corresponding methyl ether, henzenediiizonium hydrogen sulphate thus giying methyl phenyl etlier or anisole ... 

In absolute ethanol solution, the ethyl ether and the corresponding hydrocarbon are formed, the latter by reduction of the diazonium compound by the ethanol, which is itself oxidised to acetaldehyde ... 

Now add the diazonium solution slowly from a dropping-funnel to the vigorously-stirred arsenite solution, keeping the temperature of the latter at 5 7°. The frothing caused by the evolution of nitrogen will probably be dispersed by the stirrer if not, the addition of 1-2 ml. of ether, preferably in a fine jet from a wash-bottle, will cause it to subside. 

Note on the laboratory preparation of monoethylaniline. Although the laboratory preparation of monomethyl- or monoethyl-aniline is hardly worth whUe, the following experimental details may be useful to those who wish to prepare pure monoethylaniline directly from amline. In a flask, fitted with a double surface reflux condenser, place 50 g. (49 ml.) of aniline and 65 g. of ethyl bromide, and boU gently for 2 hours or until the mixture has almost entirely sohdified. Dissolve it in water and boil off the small quantity of unreacted ethyl bromide. Render the mixture alkaUne with concentrated sodium hydroxide solution, extract the precipitated bases with three 50 ml. portions of ether, and distil off the ether. The residual oil contains anihne, mono- and di-ethylaniline. Dissolve it in excess of dilute hydrochloric acid (say, 100 ml. of concentrated acid and 400 ml. of water), cool in ice, and add with stirring a solution of 37 g. of sodium nitrite in 100 ml. of water do not allow the temperature to rise above 10°. Tnis leads to the formation of a solution of phenyl diazonium chloride, of N-nitrosoethylaniline and of p-nitrosodiethylaniline. The nitrosoethylaniline separates as a dark coloured oil. Extract the oil with ether, distil off the ether, and reduce the nitrosoamine with tin and hydrochloric acid (see above). The yield of ethylaniline is 20 g. 

Phenyldiazonium chloride and other similar diazonium compounds are very soluble in water, are completely insoluble in ether and other organic solvents, and are completely dissociated in aqueous solution to organic cations and inorganic anions (e.g., chloride ions) a convenient formulation is therefore, for example, CjHjNj+CP. 

To prepare the solid phenyldlazonlum chloride or sulphate, the reaction is conducted in the absence of water as far as possible. Thus the source of nitrous acid is one of its organic esters (e.g., amyl nitrite) and a solution of hydrogen chloride gas in absolute alcohol upon the addition of ether only the diazonium salt is precipitated as a crystalline solid, for example ... 

Dissolve 3-5 g. of aniline hydrochloride in 20 ml. of absolute ethyl alcohol contained in a 50 ml. conical flask, and add 0-5 ml. of a saturate solution of hydrogen chloride in absolute ethyl alcohol. Cool in ice and add 4 g. (4 -6 ml.) of iso-amyl nitrite (compare Section 111,53) gradually. Allow the mixture to stand for 5-10 minutes at the room temperature, and precipitate the diazonium salt by the gradual addition of ether. Filter ofiF the crystals at the pump on a small Buchner funnel, wash it with 5 ml. of alcohol - ether (1 1), and then with 10 ml. of ether. Keep... 

Dissolve 34 g. of o-nitroaniline in a warm mixture of 63 ml. of concentrated hydrochloric acid and 63 ml. of water contained in a 600 ml. beaker. Place the beaker in an ice - salt bath, and cool to 0-5° whilst stirring mechanically the o-nitroaniline hydrochloride will separate in a finely-divided crystalline form. Add a cold solution of 18 g. of sodium nitrite in 40 ml. of water slowly and with stirring to an end point with potassium iodide - starch paper do not allow the temperature to rise above 5-7 . Introduce, whilst stirring vigorously, a solution of 40 g. of sodium borofluoride in 80 ml. of water. Stir for a further 10 minutes, and filter the solid diazonium fluoborate with suction on a sintered glass funnel. Wash it immediately once with 25 ml. of cold 5 per cent, sodium borofluoride solution, then twice with 15 ml. portions of rectified (or methylated) spirit and several times with ether in each washing stir... 

Dissolve 200 g. of sodium nitrite in 400 ml. of water in a 2-litre beaker provided with an efficient mechanical stirrer, and add 40 g. of copper powder (either the precipitated powder or copper bronze which has been washed with a little ether). Suspend the fluoborate in about 200 ml. of water and add it slowly to the well-stirred mixture. Add 4-5 ml. of ether from time to time to break the froth. The reaction is complete when all the diazonium compound has been added. Transfer the mixture to a large flask and steam distil until no more solid passes over (about 5 litres of distillate). Filter off" the crystalline solid in the steam distillate and dry upon filter paper in the air this o-dinitrobenzene (very pale yellow crystals) has m.p. 116° (t.c., is practically pure) and weighs 29 g. It may be recrystallised from alcohol the recrystallised solid melts at 116-5°. 

Decomposition of diazonium salts obtained from 2-aminothiazole (4) (29, 34. 35) could be an interesting reaction to introduce O in A-4-thiazoline-2-one. Acidic hydrolvsis of ethers (36. 37). oxidative hydrolysis... 

In contrast to the Gomberg-Bachmann reaction, the intramolecular variant, the Pschorr reaction, is carried out in strongly acidic solution, and in the presence of copper powder. Diazonium biphenyl ethers are converted to dibenzofurans, e.g. 8 9 ... 

The pharmacological versatility of this general substitution strategy is further illustrated by diazonium coupling of 14 with 2-nitrobenzenediazonium chloride to produce biarylal-dehyde 18. Formation of the oxime with hydroxylamine is followed by dehydration to the nitrile. Reaction with anhydrous methanolic hydrogen chloride leads to imino ether and addition-elimination of ammonia leads to the antidepressant amid-ine, nitrafudam (20). ... 

Diazomethane, reaction with 2,4,6-tri-nitrobenzenesulfonic acid and dimethyl ether, 46,122 Diazonium xanthates, detonation of, 47, 107... 

The ice-cold fluoboric acid solution is added rather rapidly, with stirring, to the finished tetrazo solution, the temperature being kept below io°. A thick paste of 4,4 -biphenylene-bis-diazonium borofluoride forms. The mixture is stirred at io° for twenty to thirty minutes. It is then collected on a 19-cm. Buchner funnel, and washed consecutively with about 200 cc. of cold water, 200 cc. of cold commercial methyl alcohol, and 200 cc. of commercial ether the cake is sucked as dry as possible between washings. It is then dried in a vacuum desiccator over concentrated sulfuric acid (sp. gr. 1.84). The yield of the dry solid is 393 400 g. (68-69 Per cent of the theoretical amount). The product decomposes at 135-1370. 

Difluorobiphenyl has been prepared from 4,4 -biphenyl-bis-diazonium piperidide (by diazotizing benzidine and coupling with piperidine) and concentrated hydrofluoric acid 1 by the action of sodium on -fluorobromobenzene in ether 2 from benzidine by tetrazotization and decomposing the biphenyl-bis-diazonium salt with concentrated hydrofluoric acid 3 by the above method in the presence of ferric chloride 4 and by the prolonged contact of the vapors of fluorobenzene with a red-hot wire.5 The method described here is the most satisfactory for... 

In the context of diazoazoles, 5-diazotetrazole (2.22) should be mentioned. It was obtained by dropwise addition of isopentyl nitrite to a solution of 5-amino-lH-tetra-zole in a 4 1 mixture of tetrahydrofuran and aqueous hydrochloric acid. The diazo-nium chloride can be extracted into ether. The extremely explosive solid diazonium... 

In most cases diazonium salts are not isolated, but are converted into products by reactions that can be carried out in situ. Moreover, it is actually recommended not to isolate these salts, not even for purification purposes, as many of them have a tendency to explode. In addition, the high solubility of most diazonium salts in water makes precipitation from this medium difficult. Therefore, to obtain solid diazonium salts the recommended method for many decades was to carry out diazotizations in ethanol followed by precipitation with ether. As inorganic salts of nitrous acid are scarely soluble in ethanol, Knoevenagel recommended alkyl nitrites (ethyl or isopentyl nitrite) as diazotization reagents as long ago as 1890. Various other solvents have subsequently been used for diazotizations with alkyl nitrites (see Saunders and Allen, 1985, p. 23 ff.), but as a method for obtaining solid diazonium salts this has been superseded by the isolation of diazonium tetrafluoroborates and, to a lesser degree, of hexafluorophosphates. 

Salts of diazonium ions with certain arenesulfonate ions also have a relatively high stability in the solid state. They are also used for inhibiting the decomposition of diazonium ions in solution. The most recent experimental data (Roller and Zollinger, 1970 Kampar et al., 1977) point to the formation of molecular complexes of the diazonium ions with the arenesulfonates rather than to diazosulfonates (ArN2 —0S02Ar ) as previously thought. For a diazonium ion in acetic acid/water (4 1) solutions of naphthalene derivatives, the complex equilibrium constants are found to increase in the order naphthalene < 1-methylnaphthalene < naphthalene-1-sulfonic acid < 1-naphthylmethanesulfonic acid. The sequence reflects the combined effects of the electron donor properties of these compounds and the Coulomb attraction between the diazonium cation and the sulfonate anions (where present). Arenediazonium salt solutions are also stabilized by crown ethers (see Sec. 11.2). 

Another redox reaction leading to arenediazonium salts was described by Morkov-nik et al. (1988). They showed that the perchlorates of the cation-radicals of 4-A,A-dimethylamino- and 4-morpholinoaniline (2.63) react with gaseous nitric oxide in acetone in a closed vessel. The characteristic red coloration of these cation-radical salts (Michaelis and Granick, 1943) disappears within 20 min., and after addition of ether the diazonium perchlorate is obtained in 84% and 92% yields, respectively. This reaction (Scheme 2-39) is important in the context of the mechanism of diazotization by the classical method (see Sec. 3.1). 

The reversibility of aromatic diazotization in methanol may indicate that the intermediate corresponding to the diazohydroxide (3.9 in Scheme 3-36), i. e., the (Z)-or (is)-diazomethyl ether (Ar — N2 — OCH3), may be the cause of the reversibility. In contrast to the diazohydroxide this compound cannot be stabilized by deprotonation. It can be protonated and then dissociates into a diazonium ion and a methanol molecule. This reaction is relatively slow (Masoud and Ishak, 1988) and therefore the reverse reaction of the diazomethyl ether to the amine may be competitive. Similarly the reversibility of heteroaromatic amine diazotizations with a ring nitrogen in the a-position may be due to the stabilization of the intermediate (Z)-diazohydroxide, hydrogen-bonded to that ring nitrogen (Butler, 1975). However, this explanation is not yet supported by experimental data. 

In Sections 5.2 and 5.3 it was shown that experimental data are consistent with a direct rearrangement of the (Z)- to the (ii)-diazohydroxide rather than with a recombination after a primary dissociation of the (Z)-isomer into a diazonium ion. Positive evidence for direct formation of the (ii)-diazohydroxide from the diazonium ion and a hydroxide ion (or water) is still lacking (see Scheme 5-15 in Sec. 5.2). For diazo ethers, however, Broxton and Roper (1976) came to the conclusion that there is no direct (Z) >(E) conversion, but rather that in the system ArNj + OCH3/(Z)-diazo ether/(Zi)-diazo ether the (Z)-ether is the kinetically determined product and the (iE )-isomer the thermodynamic product, as shown in Scheme 6-3. 

Semiquantitatively, the reaction of an aromatic diazonium ion with the methoxide ion occurs in three phases. The first is the extremely rapid formation of the (Z)-diazo methyl ether. This is followed by a second, partitioning, phase which in the case of the 4-nitrobenzenediazonium ion at 30 °C is completed in 60 s (Boyle et al., 1971). During this phase, some of the (Z)-diazo ether decomposes to form dediazoniation products (mainly nitrobenzene via the hydro-de-diazoniation reaction) and the rest is converted into the (Zi)-diazo ether. 

Broxton and Roper measured the rate of dissociation (A 3) of the (ii)-diazo ether, A 2, and the rate of the protection reaction (A p), i.e., the transformation of the (Z)-into the (ii)-ether ( protection because the diazo ether is protected against dediazoniation almost completely if present as the ( >isomer). Rate constants kx and k are known from Ritchie and Virtanen s work (1972). The results demonstrate firstly that the initial reaction of the diazonium ion takes place in such a way that almost exclusively the (Z)-ether is formed directly (ki/k3 = 120). The protection rate constant kp is a simple function of the intrinsic rate constants as shown in Scheme 6-4. 

The reactions of arenediazonium ions with 7V-alkyl- or 7V-arylhydroxylamines were investigated by Bamberger (1920b, and earlier papers). Mitsuhashi et al. (1965) showed that the l,3-diaryl-3-hydroxytriazenes are tautomeric with 1,3-diaryltriazene-3-oxides (Scheme 6-16). Oxidation of 1,3-diaryltriazenes with peroxybenzoic acid in ether yields the same product as that from diazonium salts and TV-arylhydroxyl-amine. The infrared spectrum of the product obtained by coupling diazotized relabeled aniline with A/-phenylhydroxylamine indicates that the diaryltriazene-oxide is the preponderant tautomer. 

First of all, there are the two products of O-coupling addition of methoxide ion to the diazonium ion, the (Z)- and (jE)-diazo methyl ethers. As discussed in Section 6.2, they are formed in reversible reactions with half-lives of the order of a fraction of a second (Z) to a minute (E). The two diazo ethers are, however, decomposed rapidly to the final dediazoniation products. We show in Scheme 8-47 the products obtained by Broxton and McLeish (1983 b) in the dediazoniation of 4-chloro-3-nitrobenzenedi-azonium ion (8.64) with methoxide ion in CH3OH. The products are 4-chloro-3-nitro-anisole (8.65, 49 9o), 2-chloro-nitrobenzene (8.66, 449o), and 2-nitroanisole (8.67). 

Coming back to the chain reaction sequence (Scheme 8-50) the inclusion of the final step shown here demonstrates clearly that the initial formation of the aryl radical from the diazo ether (Scheme 8-49) may be only an initiation step. The arguments of Broxton concerning whether the homolytic dediazoniation starts with the diazo ether or with the diazonium ion therefore become irrelevant. 

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