Fluoro-nitrogens

Rebertus 8c B.W. Nippoldt, JOC 32(12), 4044—45 (l967) CA 68, 21462(1968) (Organic fluoro-nitrogens. VIII. Hydrolytic reactions of tetra-fluoroformamidine and pentafluoroguanidine)... 

FIGURE 15.32 (a) Replacement of ester ether oxygen by a fluoro-nitrogen (b) Exo-endo amidine in place of a car-... 

Clark HR, Beth LD, Burton RM, Garrett DL, Miller AL, Muscio OJ (1981) Kinetic study of the acid-promoted hydrolysis of some representative 2-fluoro nitrogen heterocycles. J Org Chem 46 4363-4369... 

An interesting illustration of a bielectrophile contributing two heteroatoms to the resultant five-membered ring is the 2-alkyl-2-chloro- (or fluoro-) sulfonylcarbamoyl chlorides (212). With methylhydrazine initial attack by the more basic nitrogen occurred on the carbamoyl chloride, and this was followed by base-induced cyclization to 1,2,3,5-thiatriazolidine derivative (213) (77JCR(S)238, 77JCR(M)2813). Other reactions of this type are discussed in Chapter 4.28. 

Diazoketones react with trifluoromcthyl hypofluorite to give a mixture of a,a-difluoro ketones and o-fluoro-a-trifluoromethoxy ketones [70, 71] With elemental fluorine, two fluorine atoms replace the nitrogen in both diazoketones and unactivated diazo eompounds [70, 72, 73] (equation 9)... 

Into a suspension of 8 g of sodium acetate m 400 mL of a solution of 1 part acetic acid and 10 parts fluorotnchloromethane is passed at -75 C a stream of fluonne diluted to 10% with nitrogen The reacuon is stirred with a Vibromixer A solution of 4-methylacetanilide (20 mmol) in a mixture of dichloromethane and fluorotnchloromethane cooled to -75 °C i s added to 20 mmol of acetyl hypofluonte as determined by titration with potassium iodide After 5 min the mixture is poured into water, and the orgamc layer is washed with sodium bicarbonate soluaon and dried over anhydrous magnesium sulfate After concentrauon and column chromatography over silica gel and elution with chloroform, 2-fluoro-4-methylacetanilide IS obtained m 85% yield... 

In the field of nucleosides, an interesting example of a cleavage of a nonfluor-inated six-membered cyclic ether containing oxygen and nitrogen atoms to give a fluoro nucleoside has been reported [5] (equation 5)... 

Nitrite ion, an ainbident nucleophile in aprotic solvents, favors nitrogen atom attack on the double bond of various fluoro(halo)olefins. 2-Monohydroperfluoro-nitroalkanes can thus be produced [5] (equation 5)... 

Nilrosated fluoro compounds are frequently prepared by electrophilic nitrosation on an electron-nch center of oxygen, nitrogen, or carbon The preparation of fluorochloronitronitrosomethane from the decarboxylation of fluorochloronitro-acetic acid in nitric acid is unique [f ] (equation 1)... 

Boranes 1 and 2 in equation 89 react with 2-fluoro-1,3-dioxa-2-phospholanes to give nng expansion products as the corresponding antimony analogues yield the products of msertion of nitrogen into the antimony-fluorme bond [775] (equation 89) (Table 31)... 

Spectroscopic evidence indicates that protonation of 2-fluoro-and 2-chloro-quinoline is not appreciable in O.OlJf aqueous hydrochloric acid. Protonation becomes evident in more strongly acidic solution in the case of the chloro compound without any accompanying decomposition, but the fluoro compound hydrolyzes to carbostyril under the latter conditions. The hydrolysis is acid-catalyzed, but it is doubtful whether protonation on the heterocyclic nitrogen is responsible, owing to its low basicity (presumably below that for the chloro compound). An alternative explanation in this case would be hydrogen bond formation with fluorine, Ar—F. .. H-O+H2. 

Formation of N- and N,0-heterocycles from fluoro-substituted nitrogen ylides 99MI23. 

Preparation of 3,20-Disemicarbazone of 9a-Fluoro-110,17a,21-Trihydroxy-16a-Methyl-l,4-Pregnadiene-3,20-Dione A mixture of 1.00 gram of 9o-fluoro-11(3,17o,21 trihydroxy 16o methyl 1,4 pregnadiene 3,20 dione, 750 mg of semicarbazide base, 280 mg of semicarbazide hydrochloride in 20 ml of methanol and 10 ml of dimethylformamide is refluxed for 20 hours under nitrogen. The mixture Is cooled to 20°C and 100 ml of water Is added with stirring. The precipitated 3,20-disemicarbazone of 9o -fluoro-11(3,17o, 21-trihydroxy-16o -methyl-1,4-pregnadiene-3,20-dione Is filtered, washed with water, and dried in air MP over 300°C. 

Preparation of A -Pregnadiene-9a-Fluoro-11, 16a,17a,2l-Tetrol-3,20-Dione A solution of 100 mg of A -pregnadiene-9a-fluoro-11, 16a,17a,21-tetrol-3,20-dione 16,21-diacetate was dissolved in 10 ml of methanol and cooled to 0°C. After flushing with nitrogen, a solution of 35 mg of potassium hydroxide in 2 ml of methanol was added to the steroid solution. After standing at room temperature for 1 hour, the solution was neutralized... 

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