Synthesis aromatic systems

Menes-Arzate M, Martinez R, Cruz-Almanza R, Muchowski Joseph M, Osomio Yazmin M, Miranda Luis D (2004) Efficient, tin-free radical cyclization to aromatic systems. Synthesis of 5,6,8,9,10,ll-hexahydroindolo[2,l-a]isoquinolines. J Org Chem 69 4001-4004... 

Triethyl phosphite is an effective reagent for the deoxygenation of appropriate nitro (or nitroso) aromatic systems. Free nitrenes or some nitrenoid-like species may be involved, and the use of this reagent is illustrated by the examples below. It has the advantage over the azide approach in that two steps in the synthesis can be avoided. 

The true, all-aromatic system (see 18, below) described by Kime and Norymberski is unusual in the sense that all of the ether linkages bridge aromatic carbons ". Synthesis of 18, therefore, required extensive use of copper mediated coupling reactions. As expected for such reactions, yields were generally low. The aromatics such as 18 were ineffective at binding either alkali metal or ammonium cations ". ... 

The following discussion of hydroxamic acids includes saturated systems, e.g., 2, compounds such as 3, derived from aromatic systems, 7V-hydroxyimides such as 7V-hydroxyglutarimide (78), and certain of their derivatives including thiohydroxamic acids. Naturally occurring cyclic hydroxamic acids are discussed to show the range of structural types that has been found, hut macrocyclic polyhydroxamic acids are mentioned very briefly, because several comprehensive reviews of these compounds are already available. The main purpose of this review is to summarize the methods available for the synthesis of cyclic hydroxamic acids, to outline their characteristic reactions, and to present some useful physical data. Their synthesis and some biological properties have previously been reviewed by Coutts. ... 

The classical age of preparative organic chemistry saw the exploration of the extensive field of five-membered heterocyclic aromatic systems. The stability of these systems, in contrast to saturated systems, is not necessarily affected by the accumulation of neighboring heteroatoms. In the series pyrrole, pyrazole, triazole, and tetrazole an increasing stability is observed in the presence of electrophiles and oxidants, and a natural next step was to attempt the synthesis of pentazole (1). However, pentazole has eluded the manifold and continual efforts to synthesize and isolate it. 

It is interesting to note that all the new aromatic systems, as described, undergo displacement polymerizations in DMAC solvent by the K2CO3 method, except perfluoroalkylene [10] and amide activated polymerization [9], which were performed in NMP solvent. The displacement polymerization in DMAC solvent was carried out at 155-164°C. poly(aryl ether ketones) require less reaction time (3-6 h) than other aromatic systems for synthesis of polyethers [15]. Synthesis of the fluorinated polyether as reported by Irvin et al. [16] was carried out at room temperature for 16 h (Mw = 75,000), whereas the same polymer by Mercer et al. [17] was synthesized at 120°C for 17 h (Mw = 78,970). 

Amination of Aromatic Heterocyclic Lactam Systems (Synthesis of Cytidines)... 

Although the Vilsmeier reaction is known best in aromatic systems, aliphatic olefins also undergo formylation. Synthesis of forwocortal (257) involves such a step. Formation of the monoketal of 255 involves the 3-ketone function with the familiar concomitant shift of the double bond to C-5,6. 

As noted previously, a wide variety of aromatic systems serve as nuclei for arylacetic acid antiinflammatory agents. It is thus to be expected that fused heterocycles can also serve the same function. Synthesis of one such agent (64) begins with condensation of indole-3-ethanol (60) with ethyl 3-oxo-caproate (61) in the presence of tosic acid, leading directly to the pyranoindole 63. The reaction may be rationalized by assuming formation of hemiketal 62, as the first step. Cyclization of the carbonium ion... 

Recently, Kraft and Osterod [157] reported the synthesis of poly(aramide) dendrimers possessing either electron-deficient 1,3,4-oxadiazole (70) or aromatic systems (71) linked by amide units to a central triphenylmethane unit (Fig. 31). 

Several synthetic pathways for the commercial manufacture of quinacridone pigments have been published. In this context, only those routes are mentioned which were developed for industrial scale production. There are four options, the first two of which are preferred by the pigment industry. It is surprising to note that these are the methods which involve total synthesis of the central aromatic ring. On the other hand, routes which start from ready-made aromatic systems and thus might be expected to he more important actually enjoy only limited recognition. 

Among syntheses which start from preformed aromatic systems, the Sandoz process in particular has stimulated interest. It is the only route which allows the manufacture of asymmetrically substituted quinacridones. A typical synthesis follows. 

Wherever the heterocyclic ring is fused to an aromatic system the starting material must always be a preformed aromatic derivative. In this context the Fischer indole synthesis (Scheme 6.12) provides a good example ... 

A second example from the same group is the synthesis of an elaborate diethynyltriphenylene derivative (Scheme 7 Table 8,entries 12,13) [58].Zn/Pd-promoted homocoupling of a 4-iodo-l,2-dialkoxybenzene furnishes the desired tetraalkoxybiphenyl, an electron-rich aromatic system. Iron trichloride-catalyzed Friedel-Crafts arylation of the biphenyl derivative with dimethoxy-benzene furnishes an unsymmetrical triphenylene derivative. Deprotection, oxidation, and subsequent Diels-Alder reaction with cyclohexadiene is followed by catalytic hydrogenation and reoxidation. TMS-CC-Li attack on the quinone delivers the alkyne modules, treatment with SnCl2 aromatizes the six-mem-bered ring, while KOH in MeOH removes the TMS groups cleanly to give the elaborate monomer. 

This reaction appears extensively in synthesis problems. Keep this reaction in mind when dealing with any synthesis problem involving an aromatic system. 

Going over the basics and mechanisms of nucleophilic substitution reactions Mastering mechanisms of elimination/addition reactions Determining synthesis strategies for aromatic systems... 

Nitrile oxides are widely used as dipoles in cycloaddition reactions for the synthesis of various heterocyclic rings. In order to promote reactions between nitrile oxides and less reactive carbon nucleophiles, Auricchio and coworkers studied the reactivity of nitrile oxides towards Lewis acids. They observed that, in the presence of gaseous BF3, nitrile oxides gave complexes in which the electrophilicity of the carbon atom was so enhanced that it could react with aromatic systems, stereoselectively yielding aryl oximes 65 and 66 (Scheme 35). ... 

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