Elimination from cyclic halides

The preference for anf/-elimination from halides can be very strong. To see this is so, we must turn from open-chain compounds to cyclic compounds. In... 

Formation of ethylenimines (aziridines) by elimination of hydrogen halides from aliphatic vicinal haloamines with alkali. The method can be extended to the preparation of five- and six-membered cyclic amines ... 

From a pharmacological viewpoint, the compounds of interest that undergo metabolic cyclization include ring-opened prodrugs of cyclic drugs [82], or linear drugs that yield a cyclic (and often inactive) metabolite. In the subsections below, we first examine cyclizations, which eliminate a halide or a relatively large molecule, and then proceed to discuss reactions of dehydration. 

Kinetics of reactions of cyclic secondary amines with benzohydrazonyl halides (31) have been measured in benzene51 at 30 °C. The products result from nucleophilic substitution at the halo-carbon via an associative addition-elimination mechanism. For X = Cl or Br, the rate equation has significant terms that are both first and second order in amine, whereas two amine molecules are essential for the fluoro compounds to react. 

Chemoselective E2 eliminations can be carried out with sterically hindered, sufficiently strong bases. Their bulkiness causes them to attack at an H atom at the periphery of the molecule rather than at a C atom deep within the molecule. These bases are therefore called nonmicleophilic bases. The weaker nonnucleophilic bases include the bi-cyclic amidines DBN (diazabicyclononene) and DBU (diazabicycloundecene). These can be used to carry out chemoselective E2 eliminations even starting from primary and secondary alkyl halides and sulfonates (Figure 4.16). 

Carboalkoxy acyl halides are made from mono esters of dibasic acids and thionyl chloride or phosphorus pentachloride. Examples are numerous. Halides with the ester group in the beta position are unstable to prolonged heating. Alkyl halide is eliminated with the formation of an anhydride. Under certain conditions a rearrangement occurs in the preparation of ester acid chlorides. The product obtained is a mixture of the expected compound and its isomer in which the ester and acid chloride groups are interchanged, viz., ROjCCHR (CI ) CO,H — RO,C(CH,) CHR COQ. The cyclic anhydride is a likely intermediate. ... 

The electron impact induced elimination of X from the molecular ions of 94 (X = H, halide R = NHCOR, NHCSR, NHCSNR2R3, NHCONR,R3 R, = alkyl, Rj, R3 = H, alkyl) has been investigated in detail by Loudon et al. i00 In agreement with the above mentioned study Griitzmacher, the (M—X)+ ions have a cyclic structure, probable 95. The reaction mechanism, however, may only formally correspond to (18). 

Benzo[c]cinnoline is a weak base with a of 2.2 in water and 1.6 in 50% aqueous ethanol.Cryoscopic measurements show that it is dipro-tonated to some extent in 100% sulfuric acid. Well-defined quaternary salts result from heating benzo[c]cinnoline with alkyl halides and sul-fates. These are reported to decompose on treatment with ammonia, regenerating benzo[c]cinnoline, but apparently nucleophilic displacements of halogen by amines have been carried out on certain highly substituted examples in the synthesis of cationic dyestuffs. Quaternizations of benzo[c]cinnoline with a,a)-dibromo-propane and -butane are accompanied by hydrogen bromide elimination to give the cyclic iminium salts 40 and 41. When 40 is dehydrogenated, or merely refluxed in ethanol. 

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