Azinium salts

An interesting extrapolation of this synthesis deals with the preparation of the bispyridinium salt 62 from 1,2-phthalic dicarboxaldehyde and its subsequent reaction with primary amines (92BSB509).Tlie expected diimines 63 readily cyclize so that 2-aryl-l-arylimino-2,3-dihydro-l//-isoindoles 64 can be isolated in excellent yields (90-95%). Contrary to the reactions performed by employing the dialdehyde and amines directly, the syntheses involving the azinium salts do not produce those typical dark-colored complex mixtures of products (77JOC4217 85JHC449) (Scheme 20). 

A series of new iV-(pyridylmethyl)azinium salts were synthesized fi om 2,4,6-triphenylpyrylium tetrafluoroborate <95T(51)12425>. 

This synthetic strategy also proved to be also suitable for the ring closure to the related [l,3,4]triazolo[2,3-a][l,3,5]tri-azinium salts, as shown in Scheme 33 <1994JHC535, 1995JHC1833> reaction of 169 with l-chloro-l,3-bis(dimethyl-amino)-3-phenyl-2-azaprop-2-enylium perchlorate gave the quaternary salt 170 in 37% yield. 

N-Amination of 2-[o-(l,3-dioxolan-l-yl)phenyl]pyridine (121) with O-tosylhydroxylamine gave an A-amino derivative, which underwent ring closure on the action of 70% perchloric acid to yield a pyrido[2,l-a]phthal-azinium salt (122, R = H) (92JHC1049). The 7-hydroxy derivative of a pyrido[2,l-fl]phthalalzinium salt (122, R = OH) was prepared similarly by cyclization of l-amino-2-(o-methoxycarbonylphenyl)pyridinium salt, ob-... 

Cycl[3,3,2]azinium salts 43, which should be potentially capable of being aromatic,lb have hitherto not been available for study.598... 

As a consequence, the properties of the ions 73 and 74 should differ much more than those of the known isoconjugates 71101 and 72.102 The cycl[4,2,2]azinium salts (73) presumably will be diatropic stable compounds. 

There are three groups of substrates for which SNH reactions are especially characteristic (i) neutral azines and azoles (ii) azinium and azolium salts and (iii) nitro-arenes. Their electron-deficiency and, thus, their ability to react with nucleophiles strongly differ from each other. Azinium salts are the more electrophilic and are able to add even neutral nucleophiles very easily. Triazines,. v-tetrazines and polynitro-arenes also possess high electrophilicity. At the same time substrates such as pyridine (82JHC1285, 72JA682) and cinnoline (03CHE87), at a low temperature (e.g. in liquid ammonia as a solvent), do not react even with sodium amide. It should also be... 

In Section II the oxidative amino-dehydrogenation of monoazines, quinolines, naphthyridines, diazines, quinazolines, quinoxalines, triazines, tetrazines, and their bicyclic analogs is extensively discussed. Section III deals with the oxidative imino-dehydrogenation of quaternised azinium salts and Section IV with NMR data of the covalent a-adducts and their kinetic and thermodynamic stabilities. 

The reactivity of halogen atoms in position 2 of oxazoles is considerably enhanced by quaternization. This is best illustrated by the synthetic utility of the salt (141) which, like other Ar-alkyl-2-halogeno-azolium and -azinium salts, effects a number of condensation reactions but it far surpasses these other salts in activity (79AG(E)707). Thus it activates carboxylic acids and it dehydrates formamides to isocyanides (Scheme 6). Amides are similarly converted into cyanides, ketones (RCH2COAr) into alkynes (RC=CAr), and cyanohydrins (RCH(OH)CN) are transformed into the corresponding chloro compounds <79CL1117>. 

Different types of activating agents have been employed in Reissert-related reactions (Scheme 6). In many cases, it is mandatory to generate, or even isolate, the corresponding azinium salt intermediate, and sequentially proceed with the nucleophilic addition. Moreover, since the former step often takes place selectively and at a fast rate, the transformation can be performed in a multicomponent manner without any functional group interference. 

By contrast, when comparing the relative reactivity of the C-3 and C-6 positions in 3,6-dichloro-5-amino-l,2,4-triazine (95) with sodium meth-oxide, a different reaction pattern was observed. Substitution takes place at C-6 and not at C-3, yielding 5-amino-3-chloro-6-methoxy-l,2,4-triazine (96). When the reaction is carried out in methanol in the presence of hydrochloric acid, C-3 substitution is observed, yielding 5-amino-6-chloro-3-methoxy-l,2,4-triazine (97) (Scheme 59) (75CCC2680). In this case we deal with N2H- and A -triazinium salts stabilized by conjugation with the amino group. In these azinium salts the electrophilicity at C-3 is likely more enhanced than at C-6. 

Cycl[2,2,2]azinium salts (5) have not been reported so far. Hiickel molecular orbital (HMO)-calculations of the isoelectronic acepentylene (6) lead to two singly occupied degenerate HOMO s. - Since there is no contribution in both the HOMO s and the LUMO from atom 6b this situation does not change in going from 6 to the 5-ion, which can be represented as an annulenone derivative of the (4 -i- 1) r-type. 

Alkylation of A-aryl-l G-benzotriazin -amines 1 leads to, depending on the reaction conditions, either 3-alkyl-Ar-aryl-l,2,3-benzotriazin-4-imines 2,2-alkyl-4-(arylamino)-l,2,3-benzotri-azinium salts 3, or mixtures of both compounds.7,8 29 (cf. Section 2.1.1.6.)... 

In a process akin to the reactions via azinium salts described in Section XIII,A, A-substituted methylpyridinium salts (13) were converted into 2-alkylidenedihydropyridines (14), and thence into indolizines (15), as shown in Scheme 4 65JCS(CC)151 67JCS(C)983], It seems likely that this sequence could be performed as a one-pot process (72CB2344), especially for the case where R Me. 

Some general reactions of the azinium salts (198) produced by reacting a-halogenocarbonyl compounds (197) with a-methylazines (196) are shown in Scheme 46. They cyclize in the presence of base to give pyrroloazines (199) or alternatively condense with a-diketones to give pyridoazinium salts (200) (the Westphal synthesis). 

Reactions of these types have been extensively utilized for synthesizing a diversity of derivatives of both types of product, and examples to demonstrate their potential are given in the following subsections. Note that the distinction between the reactions covered here and those noted in Section II,D, depending on whether the azinium salt intermediate is, or has to be, isolated, is not always clear-cut. 

Routes to the novel cyclo[4.2.2]azinium salts are shown in Scheme 16. 

The NMR spectra of 2-carbamoylmethylphthalazinium iodide (137, R = H) and its A -acyl derivatives (137, R = acyl) have been studied in some detail " the p fa values for dibenzoyl(2-phthalazinio)methanide (138) and related ylides have been measured, " and the interionic association of 2-methylphthalazinium perchlorate (139) has been compared with values for other such azinium salts." ... 

Azines, Quaternary Azinium Salts, and Azine N-Oxides... 

There are plenty of examples for the formation of o -adducts derived from the nucleophilic attack by carbanions of C-H-active compounds at unsubstituted carbon atoms of nitroarenes, azines, azinium salts, and other types of aromatic and heteroaromatic compounds [1, 2, 10-18, 45, 114—117]. As a rule, the formed C-adducts can be identified spectroscopically, and in many cases, these... 

ONSH is an efficient tool for introduction of perfluoroalkyl groups into electron-deficient arenes. Due to moderate nucleophilicity and stability of perfluoroalkyl carbanions, the reaction proceeds only with highly electrophilic arenes such as azinium salts (Scheme 11.10) [20, 21]. 

---