Benzoannelation

Krivopalov et al. investigated the formation of the ditetrazolo form 90TT and the dependence of equilibria on the solvent and on the substitution and benzoannelation in the diazides of type 90AA (86BAU1745 88MRC42 89BAU1839). 

Heterocyclic [3,2-d]-fused pentalenes and their benzoannelated derivatives 97CLY547. 

BENZOANNELATION OF KETONES 3,4-CYCLODODECENO-1-METHYLBENZENE (Benzocyclododecene, 5,6,7,8,9,l0,n,l2,l3,l4-decahydro-2-methyl-)... 

This preparation describes a highly practical and efficient method for the benzoannelation of ketones. The classical approach to the synthesis of aromatic... 

Several related methods for benzoannelation have been reported.7 Most provide aromatic sulfides or phenols that require additional manipulation. The present method provides convenient and highly efficient access to structurally diverse benzoannelated products. The ease of the reactions, the high yields, and the convenience recommend its use. 

Marcus A. Tius and G. S. Kamali Kannangara 158 BENZOANNELATION OF KETONES 3.4-CYCLODODECENO-1 -METHYL-BENZENE... 

The present method is successful with a wide variety of ketones (see Table). Cyclic ketones (entries 1-4, 8) produce benzoannelated products in excellent overall yields. There is no need to purify the intermediate both the nucleophilic addition of methallylmagnesium chloride and the aromatic cyclization take place cleanly. Acyclic ketones (entries 5-7) also provide high yields of benzoannelated product. Aromatic ketones are particularly interesting substrates for this reaction since they provide substituted biphenyls, which are potentially useful materials for liquid crystal synthesis and whose preparation through classical methodology is often not straightforward. The conditions for the cationic cyclization step can be modified to accommodate acid-sensitive functionality. For example, cyclization of 3 to 4, the latter a precursor for 3-methyl-8,14-dehydromorphinan, was accomplished in 77% yield by treatment of 3 at... 

We suspect fewer problems would have arisen had Oth and coworkers (see Reference 97) decided to perform enthalpy of hydrogenation measurements on [18]annulene. Nonetheless, we note that Oth s suggested value for the enthalpy of formation of benzo-l,3,5-cyclooctatriene is within 2 kJ mol of that estimated summing Roth s enthalpy of formation of 1,3,5-cyclooctatriene and Liebman s (cited in Reference 68) benzoannelation constant. 

Replacement of the chloro substituents and hydroboration of the benzoannelated diborafulvene 21 with LiBH4 leads to an anionic product, which after protonation affords the l-carbapentaborane(lO) 22 in 36% yield (Scheme 3.2-12) [34],... 

The recent impact of solid-phase synthesis on medicinally relevant benzoaime-lated nitrogen heterocycles has been recently reviewed [16], therefore in this section only recent publications are included. Benzoannelated heterocycles can be prepared efficiently through cyclization on solid supports employing classical heterocycle forming reactions such as the Fischer [425], the Bischler-Napieralski [426], Tsuge [427], Nenitzescu [428], and Richter [140] reactions. In addition, the... 

Fig. 3.12 Skeletons of five-membered benzoannelated nitrogen heterocycles.

There are many examples for seven-membered benzoannelated heterocycles that include benzazepines (332) [245, 454] benzothiazepines (333) [455, 456] and the very important pharmacological family of benzodiazepines (334) [285, 457, 458], which was the first class of small molecules synthesized on solid supports [459]. Benzoxazocines (335) [460] are examples for benzoannelated eight-mem-bered heterocycles obtained on solid supports (Fig. 3.14). 

In contrast to the benzoannelated nitrogen heterocycles, only a few kinds of benzoannelated systems without nitrogen have been described (Fig. 3.15). Five-mem-bered rings such as benzo[b]furans (336) [184, 461] and hydrobenzo[b]furans (337) (Scheme 3.41) [337, 462, 463] and six-membered rings like 4H-l-benzopyran-4-ones (4-chromones) (338) and 2H-l-benzopyran-2-ones (coumarines) (339) [96, 464, 465] 2,3-dihydro-4H-l-benzopyran-4-ones (chroman-4-ones) (340) [466] and 3,4-dihydro-lH-2-benzopyrans (isochromans) (341) [444] have been reported. 

Fig. 3.15 Skeletons of five- and six-membered benzoannelated oxygen heterocycles.

The spectra of aromatic 3-azapyrylium salts 3 are very much like those for pyrylium salts [82AHC(S)1 88ZOR2232 91ZOR1986]. Benzoannelated... 

As in the case of the 1,2-dioxins, the 1,2-dithiins exist in various states of saturation, oxidation, and benzoannelation (cf. Scheme 1, 17-27) and they have been studied in detail both theoretically and experimentally. Not only were the conformations of the ring and attached substituents investigated, but the valence isomerism of 1,2-dithiin by both NMR and high-level ab initio molecular orbital (MO) calculations and the dithiol/disulfide equilibrium by MP2 calculations were also examined. The latter equilibrium has been applied successfully as a luminescent molecular switch (cf. Section 8.10.2.1). Finally, as a very interesting 1,2-dithiin derivative, the synthesis, structure, and reactivity of the (-l-)-camphor-derived analog 25 and its sulfoxide 26 and sulfone 27 have been reported. Both the synthesis and the antimalarial activity of the 2,3-dioxabicyclo[3.3.1]nonane pharmacophore 28, which contains the 1,2-dioxane moiety, have been reviewed recently <2006BML2991>. 

Adhering to the same principle, the (< -iodophenyl)diene 129 undergoes a sequence of two intramolecular S-exo-trig carbopalladations (Scheme 34) to yield the benzoannelated spiro[4.4]nonane derivative 129. ... 

Benzoannelation of the oxepane ring system leads to an increase in the barrier to ring inversion. Thus variable temperature NMR spectra on l,2,4,5-tetrahydro-3-benzoxepin (2) suggested that a chair conformation was preferred with a barrier to ring inversion of ca. 39.7 kJ mol"1. 

Two substrates of special interest are 2-(2-hydroxyethoxy)-3-nitro-thiophene and its 3-(2-hydroxyethoxy)-2-nitro isomer. Both compounds form Meisenheimer-type spiro adducts, 135 and 136, by ring closure at the 2-and 3-positions, respectively.177 Intramolecular cyclization brings in an extra driving force for the formation of the adduct, which is also observed in the trinitrobenzene series.31 This would account for the structure of adduct 136, which exceptionally bears the sp3-hybridized carbon on a ft position. No other examples of such a structure from 5-membered heteroaromatic substrates is known even for transient species, except for benzoannelated derivatives (see Section III,A,3). 

For relatively unstrained medium-size rings, benzoannelation seems to exert a rather small effect on enthalpies of formation104. For example, the transformation of cyclopen-tene, cyclopentadiene and cyclohexene to indane (20, n = 5), indene and tetralin (20, n = 6) results in a change of gas-phase enthalpies of formation of (26.8 2.2), (29.1 2.6) and (31.0 2.1) kJ mol-1. For the rather strained cyclobutene, annelation to form benzocy-... 

Barbier reaction Samarium(II) iodide, 270 Benzoannelation Chromium carbene complexes, 82 Dicarbonylcyclopentadienylcobalt, 96 Ethyl (Z)-3-bromoacryIate, 130 Grignard reagents, 138 Methyl acrylate, 183 Methyllithium, 188 Ruthenium(III) chloride, 268 Benzoin condensation Benzyltriethylammonium chloride, 239 3-EthyIbenzothiazolium bromide, 130 Benzoylation (see also Acylation) Cadmium, 60 Dibutyltin oxide, 95 Birch reduction Birch reduction, 32... 

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