Diazotates Isomerism

If pure isomers are required, the ortho and meta compounds can be prepared by indirect methods. o-Nitrotoluene can be obtained by treating 2,4-dinitrotoluene with ammonium sulfide followed by diazotization and boiling with ethanol. / -Nitrotoluene can be prepared from -toluidine by acetylation, nitration deacetylation, diazotization, and boiling with ethanol. A fairly pure -nitrotoluene, which has been isolated from the isomeric mixture, can be purified further by repeated crystallization. 

These compounds were not stuicturally but stereo-isomeric, the relation being similar to that which exists between fumaric, maleic or mesaconic and citraconic acids (p. 265), or again between the tw O diazotates of potassium (p. 283), and wdiich may be represented as follow s ... 

Diazotization of 5-amino[l, 2,3]triazole 692 afforded (88BSB179) triaz-olo[l, 5-i>][l, 2,4]triazine 694 as a result of a Dimroth rearrangement of the initially formed isomeric structure triazolo[5,l-c][l,2,4]triazine 693. Molecular structure of 694 was determined by single X-ray diffraction (Scheme 146). 

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). 

More recently, Stepanov et al. (1989) investigated the acid-base properties of the zwitterion 3.22 which is obtained in the diazotization of 5-amino-3-nitro-l,2,4-triazole. Under alkaline conditions the (Z)-diazoate dianion 3.23 is formed. It can be isomerized thermally to give the (E)-diazoate dianion 3.24. If the solution of this compound is acidified, the primary addition of a proton takes place at the anionic ring nitrogen yielding 3.25, and subsequently the hydrogen-bond-stabilized (Z)-iso-mer (3.26). Further acidification gives the nitrosoamine (3.27). 

Scheme 5-14 may be called a two-dimensional system of reactions, in contrast to Scheme 5-1 which consists of a one-dimensional sequence of two acid-base equilibria. In Scheme 5-14 the (Z/E) configurational isomerism is added to the acid-base reactions as a second dimension . The real situation, however, is yet more complex, as the TV-nitrosoamines may be involved as constitutional isomers of the diazohydroxide. In order not to make Scheme 5-14 too complex the nitrosoamines are not included, but are shown instead in Scheme 5-15. The latter also includes the addition reactions of the (Z)- and ( )-diazoates (5.4 and 5.5) to the diazonium ion to form the (Z,Z)-, (Z,E)- and (2 2i)-diazoanhydrides (5.6, 5.7 and 5.8) as well as proto-de-nitrosation reactions (steps 10, 11 and 12). This pathway corresponds to the reverse reaction of diazotization, as amine and nitrosating reagent (nitrosyl ion) are formed in this reaction sequence.

The reaction sequence starts from tetrazolyldiazonium salt 42 prepared from aminotetrazole 41 by diazotation. This compound when reacted with arylformylacetonitrile 43 leads to the intermediate formation of the condensation product 44, which easily undergoes ring closure to 45. This tetrazolo[5,l-z][l,2,4]triazine compound, however, forms an equilibrium with the valence bond isomeric azide 46, which can participate in a different ring closure than the reverse route, and yields the tetrazolo[l,5-A][l,2,4]triazine product 47. The reaction was carried out with a series of various aryl derivatives and proceeded in good to excellent yields (68-87%). 

In this connexion the spatial isomerism of the oximes must also be mentioned. A theory for this type of isomerism had already been suggested by Werner and Hantzsch and is similar to that already discussed in the case of the diazotates. According to this theory, those oximes in which the C-atom bearing the isonitroso-group is also united to two different radicles exist in a syn- and an anti-form ... 

Acylhydrazides of anthranilic acid (35, R = NHCOR ) give 3-acylamino-l,2,3-benzotriazin-4(3H)-ones (10, R = NHCOR on treatment with nitrous acid. The triazine hydroxamic acid (40) and its benzo-substituted derivatives are available by diazotization of the corresponding o-aminobenzohydroxamic acids. The pyrido[2,3-e]triazine analog (41) was prepared similarly from 3-aminoisonicotino-hydroxamic acid, but the isomeric 2-aminonicotinohydroxamic acid failed to react under the same conditions to give 42. ... 

Quinazolino[3,2-c]l,2,3-benzotriazin-8(7//)-imine (611) was prepared from 4-amino-2-(2-aminophenyl)quinazoline (609) by diazotization, followed by basilication of the resulting diazonium salt (610). The isomeric... 

The coupling of diazotized 3-amino-l,2,4-triazole to aromatic amines affords azo dyes that require two equivalents of an alkylating agent to convert them to diazadimethine dyes. A mixture of two isomeric dyes is obtained, e.g., 34a and... 

Azine approach. Diazotization of 3-amino-2-mercaptopyridine is a very convenient way for preparing simple members of this ring system (743) <74CS(6)222>. 7-Amino derivatives (663) are available by the isomerism reaction of u-triazoles (662 R = H) on heating in 1-propanol (72JOC3601). The same transformation occurs in pyridine nucleosides (662 R = (3-D-ribose) (76JOC1449). 

If the procedure is reversed, and the diamine is coupled first with the intei-mediate benzidine-salicyclic acid compound and then with diazotized sulfanilic acid, an isomeric dye, having the following structure, is formed ... 

The nitrobenzene solution, together with the suspended solid material, is shaken with a mixture of 300 cc. water and 100 grams of ice, then twice with 100-cc. portions of cold water. The combined aqueous extracts are filtered through a moistened paper and then saturated with 200 grams of salt, whereupon sodium 2-naphthol-l-sulfonate is precipitated in colorless plates. Stirring is continued until all of the salt is dissolved, and the mixture is allowed to stand overnight, then filtered. The product is pressed out and washed twice with saturated salt solution. The filter cake is used directly for the preparation of 2-naphthyl-amine-l-sulfonic acid after tests have shown that it does not fluoresce in soda solution and does not yield a water soluble, orange red dye with diazotized aniline and thus does not contain isomeric naphtholsul-fonic acids. 

The isomeric nitrochloroanilines can also be diazotized in this way when they are available in paste form. If the bases are to be used in the dry state, the procedure of example 11 can be used. Alternatively, the base can be made into a paste fay dissolving in about 10 parts of concentrated sulfuric acid, pouring the resulting solution, with stirring, onto ice, filtering off the precipitate, and washing it with cold water until it is free from sulfuric acid. 

Halopyridazines were likewise successfully iV -oxidized. 3-Chloro-pyridazine gives the corresponding 1-oxide with perbenzoic acid, whereas the isomeric 2-oxide is prepared indirectly by adding powdered copper to a diazotized solution of 3-aminopyridazine 2-oxide in hydrochloric acid-. " After earlier reported - failures to prepare 3,6-dichloropyridazine A-oxide from 3,6-dichloropyrid-azine and hydrogen peroxide in acetic acid [6-chloro-3(2/ )-p3nrid-azinone was isolated due to hydrolysis], the desired A-oxide was later obtained in low yield. " The yield of 3,6-dichloropyridazine A-oxide can be improved when using monoperphthalic acid in ethereal solution or perbenzoic acid in chloroform. ... 

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