Hydrodehalogenation

Pyridazine itself is best prepared (in about 60-67% yield) from 2,5-diacetoxy- or 2,5-dimethoxy-2,5-dihydrofuran (50ACS1233, 56JOC764) or by hydrodehalogenation of 3-chloro-... 

Scheme 8.1 General mechanistic cycle proposed for Ni and Pd catalysed hydrodehalogenation...

Palladium NHC systems for the hydrodehalogenation of aryl chlorides and bromides and polyhalogenated aromatic substrates originate from about the same time as the first reports on Ni chemistry, and show many similarities. Initial efforts showed that the combination of PdCdba) (2 mol%), one equivalent of imidazolium chloride and KOMe produced an effective system for the reduction of 4-chlorotolu-ene, especially upon use of SIMes HCl 2 (96% yield of toluene after 1 h at 100°C) [7]. Interestingly, higher ligand to metal ratios severely inhibited the catalysis with only 7% yield of toluene achieved in the same time in the presence of two equivalents of SIMes HCl 2. Variation of the metal source (Pd(OAc)2, Pd(CjHjCN)jClj), alkoxide (NaOMe, KO Bu, NaOH/ ec-BuOH) or imidazolium salt (IMes HCl 1, IPr HCl 3, lAd HCl, ICy HCl) all failed to give a more active catalyst. 

Table 8.3 Pd-NHC catalysed hydrodehalogenation of polychlorinated phenyls and biphenyls ...

FIGURE 2.36 Catalyst modifier for inhibiting hydrodehalogenation during nitro hydrogenation. 

Hydrodehalogenations of chloro-, bromo-, and iodobenzene were carried out individually as well as in competitive reactions. When the reactions were carried out separately, the reduction of chlorobenzene closely paralleled that of bromobenzene, whereas the reduction of iodobenzene was slower. When they were allowed to react competitively, the reduction was highly selective, and the reaction was delayed, but iodobenzene reacted first followed by bromobenzene and then chlorobenzene. 

Hydrodehalogenation - that is, hydrogenolysis of the carbon-halogen bond -involves the displacement of a halogen bound to carbon by a hydrogen atom. This chapter is devoted to dehalogenations mediated by transition-metal complexes (Eq. (1)) ... 

This type of hydrodehalogenation has been performed generally in the presence of organic or inorganic bases to neutralize the hydrogen halides formed. Among published results, the use of rhodium complexes as catalysts dominates, but palladium and ruthenium complexes have also been applied on a frequent basis. 

Rocek and coworkers [10] attempted to compare the activity of various transition-metal complexes in the hydrodehalogenation of 5-iodouracil with atmospheric H2 at 70-80 °C. The majority of the examined complexes decomposed to metal, but [(PPh3)2CoCl2], and [(PPh3)3RuCl2] in DMA (N, N-d i me lb yl -act I a-mide) remained homogeneous. The more active Ru complex catalyzed also the preparation of [5-2H]uracil using D2 instead of H2. 

Setti and Mascaretti [15] realized the highly chemoselective and stereocon-trolled hydrodehalogenation of the carbon-6-halogen bond of (pivaloyloxy)-methyl-6,6-dihalopenicillanate by [(PPh3)3RhCl] in EtOAc and/or MeOH solvent systems with atmospheric H2. For the diiodo derivative (Eq. (2)) ... 

It has not been shown unambiguously, however, whether the rhodium remains coordinated to the ligands 2 and 3 during the catalysis. Kantam and associates [23] have used a Pd(II) catalyst anchored onto MCM-41/silylamine (MCM-41 a molecular-sieve) for hydrodehalogenation of aryl halides by atmospheric hydrogen. The catalyst was reused for several cycles with constant activity. 

The mechanisms of the homogeneous catalytic hydrodehalogenation have been examined by the following methods ... 

Products of SNAr-type oxidative additions in some active Pd- or Ni-containing hydrodehalogenating systems have been isolated and characterized structurally (e.g., [(PEtNiCl(p-C6Cl5C6Cl4) [31], [(PPh3)2PdBr(3,4,5-tribromo-2-thienyl)]... 

Atom Transfer Atom Transfer (AT) takes place typically in the case of d7 complexes, which abstract the halogen atom from RX. The radical formed combines then with a second metal [193, 194]. A classical example of this mechanism is the hydrodehalogenation with cyanocobaltates(II) (see Section 18.2.1) [8, 9], but an analogous pathway was suggested recently for the Co(II) corrin-catalyzed dechlorination of CC14 in the presence of S2 /cysteine as reductant (Eqs. (11)—(12))... 

The double role of the reducing agents in homogeneous hydrodehalogenations... 

In outer-sphere SET reductions (e.g., in electrochemical dehalogenations), hydrogen abstraction by R leads to the product RH (i.e., no step related to (ii) is required to occur). Process (ii) follows generally the activation of the substrate in the proposed hydrodehalogenation cycles, but we know also of opposite examples [77, 82, 106, 112],... 

Rhodium(III) complexes [e.g. (i-Pr,P)2Rh(H)Cl2] in the presence of quaternary ammonium salts are excellent catalysts for the hydrogenolysis of chloroarenes under mild conditions [5] other labile substituents are unaffected. Hydrodehalogenation of haloaryl ketones over a palladium catalyst to give acylbenzenes is also aided by the addition of Aliquat [6]. In the absence of the phase-transfer catalyst, or when the hydrogenation is conducted in ethanol, the major product is the corresponding alkyl-benzene, which is also produced by hydrodehalogenation of the halobenzyl alcohols. 

The hydrodehalogenation reaction of haloaromatics involved the substitution of halide atoms bound to the ring, with hydrogen. For example, tetrachloroben-zene could be reduced to benzene in 30 minutes, at 50°C, by bubbling H2 at atmospheric pressure in the multiphasic system constituted by isooctane, 50% aqueous KOH, 0.2 molar A336, in the presence of Pd/C (0.02 molar) (Figure h.lS)." ... 

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