1.3- dibromo-dimethylhydantoin

Bromine sticks are composed of 1,3-bromo-chloro-dimethylhydantoin (BCDMH) [II, 21.2.11.]. 1,3-dibromo-dimethylhydantoin (DBDMH) was introduced in 2000. The BCDMH hydrolyzes to form both hypobromous and hypochlorous acids, whereas, the DBDMH only releases hypobromous acid [II, 21.2.3.] upon hydrolysis. 

Additions of the halogen fluorides to unsaturated steroids [62, 95, 96, 97, 98, 99] and carbohydrates [62, 75] are well known Typical reagent combinations include l,3-dibromo-5,5-dimethylhydantoin (DBH) or the Af-halosuccinimides with hydrogen fluoride Reversal of the expected regiochemistry can be observed with certain steroidal olefins [JOO, 101] (equation 7)... 

The preparation of e/n-difluoro compounds by the oxidative fluorodesul-furization ot 1,3-dithiolanes readily proceeds by treatment with a pyridinium polyhydrogen fluoride-Af-halo compound reagent the latter serves as a bromonium ion source [2], l,3-Dibromo-5,5-dimethylhydantoin is the most effective of several At-halo oxidants. It is believed that /V-halo compounds combine with hydrogen fluoride to generate in situ halogen fluorides, the oxidants. Formation of gem-difluorides from dithiolanes derived from ketones is efficient and rapid, even at -78 °C, whereas the reaction of dithiolanes derived from aldehydes requires higher temperature (0 °C) (equation 4). 

Aromatic thio orthoesters are successfully converted into trifluoromethyl arenes by treatment with a pyridinium polyhydrogen fluoride-A -halo imide reagent. The reactions are conducted at -30 to -20 °C, and the nature of A-halo imide is critical both 1,3-dibromo-5,5-dimethylhydantoin and A-bromosuccin-imide give similar yields of trifluoromethyl compounds [5] (equation 7)... 

Figure 2.9. Synthesis of conditurol C Reagents and conditions i, E. coli JM109 (pDTGbOIA) ii, 2,2-dimethoxypropane, acetone, / -TsOH iii, 1,3-dibromo-5,5-dimethylhydantoin, H20-acetone iv, NaOH, H20-dimethoxyethane, heat v, e, MeCN, Et4NBr vi, NaOBz, H2O.

Figure 5-4. 2-Bromo-2-bromomethylglutaronitrile, 2,2-dibromo-3-nitrilo-propionamide, 1,2-dimethyl-5-nitro-1 H-imidazole, 4,4-dimethyl-2-oxazo-lidinone, dimethylaminopropyl acrylamide, dimethylaminopropyl methacrylamide, or dimethylaminopropyl acrylamide, 5,5-dimethylhydantoin, dimethylurea.

Walash et al. [10] determined primaquine and other quinoline drugs in bulk and in pharmaceuticals by a titrimetric method. The method is based on reaction with l,3-dibromo-5,5-dimethylhydantoin or TV-bromosuccinimide as the titrant. Primaquine was determined either by usual titration or by potentiometric titration with the brominating agents. The recovery was approximately 100%. The method was simple, precise, and accurate. 

The acylation of 3-arylsydnones (Section 5.03.5.2.4) at position C4 occurs under neutral conditions and in satisfactory yield, in the presence of acetic anhydride and l,3-dibromo-5,5-dimethylhydantoin as an efficient promoter <2007JHC467>. 

Cyclodesulfurization of thiosemicarbazides, containing pyrazole <2002PS67> or benzofuran <2002PS863, 2004PS1577> units, by yellow mercuric oxide or by l,3-dibromo-5,5-dimethylhydantoin in the presence of potassium iodide <2006TL4889> afforded the respectively substituted oxadiazoles. 

GABA HMG-CoA HMPA HT LDA LHMDS LTMP NADH NBH NBS NCS NIS NK NMP PMB PPA RaNi Red-Al RNA SEM SnAt TBAF TBDMS TBS Tf TFA TFP THF TIPS TMEDA TMG TMP TMS Tol-BINAP TTF y-aminobutyric acid hydroxymethylglutaryl coenzyme A hexamethylphosphoric triamide hydroxytryptamine (serotonin) lithium diisopropylamide lithium hexamethyldisilazane lithium 2,2,6,6-tetramethylpiperidine reduced nicotinamide adenine dinucleotide l,3-dibromo-5,5-dimethylhydantoin A-bromosuccinimide A-chlorosuccinimide A-iodosuccinimide neurokinin 1 -methyl-2-pyrrolidinone para-methoxybenzyl polyphosphoric acid Raney Nickel sodium bis(2-methoxyethoxy)aluminum hydride ribonucleic acid 2-(trimethylsilyl)ethoxymethyl nucleophilic substitution on an aromatic ring tetrabutylammonium fluoride tert-butyldimcthyisilyl fert-butyldimethylsilyl trifluoromethanesulfonyl (triflyl) trifluoroacetic acid tri-o-furylphosphine tetrahydrofuran triisopropylsilyl A, N,N ,N -tetramethy lethylenediamine tetramethyl guanidine tetramethylpiperidine trimethylsilyl 2,2 -bis(di-p-tolylphosphino)-l,r-binaphthyl tetrathiafulvalene... 

Nucleophilic displacement using [ F] fluoride works well in aUphatic systems where reactive haUdes or sulfonates esters can undergo substitution at unhindered sites. In order to introduce a F fluorine atom in a secondary or tertiary position, a two steps strategy was developed. It involves a F-bromofluorination of alkenes, followed by reductive debromination (n-BujSnH, AIBN). [ F]BrF is usually generated in situ from [ F]potassium fluoride and l,3-dibromo-5,5-dimethylhydantoin (DBH) in sulfuric acid. This methodology was successfully applied to label steroids at the 11 and 6a positions [245] (Scheme 60) and to prepare [ F]fluorocyclohexanes [246]. 

Bromo [ F]fluoride is different from the other electrophilic radiolabelling agents discussed so far in the sense that the electrophilic part of the molecule is not fluorine but bromine. This is reflected by its synthesis from nucleophilic p F]fluoride and it can be obtained in high specific radioactivity. Bromo p F]fluoride was developed for fluorine-18 labelling of steroids (see Section 3.2) [64-66]. It was prepared (Scheme 11) in situ by reaction of dried p Fjfluoride with 1,3-dibromo-5,5-dimethylhydantoin and sulphuric acid in dichloromethane containing also the substrate. 

The reactions of 5,6-dihydro-2-methoxy-2H-pyran (101) with 1,3-dibromo-5,5-dimethylhydantoin in ether-methanol,137 and with ethanesulfenyl chloride,138 have been described by Baldwin and Brown. The former reaction gave a 2 1 mixture of the isomers 3/3-bromotetrahydro-2a ,4a-dimethoxypyran (102) and 3a-bromotetrahy-dro-2a,4/3-dimethoxypyran (103), respectively the structures and favored conformations of the isomers are shown. The reaction of ethanesulfenyl chloride with 5,6-dihydro-2-methoxy-2H-pyran (101)... 

Bromofluorination of dodec-2-ene, styrene, and methyl undec-10-enoate are carried out using similar conditions but using l,3-dibromo-5,5-dimethylhydantoin instead of A-halosuc-cinimide however, chlorofluorination with A-chlorosuccinimide as a chlorinating reagent is not successful at all and starting alkenes are recovered unchanged.336... 

Silver(I) fluoride dispersed on the surface of finely powdered calcium fluoride shows improved fluoride nuclcophilicity for addition to alkenes in halofluorination reactions.56 For example, hex-1-ene with l,3-dibromo-5,5-dimethylhydantoin and silver(I) fluoride/calcium fluoride in dichloromethane at 20 C gives, within 1 hour, l-bromo-2-fluorohexanc in 90% yield while with silver(I) fluoride, under similar conditions, the yield is only 39%. 

Trifluoromethyl-substituted aromatic compounds are obtained by reacting methyl arenecar-bodithioates with tetrabutylammonium dihydrogen trifluoride and l,3-dibromo-5.5-dimethyl-hydantoin. The use of /V-bromosuccinimide or A-iodosuccinimide instead of l,3-dibromo-5,5-dimethylhydantoin affords difluoro(methylsulfanyl)methyl-substitutcd aromatics.62... 

In combination with hydrogen fluoride/pyridine, any of l,3-dibromo-5,5-dimethylhydantoin, A-iodosuccinimide, A-bromosuccinimide and A-chlorosuccinimide with methyl 1-naph-... 

When an electron-withdrawing bromine substituent is in the carbodithioatc, e.g. methyl 4-bromobenzenecarbodithioate, a mixture of products is obtained but when hydrogen fluoride/ pyridine, in place of tetrabutylammonium dihydrogen trifluoride, is used with 1,3-dibromo-5,5-dimethylhydantoin, the yield of 1-bromo-4-(trifluoromcthyl)benzene is as high as 82%.62... 

The products ArCF2SMe are assumed to be precursors of ArCF3. Indeed, l-(tri-fluoromethyl)naphthalene is obtained in 83% yield by the reaction of l-[difluoro(methylsul-fanyl)mcthyl]naphthalene with tetrabutylammonium dihydrogen trifluoride/ l,3-dibromo-5,5-dimethylhydantoin. It should be noted that under the oxidative desulfurization conditions the electron-rich aromatic compounds can undergo ring bromination. 

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