Substitution halogen

It was seen earlier that MA derivatives can add the elements of a halogen. It is also known that halogens, particularly chlorine and bromine, undergo substitution reactions as well. Thus, monochloromaleic anhydride 66 is formed when chlorine is allowed to react with MA in the presence of aluminum chloride and barium chloride. 

Milone has shown that in the presence of aluminum chloride alone, at 90-100°C, the primary product is dichlorosuccinic anhydride (DCSA). At this stage, no significant evolution of hydrogen chloride occurred. On addition of barium chloride, a rapid evolution of hydrogen chloride occurred. Thus, it would appear that the primary reaction catalyzed by AICI3 was the addition of chlorine and barium chloride promoted the elimination of HCl as shown in the scheme. 

Since qualitative yields were described, it is difficult to conclude the quantitative nature of the promotions. The total reaction time in the presence of barium chloride was reported to be much shorter as well. This dual-function catalysis warrants further investigation. 

Bromination is generally accomplished in two steps. Dibromosuccinic acid 67, obtained from bromine addition, when boiled with water yields monobromomaleic acid 68. 

The ease of hydrogen halide elimination can also be used for forming chloromaleic acid 69 from dichlorosuccinic acid 56. 

The deshielding effect of I Br Cl, with a greater deshielding effect within the methane series than the primary alkyl series. 

Replacing the hydrogens of CF3CH2F with CF3 groups gives the secondary and tertiary fluoride compounds below, which absorb at 

A few pertinent proton chemical shifts are also provided in this scheme. 

Alcohol, Ether, Epoxide, Ester, Sulfide, Sulfone, 

Similar sulfur substitution, as in a fluoromethyl sulfide, also leads to deshielding, but somewhat less than for the analogous ether. 

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CF3CO2H. Colourless liquid, b.p. 72-5 C, fumes in air. Trifluoroacetic acid is the most important halogen-substituted acetic acid. It is a very strong acid (pK = o y) and used extensively for acid catalysed reactions, especially ester cleavage in peptide synthesis. 

Conjugate addition to a P-halogen substituted methaciylate results in an addition—elimination reaction which regenerates the tZ,/ -unsaturated moiety (19-21). 

Silicon reacts at elevated temperatures with the halogens, forming SiCl, Sil, SiBr, and SiF. There is also a series of halogen-substituted silanes such as trichlorosilane, SiH Cl, and dichlorosilane, S1H2CI2. Both SiCl and SiH Cl are relatively easy to make, purify, and reduce to silicon. These are the silicon compounds most often used as feedstocks in the manufacture of high purity silicon. 

Halogen-substituted succinimides are a class of products with important appHcations. /V-Bromosuccinimide [128-08-5] mp 176—177°C, is the most important product ia this group, and is prepared by addition of bromine to a cold aqueous solution of succinimide (110,111) or by reaction of succinimide with NaBr02 iu the presence of HBr (112). It is used as a bromination and oxidation agent ia the synthesis of cortisone and other hormones. By its use it is possible to obtain selective bromine substitution at methylene groups adjacent to double bonds without addition reactions to the double bond (113). 

The method is general for alkyl- and halogen-substituted aromatic amines. 

This compound is also described as diethanol-p-toluidine in the older literature. Anilines bearing hydroxyl groups are preferred because they are less volatile than anilines without polar substituents. Tertiary aromatic amines with para-halogen substitution have also been reported for use in adhesives [42]. 

Halogen-substituted olefins may be obtained from hydrazones by the action ofN-halocompounds. 327, /. 328.372 (Chloro compounds of this type may also be made by the direct action of phosphorous pentachloride on the ketone, e.g. ref. 329, 330.)... 

An electronegative substituent, particularly if it is attached to the a carbon, increases the acidity of a carboxylic acid. As the data in Table 19.2 show, all the rnono-haloacetic acids are about 100 times more acidic than acetic acid. Multiple halogen substitution increases the acidity even more trichloroacetic acid is 7000 times more acidic than acetic acid ... 

Halogen-substituted phenols were originally introduced for phosphate protection to minimize intemucleotide bond cleavage during deprotection. 

Quadrupole coupling constants for molecules are usually determined from the hyperfine structure of pure rotational spectra or from electric-beam and magnetic-beam resonance spectroscopies. Nuclear magnetic resonance, electron spin resonance and Mossbauer spectroscopies are also routes to the property. There is a large amount of experimental data for and halogen-substituted molecules. Less data is available for deuterium because the nuclear quadrupole is small. 

Despite the increasing information on the photochemistry of 2,4-dienones and other unsaturated ketones, as well as on the ring-chain valence isomerism of halogen-substituted pyran and dihydi opyran systems,the data are still very scarce. The intermediate formation of pyrans valence-isomeric with unsaturated carbonyl compounds in the pyridine syntheses based on reactions of ammonia with aldehydes or ketones, advocated by various authors (cf. Section II,B,2,f), is still rather speculative. (See also Section II,B,2,e for the valence isomerism of 5-chloro-2,4-dienones with pyrylium chlorides.)... 

Because inductive effects operate through cr bonds and are dependent on distance, the effect of halogen substitution decreases as the substituent moves farther from the carboxyl. Thus, 2-chlorobutanoic acid has p/chlorobutanoic acid has p/chlorobutanoic acid has p/C., = 4.52, similar to that of butanoic acid itself. 

It has been shown that halogen-substituted alkenes can participate in the metathesis reaction, e.g. 5-bromo-l-pentene reacts with 2-pentene 11). A very interesting reaction is the conversion of methyl-9-octa-decenoate into 9-octadecene and dimethyl-9-octadecenedioate 12) ... 

If the water content of the diazotization system is too high, the halogen atom in halogen-substituted mono- and dinitroanilines may be replaced by a hydroxy group in a bimolecular aromatic substitution. Analogous behaviour was observed in the diazotization of pentafluoroaniline, where the 4-fluoro substituent became hydrolysed (Brooke et al., 1965). As already mentioned in Section 2.1, this side reaction does not take place if the diazotization is conducted in a dichloromethane-aqueous sulfuric acid two-phase system in the presence of tetrakis[3,5-bis(trifluoromethyl)-phenyl]borate (Iwamoto et al., 1983a, 1984). 

Inasmuch as the conjugation properties of a double bond and a benzene ring are closely similar,11 we expect for the halogen substituted benzenes interatomic distances similar to those for the halogen ethylenes. De Laszlo12 has reported the values C-Cl = 1.69 A., C-Br = 1.88 A., and C-I = 2.05 A., corresponding to 14., 6, and 10% double bond character, respectively.15... 

Halogen-substituted 2-pyridones are key intermediates for further metal-catalyzed coupling reactions and the halogenation of these scaffolds has already been described in previous sections. In the following section, a variety of C - C and C - N cross-coupling reactions under microwave-assisted conditions are described with some illustrative examples. 

The alkylation of halogen-substituted benzenes such as fluorobenzene and dichlorobenzenes with other (dichloroalkyl)silanes in the presence of aluminum chloride catalyst afforded isomeric mixtures of the corresponding (dihalogen-substituted phenyl)alkylsilanes in moderate yields (Eq. (13)). These results are summarized in Table Xll. 

D. J. Edge and J. K. Kochi, Effects of halogen substitution on alkyl radicals conformational studies by electron spin resonance. J. Am. Chem. Soc. 94(18), 6485-6495 (1972). 

Allard A-S, M Remberger, AH Neilson (1987) Bacterial O-methylation of halogen-substituted phenols. Appl Environ Microbiol 53 839-845. 

Hughes DE (1965) The metabolism of halogen-substituted benzoic acids by Pseudomonas fluorescens. Biochem J 96 181-188. 

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