Chlorobenzene, carbonylation

Usually, iodides and bromides are used for the carbonylation, and chlorides are inert. I lowever, oxidative addition of aryl chlorides can be facilitated by use of bidcntatc phosphine, which forms a six-membered chelate structure and increa.scs (he electron density of Pd. For example, benzoate is prepared by the carbonylation of chlorobenzene using bis(diisopropylphosphino)propane (dippp) (456) as a ligand at 150 [308]. The use of tricyclohexylphosphine for the carbonylation of neat aryl chlorides in aqueous KOH under biphasic conditions is also recommended[309,310]. 

The benzoic acid derivative 457 is formed by the carbonylation of iodoben-zene in aqueous DMF (1 1) without using a phosphine ligand at room temperature and 1 atm[311]. As optimum conditions for the technical synthesis of the anthranilic acid derivative 458, it has been found that A-acetyl protection, which has a chelating effect, is important[312]. Phase-transfer catalysis is combined with the Pd-catalyzed carbonylation of halides[3l3]. Carbonylation of 1,1-dibromoalkenes in the presence of a phase-transfer catalyst gives the gem-inal dicarboxylic acid 459. Use of a polar solvent is important[314]. Interestingly, addition of trimethylsilyl chloride (2 equiv.) increased yield of the lactone 460 remarkabiy[3l5]. Formate esters as a CO source and NaOR are used for the carbonylation of aryl iodides under a nitrogen atmosphere without using CO[316]. Chlorobenzene coordinated by Cr(CO)j is carbonylated with ethyl formate[3l7]. 

Other reactions shown to occur at the same rate under the two heating methods include the acid-catalyzed isomerization of carvone 40 to carvacrol 41 [33], and ene reactions involving carbonyl enophiles (Scheme 4.21) [32], The former reaction was performed in a mixture of chlorobenzene (slightly polar) and dioxane (nonpolar) and in the latter reaction a large excess of 1-decene was used and so the reaction was effectively performed in a solution of low polarity. 

Vardanyan [65,66] discovered the phenomenon of CL in the reaction of peroxyl radicals with the aminyl radical. In the process of liquid-phase oxidation, CL results from the disproportionation reactions of primary and secondary peroxyl radicals, giving rise to trip-let-excited carbonyl compounds (see Chapter 2). The addition of an inhibitor reduces the concentration of peroxyl radicals and, hence, the rate of R02 disproportionation and the intensity of CL. As the inhibitor is consumed in the oxidized hydrocarbon the initial level of CL is recovered. On the other hand, the addition of primary and secondary aromatic amines to chlorobenzene containing some amounts of alcohols, esters, ethers, or water enhances the CL by 1.5 to 7 times [66]. This effect is probably due to the reaction of peroxyl radicals with the aminyl radical, since the addition of phenol to the reaction mixture under these conditions must extinguish CL. Indeed, the fast exchange reaction... 

Similarly, interphase catalysis permits carbonylation of haloaryls and halovinyls by NaCo(CO)4 with CO in water. The reaction proceeds according to S l mechanism and leads to high enough yields of carboxylic acids. Because C r-Cl bond is inert in these conditions, the direct and selective synthesis of chlorocarboxylic acids becomes possible. Thus, l-bromo-4-chlorobenzene gives 4-chlorobenzoic acid only (Brunet et al. 1983 Scheme 7.67). 

Nitro compounds in presence of carbonyl group are selectively reduced to amines in the presence of Raney nickel catalyst. Hydrazine reduces nitrdes yielding hydrazones. Under controlled reaction conditions other functional groups, including nitroso and oxime, may be reduced. Many partially hydrogenated derivatives, such as azo-, hydrazo-, and azoxy compounds may be obtained by partial reduction with hydrazine. Reaction with chlorobenzene yields benzene. 

In 1972 Wright prepared 3-chlorothieno[3,2-6]thiophene-2-carbonyl chloride (94) in 11-13% yield by heating 3-(2-thienyl)acrylic acid, thionyl chloride, and pyridine, a method of synthesis of benzo[6]-thiophene-2-carbonyl chloride derivatives. " Methyl 3,5-dichloro-thieno[3,2-6]thiophene-2-carboxylate (95) and methyl 2-chloro-3-(5-chloro-2-thienyl)acrylate were also isolated. When fte reaction was carried out in refluxing toluene or chlorobenzene, the acid chloride (94)... 

Formation of aldehydes. Aldehydes can be prepared by the carbonylation of halides in the presence of various hydride sources. The carbonylation of aryl and alkenyl iodides and bromides with CO and H (1 1) in aprotic solvents in the presence of tertiary amines affords aldehydes[373,374]. Aryl chlorides, as tricarbonylchromium derivatives, are converted into aldehydes at 130 C[366], Sodium formate can be used as a hydride source to afford aldehydes. Chlorobenzene (514) was carbonylated at 150 °C to give benzaldehyde with CO and sodium formate by using dippp as a ligand[375,376]. 

Franz and Black539 have studied the thermolysis and photolysis of l,3,4-oxathiazol-2-one (l).530 This compound is thermally labile and yields benzonitrile and sulfur instead of the expected phenyl isocyanate and carbonyl sulfide. It is probable that benzonitrile sulfide (3) is an intermediate and this appears to be confirmed by formation of the adduct 4 in 90% yield when 1 is heated with 2 moles of DMAD at 130° in chlorobenzene. Heating a mixture of benzonitrile and sulfur with DMAD gave tetramethyl thiophenetetracarboxylate (6), also obtained without the nitrile. The formation of the isomeric isothiazoles 7 and 8 from 1 and EP531 is similar to the production of the corresponding... 

The asymmetry parameters of substituted chlorobenzenes and iodobenzenes have been discussed above in Section III.A.3 (Tables 4 and 5). The asymmetry parameters of several systems are discussed below carbonyl chlorides in Section III.B.4, a variety of substituted vinyl chlorides in Section III.B.9 and methylene dichloride and chloroform in Section III.B.lO.c. There remain a number of measurements of asymmetry parameters30-33, mainly of aliphatic systems, that are not covered elsewhere and these are listed in Table 7. It will be seen that the asymmetry parameters of chlorine atoms bonded to saturated carbon atoms are always small, of the order of 0.05 or less, while if the chlorine atom is bonded to an sp2-hybridized carbon atom then the asymmetry parameter is generally equal to or greater than 0.1. 

Arylation of N, N-dimethylhydrazone 77 with ( fl-chlorobenzene)tricarbonylchromium complex lb can be achieved in 64 % yield. The copper lithium azaenolate 78 is trapped with the chromium complex at 70 °C to give a-phenyl ketone 80 as a result of an ipso substitution (Scheme 35) [59]. This represents an easy access to a-aryl carbonyl compounds, some of which may exhibit anti-inflammatory properties. 

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