Bromine placement

The dream of every X chemist is to get that amine function directly on the safrole molecule without having to go thru any intermediate such as the ketone of MD-P2P or the bromine of bromosafrole. But Strike can tell you right now that that is very, very tough (that is why there ain t no methods for it). About the only article Strike has ever found for the actual placement of an amine directly on a terminal alkene (a.k.a. safrole) is the following [79] ... 

Consider the proper placement of tellurium and iodine in the periodic table, as shown in Figure 1-3. Te has the heavier atomic weight. The chemical properties of tellurium are like those of selenium because both are semi-metallic elements that form compounds like those of sulfur. Iodine resembles bromine because these elements are nonmetallic halogens that form compounds like those of chlorine. Therefore, the order in the table cannot be based solely on atomic weight. 

Besides new insight into the reactivity of free radicals, methods for die production of carbon-centered free radicals have also seen major improvements in die last several years. One very common new mediod is to use tin-based reagents as radical chain carriers. Trialkyltin radicals readily abstract bromine or iodine from carbon to produce a carbon-centered free radical. Placement of a bromide or iodide substituent on a substrate dius permits formation of a carbon-centered free radical at diat position using tin-based mediodology. This process was initially developed for die reduction of alkyl halides, and it remains an excellent synthetic method for diat purpose. The complete chain mechanism for die reduction is shown. 

An unusually large inverse secondary deuterium kinetic isotope effect (1.53-2.75, depending on the reaction conditions) has been reported for bromination of the sterically congested olefin 74. This behaviour can be rationalized by decreased steric hindrance due, in particular, to the ewrfo-placement of the deuterium atoms relative to the double bond135. 

In contrast, the regiochemistry of bromine introduction with 2,4,4,6-tetra-bromocyclohexa-2,5-dienone was R2, R2Ri, R2RiR3, and finally R2RjR3R4 (see 546).427 Apparently, placement of the first bromine at R2 activated Rt to electrophilic attack by this reagent such that substitution at the proximate tertiary site was kinetically favored over that at R3. 

The second innovation Mendeleev made involved the relative placement of tellurium and iodine. If the elements are listed in strict order of their atomic masses, then iodine should be placed before tellurium, since iodine is lighter. That would place iodine in a group with sulfur and selenium and tellurium in a group with chlorine and bromine, an arrangement that does not work for either iodine or tellurium. Therefore, Mendeleev rather boldly reversed the order of tellurium and iodine so that tellurium falls below selenium and iodine falls below bromine. 

Nair, M.S., Sudhir, U., Joly, S., and Rath, N.R, Two fascinating rearrangements through selective placement of bromine substituents. Photochemical synthesis of 3-bromo-7-(bromomethyl)tetra-cyclo[5.3.1.02,6.04,8]undec-10(12)-ene-9,ll-dione and its rearrangements with amines, Tetrahedron, 55, 7653, 1999. 

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