Bromo fluoride

Aliphatic, aromatic, and alicyclic alkenes have been converted into the corresponding bromo fluorides 2 by reaction with l,3-dibromo-5,5-dimethylhydantoin (DBH) and silicon tetrafluoride in 1,4-dioxane at room temperature in a highly regio-, stereo- and chemoselective manner.9... 

Chlorobenzenes activated by coordination of Cr(CO)3 react with terminal alkynes[253). The 1-bromo-1,2-alkadiene 346 reacts with a terminal alkyne to afford the alka-l,2-dien-4-yne 347[254], Enol tritlates are used for the coupling with terminal alkynes. Formation of 348 in the syntheses of ginkgolide[255] and of vitamin D are examples[256] Aryl and alkenyl fluorides are inert. Only bromide or iodide is attacked when the fluoroiodoalkene 349 or fluoroiodoar-ene is subjected to the Pd-catalyzed coupling with alkynes[257-259]. 

Bromo or chloro-2,6-difluoropyridines can be prepared in 50% yield by diasotization of the corresponding 3-halo-2,6-diarninopyridine in ammonium fluoride—hydrogen fluoride solvent (371). 5-Chloro-2,3-difluoropyridine [89402-43-7], a precursor to the herbicide pyroxofop [105512-06-9], was synthesized by a multistep sequence based on aHyl chlorodifluoroacetate [118337-48-7], C1CF2C02-CH2CH=CH2 (415). 

Synthetic procedures are available for the preparation of fluoro, chloro, bromo and iodo compounds from the corresponding lithio derivatives. Perchloryl fluoride (FCIO3), N-chlorosuccinimide, bromine and iodine are examples of reagents which can be used to introduce fluorine, chlorine, bromine and iodine, respectively. 

Purine, 6-bromo-9-/3-D-(2,3,5-tri-0-acetyl)ribofuranosyl-synthesis, 5, 598 Purine, 6-carboxy-reactions, 5, 549 Purine, 8-carboxy-reactions, 5, 549 Purine, 2-chloro-reactions, 5, 561 synthesis, 5, 597 Purine, 6-chloro-alkylation, 5, 529 glycosylation, 5, 529 oxidation, 5, 539 3-oxides reactions, 5, 554 synthesis, 5, 595 reactions, 5, 561, 595 with ammonia, 5, 562 with fluorides, 5, 563 with trimethylamine, 5, 562 9- -D-ribofuranoside synthesis, 5, 560 synthesis, 5, 597, 598 Purine, 8-chloro-amination, 5, 542 Purine, 6-chloro-8-ethoxy-synthesis, 5, 591 Purine, 6-chloro-9-ethyl-dipole moment, 5, 522 Purine, 6-chloro-2-fluoro-riboside... 

The o-bromo derivative is quantitatively cleaved with hydrogen fluoride (0°, 10 min). ... 

A suspension of 17a,21-dihydroxypregna-4,9(ll)-diene-3,20-dione 21-acetate (0.77 g) and iV-bromoacetamide (0.3 g) in anhydrous methylene dichloride (40 ml) is added over 2-3 min with stirring to a mixture of anhydrous hydrogen fluoride (10.19 g), and anhydrous tetrahydrofuran (18 g) in a polyethylene bottle at —80° (acetone-dry ice). After 1 hr at —80° the reaction mixture is kept for a further 1 hr at 0° and then added cautiously to an excess of an ice-cold solution of sodium carbonate. Extraction with methylene dichloride and crystallization from acetone-hexane furnish 9a-bromo-ll -fluoro-17a,21-dihydroxypregn-4-ene-3,20-dione 21-acetate (0.69 g), mp 205-208°, raised by several crystallizations from acetone-hexane to 215-217° [aju 142° (CHCI3) max 240-242 mju (e 15,500). 

Addition of fluorohalides to double bonds preparation of 9a-bromo-ll/3-fluoro-17q , 21-dihydroxypregn-4-ene-3, 20-dione 21-acetate by reaction with N-bromoacetamide-hy drogen fluoride, 458... 

With Freon 112 or 113 as a solvent, fluonnation of pnmary butyl halides with bromine trifluonde can give mixtures of primary and secondary fluorides When 1,4 dibromobutane is the substrate, 93% l-bromo-4-fluorobutane and 1% 1-bro-mo-3-fluorobutane is obtained, with 1,4 dichlorobutane, the product contains 65% l-chloro-3-fluorobutane and 35% 1-chloro 4 fluorobutane When 4-bromo- or 4-chlorobutyl trifluoroacetate is used, the ratio of 4-fluorobutyl tnfluoroacetate to 3 fluorobutyl trifluoroacetate is 1 4 The effect of solvent is measured in another set of experiments When the reaction of bromine trifluonde and l,3-dichloro-2-fluoropropane in either Freon 113 or hydrogen fluoride is allowed to proceed to 40% conversion, the product mixture has the composition shown m Table 1 [/O] When 1 chloro 2,3-dibromopropane is combined with one-third of a mole of bromine trifluonde, both 1 bromo 3 chloro-2-fluoropropane and l-chloro-2,3-di-fluoropropane are formed [//] (equation 10)... 

Both methyltriethylphosphonium fluoride and methyltributylphospho-nium fluoride have been prepared The latter generates benzyl fluoride from benzyl chloride in 80% yield and ethyl fluoroacetate from ethyl bromoacetate in 53% yield Methyltnbutylphosphonium fluoride converts 1-bromododecane to a 50 50 mixture of 1-fluorododecane and 1-dodecene Methyltnbutylphosphonium fluoride also quantitatively forms styrene from 1-bromo-1-phenylethane [26] Methyl-tnbutylphosphonium fluonde is the reagent of choice for the conversion of N,N dimethylchloroacetamide to its fluoride, but it is not able to convert chloro-acetonitnle to fluoroacetomtrile Methyltnbutylphosphonium fluoride changes chloromethyl octyl ether to the crude fluoromethyl ether in 66% yield The stereoselectivity of methyltnbutylphosphonium fluoride is illustrated by the reac tions of the 2-tert-butyl-3-chlorooxiranes [27] (Table 2)... 

A nonconventional synthesis of the known inhalation anaesthetic, 2-bromo-2 chloro-l,l,l-trifluoroethane (Halothane), based on the reaction of ethyl 1,2 di bromo-1,2-dicliloroethyl ether with anhydrous hydrogen fluoride and sulfur tetrafluoride, has been patented The reaction presumably involves cleavage of the ether linkage, followed by fluorination of the intermediate bromochloroacetyl halide with sulfur tetrafluoride, ethyl halides are the by-products [2] (equation 2)... 

Substituted aryl hydrazones can be converted to geminal difluondes in satis factory yields by molecular fluorine [H4, iodine fluoride [ 5], and N bromo-suc-cinimide-pyridinium polyhydrogen fluoride or A -bromosuccinimide-polyvi-nylpyridinium polyhvdrogen fluoride [5(5] (equation 21) (Table 6)... 

Alkyl fluorides are more reactive than other alkyl halides under Friedel-Crafts conditions, whereas trifluoromethyl groups are less reactive than other trihalomethyl groups Thus, a bromoindane is prepared from 1-bromo-l-fluoro-2,2,3,3-tetramethylcyclopropane and benzene [5] (equation 8) whereas 3-tnfluo romethylphenyldiphenylchloromethane is obtained from 3-trifluoromethyl-benzotrichloride and benzene [9] (equation 9)... 

A -Halogenated compounds such as iV-chlorotnfluoroacetamide, A -chloro-imidosulfuryl fluonde and N N dichlorotnfluoromethylamine add across C=C bonds to form saturated amides [14] tmidosulfury I fluorides [15] and amines [16], respectively Allylic halogenation also occurs with the use of A-bromo- or A-chIo roperfluoroamides The primary amine A,A-dichlorotrifluororaethylamine selectively affords 11 or 2 1 adducts with either tetrafluoroethylene or chlorotrifluoroethylene [16] (equation 7) The reaction mechanism is believed to involve thermal free radicals, with control achieved principally by reaction temperature The 1 1 adduct is formed even in the presence of a large excess of olefin... 

Dehydrochlorination of bis(tnfluoromethylthio)acetyl chloride with calcium oxide gives bis(trifluoromethylthio)ketene [5] (equation 6) Elimination of hydrogen chloride or hydrogen bromide by means of tetrabutylammonium or potassium fluoride from vinylic chlorides or bromides leads to acetylenes or allenes [6 (equation 7) Addition of dicyclohexyl-18-crown-6 ether raises the yields of potassium fluoride-promoted elimination of hydrogen bromide from (Z)-P-bromo-p-ni-trostyrene in acetonitrile from 0 to 53-71 % In dimethyl formamide, yields increase from 28-35% to 58-68%... 

It IS interesting that the rates of elimination of hydrogen fluoride from all fluormated succinic acids span hardly 1 order of magnitude, whereas the rates of preferential dehydrofluorination of both a-bromo-a -fluorosuccimc acids are higher by almost 2 orders of magnitude [35, 36, 37, 38] (Table 3)... 

The preferential syn elimination of hydrogen fluoride from trans-l-bromo-2-fluorocyclohexane to give 1 -bromocyclohexene is achieved only when a strong base such as sodamide is used [55, 56] Potassium rcrt-butoxide causes elimination of hydrogen bromide to form 3-fluorocyclohexene [56] (equation 27)... 

Halo-2-methylbutanes (X = F, Cl, Br) all produce the same carbocation upon dissociation, yet one of these halides is unreactive. Calculate the dissociation energies for 2-metbyl-2-butyl fluoride and 2-metbyl-2-butyl-cbloride. (Energies of fluoride and chloride are given at right.) Compare these to the dissociation energy of the corresponding bromo derivative. Which hahde is most likely to be unreactive ... 

Examples of dehydrobromination leading to bromoethynylpyrazoles as illustrated by Scheme 36 are described in a patent (99USP5925769). Treatment of 1,1-dibromooleflns with tetrabutylammonium fluoride in THE at room temperature for about 24 h under N2 gives the l-bromo-2-(pyrazol-3-yl)acetylenes where R, R, R, and R" are independently selected from H and alkyl, alkoxy. 

Bromo-6/3-fluoro-17a.21 dihydroxy-9/3,11 3-oxido-pregna-1,4-diene. 3,20dione-17-21 -diacetate Hydrogen fluoride... 

The reaction can be applied to simple epoxides if polyhydrogen fluoride-pyridine is the reagent. The epoxide-to-fluorohydrin conversion has also been carried out with Sip4 and a tertiary amine.Chloro-, bromo-, and iodohydrins can also be... 

HI, or Cdl2 iodofluorination with mixtures of AgF and U and mixtures of N-bromo amides in anhydrous HF give bromofluorination. Bromo-, iodo-, and chlorofluorination have also been achieved by treatment of the substrate with a solution of Br2,12, or an N-halo amide in polyhydrogen fluoride-pyridine while... 

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