Syntheses and degradations of fluorinated heterocyclics III. Perfluoroalkyl and perfluoroalkylether-1,3,4-oxadiazoles

2,5-Bis(perfluoro-n-heptyl)-, 2-perfluoroalkylether-5-perfluoro-n-heptyl-, and 2,5-bisperfluoroalkylether-1,3,4-oxadiazoles were synthesized and characterized. 2,5-Bis(perfluoro-n-heptyl)-1,3,4-oxadiazole was thermally and hydrolytically stable at 325°C; however, in the presence of air, degradation took place at 235°C. The perfluoroalkylether analogue exhibited thermal and hydrolytic stability at 325°C; it was found to be unaffected by Jet-A fuel and air at 235°C. At 325°C in air some degradation occured as evidenced by volatiles production, oxygen consumption, and 96% starting material recovery.     

Syntheses and degradations of fluorinated heterocyclics

Tris (perluoro-n-heptyl)-s-triazine, the perfluoroether substituted-s-triazine [C₃F₇OCF(CF₃)CF₂OCF(CF₃]₃C₃N₃, 1,4-bis[(5-perfluoro-n-heptyl)-1, 2,4-oxadiazolyl]benzene, its perfluoroalky ether substituted analogue, and 3,5-bis(perfluoro-n-heptyl)-1,2,4-oxadiazole were synthesized and characterized. Each of these compounds was subjected to thermal and oxidative degradation at 235 and 325°C and to hydrolytic degradation at 235°C. Two benzene derivatives decomposed completely during heating in nitrogen or air at 325°C, tris(perfluoro-n-heptyl)-s-triazine was quantitatively hydrolyzed at 235°C. The perfluoroalkyl ether substituted triazine and 3,5-bis(perfluoro-n-heptyl)-1,2,4- oxadiazole were found to be stable under all conditions employed as evidenced by practically quantitative recovery of the test samples.     

Syntheses and degradations of fluorinated heterocyclics. IV. Imidoylamidoximes, 1,2,4-oxadiazole precursors

Perfluoroalkylether amidoximes free from amide-contamination were prepared from imidate esters. The amidoximes were stable at 110°C; at ～170°C partial decomposition to 1,2,4-oxadiazoles, admixed with other compounds, took place. Interactions between nitriles and amidoximes at 50°C resulted in the formation of imidoylamidoximes; these dissociated readily into their constituents when subjected to higher temperatures. At 70°C and above, in the presence of excess nitrile or other ammonia acceptors, the imidoylamidoximes afforded high yields of the corresponding 1,2,4- oxadiazoles.     

Synthesis of fluorinated 1,2,4-oxadiazin-6-ones through ANRORC rearrangement of 1,2,4-oxadiazoles

The reaction of 3-ethoxycarbonyl-5-perfluoroalkyl-1,2,4-oxadiazoles with hydroxylamines has been investigated, evidencing the possibility of competitive reaction paths. Nucleophilic addition of hydroxylamine to the electrophilic C(5) of the 1,2,4-oxadiazole ring, followed by ring-opening and ring-closure with enlargement, leads to high yield and in very mild experimental conditions to the formation of 5-hydroxyamino-3-perfluoroalkyl-6H-1,2,4-oxadiazin-6-ones, one of these presenting water gelation ability. In turn, reactions with N-methylhydroxylamine lead the exclusive formation of 4-perfluoroacylamino-2-methyl-2H-1,2,5-oxadiazol-3-ones through the well known Boulton-Katritzky rearrangement.     

Photochemistry of fluorinated heterocyclic compounds. An expedient route for the synthesis of fluorinated 1,3,4-oxadiazoles and 1,2,4-triazoles

The photochemistry of some 3-N-alkylamino-5-perfluoroalkyl-1,2,4-oxadiazoles in the presence of nitrogen nucleophiles such as ammonia and primary and secondary aliphatic amines has been investigated. The primary photolytic intermediate from the cleavage of the ring O-N bond follows two distinct and competing pathways leading to (i). 5-perfluoroalkyl-1,3,4-oxadiazoles, through the ring contraction-ring expansion photoisomerization route favored by the presence of the base or (ii). 5-perfluoroalkyl-1,2,4-triazoles, through the intervention, as an internal nucleophile, of the exocyclic N-alkylamino moiety of the oxadiazole followed by the attack of the external nitrogen nucleophile and subsequent heterocyclization. Some comments on the photoreactivity of fluorinated oxadiazoles and on the applications of these photoprocesses in the synthesis of target fluorinated structures are emphasized. In this context, irradiations of 3-perfluoroalkanoylamino-4-phenylfurazan in the presence of primary aliphatic amines are reconsidered as feasible one-pot synthetic methodologies toward fluorinated heterocycles. X-ray analysis of two representative products 1-methyl-3-methylamino-5-perfluoroheptyl-1,2,4-triazole and 2-methylamino-5-trifluoromethyl-1,3,4-oxadiazole confirmed the proposed structures and furnished interesting information on the crystal packing of these fluorinated five-membered heterocycles.     

Synthesis of fluorinated indazoles through ANRORC-like rearrangement of 1,2,4-oxadiazoles with hydrazine

A series of 6-substituted fluorinated indazoles has been obtained through an ANRORC-like rearrangement (Addition of Nucleophile, Ring-Opening and Ring-Closure) of 5-tetrafluorophenyl-1,2,4-oxadiazoles with hydrazine. The initial addition of the bidentate nucleophile to the electrophilic C(5) of the 1,2,4-oxadiazole ring, followed by ring opening and ring closure, leads to the formation of fluorinated indazoles in high yield under mild experimental conditions. Functionalization of the C(6) in the final indazole nucleus was preliminarily achieved through a nucleophilic aromatic substitution on the starting 5-pentafluorophenyl-1,2,4-oxadiazole.     

Syntheses of substituted-oxazolo-1,3,4-thiadiazoles, 1,3,4-oxadiazoles,and 1,2,4-triazoles

Starting from readily available methyl 5-methyloxazole-4-carboxylate ( 1 ) and 4-methyl-5-oxazolylcar-boxylic acid hydrazide ( 11 ) the title compounds were prepared. The reaction of compound 1 with hydrazine hydrate afforded the corresponding hydrazide 2 . The reaction of compound 2 with formic acid yielded 1-formyl-2-(5-methyloxazole-4-carboxyl)hydrazine ( 3 ). Refluxing of the latter with phosphorus pentasulfide in xylene gave compound 5 in 62% yield. The reaction of compound 3 with phosphorus pentoxide afforded compound 4 . Starting from hydrazide 11 , compounds 13 and 14 were prepared similarly. Reaction of compound 2 with substituted isothiocyanate yielded compound 9 which was cyclized in basic medium to 4-alkyl-5-(5-methyl-4-oxazolyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione ( 10 ). The isomer 19 was prepared similarly. Methylation and subsequent oxidation of compound 19 gave compound 21 . Reaction of the acid 7 with thiosemicarbazide in the presence of phosphorus oxychloride gave 2-amino-5-(5-methyl-4-oxazolyl)1,3,4-thiadiazole ( 8 ). 2-Amino-5-(4-methyl-5-oxazolyl)-1,3,4-thiadiazole ( 17 ) was prepared from acyl chloride 15 by the usual method.     

3,5-Disubstituted-1,2,4-oxadiazoles and 4,5-dihydro-3,5-disubstituted-1,2,4-oxadiazoles

A series of 3,5-disubstituted-1,2,4-oxadiazoles ( 2 ) were prepared from a mono- or dichlorophenyl-substituted amidoxime and (i) an acid chloride, (ii) an isatoic anhydride, or (iii) a β-keto ester. Although cyclizations of the same amidoximes with acetaldehyde gave 4,5-dihydro-5-methyl-substituted derivatives ( 5 ), that annulation procedure either failed or gave low yields with other aldehydes. A novel alternative method, the diborane reduction of 2 , has been found to be a generally applicable procedure for preparing 5 . The reduction is regioselective, i.e., only the 4,5-(C=N) linkage is reduced even when a large excess of diborane is present.     

Synthesis of fluorinated first generation starburst molecules containing a triethanolamine core and 1,2,4-oxadiazoles

5-Pentafluorophenyl-1,2,4-oxadiazoles, differently substituted at C(3), have been synthesized and used to functionalize the aliphatic primary hydroxyl functionalities of triethanolamine, under mild conditions. UV-visible absorption and emission spectra are reported, for both tri- and difunctionalised molecules, showing their potential applications as light-emitters in optoelectronic devices.     

Synthesis of 1,2,4-triazoles and 1,2,4-oxadiazoles

Monothiodiacylamines reacted regiosepecifically with hydrazines and hydroxylamine to give substituted 1,2,4-triazoles and 1,2,4-oxadiazoles in excellent yields.     

Syntheses,Crystal Structures,and Biological Activities of Two 5-Pyrimidinyl-1,2,4-oxadiazoles

Two 5-pyrimidinyl-1,2,4-oxadiazoles were synthesized through two different routes and their structures were characterized by single-crystal X-ray diffraction, NMR and MS. Compound 3, 5-(2-chloro-4-methyl-6-phenylpyrimidin-5-yl)-3-phenyl-1,2,4-oxadiazole, crystallizes in orthorhombic, space group Pbca with a = 19.1575(11), b = 8.2115(5), c = 21.2035(12), V = 3335.6(3)3 and Z = 4. Compound 6, 5-(2,6-dichloropyrimidin-4-yl)-3-phenyl-1,2,4-oxadiazole, crystallizes in monoclinic space group Pn with a = 8.4275(13), b = 5.4088(8), c = 13.493(2), β = 99.768(3)o, V = 4658.6(6)3 and Z = 8. Preliminary bioassay indicated that the two title compounds had good herbicidal activities.     

1,2,4- and 1,2,5-oxadiazoles

It is shown that the first step in the reduction of the investigated oxadiazoles on a dropping mercury cathode in dimethylformamide corresponds to two-electron cleavage of the N-O bond. The degree of reduction is determined by the nature and position of the substituents in the oxadiazole ring and by the rate of protonation of the intermediately formed particles.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 38–40, January, 1979.     

Diphosphatetraazacyclooctatetraenes. II. Properties and degradations

1,5-Bis(diphenylphospha)-3,7-bis(perfluoroalkylether)-2,4,6,8- tetraazacyclooctatetraene and 1,3-bis(diphenylphospha)-5,7-bis(perfluoroalkylether) -2,4,6,8-tetraazacyclooctatetraene were found to decompose at 316°C to phospha-s-triazines. The symmetrical arrangement liberated perfluoroalkylether nitrile with concommitant formation of the corresponding diphospha-s-triazine; the unsymmetrical isomer eliminated the (C₆H₅)₂PN unit to give the monophospha-s-triazine. The thermal and oxidative stabilities of the two compounds differed widely, with the unsymmetrical isomer being significantly more stable than the symmetrical arrangement. Spectral data pertinent to these results are discussed. Both materials were found to be effective in arresting perfluoroalkylether fluid degradation in oxidizing atmospheres in the presence of metal alloys.     

Solid-phase synthesis of 1,2,4-oxadiazoles

The synthesis of 3,5-substituted 1,2,4-oxadiazoles on solid support is described. Benzoic acids bound to the Wang linker on a polystyrene resin are activated and allowed to react with N-hydroxyamidines. The resulting acylated N-hydroxyamidines are converted into 1,2,4-oxadiazoles at 125°C.     

On the reaction of some 5-polyfluoroaryl-1,2,4-oxadiazoles with methylhydrazine: synthesis of fluorinated indazoles

The reaction of 5-polyfluoroaryl-1,2,4-oxadiazoles with methylhydrazine has been studied and the synthesis of fluorinated N-methylindazoles has been realized. Rearrangement reactions showed predominantly formation of N(1)-methylindazole regioisomers. Starting compounds were preliminarily functionalized at the polyfluoroaryl moiety through fluorine displacement with nucleophiles (methanol, methylamine, dimethylamine), allowing the obtainment of target indazoles substituted at the C(6) position.     

One-pot synthesis of fluorinated 2-amino-pyrimidine-N-oxides. Competing pathways in the four-atom side-chain rearrangements of 1,2,4-oxadiazoles

Trifluoromethylated 2-amino-pyrimidine N-oxides have been synthesized by reaction of the 3-amino-5-methyl-1,2,4-oxadiazole with trifluoromethyl-β-diketones in the presence of perchloric acid, followed by hydrolysis. In this ring-to-ring transformation an initial formation of (unisolated) 1,2,4-oxadiazole-pyrimidinium salts, and subsequent ring-opening at the oxadiazole moiety occurs. Isolation of 2-(hydroxyamino)-pyrimidine from the reaction mixture evidenced the presence of a competing pathway where the N(4) nitrogen of the oxadiazole is involved in the formation of a regioisomeric pyrimidinium salt. The effect of the trifluoromethyl group on the product distribution is discussed. By X-ray analysis, the crystal structure of two different N-oxide regioisomers has been unambiguously ascertained.     

Photochemistry of 1,2,4-oxadiazoles. A DFT study on photoinduced competitive rearrangements of 3-amino- and 3-n-methylamino-5-perfluoroalkyl-1,2,4-oxadiazoles

The photoinduced competitive rearrangements of 5-perfluoroalkyl-3-amino(N-alkylamino)-1,2,4-oxadiazoles have been investigated by DFT calculations and UV-vis spectroscopy. The observed product selectivity depends on the number of hydrogen atoms present in the amino moiety and involves two or three possible routes: (i) ring contraction-ring expansion (RCRE), (ii) internal-cyclization isomerization (ICI), or (iii) C3-N2 migration-nucleophilic attack-cyclization (MNAC). UV absorption and fluorescence spectra of the reactants, and vertical excitation energy values, calculated by time dependent DFT, support the involvement of a neutral singlet excited state in the photoexcitation process. The values of the standard free energy of the most stable prototropic tautomers of reactant, products, proposed reaction intermediates, and deprotonated anionic transition states allowed us to rationalize the competition among the three rearrangements, in agreement with chemical trapping experiments, in terms of: (i) the evolution of the excited state toward three stable ground-state intermediates, (ii) tautomeric and deprotonation equilibria occurring in methanol solution for each intermediate, and (iii) relative stabilization of intermediates and transition states in the thermally driven section of the reaction.     

Synthesis of 3-carbamoyl-1,2,4-oxadiazoles

A convenient method for the synthesis of 3-carbamoyl-1,2,4-oxadiazoles from carbamoylamidoximes and chlorides or anhydrides of haloacetic acids was developed. The reactions of 3-carbamoyl-5-trichloromethyl-1,2,4-oxadiazoles with amines and N,N-dimethylhydrazine were studied.     

Heterocyclic photorearrangements. Photoinduced rearrangement of 3-styryl-1,2,4-oxadiazoles

The photochemical behaviour of 3-styryl-5-phenyl-(5-methyl)-1,2,4-oxadiazoles in methanol at 254 nm has been investigated. A photoinduced rearrangement to the quinoline system has been pointed out and explained as proceeding through an initial photolysis of the ring O? N bond, followed by a six membered ring closure reaction involving the styryl moiety.