Preparation of Benzene Derivatives

Several new methods have been put forward for the functionalization of benzene derivatives. 1. S. Yadav of the Indian Institute of Chemical Technology, Hyderabad has devised (Chem. Lett. 2008, 37, 652) a procedure for direct thiocyanation, converting 1 into 2. Sukbok Chang of KAIST has established Chem. Commun. 2008, 3052) that both NH Cl and aqueous NHj could be used to directly aminate an aryl iodide such as 3. lohn F. Hartwig of the University of Illinois has developed J. Am. Chem. Soc. 2008,130, 7534) a protocol for the directed borylation of anilines such as 5 and of phenols, based on a transient sUyla-tion. Karsten Menzel of Merck West Point Tetrahedron Lett. 2008, 49,415) has observed selective exchange of tribromobenzene derivatives such as 7, with the direction of the selectivity being controlled by the fourth substituent on the benzene. 

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Typical Procedure for the Preparation of Benzene Derivatives from Three Different Alkynes using NiCI2(PPh3)2 (see Eq. 2.53) To a solution of a zirconacyclopentadiene (1.0 mmol) [4] prepared from two different alkynes in THF (20 mL), the third alkyne (1.5 mmol)... 

Diacetoxy-1,3-butadiene is a reactive diene in the Diels-Alder reaction. It has been used as the starting material in stereospecific syntheses of conduritol-D8 and shikimic acid,9,10 and in a simple general method of preparation of benzene derivatives, especially unsymmetrical biphenyls.11,12... 

The preparation of benzene derivatives containing ortho-substituted t-butyl groups via cobalt complexes of the formula type Co2(CO) [acetylene] has raised questions of the structural arrangements in these complexes. The analysis of Co2(CO) [Bu C HyHC2H], from which ortho-di t-butylbenzene is obtained, has been shown to involve six carbon atoms bonded bifunctionally... 

Preparation of Benzene Derivatives The Barrett Syntheses of Dehydroaltenuene B and 15G256p... 

Benzoic acid and naphthoic acid are formed by the oxidative carbonylation by use of Pd(OAc)2 in AcOH. t-Bu02H and allyl chloride are used as reoxidants. Addition of phenanthroline gives a favorable effect[360], Furan and thiophene are also carbonylated selectively at the 2-position[361,362]. fndole-3-carboxylic acid is prepared by the carboxylation of 1-acetylindole using Pd(OAc)2 and peroxodisulfate (Na2S208)[362aj. Benzoic acid derivatives are obtained by the reaction of benzene derivatives with sodium palladium mal-onate in refluxing AcOH[363]. 

The bicyclo[2.2.0]hexa-2,5-diene ring system is a valence isomer of the benzene ring and is often referred to as Dewar benzene. After many attempts to prepare Dewar benzene derivatives failed, a pessimistic opinion existed that all such efforts would be finitless because Dewar benzene would be so unstable as to immediately revert to benzene. Then, in 1962, van Tamelen and Pappas isolated a stable Dewar benzene derivative by photolysis of 1,2,4-tri(/-butyl)benzene. ... 

Carboxylic acids and their anhydrides acy late a variety of benzene derivatives, fused ring systems, and heterocyclic compounds. An improved procedure for the preparation of l,4-difluoroanthracene-9,10-dione involves reacting phthalic anhydride and 1,4-difluorobenzene to prepare an intermediate carboxylic acid [35] Intramolecular acylation in polyphosphonc acid completes the synthesis (equahon 24). 

The scope of the microwave technique in the preparation of fullerene derivatives was determined in the well known Diels-Alder reaction of C6o with anthracene (1) [71], which has been reported to occur under thermal conditions (13% [71a], reflux, toluene, three days 25% [71b], reflux, benzene, 12 h) (Scheme 9.22). In addition to 76, multiply-substituted adducts that undergo cycloreversion to the starting materials were formed. 

General Procedure for the Formation of Benzene Derivatives (see Eq. 2.48) At 0°C, dimethyl acetylenedicarboxylate (284 mg, 2 mmol) and CuCl (198 mg, 2 mmol) were added to a solution of zirconacyclopentadiene (1 mmol) in THF, prepared in situ according to the known procedure [12]. The reaction mixture was then allowed to warm to room temperature and was stirred for 1 h. After hydrolysis with 3 n HC1, the mixture was extracted with diethyl ether. The combined extracts were washed sequentially with water, aq. NaHC03 solution, brine, and water, and then dried over MgS04. Concentration in vacuo followed by flash-chromatography eluting with a mixture of hexane and diethyl ether (10 %) afforded benzene derivatives. 

It is well-known that the anodic trifluoroacetoxylation of benzene derivatives is a useful method for the preparation of phenol derivatives (Eq. 30). Schafer et al. have successfully achieved CH-functionalization of various hydrocarbons by anodic oxidation in 0.05 M Bu4NPF6/CH2Cl2 containing 20% TFA and 4% (CF3C0)20 as shown in Eqs 31 and 32 [75]. 

The amide alcohol 320 submitted to the reaction of benzaldehyde and TsOH in benzene afforded the aminal function of the bicyclic lactam 321 as a single diastereomer (Equation 57) <2002TL6609>. This type of reaction has been often used for the preparation of perhydro derivatives as well. 

Although anthraquinone is the starting point for the preparation of many derivatives, involving substitution and replacement reactions, certain compounds are obtained directly by varying the components in the above synthesis. Thus, for example, replacement of benzene with methylbenzene (toluene) leads to the formation of 2-methylanthraquinone. A particularly important variation on the phthalic anhydride route is the synthesis of 1,4-dihydroxyanthraquinone (6.6 quinizarin) using 4-chlorophenol with sulphuric acid and boric acid as catalyst (Scheme 6.3). The absence of aluminium chloride permits hydrolysis of the chloro substituent to take place. 

As discussed, there are various methods of cation-radical generation. Every individual case needs its own appropriate method. A set of these methods is continuously being supplemented. For example, it was very difficult to prepare the cation-radicals of benzene derivatives with strong acceptor groups. However, some progress has been achieved, thanks to the use of fluorosulfonic acid, sometimes with addition of antimony pentafluoride, and lead dioxide (Rudenko 1994). As known, superacids stabilize cationic intermediates (including cation-radicals) and activate inorganic oxidants. The method mentioned is effective at -78°C. Meanwhile, -78°C is the boundary low temperature because the solution viscosity increases abruptly. This leads to the anisotropy of a sample and a sharp deterioration in the ESR spectrum quality. 

Preparation Phenol, also known as carbolic acid, was first isolated in the early of Phenols nineteenth century from coal tar. Nowadays, phenol is commercially produced synthetically. In the laboratory, phenols are prepared from benzene derivatives by any of the following methods ... 

A rather more complex scheme is required for the preparation of a derivative that bears a trifluoromethyl substituent on one of the benzene rings. The scheme starts with the condensation of the nitrile group in (32-1) with phenyhnagnesium bromide to give the corresponding imine treatment with aqueous acid leads to the substituted benzophenone (32-2). The future methyl on one of the bridges is introduced in a sequence involving the addition of a trimethylsulfonium yhde. 

Sometimes the formation of benzene derivatives can be explained by cycloaddition rather than by ketolization. Thus the excellent preparation of substituted benzophenones 553 from 2//-pyrans 552 on heating with acetic anhydride253 is interpreted as in Scheme 30. 

These were prepared by tethering Rh and Pt complexes to silica-supported metal catalysts (metal = Pd, Ni, Ru, Au). The catalysts are very active in the hydrogenation of benzene derivatives to the corresponding substituted cyclohexanes under mild conditions. The activities are higher than those of the separate homogeneous complexes, complexes just tethered to silica, or the silica-supported heterogeneous catalysts. When the sol-gel-entrapped [Rh2Co2(CO)12] complex was heat-treated at 100°C, immobilized metallic nanoparticles were formed.425 The catalyst thus prepared efficiently catalyzed substituted benzene derivatives. 

The preparation of quinoxaline derivatives carrying a substituent in the benzene ring requires suitably substituted o-phenylenediamines. These have been prepared by reductive cleavage (SnCl2) of appropriately substituted 2,1,3-benzoselenadiazoles (I9).21 Benzo-selenadiazoles, readily prepared from 1,2-diaminobenzenes and selenium dioxide, undergo halogenation at positions 4 and 7 and sulfonation at C-4. 5,6-Dichloro- 2,3-diphenylquinoxaline has been synthesized from benzil and l,2-diamino-3,4-dichlorobenzene, the diamine in turn was obtained from 4,5-dichloro-2,l,3-benzoselenadiazole.22... 

No general experimental details for the preparation of nitro derivatives can be given, as the ease of nitration and the product formed frequently depend upon the exact experimental conditions. Moreover some organic compounds react violently so that nitrations should always be conducted on a small scale. Typical procedures for benzene hydrocarbons are illustrated by the following concise notes for the nitration of benzene and toluene to yield the solid dinitro compounds. (Full experimental details are given in Expts 6.17 and 6.18). 

Since alkylation greatly reduces the ionization potential of benzene derivatives it was hoped that alkylated benzene cations could be prepared by oxidation in sulphuric acid (Bolton and Carrington, 1961b Hulme, unpublished results). However, although oxidation of p-xylene... 

The difficulty associated with the preparation of the starting materials for these carbonium ion reactions decreases their general utility for the preparation of protoadamantyl derivatives. A recently reported isomerization of the 1-adamantyloxy radical conveniently overcomes this problem. Thermolysis of 1-adamantanol hypoiodite, prepared in situ in dry benzene, gives endo-3-iodomethylbicyclo [3.3.1 ] nonane-7-one, which, when treated with base, gives 4-protoadamantanone (Eq. (22)) in an overall yield from 1-adamantanol of approximately 30 % 79,79af... 

The synthesis of 1,3,2-dithiazolidines from bis(sulfenylchlorides) and amines has been developed in the 1990s and 2000s (Equations 12 and 14). Trimethylsilyl azide confirmed its important role in the preparation of fused mono- and bis-l,3,2-dithiazolium cations (Equation 18). Oakley and co-workers showed that o-dimercapto derivatives can be used in the synthesis of these compounds if treated with trithiazyl trichloride (Equation 19). Synthesis of iV-substituted 1,3,2-benzodithazole tetraoxide has been successfully carried out from benzene-bis(sulfonylchloride) and aliphatic amines (Equation 15). An important feature in this reaction is the preparation of chiral derivatives from optically pure amines (Equations 16 and 17). 

Fig. 6.21. Electrochromatographic separation of benzene derivatives on monolithic capillary column prepared by UV initiated polymerization. Conditions capillary column, 100 pm i.d. x 25 cm active length stationary phase poly(butyl methacrylate-co-ethylene dimethaciylate) with 0.3 wt. % 2-acrylamido-2-methyl-l-propanesulfonic acid pore size, 296 nm mobile phase, 75 25 vol./vol mixture of acetonitrile and 5 mmol/L phosphate buffer pH 7 UV detection at 215 nm 25 kV pressure in vials, 0.2 MPa injection, 5 kV for 3 s. Peaks thiourea (1), benzyl alcohol (2), benzaldehyde (3), benzene (4), toluene (5), ethylbenzene (6), propylbenzene (7), butylbenzene (8), and amylbenzene (9).

The X-ray crystal structure of benzene, proving the equivalence of the six C-C bonds, appeared in 1929 and 1932, and Pauling reported its electron-diffraction data in 1931. Note that several of the structures proposed in the 19th century, such as Dewar benzene (non-planar) and Ladenburg s prismane, which are valence isomers of benzene, have now actually been prepared from benzene derivatives photochemically. They are kinetically stabilized, since they do not spontaneously revert to benzene or its derivatives [17-20]. 

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