Diazonium conversion

C,H5N,NHC,Hs+HC1 = C,H 5N C1+H,NC,H5- C H5N NC H NH +HC1 gen atom of the aniline molecule, giving aminoazobenzene. Since this reaction is irreversible, whilst the former is freely reversible, the final result is the complete conversion of the diazoaminobenzene into the aminoazobenzene. (The intermediate formation of the benzenediazonium chloride can be demonstrated by adding dimethylaniline, with which the diazonium chloride couples preferentially, giving dimethylaminoazobenzene, C6HsN NC6HiN(CH3)i.)... 

The conversion of an aromatic diazonium compound into the corresponding arsonic acid by treatment with sodium arsenite in the presence of a catalyst, such as copper or a copper salt, is called the Bart reaction. A modification of the reaction employs the more stable diazonium fluoborate in place of the diazonium chlorid.i. This is illustrated by the preparation of />-nitrophenylarsonic acid ... 

An important reaction of aryl diazonium ions is their conversion to phenols by hydrolysis... 

The behaviour of pyrazoles towards nitrosation is similar to their behaviour described above towards diazo coupling, i.e. aminopyrazoles and pyrazolones readily react with nitrosation agents, like alkyl nitrites (81FES1019), to afford stable nitroso derivatives. Some simple nitrosopyrazoles have been isolated, for example the blue-green 3,5-dimethyl-4-nitrosopyrazole, and many others have been proposed as reactive intermediates in the direct conversion of pyrazoles into diazonium or diazo derivatives (Scheme 25) (B-76MI40402). 

The most interesting property of diazonium salts (448 = H) is their conversion into... 

Until recent years the only syntheses of 3-hydroxy quinoline involved multistep processes, the last step of which consisted of the conversion of 3-aminoquinoline to 3-hydroxyquinoline via the diazonium salt. " Small quantities of quinoline have been oxidized to 3-hydroxyquinoline in low yields by using oxygen in the presence of ascorbic acid, ethylenediaminetetraacetic acid, ferrous sulfate, and i)hosi)halc buffer. The decarboxylation of 3-hydroxycinchoninic, acid in boiling nitrobenzene has been re-... 

A nitro group in the 4-position markedly increases the instability of the isoxazole ring in alkaline medium. This effect is clearly demonstrated by 3,5-dime thy 1-4-nitroisoxazole. Whereas 3,5-dimethyl-isoxazole is not affected by alkali, its 4-nitro-derivative (134) is cleaved by 2% sodium hydroxide. The structure of the product was proved by its conversion into a triazole (135) with phenyl diazonium chloride, according to the original authors. ... 

While the direct halogenation of toluene gives a mixture of isomers that is difficult to separate into the pure isomers, the isomeric o- and /r-nitrotoluenes 6a and 6b, formed by nitration, are easy to separate from each other. Thus reduction of the single o- or /j-nitrotoluene 6 to the o- or /j-toluidine 7a or 7b respectively, followed by conversion into the corresponding diazonium salt 8 and a subsequent Sandmeyer reaction leads to the pure o- or /j-halotoluene 9. 

Tiazofurine (142) is an antimetabolite with antineoplastic activity. It preferentially affects leukemic lymphocytes over normal cells due to selective activation by formation of its adenine dinucleotide by transformed cells. Of the syntheses available, one starts by conversion of iniidate 138 to methyl 2,5-anhydroallonothioate (139). Next, condensation with ethyl 2-amino-2-cyanoac-etate leads to the thioamide which undergoes thiol addition to the nitrile function to produce the amminothiazolecarboxyester system of 140 directly. Sodium nitrite in aqueous hypophosphorus acid eliminates the superfluous amino group via the diazonium transformation to give 141. This synthesis of tiazofurine (142) concludes by ester amide exchange in methanolic ammonia [48]. 

Diazotization (Section 24.8) The conversion of a primary amine, RNH2, into a diazonium ion, RN2+, by treatment with nitrous acid. 

Fluorination. Attention has been focused on the direct fluorination of isoquinolines activated by conversion into 2-methylisocarbostyril (80). With gaseous fluorine (diluted to 10% with argon) in acetic acid a 54% yield of the 4-fluoro derivative was obtained. (Scheme 40). With methylene chloride as the solvent, only the 4-chloro analogue was formed [82H( 17)429]. Fluoroisoquinolines have also been made by displacement of nitro groups, and from diazonium fluoroborates (87JHC181). Hepta-chloroisoquinoline was converted into a perfluoro derivative by heating it in an autoclave with anhydrous potassium fluoride [66JCS(C)2328]. 

Conversions of diazonium salts into halogenated derivatives have been reported for compounds of type 128 and 129 [73JCS(P1)2901 80JCS(P 1)2398], Although some 7-substituted pyrazolo[ 1,5-u]pyridines have been made from the lithiated precursors, no halogeno products have been reported (92JOC5538). 

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). 

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. 

Conversion of Diazonium Salts to Aldehydes, Ketones, or Carboxylic Acids... 

Diazonium salts react with oximes to give aryl oximes, which are easily hydrolyzed to aldehydes (R = H) or ketones." A copper sulfate-sodium sulfite catalyst is essential. In most cases higher yields (40-60%) are obtained when the reaction is used for aldehydes than for ketones. In another method for achieving the conversion ArNj —> ArCOR, diazonium salts are treated with R4Sn and CO with palladium acetate as catalyst. In a different kind of reaction, silyl enol ethers of aryl ketones, Ar C(OSiMe3)=CHR, react with sohd diazonium fluoroborates, ArNj BF4, to give ketones, ArCHRCOAr. " This is, in effect, an arylation of the aryl ketone. 

Entries 7 and 8 illustrate conversion of diazonium salts to phenols. Entries 9 and 10 use the traditional conditions for the Sandmeyer reaction. Entry 11 is a Sandmeyer reaction under in situ diazotization conditions, whereas Entry 12 involves halogen atom transfer from solvent. Entry 13 is an example of formation of an aryl iodide. Entries 14 and 15 are Schiemann reactions. The reaction in Entry 16 was used to introduce a chlorine substituent on vancomycin. Of several procedures investigated, the CuCl-CuCl2 catalysis of chlorine atom transfer form CC14 proved to be the best. The diazonium salt was isolated as the tetrafluoroborate after in situ diazotization. Entries 17 and 18 show procedures for introducing cyano and azido groups, respectively. 

Coupling of 5-aminobenzotriazole 297 with a diazonium salt derived from 4-methoxyaniline generates diazo derivative 298. Conversion of the amino group into maleinimide produces dye 299 (Scheme 45). Diels-Alder cycloadditions of dye 299 to diene tagged nucleotides allows for their efficient labeling <2002CC2100>. 

An alternative approach to developing new reagents for DNA cleavage was founded in the conversion of aryl diazonium salts to aryl halides by the well-known Sandmeyer reaction. The reaction (Eq. 1) is thought to proceed via aryl radicals [7]. These reactions are high yielding and catalytic with respect... 

The isolation of diazobenzo[fr ]fluorenes as stable antitumor natural products raises several questions about their mode of action. The inability to cleave DNA by diazotization of 9-aminofluorene may imply that if the diazo functionality is involved in the mode of interaction of kinamycins with DNA, its conversion to diazonium and the ensuing reduction may seem to be of negligible importance. An additional possibility, which will be discussed later, is that 9-diazofluorene may not be the ideal model for these natural products. In exploring DNA cleavage as a possible route to the kinamycins role as a stable antitumor agent, which may supplement their speculative and as yet unconfirmed role as alkylating molecules [67], this early model seemed to suggest that the well-established activation of diazonium may not be relevant. 

A secondary reaction yields at the same time phenol ether by the replacement of the diazonium group by alkoxyl. This is clearly analogous to the conversion of diazonium salts to phenols. 

Whilst the conversion of the simple phenyl-syw-diazotate into its isomeride requires strong alkali, the syn-iotms of other diazotates are so labile that, almost instantaneously after formation from the diazonium salts, they change into the anti-iorm and hence can never be obtained in solution. An important example of this change is described under (/), namely, p-nitrophenyldiazotate, which, on coupling with j8-naphthol, yields the much-used dye para-red . 

The profitable conversion of thiouronium salts into dialkyl thioethers (see Section 4.1) is less successful for synthesis of diaryl thioethers. For example, l-chloro-4-nitrobenzene reacts with bis-thiouronium salts of the type (H2N)2CS(CH2) SC(NH2)2+ under soliddiquid and liquidrliquid conditions to produce the desired bis-thioethers, ArS(CH2) SAr, (20-35%), together with the diaryl sulphide, Ar2S (5-15%). Higher yields of the diaryl sulphide are observed under liquiddiquid conditions whereas, under solidiliquid conditions, the diaryl disulphide, (ArS)2, (20%) is also formed [56], Diaryl disulphides are the sole products (>65%) from the stoichiometric reaction of aryl diazonium salts with benzyltriethylammonium tetrathiomolybdate [57],... 

This constitutes a useful method for generating ArC02 , as in the thermolysis of (28) there is a danger of the further decomposition of (29)toAr- -f COj.Cu is also involved in the conversion of diazonium salts, ArN2 Cl , to ArCl + N2 (Sandmeyer reaction), where Ar is very probably formed transiently as an intermediate ... 

Benzenedlazonlum chloride is prepared by the reaction of anUme with nitrous acid at 273-278K. Nitrous acid is produced In the reaction mixture by the reaction of sodium nitrite with hydrochloric acid. The conversion of prlmaiy aromatic amines into diazonium salts is known as diazotisation. Due to its Instability, the diazonium salt Is not generally stored and is used immediately after its preparation. 

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