Halogenated labeling studies

For halogenated pyrimidines, dehydrohalogenation competes with elimination of the hydride ion, as shown for 5-bromopyrimidine (173) in Scheme 64 (82JHC1285). Other examples are the amination of 4-tert-butyl-5-chloropyrimidine (174) and 2,4-di-fert-butyl-5-chloropyrimidine (175) with potassium amide in liquid ammonia (78RTC288). Some cine-substitution products (176 and 177) were also obtained (Scheme 65). From isotopic labeling studies, it was determined that the Sn(ANRORC) mechanism was not involved. 

Rather surprisingly, if the hydroxy group is replaced by a halogen atom, elimination of HX (X = Cl or Br) appears to prefer a five-membered transition state (Equation 2.53). Deuterium-labeling studies with n-butyl and -pentyl chloride demonstrate that abstraction of the hydrogen from the y-carbon is the favored process. There are also indications that cyclic chlorides and bromides eliminate HX by the 1,3-mechanism. 

The influence of the halogen on the mechanistic course of carbanionic rearrangement of 3-hexylhalomethylenecyclobutanes (Scheme 11, X = F, Cl, Br, I) to l-halo-4-hexylcyclopentenes has been explored by studying the fate of C-labelled methylene... 

I. Doignon, F. Pillon, C. David, C. Crouzel, B. Tavitian, A general method to label antisense oligonucleotides with radioactive halogens for pharmacological and imaging studies, Bioconj. Chem. 11 (2000) 627-636. 

Both title compounds have been synthesized44 by halogen exchange reaction of Cs 18F with 2- and 6-bromonicotine (equation 21). NCA 18F-labelled 2-fluoronicotine has been obtained ready for injection in humans for study of the regional cerebral blood flow (rCBF) by PET and of the distribution of the nicotinic cholinergic receptors45,46. 

Direct evidence for a combination of catalytic fluorination and chlorination [4] was obtained from radiotracer studies in which fluorinated chromia catalysts were labelled with the short-lived (t /2 = 110 min) / + emitting isotope fluorine-18 [11]. Using this isotope it was possible to probe the interactions between HF and various fluorinated chromia catalysts more directly than had been possible hitherto. Three types of surface F-containing species were differentiated, weakly adsorbed HF which was easily removed by an inert gas flow, non-labile F, believed to be bound directly to surface Crin, and catalytically active F which could be incorporated into the organic products [12]. The controversy between dismutation (concerted F-for-Cl and Cl-for-F transfers) and non-concerted halogen exchange processes has been resolved more recently and the evidence is described later in the chapter. What is clear from this early work however, is the importance of aluminium and chromium(III) oxides as catalyst precursors. Fluorination of the surfaces of these oxides is slow (cf [12]) and although there are many references to alu-... 

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