Synthesis of Dibenzothiophenes

Dibenzothiophene is now commercially available. However, laboratory preparations from biphenyl, sulfur, and aluminum chloride have continued to be studied, yields of up to 80 being recorded. The synthesis from biphenyl and hydrogen sulfide in the presence of a catalyst has also been reinvestigated.  

A useful review of methods available up to 1960 for the synthesis of condensed thiophenes, including dibenzothiophene, has been made by Tilak, and a similar but shorter review has been made by Mlochowski and Skrzywan.  

Well-established routes to dibenzothiophenes such as reaction of 2,2 -dihydroxy derivatives of biphenyl with phosphorus pentasulfide are still encountered in the literature but have been omitted from the present work as they have already been well documented.  

McClellan, Tables of Experimental Dipole Moments. Freeman, London, 1963. 

Obolentsev, S. V. Netupskaya, L. K. Gladkova, V. G. Bucharov, and A. V. Mashkina, Khim. Seraorgan. Soedin.., Soderzh. Neftyakh Nefteprod., Mater. VtoriSessii, 87 (1956) Chem. Abstr. 54, 250 (1960). 

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The total synthesis of dibenzothiophene from thiophene is described in Section V, A. 

The total synthesis of dibenzothiophene from thiophene has made available two ketones of potential synthetic interest. Stepwise succinoy-lation and reduction of thiophene in the 2- and 5-positions gave the... 

Several substituted derivatives of 64 have been prepared in high yield during the synthesis of dibenzothiophenes via the 2-chlorocyclohexa-none route (Section IV,A), namely, 8-methyl-,7-methyl-, ... 

If the moeity adding to the aryne carries a suitably placed electrophilic center, cyclization with the initially formed anion can occur as observed in the synthesis of dibenzothiophene (60).92 Of wider synthetic import in this context is enolate addition to arynes. Here, after the initial ring closure many types of products can be formed (Scheme ll).35 However, with some substrates, a particular reaction course can predominate 93 94 for example, reaction of cyclodecanone with bromobenzene provides an efficient method for benzo-annulation and ring expansion. Similarly, high yields of benzocyclobutenols can be obtained from the monoketals of ot-diketones.9s... 

Chloro-2,3-diethyl-2-cyclobutenone (611) undergoes a palladium-catalyzed cross-coupling with 2-(tri- -butyl)stannyl-5-trimethylsilylthiophene (612) to give the intermediate compound (614) (Equation (110)). Without isolation, (614) is converted to the benzothiophene (613) on thermolysis at 100°C followed by acetylation. Although this procedure seems not to be generally applicable to benzo[6]thiophene synthesis, it provides a general synthesis of dibenzothiophenes, and thus a series... 

Along with C—N and C—O bond formation reactions, transition-metal-catalyzed C—S bond formation reaction has also been developed. However, the reaction has scarcely been applied to the synthesis of dibenzothiophenes. In this context, Samanta and Antonchick reported the palladium-catalyzed synthesis of 1-formyldibenzothiophene 80 from benzyl phenyl sulfoxides 78 (Scheme 23.30) [41]. 

Scheme 4.3 Palladium-catalyzed synthesis of dibenzothiophenes from aryl sulfoxides.

Scheme 4.5 Synthesis of dibenzothiophenes by Pd-catalyzed dual C-H activation.

These dienes are valuable for the Diels-Alder based synthesis of dibenzofurans, dibenzothiophenes, carbazoles and other classes of complex polycyclic heterocyclic compounds. Scheme 2.32 summarizes some of the cycloadditions [81] of 2-vinylbenzofurans (80). 

N. Nemoto, H. Kameshima, Y. Okano, and T. Endo, Synthesis of novel ir-conjugating polymers based on dibenzothiophene, J. Polym. Sci., Part A Polym. Chem., 41 1521-1526, 2003. 

Several important new synthetic routes to dibenzothiophenes have been described, including two routes to compounds substituted at C-1 and C-1,9, hitherto extremely inaccessible positions. The synthesis of several derivatives of (1) bearing substituents at C-9b or at S(5) has also been described, both novel types. 

The synthesis of 2,7-dinitrodibenzothiophene via cyclization of the biphenyl derivative (38) with bromine, at 200°, could be usefully extended to the synthesis of other deactivated dibenzothiophenes. The 2,7-disubstitution pattern is rare, the only other reference to it being the... 

The synthesis of a substituted derivative of 2-keto-l,2,3,4-tetrahydro-dibenzothiophene is discussed in Section VI, D. 

The literature concerning hydroxydibenzothiophenes has not progressed very much over the last 20 years, although the necessary intermediates and methods are now available for the synthesis of these compounds. The isolation of 1-hydroxydibenzothiophene 5,5-dioxide as a metabolite of dibenzothiophene is the only reference to the 1-hydroxy compound (Section III,C,3) however, two possible precursors,... 

An improved synthesis of 2-(r-hydroxyethyl)dibenzothiophene has been reported involving Meerwein-Ponndorf reduction of 2-acetyldi-benzothiophene. An alternative synthetic route has been employed in the synthesis of 4-(l -hydroxyethyl)dibenzothiophene (101) involving treatment of 4-lithiodibenzothiophene with acetaldehyde (36%). Both of these compounds are readily dehydrated to the corresponding vinyl compounds, the polymerization of which is discussed in Section VII. 

Direct nitration of dibenzothiophene occurs in the 2-position, while prior oxidation of the sulfur atom to either the sulfoxide or sulfone causes nitration to be directed to the 3-position. These two reactions form the starting point for the synthesis of most of the known derivatives of dibenzothiophene, which normally proceed via the derived amines. This has now been further illustrated by the synthesis of both 1-nitro- and 4-nitrodibenzothiophene from iV -derivatives of 2- and 3-aminodibenzo-thiophene, respectively, as described below. The synthesis of these two compounds thus completes the series of mononitrodibenzothiophenes. Unfortunately hopes of s3mthesizing nitrodibenzothiophenes via the chlorocyclohexanone route have been almost certainly ruled out by the failure to produce 2-nitrodibenzothiophene by this route (Section IV, A). 

Three derivatives of 3-aminodibenzothiophene, 110a, 110b, and 110c, have been nitrated, and in each case substitution occurred in the 4-position. Hydrolysis of the products yielded 3-amino-4-nitro-dibenzothiophene, which was different from the previous two nitro-amines and which formed an imidazole different from both 104 and 109. Deamination of this nitroamine via diazotization gave a small amount of 4-nitrodibenzothiophene. An alternative synthesis of the 4-nitro compound is described later. The spectroscopic techniques used above by Sawicki were later extended to determine the positions of substitution in dibenzoselenophene, in this case by comparison with the above-established derivatives of dibenzothiophene. - ... 

An alternative synthesis of 4-nitrodibenzothiophene involves heating 2-amino-2 -nitrodiphenyl sulfide in a sealed tube at 190° (20%). The reaction probably proceeds via homolytic cleavage of the derived diazonium ion which could have been formed from nitrous acid liberated during the formation of phenothiazines, which were also detected. Similarly, 2-methyl-4-nitrodibenzothiophene is formed from 2-amino-2 -nitro-4 -methyldiphenyl sulfide (10%), and in this case the intermediacy of the diazonium ion was further indicated in that the same material was obtained by pyrolysis of the separately prepared diazonium salt of the sulfide. Although yields are poor in this reaction, it nevertheless represents the only route to substituted dibenzothiophenes containing a nitro substituent in the 4-position and as such is worthy of further attention. 

The synthesis of 1-aminodibenzothiophene by reduction of the 1-nitro compound with hydrogen and Raney nickel (57%) completes the series of monoaminodibenzothiophenes. A synthesis of 2-amino-dibenzothiophene 5,5-dioxide from the corresponding 2-bromo compound has been described involving heating with ammonium hydroxide and copper at 200° (66 /o). 8-Bromo-2-aminodibenzothiophene has been prepared by catalytic reduction of the corresponding nitro compound... 

The synthesis of the four monocarboxylic acids of dibenzothiophene has been recorded in the previous review. However, several modified preparations have since been described. Ethyl 1-dibenzothiophene-carboxylate has been synthesized from 2-allylbenzo[6]thiophene (Section IV,B, 1) hydrolysis afforded the 1-acid (57% overall). In a similar manner, 3-methyl-1-dibenzothiophenecarboxylic acid was obtained from the appropriately substituted allyl compound. This method is now the preferred way of introducing a carbon-containing substituent into the 1-position of dibenzothiophene. 2-Dibenzothiophenecarboxylic acid has been prepared by oxidation of the corresponding aldehyde or by sodium hypoiodite oxidation of the corresponding acetyl compound. Reaction of 2-acetyldibenzothiophene with anhydrous pyridine and iodine yields the acetyl pyridinium salt (132) (92%), hydrolysis of which yields the 2-acid (85%). The same sequence has been carried out on 2-acetyldibenzothiophene 5,5-dioxide. The most efficient method of preparing the 2-acid is via carbonation of 2-lithio-... 

There is still no efficient synthesis of 3-dibenzothiophenecarboxylic acid. The only recorded preparation is via metallation of dibenzothiophene with phenylcalcium iodide followed by carbonation, but the yield was poor. The successful use of 3-lithiodibenzothiophene to give the 3-aldehyde indicates that 3-bromodibenzothiophene would probably be the best precursor of the 3-acid. Both l,4,4a,9b-tetrahydrodibenzo-... 

During the period covered by this review the preparation of most of the sets of four isomeric monosubstituted dibenzothiophenes have been completed. The successful synthesis of the 1-, 3-, or 4-substituted isomers is due largely to the synthesis of the four monolithiodibenzo-thiophenes by several groups of workers. Despite the success of this work which is due mainly to the established versatility of lithium reagents, the need exists for a separate study of the optimum conditions for the... 

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