Azines, fluorination

Azides, Diazoalkanes, Diazirines, Azo-compounds, and Azines. Fluorinated alkanoyl azides have been dealt with already in other sections, mainly that concerned with isocyanates (see pp. 227,228, and 229). The azides CHFa Ns, (CFs)2C(N3) O SiMes, and (CF3)sC(Ns) O SOsO have been obtained from the reaction systems CHFsCl-NaNs-alkali-HsO-dioxan, (CF3)2CO-Me8Si N3,i and (CF3)2C(Ns) ONa-S2O5CIX (X = F or Cl), respectively. Eleven 2-azido-3,3>difluorocyclobutenes have been synthesized as indicated in Scheme 49 and converted thermally or photo-chemically into the corresponding 2,2-difluorocyclopropanes decomposition of the 1-cyano- and 1-methoxycarbonyl-cyclobutenes in the presence of electron ri( aromatics gave pyrrole derivatives. These results have been discussed in terms of the mechanistic pathways contained in Scheme SO Neber rearrangement with EtsN... 

Fluorine and phosphorus occasionally appear attached to, or as part of, heterocyclic rings. However, very little systematic attention has been paid to them, in the area of the azines,... 

Simple criss-cross cycloadditions described so far are in fact limited to aromatic aldazines and cyclic or fluorinated ketazines. Other examples are rather rare, including the products of intramolecular criss-cross cycloaddition. The criss-cross cycloadditions of hexafluoroacetone azine are probably the best studied reaction of this type. It has been observed that with azomethine imides 291 derived from hexafluoroacetone azine 290 and C(5)-C(7) cycloalkenes < 1975J(P 1)1902, 1979T389>, a rearrangement to 177-3-pyrazolines 292 competes with the criss-cross adduct 293 formation (Scheme 39). 

Fluorine and phosphorus occasionally appear attached to, or as part of, heterocyclic rings. However, very little systematic attention has been paid to them, in the area of the azines, and it would not be appropriate to detail the work here. With other nuclei (2H, 3H, 29Si, etc.) information is still more scarce, and reference should be made to the specialized reviews in this area. 

Although the last method gives satisfactory results, it requires a large excess of iodine monofluoride which has to be prepared from iodine and fluorine just prior to use. Furthermore, most of the unsubstituted hydrazones are rather unstable and undergo transformation into azines which are unrcactive towards iodine monofluoride. O-Methyloximes are also inactive with respect to iodine monofluoride. The procedure with bromine trifluoride is free of such limitations. 

Fluoroalkylketenimines may be obtained from fluorinated alkenes and 60 undergoes a series of cycloaddition reactions, including formation of the quinoline derivative 61.149 Hexafluoroacetone azine (62) also reacts with acetylenes150 and the formation of pyrazoles (63) has been formulated as involving the quite novel migration of a trifluoromethyl group. 

Displacement of an aryl halogen by a nucleophile such as an amino group is more easily achieved with fluorine this is usually evident in greater yield and/or milder conditions. This is exemplifled in the following two syntheses of the antipsychotic drug thioridazine (9.5) [3730] the related antiemetic metopim-azine may also be synthesized in this way. Phenothiazines have been reviewed [B-44j. 

To sulfolane (tetrahydrothiophene 1,1-dioxide 930 g) heated up to 60"C, were added pulverized NaF (360 g, 8.6 mol) and 2,4,6-trichloro-l,3,5-triazine (1 450 g, 2.44 mol). The mixture was stirred and heated to 75 C to initialize the reaction. The temperature was then raised to about 120 "C so that the 2,4.6-triflu-oro-l,3,5-triazine formed could begin to distill off further heating to 220X caused the product to distill over completely. N2 gas bubbled into the distillation flask evaporated the residual 2,4,6-trifluoro-l,3,5-tri-azine yield 286 g (86.8%) bp 70-74 X. The distillation residue was 1460 g of a suspension of NaCl in sulfolane, which contained HF and partially fluorinated triazines. 

Similarly to fluorinated ketones, electrophilic polyfluorinated azines and rmidoyl fluorides undergo [2 + 2 + 2] cycloaddition reaction with quadricyclane (12) to afford fluorinated norbornenazetidines 73-74 (Scheme 2.35). 

Barlow, M.G. Suliman, N.N.E. Tipping, A.E. Unsaturated nitrogen compounds containing fluorine. Part 18. Novel cycloaddition products from the reaction of quadricyclane with fluorinated azines and the azomethine imide 2-hexafluoroisopropylidene-3-methyl-3-phenyl-5,5-bis(trifluoromethyl)tetrahydropyrazol-2-ium-l-ide. J. Fluorine Chem. 1995, 72(1), 147-156. 

Criss-cross cycloaddition reactions with hexafluoroacetone azine to give partially fluorinated heterocycles and polymers 06H(67)443. gem-Disubstituent effect in formation of heterocycles 05CRV1735. 

KhudinaOG, Shchegol kovEV, BurgartYV, Kodess MI, Kazheva ON, Chekhlov AN, Shilov GV, Dyachenko OA, Saloutin VI, Chupakhin ON (2005) Synthesis and the reactions of tri-fluoromethylated 1,2,3-triketones 2-(het)arylhydrazones and 4,7-dihydroazolo[5,l-c]tri-azines. J Fluorine Chem 126 1230-1238... 

Various reviews have been published about this topic. Jeschke and Leroux [2] pubhshed about the medical apphcation of a-fluorinated ethers. Leroux and Pazenok [1] wrote about the synthesis and the properties of trifluoromethyl ethers. Leroux, Jeschke and Schlosser [3b] reviewed the properties of a-fluorinated ethers, thioethers and amines. The work of Boiko [4a] is dedicated to aromatic and heterocyclic perfluoralkyl sulfides. Vovk and Gakh [4b] gave a detailed review about trifluoro-methoxy containing azoles and azines. This review summarized the literature data on synthesis and biological activity of trifluoromethoxy, difluoromethoxy and a-fluorinated sulfides derivatives of five and six membered heterocycles. 

Taking into account that nucleophilic substitution reactions of azines 55,56 typically do not occur in untreated DMSO and KF 2H2O under traditional heating, it is safe to assume that microwave irradiation promotes dissociation of KF and desolvation of the fluorine anion, which subsequently takes part in the nucleophilic substitution reaction, similarly to spray-dried KF in anhydrous DMSO (Fig. 2). 

The methods of synthesis of fluorine-containing pyridines described in the given review specify growing interest to chemistry of these compounds that is caused by the big practical importance of fluorinated azines. 

Therefore in the literature there are some N NMR data of ring fluorinated diazines. The N NMR of perfluorinated diazines are summarized in Table 7 [144], Also recently few works devoted to theoretical calculations of couphng constants in fluorinated azines were published [145,146],... 

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