Halo Groups

Many other examples are known of non-selective reactions of halo groups in pyridopyridazines with amines, alkoxides, sulfur nucleophiles such as hydrosulfide and thiolate ions, or thiourea, hydrazine(s), cyanide ion and dimethyl sulfoxide, or on catalytic reduction. 

The accelerative effect of quaternization on the reactivity of 1-halo groups toward water, alcohol, or ammonia has been reported. ... 

Hagemann s ester, synthesis of, 912 Halo group, directing effect of, 567-568... 

Amino groups can be exchanged for sulfo or halo groups via diazotization and application of the Sandmeyer procedure. An example is the preparation of zinc(II) 2-chloro-9,16,23-trwer/-butylphthalocyaninc (6).3,9... 

Triple bonds in the P position (in propargyl systems) have about the same effect as double bonds. Alkyl, aryl, halo, and cyano groups, among others, in the 3 position of allylic substrates increase Sn2 rates, owing to increased resonance in the transition state, but alkyl and halo groups in the 1 position decrease the rates because of steric hindrance. 

A more traditional cephalosporin analogue is cephapirin (22). It was made by reacting 7-aminocephalo-sporanic acid with bromoacetyl chloride to give amide 21. The halo group was displaced by 4-thiopyridine... 

The structure of compounds 8, containing trifluoromethyl and halo groups in many combinations, was analysed by 13C, 19F and 119Sn NMR, IR in the gas phase and Raman spectroscopy in the liquid phase115. 

Finally, this obituary and retrospective survey could not close without a significant mention of Richardson s celebrated rules for nucleophilic replacement of tosylates, mesylates, and halo groups by charged nucleophiles in carbohydrate pyranoid derivatives. They emanated out of his early studies at Reading on the preparation of... 

Rearrangement of acyl and halo groups are the most common reactions of nitrogen substituents of triazoles. 

The spectra of other norbornyl cations have also been investigated at low temperatures. Spectra of the tertiary 2-methyl- and 2-ethylnorborny cations show less delocalization,153 and the 2-phenylnorbornyl cation (54) is essentially classical,154 as are the 2-methoxy-155 and 2-chloronorbornyl cations.156 We may recall (p. 170) that methoxy and halo groups also... 

In general, SnI rates at an allylic substrate are increased by any substituent in the 1 or 3 position that can stabilize the carbocation by resonance or hyperconjugation.262 Among these are alkyl, aryl, and halo groups. 

Phosphonium salts, when functionalized (with e.g. keto, hydroxy, halo groups), are able to give characteristic reactions of such specific functions. This has been used in the synthesis of modified species nevertheless, the absence of any strong basic agent is the required condition (see 3A-C). 

Biphenyldicarboxylicacids.1 Phenanthrenequinone (1) isoxidized by oxygen in the presence of CuCl in pyridine to 2,2 -biphenyldicarboxylic acid (2) in high yield. Under the same conditions the monoimine 3, prepared in situ, is oxidized to 4. Amino and hydroxyl substituents interfere with this reaction, but alkyl, nitro, and halo groups are well-tolerated. 

Selective reduction of ot,a-dihalo ketones." Reduction of a,a-dihalo ketones can he effected without hydrogenolysis of the halo groups with either DIBAH or borane dimethyl sulfide. Reactions with the former reagent are generally faster but work-up can be complicated by gelatinous aluminum salts. In general, the yields are roughly comparable. 

However, the reactions of 2- and 4-halopyridines are modified by co-ordination to a metal. The most unambiguous studies are concerned with the relative rates of reaction of free and co-ordinated ligands. Co-ordination of 4,4 -dichloro-2,2 -bipyridine to a ruthenium(il) centre dramatically activates the halo groups towards nucleophilic displacement. The rate of displacement of halide is many times greater than that of the free ligand (Fig. 8-32). Nucleophiles such as HS03", which do not react with the free ligand, are effective in these reactions and this provides a useful method for the preparation of pyri-dine-4-sulfonic acids. 

ArC=N.1 Aryl triflates react with KCN at 60° in CH3CN in the presence of Ni(0) (5 mole %), generated in situ from Br2Ni[P(C6H5)3]2 and zinc, to form aryl nitriles in 69-78% yield. This coupling is not useful in the case of haloary 1 triflates because of coupling of KCN with the halo groups. Pd catalysts are not useful. 

AIBN selectively reduces the a-halo group, whether Cl, Br, or I, of pivaloyloxy-methyl 6,6-dihalopenicillanates. The order of reactivity is I > Br > Cl > F. 

Alkyl- and Aryl-Halides. Because the halo-groups of organic molecules have large electronegativities and electron affinities, all halo-carbon molecules are electrophilic. Their electrochemical reduction potential is a measure of their electrophilicity (and electron affinity), which is illustrated in Figure 12.1 for hexacWorobenzene (C6C16), 1,2,3,4-tetrachlorobenzene (1,2,3,4-C6H2C14), and n-butyl iodide (n-BuI).8,9 Table 12.1 summarizes the reduction potentials for several alkyl-halides and ary 1-chlorides.810... 

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