Perfluoro-2-methylpent-2-ene

From the reaction mixture of 2-aminopyridine and perfluoro-2-methylpent-2-ene in MeCN a 9 1 mixture of 2,4-difluoro-2-penta-fluoroethyl-3-trifluoromethyl-4//- and isomeric 2,4-difluoro-4-penta-fluoroethyl-3-trifluoromethyl-2//-pyrido[l, 2-a]pyrimidine (64%), and 2-pentafluoroethyl-3-trifluoromethyl-4//-pyrido[l,2-a]pyrimidine-4-one (20%) was isolated (00JFC105). 

Cyclocondensation of 2-iminopiperidine and 3-aryl-2-propynylnitriles afforded 4-aryl-2-imino-6,7,8,9-tetrahydro-22/-pyrido[l,2- ]pyrimidines <20000L3389, 2002W002/00629>. The minor isomers, 2-aryl-4-imino-6,7,8,9-tetrahy-dro-4/7-pyrido[l,2- ]pyrimidines could also be isolated in 2-30% yields from the reaction mixtures <20000L3389>. When the reactions were carried out in the presence of 2 equiv of NaHMDS, the product ratio was reversed. From the reaction mixture of 2-aminopyridine and perfluoro-2-methylpent-2-ene in MeCN, a 9 1 mixture of 2,4-difluoro-2-pentafluoroethyl-3-trifluoromethyl-477- and the isomeric 2,4-difluoro-4-pentafluoroethyl-3-trifluoromethyl-277-pyr-ido[l,2- ]pyrimidine (64%), and 2-pentafluoroethyl-3-trifluoromethyl-47/-pyrido[l,2- ]-pyrimidine-4-one (20%) was isolated <2000JFC(103)105>. 

Fluorinated azetines 1 and 2 are obtained by treatment of perfluoro-2-methylpent-2-ene with heteroaromatic amines (e.g. 6-bromobenzothiazole) and with the more nucleophilic aliphatic amines (e.g. isopropylamine), respectively <00MI99>. 

Two approaches have been applied for the synthesis of imidazo[2,l + thia/,ole ring systems. Reaction of 2-mercapto-benzimidazole with perfluoro-2-methylpent-2-ene in the presence of triethylamine gave compound 419 (Equation 192), and cyclocondensation of 2-imidazolidinethione with the alkynyl(phenyl)iodonium salt 420 afforded product 421 (Equation 193) <2001RCB1446, 2003JCM715>. 

A complex reaction between perfluoro 2-methylpent-2-ene and carboxylic acids in the presence of potassium carbonate and Aliquat produces the acid fluoride, as the major product, with variable amounts of the 3-acyloxy perfluorinated alkene [37]. The procedure has little value for the synthesis of either compound. 

The reaction between 2-aminopyridine and 2-amino-4-methylpyridine with perfluoro-2-methylpent-2-ene gave pyrido[l,2-a]pyrimidines, but 2-amino-6-methylpyridine gave the naphthyridine (220) (74CC134). 

The acidic form of sodium fluoride, sodium bifluoride is scarcely used for introduction of fluorine in organic compounds. One reported example is the addition of bromofluorine to perfluoro(2-methylpent-2-ene) (20) generated by reacting A V -dibromodimethylhydantoin with acidic sodium fluoride in the presence of tetrabutylammonium hydrogen difluoride at 0°C to give 21.20... 

In the presence of freeze-dried potassium fluoride, perfluoro-2-methylpent-2-ene reacts with activated methylene compounds to yield pyrans (81MI22400). The fluoride ion abstracts a proton from the methylene group and subsequent condensation of the carbanion with the perfluoroalkene affords a dienone (19) which ring closes to the pyran (20 Scheme 3). In the case of pentane-2,4-dione a divinyl ether (21) is also formed. This product is considered to arise from reaction of the alkene at the oxygen of the enolate ion. 

A patent assigned to Central Glass describes the rearrangement of internal perfluoroalkenes with potassium fluoride and a crown ether in acetonitrile. For example, periluoro(4-methylpent-2-ene) (7) can rearrange to the more stable isomer perfluoro(2-methylpent-2-ene) (8) by heating for 3 hours at 40 C in acetonitrile in the presence of catalytic amounts of potassium fluoride and 18-crown-6.32... 

The reaction of perfluoro-2-methylpent-2-ene 641 with 2-amino-6-bromobenzothiazole 642 and with more nucleophilic isopropyl amine 643 afforded 2-azetines 644 (Equation 244) and 645 (Equation 245), respectively <2000RJ099>. 

Second, intramolecular cyclization involving the azido group and the double bond could yield 1,2,3-triazoline derivatives these may be thermally unstable and may undergo nitrogen elimination to afford azirine derivatives. The reaction of perfluoro-2-methylpent-2-ene with NaN3 in a 1 2 acetonitrile-ethanol mixture at — 10°C (2 h) yielded stable 5-ethoxy-5-pentafhioroethyl-4,4-bis(trifluoromethyl)-4,5-dihydro-1H-1,2,3-triazole 9, whose structure was confirmed by X-ray analysis, Fig. 1 (01 JFC(110)21, 97ZOR772). 

The reaction of hexamethyldisilazane with the adduct of perfluoro-2-methylpent-2-ene and triethylamine yields perfhioro-3-methyl-4-ethylazete and perfhioro-2-methyl-3-ethylazetine, the former being predominant (98ZOR42). 

Thus isomerization of perfluoro-2-methylpent-2-ene can give perfluoro-2-methyl-l-pent-l-ene. The terminal multiple bond of the latter is rather labile with respect to the nucleophilic reagents. This can change the reaction... 

These results clearly demonstrate the importance of steric factors in reactions of perfluoro-2-methylpent-2-ene with primary alkylamines. 

When perfluoro-2-methylpent-2-ene reacts with glycidol, the initially formed product is vinyl ether 38, whose epoxide ring opens under the action of mineral acids (8% HBr, 33% HC1). Alcohol 39 formed in the course of ring cleavage is readily cyclized into 1,3-dioxolane 40 in the presence of catalytic amounts of NEt3. 

The interaction of perfluoro-2-methylpent-2-ene and epichlorohydrin in the presence of CsF or triethylamine in aprotic solvents forms tetrahydrofuran 49. The reaction occurs by cleavage of the epoxide ring under the action of the fluoride ion generating an O-nucleophilic center, which reacts at the multiple bond of the perfluoroolefin. Further cyclization the new terminal double bond gives the final reaction product. 

Table II. Dependence of the Ratio of the Products of the Reaction between Perfluoro-2-methylpent-2-ene and Ethylene Glycol in the Presence of NEt3 in Various Solvents (85IZV2066)...

Table IV. Products of the Reaction of Perfluoro-2-methylpent-2-ene with Binucleophiles...

Based on the assumptions about the reaction mechanism, one can predict that this technique will be applicable to other binucleophiles for the synthesis of perfluoroalkylated heterocyclic compounds. For example, the reaction of arylhydrazine with perfluoro-2-methylpent-2-ene in the presence of triethylamine led to N-arylperfluoro-3-ethyl-4-methylpyrazole 58 and N-arylperfluoro-4-methyl-5-ethylpyrazole 59 in different ratios depending on the reaction conditions (89RP1456419, 87RP1456418, 90IZY2583 89JAP(K)01 22855 99JFC(98)29). Syn- and /-aminoimines are intermediates in syntheses of pyrazoles they were isolated individually. On heating in the presence of triethylamine they are transformed into mixtures of 58 and 59. 

Polyfluorinated arylhydrazines proved to be sufficiently active nucleophilic reagents in reactions with perfluoro-2-methylpent-2-ene, giving fluorine-containing pyrazoles. 

At the same time, the interaction between perfluoro-2-methylpent-2-ene and hydrazine hydrate under the same conditions leads to the formation of the imine of the corresponding ketones 60 and 61. 

In the case of the reaction of perfluoro-2-methylpent-2-ene with 1,1-dimeth-ylhydrazine in the presence of triethylamine as the dehydrofluorinating agent and Et20 as a solvent at —50 to 0°C, the product is 5,5-difluoro-l,l-dimethyl-3-pentafhioroethyl-4-trifluoromethyl-1 -pyrazolin-2-yl 64 (87RP14 56418, 90IZY2583). 

This reaction is probably of general character. Thus the reaction of cyclopentanone and cyclohexanone oximes with perfluoro-2-methylpent-2-ene forms perfluoroalkenyl ethers. Thermolysis of the latter leads to... 

Thus reactions of perfluoro-2-methylpent-2-ene and perfluoro-5-azanon-4-ene with urea in the presence of triethylamine in dipolar aprotic solvents (MeCN, DMF) form 6-fluoro-4-pentafluoroethyl-5-trifluoro-methyl-l//-pyrimidin-2-one 93 and an s-triazine derivative, respectively (00JFC(103)105, 80/82JAP(K)85377). 

The reaction of perfluoro-2-methylpent-2-ene with benzamidines in the presence of sodium hydroxide affords 4-fluoro-2-phenyl-6-pentafluoro-ethyl-5-trifhioromethylpyrimidine 95 (00JFC(103)105). In compound 95, the fluorine atom in the 5 position possesses high mobility in a... 

When perfluoro-2-methylpent-2-ene reacts with amidine, the products may be vinylamidine, fluoropyrimidine, or hydroxypyrimidine depending on the reactivity of the amidine and on the presence of a catalyst as well as reaction time. In moderately polar media such as diethyl ether, the initial product is vinylamidine, promoting subsequent cyclization and dehydrofluorination the products of these transformations may be isolated and characterized. Meanwhile, other transformations occur with comparable rates. Therefore, the reaction in diethyl ether may not be used for the synthesis of fluoro-pyrimidines. However, hydroxypyrimidine may be obtained under these conditions with a yield of up to 60%. Analogous results were obtained when the reaction was conducted in Freon-113 (97IZY2024). 

Another nucleophilic center can also appear due to tautomerization of the unsaturated bonds induced by bases such as the fluoride ion. Thus the reaction of perfluoro-2-methylpent-2-ene with active methylene compounds, for example, acetylacetone, ethylacetoacetate, benzoylaceto-nitrile, and benzoylmethylperfluoroalkylketones in the presence of KF gives not only the products of nucleophilic substitution of fluorine... 

In the reaction of perfluoro-2-methylpent-2-ene with 2-methoxy-5-aminopyridine it is converted to a derivative of [l,5]naphthyridine (94JCS(CC)134). It is interesting to note that the carbon atom next to the amino group in the l,3(N,C)-binucleophilic reagents acts as the second nucleophilic center to form a heterocycle. Two equivalents of a- and / -aminonaphthalene react with one equivalent of perfluoro-2-methylpent-2-ene to yield the final product (02BKCS1017). 

It was shown (00JFC( 104)263) that perfluoro-2-methylpent-2-ene and perfluoro-5-azanon-4-ene smoothly react with two moles of aniline, 4-fluoroaniline, and 4-methoxyaniline in the presence of three moles of Et3N in acetonitrile, forming derivatives of quinoline and quinazoline. 

Me, MeO), then cyclization by the C-anion center is possible. Thus the reactions of perfluoro-2-methylpent-2-ene and perfluro-5-azanon-4-ene with 2,6-dimethylaniline form dihydroquinoline and dihydroquinazoline derivatives, respectively. 

In the presence of sodium hydride in tetrahydrofuran, amides of benzoic acid derivatives are effective N-nucleophiles. With a bidentate nucleophile such as sodium salt of benzoic acid amide, perfluoro-2-methylpent-2-ene forms 6,6-difluoro-4-pentafluoroethyl-2-aryl-5-trifluoromethyl-6i7-[l,3]-oxazine in a moderate yield (98JOC569). 

When perfluoro-2-methylpent-2-ene interacts with the 2-quinoline-2-methyl anion generated from 2-(trimethylsilylmethyl)quinoline in the presence of catalytic amounts of tetrabutylammonium fluoride or KF, the product is 3-pentafluoroethyl-2-trifluoromethyl-pyrido[l, 2- ]quinolin-l-one 125 in 36% (93%) yield (92NKK1455). 

Syntheses include nucleophilic addition or substitution of a binucleophilic reagent to perfluoroolefins followed by an intramolecular nucleophilic cyclization to afford seven-membered heterocycles. Thus, with the reaction of perfluoro-2-methylpent-2-ene with hydroxylamine, the major product is compound 131, whereas the expected compound 132 is obtained in a low yield (01 JFC(110)11). 

The case is similar for other perfluoroolefins. Thus treatment of perfluoro-2-methylpent-2-ene with 2-mercaptoethanol in acetonitrile in the presence of potash led to 5,7-difluoro-5-pentafluoroethyl-6-trifluoromethyl-3,5-dihy-dro-2//-[l, 4]-oxathiepin (94IZV1073, 89JAP(K)01 265087) but not to its isomer 5,5-difluoro-6-trifluoromethyl-6-(pentafluoroethyl)-l,4-oxathiepin-6... 

Monoethanolamine reacts with perfluoro-2-methylpent-2-ene in the presence of triethylamine, forming 7-fluoro-5-pentafluoroethyl-6-trifluoro-methyl-2,3-dihydro[l,4]oxazepin 135 (OlJFC(llO)l 1). If the compound has bulky substituents in the -position relative to the amino group, attack at the internal double bond is sterically hindered, and the internal olefin isomerizes in the presence of the base to the terminal olefin. The attack of the N-nucleophilic center of monoethanolamine occurs at the carbon atom of the terminal double bond, giving 5-fhioro-3,3-dimethyl-7-pentafluoroethyl-6-trifhioromethyl-2,3-dihydro[l,4]-oxazepin 136 or 137 as the major product. 

The interaction between perfluoro-2-methylpent-2-ene and ethylenedia-mine in the presence of triethylamine forms 5,9-bis(pentafluoroethyl)-6,8,8-tris(trifhioromethyl)-9-fluoro-1,4-diazabicyclo[5.2.0]nona-4,6-diene 148. With hexane-1,6-diamine, the product is 1 l-(pentafluoroethyl)-10-trifhioro-methyl-1,8-diazabicyclo[7.2.0]undeca-8,10-diene 149 (99IZY1578). The structure of 148 was confirmed by X-ray analysis (Fig. 7) (99IZV1578). 

Apparently, ethylenediamine initially attacks the carbon atom of the double bond to give an anion. Elimination of the fluoride ion from the CF3 group and elimination of HF affords A(2-(trifhioromethyl)-perfluoropent-1 -en-3-ylidene)ethylene-1,2-diamine. Subsequent transformations of this compound can follow different pathways. For instance, one pathway includes intramolecular nucleophilic cyclization, resulting in compound A. This product can react with perfluoro-2-methylpent-2-ene... 

The reaction between perfluoro-2-methylpent-2-ene 1 and benzimidazo-line-2-thione in the presence of triethylamine forms (2 )-2-(l,2,2,2-tetra fhioroethyhdene)-3,3-bis(trifhioromethyl)-2,3-dihydro-[l,3]thiazolo-[3,2-a]-benzoimidazole 153 (Table IV), whose structure was confirmed by X-ray... 

In this case, aprotic bipolar solvents and triethylamine are employed. Thus, interaction of perfluoro-2-methylpent-2-ene with 2-aminophenol in the presence of triethylamine in diethyl ether affords 4-fluoro-2-(pentafluoroethyl)-3-(trifhaoromethyl)-l,5-benzoazepine 154 (80JFC(16)75). 

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