1.4- Dihydroaromatic compounds

Fig. 17.82. Birch reduction of benzenes give 1,4-cyclohexa-dienes. The radical anion C is formed by capture of a solvated electron in an antibonding n -orbital of an aromatic compound. The alcohol protonates this radical anion to the radical D, which captures another electron from the solution to form the carbanion E. The carbanion is protonated by a second equivalent of the alcohol, and the 1,4-dihydroaromatic compound results.

Protonation of the radical anion C of Figure 14.71 results in the radical D. This radical regains its valence electron octet by capturing another solvated electron to form the carbanion E. Carbanions of this type are protonated regioselectively by the second equivalent of alcohol. The regioselectivity is independent of the substituents protonation forms a 1,4-dihydroaromatic compound rather than a 1,2-dihydroaromatic compound. Hence, the 1,4-dihydrobenzene A is the reduction product in the example of Figure 14.71. 

Homogeneous hydrogenation catalyst. This catalyst is useful for reduction of 1,4-dihydroaromatic compounds. Aromatic compounds are not formed by disproportionation, as is the case when the usual heterogeneous catalyst are used. Moreover it is possible to reduce disubstituted double bonds in the presence of letrasubstituted double bonds. Thus isotetralin (1) or 1,4-dihydrotetralin (2) is reduced with this catalyst to an identical 80 20 mixture of 9,10-octalin (3) and 1,9-octalin (4). The latter octalin evidently arises by isomerization of the double... 

Lukeman, M. Wan, P. Excited-state intramolecular proton transfer in o-hydroxybiaryls a new route to dihydroaromatic compounds. J. Am. Chem. Soc. 2003, 125, 1164— 1165. 

BW-755C and its congeners can be considered as reducing agents either because they are dihydroaromatic compounds, or because of the presence of a hydrazine moiety, which is easily oxidized. In the latter vein, the amid-razone CBS-1114 (100) inhibited platelet CO and 12-LO, the release of 5-LO products from human or rabbit neutrophils (1-10 /M), and leukocyte... 

While this process does not involve the interaction of an excited stilbene with an amine, it does provide a convenient method for the synthesis of dihydroaromatic compounds (5,6). 

The photolysis of silicon-bridged dihydroaromatic compounds has been utilized to prepare reactive organosilicon species such as disilenes. Thus, photolysis of the... 

Photochemical electron transfer reactions of electron donor-acceptor pairs in polar solvents provide a convenient and effective method for the generation of radical cations which can be trapped by complex metal hydrides. One of the most effective systems is based on irradiation of a solution of substrate, sodium borohydride and 1,4- or 1,3-dicyanobenzene. A range of bi- and poly-cyclic aromatic hydrocarbons has been converted into the dihydro derivatives in this way. An especially important aspect of this route to dihydroaromatic compounds is that it may give access to products which are regioisomeric with the standard Birch reduction products. Thus, o-xylene is converted into the 1,4-dihydro product (229) rather than the normal 3,6-dihydro isomer (228). The m- and p-xylenes are similarly reduced to (230) and (231), respectively. ... 

The dihydroaromatic compound, methyl 3-methoxycarbonylcyclohexa-3,5-dien-ol has been prepared by the Diels-Alder addition of furan and methyl acrylate in the presence of zinc iodide at 40°C during 48 hours to give first the adduct shown in 55% yield. A solution of this in tetrahydrofuran added dropwise to lithium bis(trimethylsilyl)amide at -78°C with subsequent warming to ambient temperature after 1.5 hours gave the cyclohexadiene product in 85% yield. This should be readily dehydrogenated to methyl 3-hydroxybenzoate (ref.43). 

With the naphthalene ensemble, recovered naphthalene was only 1.8 times more abundant than the most prevalent dipentyldihydronaphthalene isomer it was only 1.2 times more abundant than the two most prevalent dipentyldihydronaphthalene isomers. In the stoichiometric alkylation of an aromatic radical anion, 1 mol of the aromatic compound is recovered for every mole of the dialkyl dihydroaromatic compound recovered. 

Photoexcited acetone has been used previously to generate aromatic compounds from dihydroaromatic compounds by hydrogen abstraction. Further studies14 have revealed the limitations of this procedure, and shown that other products are often formed from ketyl and hydroaromatic radical coupling. Only the conversion of indoline into indole occurs in reasonable yield (46%). Hydrogen abstraction by excited acetone also appears to be responsible for an unusual reaction on irradiation of friedelin (13) in ether-acetone.16 The known intramolecular reaction which occurs in the cyclohexanone ring gives a keten (Scheme 2), but this is followed by addition of a ketyl radical and subsequent reduction to produce an hydroxycarbonyl compound (14). 

Carbonyl derivatives of dihydroaromatic compounds can be used to generate polycyclic hydroxyarenium ions, e.g. 

Another way of generating arenium ions based on dihydroaromatic compounds is to break off, with a pair of electrons, a substituent located at one of the ring sp -hybridized carbon atoms. G. Olah et al. have used this method to obtain tetra-fluoroborate of the methylbenzenium ion by the action of AgBF on the bromination product of l-methylcyclohexa-l,4-diene at —60 °C. 

If an eliminated substituent in a dihydroaromatic compound is an OR group, then the respective arenium ion can be generated by dissolving this compound in a strong protonic add. Thus, the dissolution of 4-hydroxy-4-R-hexamethylcyclohexa-2,5-... 

According to the Woodward-Hoffmann rules for electrocychc reactions, a 6k electrocychzation is thermally allowed in a disrotatory manner and photochemically allowed in a conrotatory manner. However, in the present context of synthesis of aromatic compounds as final products, which are devoid of any stereocenters, the stereochemical aspects of the substituents in the intermediate dihydroaromatic compound should not matter. The photochemical 6x electrocychzation of c/s-stilbene derivatives followed by oxidation of the dihydroaromatic intermediate provides access to angularly fused polycyclic aromatic compounds (Scheme 16.2) [4]. 

The cobalt-catalyzed Diels-Alder reaction allowed the flexible formation of various functionalized dihydroaromatic compounds besides 26 which are essential for the synthesis of arene-ruthenium complexes in good yield and regioselectivities on a larger scale. 

Preparation of Aromatic Compounds via Dehydrogenation. Dihydroaromatic compounds are easily converted into the corresponding aromatic compound by treatment with triphenylcarbenium tetrafluoroborate followed by base. Certain a,a-disubstituted dihydroaromatics are converted to the 1,4-dialkylaromatic compounds with rearrangement (eq 1). Nonbenzenoid aromatic systems, e.g. benzazulene or dibenzosesquifulvalene, are readily prepared from their dihydro counterparts. Aromatic cations are also easily prepared by hydride abstraction, for example, tropylium ion (e.g. in the synthesis of heptalene (eq 2)), cyclopropenyl cation, and others, including heterocycUc systems. Some benzylic cations, especially ferrocenyl cations, can also be formed by either hydride abstraction or trityl addition. 

Reduction, see also Hydrogenation electrolytic, see Electrolysis of anisoin to deoxyanisoin by tin and hydrochloric acid, 40, 16 of aromatic compounds to dihydroaromatics by sodium and ammonia, 43, 23... 

The antioxidant ethoxyquin (94) is conceptually similar to (88) in that it contains a benzene ring with two heteroatoms in a 1,4-relationship, one of which lies in a dihydroaromatic ring. This compound was reported to inhibit the release of LO products from rat ISN, although it was more potent against CO [244]. Orally-dosed ethoxyquin inhibited cell influx in a rabbit hydronephrotic kidney model [245], and was anti-inflammatory in guinea-pig UV erythema [246]. No relationship was drawn between these activities and 5-LO inhibition. 

In case of benzene, the potassium salt of its anion-radical can be separated as a precipitate after benzene reduction by potassium in the presence of low concentrations of 18-crown-6-ether. For benzene, the heavy-form content is greatest in the solution, not in the precipitate. It is in the solution where most of the nonreduced neutral molecules remain. Since the neutral molecules are inert toward protons, the anion-radicals combine with the protons to give dihydro derivatives (products of the Birch reaction). Therefore, it is possible to conduct the separation chemically. The easiest way is to protonate a mixture after the electron transfer, than to separate the aromatic compounds from the respective dihydroaromatics (cyclohexadiene, dihydronaphthalene, etc.) (Chang and Coombe 1971, Stevenson and Alegria 1976 Stevenson et al. 1986a, 1986c, 1988). 

Dihydroaromatics find diverse applications. The main way to prepare them is through Birch reduction of aromatic compounds (Birch 1944, Wooster and Godfrey 1937, Hueckel and Bretschneider 1939). Aromatic compounds are hydrogenated in diethyl ether or liquid ammonia, with alkali metals as reductants and alcohols as proton sources. 

A clever application of this reaction has recently been carried out to achieve a high yield synthesis of arene oxides and other dihydroaromatic, as well as aromatic, compounds. Fused-ring /3-lactones, such as 1-substituted 5-bromo-7-oxabicyclo[4.2.0]oct-2-en-8-ones (32) can be readily prepared by bromolactonization of 1,4-dihydrobenzoic acids (obtainable by Birch reduction of benzoic acids) (75JOC2843). After suitable transformation of substituents, mild heating of the lactone results in decarboxylation and formation of aromatic derivatives which would often be difficult to make otherwise. An example is the synthesis of the arene oxide (33) shown (78JA352, 78JA353). 

Aromatic compounds are dechlorinated by the general mechanism shown in Sch. 1. Electron transfer to a ir-antibonding orbital forms an aromatic radical anion, which then ejects Cl" to give an aromatic radical. This radical picks up a second electron to give a very basic cx-anion, which abstracts a proton either from NH3 or from a more acidic source like water, when water is present. If water is not present, then an NH2 anion can be formed. The presence of ME can lead to the formation of aminated products via the benzyne mechanism. Aminated products were formed in dry NH3 but not when water was present [24], A further reduction via radical anion formation and proton abstraction can give dihydroaromatics or tetrahydroaromatics, or dimerization may occur. In soils, both water and... 

A Suzuki coupling of 2,6-dimethoxyiodobenzene with the dihydroaromatic boron compound 13 forms the basis of a synthesis of the dibenzo[6,t/]pyran ring system <03AG(E)2795> and naphtho[2,3-c]chromenes result from an intramolecular dehydro DA reaction on the diarylalkynes 14 <03SL1524>. 

Using the tforementioned cyclization of 1-amindiexatrienes, cf. (68) to (70) and (79) to (80), several aromatic compounds have been synthesized upon elimination of a dialkylamine from a dihydroaromatic precursor formed by the 6e electrocyclization process. As an example, dihydrophenanthrene (175) can be synthesized in two different ways depending on the choice of the allyl anion synthon (171 or 173) or... 

---