Heterocyclic amines diazotization

Butler recently reviewed the diazotization of heterocyclic amines (317). Reactions with nitrous acid yield in most cases N-exocyclic compounds. Since tertiary amines are usually regarded as inen to nitrosation, this... 

Compounds which correspond to 1,2-quinone diazides can also be obtained by diazotization of aromatic and nonaromatic heterocyclic amines with a hydroxy group in the ortho position. Examples include 3,4-quinolinequinone-3-diazide (2.35, Sus et al., 1953 Sus and Moller, 1955) and 3-diazochromane-2,4-dione (2.36, Arndt et al., 1951). Syntheses of more complex heterocyclic quinone diazides have been tabulated by Ershov et al. (1981, p. 105). More recent publications are cited in a paper by Tisler s group (Klotzer et al., 1984). 

Reaction of phenacyldimethylsulfonium bromides 114 with diazotized heterocyclic amine 99a yielded 7V-heteroaryl-2-oxo-2-arylethanehydrazo-noyl bromides 5e (87JHC1341). 

Heterocyclically Linked Cyclic Ammo nium Groups. Reaction of chloroacetamide with pyridine, followed by condensation with acetoacetic esters in alcoholic sodium hydroxide, leads to a 2,6-dihydroxy-4-methylpyridine that is substituted in the 3-position by a pyridinium moiety. If this is coupled with diazotized aromatic or heterocyclic amines, yellow to red cationic azo dyes (e.g., 15 [92691-25-3]) are obtained [46],... 

Triazene Dyes. If diazonium salts of N-heterocyclic amines are coupled to A-alkyl anilines, e.g., diazotized 2-aminoinomethoxybenzothiazole to A-methyl-4-nitroaniline, a triazene is obtained. A cationic triazene dye (16, diazadimethine-hemicyanine dye) is formed by subsequent A-alkylation, and dyes polyacrylonitrile a very lightfast yellow shade [39],... 

A series of 25 disperse dyes 5-7 obtained by diazotization of nitroanilines and heterocyclic amines and coupling with dialkylanilines was prepared40 and their H chemical shifts are given in Table 2. 

Most diazotized heterocyclic amines undergo normal coupling reactions with common aromatic coupling components, as well as with some C—H acidic compounds . This pertains for five-membered ring systems such as pyrrols 46 pyrazoles imidazoles 45 , l,2,4-(49) and 1,2,3-triazoles 50... 

The Bart reaction is successful with a wide variety of aromatic and heterocyclic amines. A variation in which an aromatic amine, in the presence of arsenic trichloride, is diazotized in an organic solvent (the Scheller reaction) has also found wide application. Both arsonic and arsinic acids can be prepared by the Scheller reaction which often gives better yields than the Bart reaction with electron-attracting substituents on the aromatic ring. For the commercial preparation of 4-aminophenylarsonic acid [98-50-0] (arsanilic acid), C HgAsNO, and 4-hydroxyphenylarsonic acid [98-14-6], C FTAsO the Bnchamp... 

Diazonium fluoroborates from some heterocyclic amines are so unstable that they cannot be obtained dry and these are decomposed, whilst still moist with ether, in light petroleum or xylene. Indeed all isolated diazonium fluoroborates should be treated as potentially unstable until their stability has been determined on small samples for instance, an explosion has been reported1250 with 3-pyridinediazonium fluoroborate1249 that was still moist with solvent diazonium fluoroborates from oc- and y-amino N-heterocycles usually decompose at or below 20°, so the amines are diazotized in tetrafluoroboric acid and decomposition is induced by warming the diazotization solution.1246,1247... 

Radical Reactions.—Thiazolyl, pyridyl, and other heteroaryl radicals formed by aprotic diazotization of the corresponding heterocyclic amines substitute homolytically on thiophen with the formation of 2-heteroaryl-thiophens as the main products in 20—50% yield. The results of competitive experiments indicate that the reactivity of thiophen in this reaction at 70—80 °C is slightly higher than that of benzene. The currently accepted mechanism of the decomposition of benzoyl peroxide in thiophen has been criticized on the basis of new experimental results. No free thienyl radicals are involved in the reaction, as demonstrated by scavenging experiments, and the bithienyls formed are probably derived from dimerization of a benzoyloxythiophen radical a-complex, with subsequent loss of benzoic acid. Nitrene insertion into the thiophen ring has been observed in the thermal decomposition of 2-(2-azidobenzyl)thiophen and similar compounds, leading to thieno[3,2-6]quinoline derivatives. ... 

Aminofurans substituted with electron-withdrawing groups e.g. NO2) are known and 3-amino-2-methylfuran is a relatively stable amine which can be acylated and diazotized. 2-Amino-3-acetylfurans are converted into 3-cyano-2-methylpyrroles on treatment with aqueous ammonia. This transformation is a further illustration of the relative instability of the amino derivatives of five-membered ring heterocycles compared with anilines (Scheme 67) (781003821). 

Another example of the analogy between pyrazole and chlorine is provided by the alkaline cleavage of l-(2,4-dinitrophenyl)pyrazoles. As occurs with l-chloro-2,4-dinitrobenzene, the phenyl substituent bond is broken with concomitant formation of 2,4-dinitrophenol and chlorine or pyrazole anions, respectively (66AHC(6)347). Heterocyclization of iV-arylpyrazoles involving a nitrene has already been discussed (Section 4.04.2.1.8(i)). Another example, related to the Pschorr reaction, is the photochemical cyclization of (515) to (516) (80CJC1880). An unusual transfer of chlorine to the side-chain of a pyrazole derivative was observed when the amine (517 X = H, Y = NH2) was diazotized in hydrochloric acid and subsequently treated with copper powder (72TL3637). The product (517 X = Cl, Y = H) was isolated. 

Curtius rearrangement, 933 diazotization reaction, 941 Gabriel amine synthesis, 929 heterocycle, 945... 

The diazotization of heteroaromatic amines is a ticklish procedure. In spite of the great increase in interest for disperse dyes based on heterocyclic diazo components,... 

The diazotization of heteroaromatic amines is basically analogous to that of aromatic amines. Among the five-membered systems the amino-azoles (pyrroles, diazoles, triazoles, tetrazoles, oxazoles, isooxazoles, thia-, selena-, and dithiazoles) have all been diazotized. In general, diazotization in dilute mineral acid is possible, but diazotization in concentrated sulfuric acid (nitrosylsulfuric acid, see Sec. 2.2) or in organic solvents using an ester of nitrous acid (ethyl or isopentyl nitrite) is often preferable. Amino derivatives of aromatic heterocycles without ring nitrogen (furan and thiophene) can also be diazotized. 

The high reactivity of heterocyclic diazonium ions in azo coupling reactions is the reason why in some cases the primary diazotization products cannot be isolated. For example, diazotization of 2-methyl-5-aminotetrazole (2.14) directly yields the triazene 2.15, i. e., the N-coupling product, since the intermediate diazonium ion is reactive enough to give the N-coupling product with the parent amine even under strongly acidic conditions (Scheme 2-8 Butler and Scott, 1967). 

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). 

The tetracyano derivative of 2.49, 5-diazo-l,2,3,4-tetracyanocyclopentadiene (2.52), and its heterocyclic analogue, 2-diazo-4,5-dicyano-imidazole (2.53) can be obtained by diazotization of the corresponding amines, namely the (anionic) 1-amino-... 

Neither the 2- nor 4-aminopyridine-l-oxides nor their substitution products can be protonated at the heterocyclic nitrogen. The findings regarding the diazotization kinetics of these compounds indicate that, under the reaction conditions studied by Kalatzis and Mastrokalos (1977), two simultaneous mechanisms take place. In the first of these, nitrosyl ions attack the free amine, whereas in the second they attack the protonated amine. 

Diazotization of A-heteroaromatic amines may result in hydrolytic opening of the heterocycle, as shown by the examples in Schemes 6-36 and 6-37 which were studied by the group of Ulsaker and Undheim (Hagen et al., 1974 Ranger et al., 1978) and by Davies and Jones (1970). 

The diazotization of heteroaromatic amines is a ticklish procedure. In spite of the great increase in interest for disperse dyes based on heterocyclic diazo components, little systematic knowledge is available. In a review of such diazo components13 practically nothing is mentioned on suitable methods of diazotization and on yields (which are in part low). The somewhat older review of Butler14 is, in this respect, more informative. So too is the section on synthesis in the general review on diazoazoles by Cirrincione and coworkers15. 

Diazatrimethine dyes have been prepared by oxidative coupling of a heterocyclic hydrazine with an active methylenic heterocycle as in the yellow dye (31). Alternatively they may be prepared by diazotization of an aromatic or heteroaromatic amine followed... 

Triazatrimethines are prepared by alkylation of linear triazene groups (diazoamino compounds) connecting an aromatic ring with a heterocyclic radical containing nitrogen. Thus, diazotization of an aromatic amine and coupling with, for example, a 2-aminoben-... 

Diazotization, coupling, and methylation may be combined in a one-pot process by dissolving the aromatic amine and the heterocyclic methylene base in an organic acid and effecting the simultaneous diazotization and coupling by addition of sodium nitrite. The dye base is released by addition of alkali and is methylated with dimethyl sulfate to form the alkylarylhydrazone dye (e g., 11) [27]. 

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