Iodi nations

Aryl chlorides and bromides are conveniently prepared by electrophilic aromatic substitution. The reaction is limited to chlorination and bromination. Fluorination is difficult to control iodi-nation is too slow to be useful. 

The group of Botta demonstrated the feasibility of their microwave-assisted iodi-nation protocol (see Scheme 6.143 d) toward a polymer-supported substrate [68], An appropriate pyrimidinone attached to conventional Merrifield polystyrene resin was suspended in N,N-dimethylformamide, treated with 2 equivalents of N-iodosuccini-mide (NIS), and subjected to microwave irradiation for 3 min. Treatment of the polymer-bound intermediate with OXONE released the desired 5-iodouracil in almost quantitative yield (Scheme 7.57). 

A mild metal-free a-iodi nation of ketones uses molecular iodine in a neutral reaction medium.296 Aliphatic ketones react predominantly on the more substituted side, with... 

Fig. 5.16. Electrophilic iodi-nation of electron-rich down to electron-poor—from top to bottom—benzene derivatives and typical reagents.

Chlorination of methane to methyl chloride, methylene chloride, chloroform, and carbon tetrachloride is practiced industrially worldwide on a large scale. Bromination and iodi-nation are similarly practiced on a smaller scale to prepare the corresponding bromine and iodine derivatives which are important pharmaceutical, synthetic, and fireproofing raw materials. 

Some Lewis acid-initiated polymerizations have been proposed to proceed by direct addition of the Lewis acid to the monomer s double bond. However, this is usually an exception, and has been clearly proven only for iodine [69,135] and boron halide [136,137] initiated systems. Iodi-nation and haloboration are reversible processes which produce deactivated alkyl halides due to the electron-withdrawing substituent at the neighboring carbon [Eq. (30)]. 

The Sonogashira reactions of both a-halothiophenes [162] and P-halothiophenes [163] proceed smoothly even for fairly complicated molecules as illustrated by the transformation of brotizolam (237) to alkyne 238 [164], Interestingly, 3,4-bis(trimethylsilyl)thio-phene (240), derived from the intermolecular cyclization of 4-phenylthiazole (239) and bis(trunethylsilyl)acetylene, underwent consecutive iodination and Sonogashira reaction to make 3,4-bisalkynylthiophenes [165], Consequently, a regiospecific mono-z / o-iodi-nation of 240 gave iodothiophene 241, which was coupled with phenylacetylene to afford alkynylthiophene 242. A second iodination and a Sonogashira reaction then provided the unsymmetrically substituted 3,4-bisalkynylthiophene 243. 

Vedejs and Luchetta developed a method for the iodi nation of oxazoles at C(4) via 2-lithiooxazoles by exploiting the aforementioned equilibrium between cyclic 5 and acyclic 6 valence bond tautomers of 2-hthiooxazole [21], When 5-(p-tolyl)oxazole (8) was treated with lithium hexamethyldisilazide (LiHMDS) in THF followed by treatment with 1,2-diiodoethane as the electrophile, 2-iodooxazole 9 was obtained exclusively. On the other hand, when 50 volume percentage of DMPU was added prior to the addition of the base, 4-iodooxazole 10 was isolated as the predominant product (73%) with ca. 2% of 9 and ca. 5% of the 2,4-diiodooxazole derivative. 

At the same time, the typical iodine level of breast milk in women in Germany increased from 14 pg in 1982 before iodi-nation of the mineral mixtures to > 100 pg in the new millenium (Anke et al. 2002) (Table 9-4.8). 

Iodine and oxygen radicals such a short-lived mechanism would only explain part of the inhibition of iodi-nation or the toxic effects of iodide (Denef et al., 1996 Many et al, 1992). It would presumably be short-lived and indiscriminate. 

A volumetric determination of phenolphthalein in mineral oil emulsion has been developed by Warren, Logun and Thatcher based on the iodi-nation of phenolphthalein in an alkaline medium. The emulsion is broken by the addition of acidified solution of sodium chloride, the coagulum... 

Figure 3.6 Determination of the reaction orders for acetone (circles) and H+ (squares) in the iodi-nation of acetone.

Halogenation of LactamsJ Selective and high yielding iodi-nation and bromination of lactams occurs vj nYi Iodine or Bromine, respectively, in the presence of TMS-I and a tertiary amine base (eq 24). The proposed reaction mechanism involves intermediacy of the silyl imino ether. 

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