Aryl halides chlorobenzene

A limitation of both methods is that the second component must be liquid at the temperature of-the reaction, which is 5-10° for the diazohydroxide reaction and room temperature or slightly higher for the nitrosoacetylamine reaction. Experiments with solid reactants in solution have not been very successful, because of the difficulty of finding a suitable solvent. The solvent should be neutral and immiscible with water, have a high solvent action and reasonably low boiling point, and be inert to the free radicals which result from the diazo compound. The last qualification is the most difficult one to satisfy. Of the solvents which have been tried, carbon tetrachloride and chloroform appear to be the most suitable.18 From diazotized aniline and biphenyl in these solvents, some p-terphenyl is obtained, and from diazotized p-nitroaniline and biphenyl a small amount of 4-nitro-4 -phenylbiphenyl is formed. In these reactions an appreciable amount of tfie aryl halide (chlorobenzene and p-nitrochlorobenzene) is produced as a by-product. In general, the yields of products obtained by coupling with reactants in solution are extremely low. 

In halogenation, benzene reacts with CI2 or Br2 in the presence of a Lewis acid catalyst, such as FeCl or FeBr3, to give the aryl halides chlorobenzene or bromobenzene, respectively. Analogous reactions with I2 and F2 are not synthetically useful because I2 is too unreactive and F2 reacts too violently. 

Aryl Halides (Chlorobenzene). The final system to be considered in this section is the aryl hakde, chlorobenzene. Based on the above assignments the group frequencies of the complete hydrocarbon portion and the heteroatom function group can be assigned as in Table 8.25 (also see Chapter 8W, IR section. Fig. W8.39). 

Because carbon is sp hybridized m chlorobenzene it is more electronegative than the sp hybridized carbon of chlorocyclohexane Consequently the withdrawal of electron density away from carbon by chlorine is less pronounced m aryl halides than m alkyl halides and the molecular dipole moment is smaller... 

Noticeably absent from Table 23 3 are nucleophilic substitutions We have so far seen no nucleophilic substitution reactions of aryl halides m this text Chlorobenzene for example is essentially inert to aqueous sodium hydroxide at room temperature Reac tion temperatures over 300°C are required for nucleophilic substitution to proceed at a reasonable rate... 

Besides benzyl chloride, methyl- and/or chlorine-substituted benzyl chlorides, phenethyl chloride, etc. are also successfully employed to give 2 -diaralkylaminofluorans in excellent yield. However, aryl halides such as chlorobenzene and bromobenzene hardly enable the reaction, though aryl iodides such as iodobenzene give 2 -diarylaminofluorans in low yield. 

The reactivity order Ni>Pd>Pt has been found for the oxidative addition of aryl halides. Steric and electronic properties, and the numbers of L as well as chelate effects, play an important role [65, 194—196]. For example, Pd(0) complexes of basic chelating phosphines react substantially more easily with chlorobenzenes than their nonchelating analogues (see Section 18.2.4) [2, 100, 196]. 

Successful lithiation of aryl halides—carbocyclic or heterocyclic—with alkyUithiums is, however, the exception rather than the rule. The instability of ortholithiated carbocyclic aryl halides towards benzyne formation is always a limiting feature of their use, and aryl bromides and iodides undergo halogen-metal exchange in preference to deprotonation. Lithium amide bases avoid the second of these problems, but work well only with aryl halides benefitting from some additional acidifying feature. Chlorobenzene and bromobenzene can be lithiated with moderate yield and selectivity by LDA or LiTMP at -75 or -100 °C . 

Table VIII shows the conversions and selectivities obtained in this reaction with the various bases. Both calcium and barium hydroxide, as well as potassium carbonate, gave good yields and selectivities, particularly barium hydroxide, which gave conversions near 100% after 14h in a batch reactor. Ba(OH)2 was tested as a basic catalyst for the reaction with other aryl halides such as iodobenzene and chlorobenzene, and in both cases the yield and selectivity were also excellent.

The reaction of the cyanide ion with alkyl halides, using PTC, has been widely studied since the first example was reported by Starks.167 However, with unactivated aryl halides (e.g., chlorobenzene and dichlorobenzene) the reaction fails.229 On the other hand, chloropyrimidine reacts with tetra-ethylammonium cyanide in acetonitrile.230 Hermann and Simchen231 have described more generally the synthesis of cyano heterocycles, using tetra-ethylammonium cyanide. 

Although the simple aryl halides are inert to the usual nucleophilic reagents, considerable activation is produced by strongly electron-attracting substituents provided these are located in either the ortho or para positions, or both. For example, the displacement of chloride ion from l-chloro-2,4-dinitrobenzene by dimethylamine occurs readily in ethanol solution at room temperature. Under the same conditions chlorobenzene completely fails to react thus the activating influence of the two nitro groups amounts to a factor of at least... 

The reactivities of aryl halides, such as the halobenzenes, are exceedingly low toward nucleophilic reagents that normally effect displacements with alkyl halides and activated aryl halides. Substitutions do occur under forcing conditions of either high temperatures or very strong bases. For example, chlorobenzene reacts with sodium hydroxide solution at temperatures around 340° and this reaction was once an important commercial process for the production of benzenol (phenol) ... 

As with most organic halides, aryl halides most often are synthetic intermediates for the production of other useful substances. For example, chlorobenzene is the starting aryl halide for the synthesis of DDT it also is a source of benzenol (phenol, Section 14-6C) which, in turn, has many uses (Section 26-1). 

Ammonolysis of aryl halides has been performed under PTC conditions.125 The reaction of 2,4-dinitro-chlorobenzene with NH3 (g) in toluene at ambient temperature and pressure gave, in the presence of 10% TBAB and after 3 h, 2,4-dinitroaniline in 16% yield (0.6% in the absence of TBAB). The reaction was complete after 24 h but the product final yield was not reported.125... 

Triarylphosphines were prepared by the reaction between lithium diphenylphosphide in THF and m-and p-iodotoluene (or the corresponding bromo compounds), 4-bromobiphenyl and p-dibromobenzene in yields of 70-80% (isolated after oxidation, as the phosphine oxides).143 The absence of cine substitution products is a synthetic advantage and would have been taken as a prima facie indication that the displacements are examples of the 5rn1 reaction, had the mechanism been recognized at the time. Operation of the radical ion mechanism in DMSO, or liquid ammonia, in which marginally improved yields are obtained, was confirmed by Swartz and Bunnett,48 but no extension to the scope of the reaction was made. Rossi and coworkers have developed a procedure for one-pot preparation of triarylphosphines starting from elemental phosphorus (Scheme 6).146 As an example of the synthesis of a symmetrical tri-arylphosphine, triphenylphosphine (isolated as its oxide) was obtained in 75% yield, with iodobenzene as the aryl halide (ArX in Scheme 6, steps i-iii only). Unsymmetrical phosphines result from the full sequence of reactions in Scheme 6, and p-anisyldiphenylphosphine (isolated as its oxide) was produced in 55% yield, based on the phosphorus used, when chlorobenzene (ArX) and p-methoxyanisole (AiOC) were used. 

As noted earlier in this section, aryl halides generally do not undergo substitution reactions. However, under conditions of high temperature and pressure, these compounds can be forced to undergo substitution reactions. For example, under high temperature and pressure, chlorobenzene can be converted into sodium phenoxide when reacted with sodium hydroxide. 

The method is an extension of the well-known Grignard synthesis in ethers to the use of nonsolvating media, and is a development of procedures previously reported.2-6 A version of it has been employed with straight-chain primary alkyl chlorides, bromides, and iodides from C2 to Cu,5-7 and in solvents (or an excess of the halide) which permit reaction temperatures above 120°, with simple aryl halides such as chlorobenzene and 1-chloro-naphthalene. Branched-chain primary, secondary, and tertiary alkyl halides, allyl, vinyl, and benzyl halides either fail to react or give extensive side reactions. Better results are reported to be obtained in such cases with the use of catalytic quantities of a mixture of an alkoxide and an ether such as diethyl ether or tetrahydrofuran in a hydrocarbon medium, but the products are not, of course, completely unsolvated.4... 

In the presence of electron donors, photodechlorination of chlorobenzene390, 4-chloroanisole378 and other aryl halides is enhanced. The key step in this process is electron transfer from the donor to the excited halide. A kinetic study, based on determination of quantum yields and fluorescence quenching efficiencies, has revealed that in the triethyl-amine-assisted dehalogenation of chlorobenzene the product-forming interaction occurs with the triplet excited state (equations 97-99)390. 

It is important to note that even if the addition of Cul as co-catalyst was desirable with deactivated aryl halides, a high yield in coupling product could be obtained under copper-free conditions. Furthermore, the reaction could be smoothly carried out with an aliphatic alkyne in short reaction times but with this catalyst system only 51% of the coupling product was formed from chlorobenzene. 

Hydrolysis of chlorobenzene and the influence of silica gel catalysts on this reaction have been studied by Freidlin and co-workers (109). Pure silica gel gave up to 45% phenol from chlorobenzene at 600°C. When the silica gel was promoted with 2% cupric chloride, up to 75% phenol was obtained (381). A number of other salts were tested by Freidlin and co-workers as promoters, but they exerted an adverse effect on the activity or selectivity of the catalyst. With 0.2% cupric chloride and 6% metallic copper, the activity of silica-gel was doubled (389). At 500° under the above conditions, the halides were hydrolyzed at rates decreasing in the following order chloride, bromide, iodide, fluoride (110). The specific activation of aryl halides by cupric chloride was demonstrated by conversion of chlorobenzene to benzene and of naphthyl chloride to naphthalene when this catalyst was supported on oxides of titanium or tin (111). The silica promoted with cupric chloride was also found to be suitable for hydrolysis of chlorophenols and dichlorobenzenes however, side reactions were too prominent in these cases (112). 

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