Preparation of the Starting Materials

The primary starting material for the synthesis of perylene tetracarboxylic acid pigments is the dianhydride 71. It is prepared by fusing 1,8-naphthalene dicar-boxylic acid imide (naphthalic acid imide 69) with caustic alkali, for instance in sodium hydroxide/potassium hydroxide/sodium acetate at 190 to 220°C, followed by air oxidation of the molten reaction mixture or of the aqueous hydrolysate. The reaction initially affords the bisimide (peryldiimide) 70, which is subsequently hydrolyzed with concentrated sulfuric acid at 220°C to form the dianhydride  

Naphthalic acid imide 69 is obtained through air oxidation of acenaphthene 72 with vanadium peroxide as a catalyst. The intermediate, naphthalic anhydride 73, is subsequently reacted with ammonia  

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The Friedlander reaction is quite versatile. The primary limitation on the o-aminobenzaldehyde component is preparation of the starting material as one might expect, these compounds are prone to self-condensation. Both electron rich and electron poor o-aminobenzocarbonyl compounds undergo the Friedlander reaction. When ketone partner 2 has only one available reactive methyl or methylene or is symmetrical, only one product is obtained. Even when two products can be formed, it is possible to choose reaction conditions such that only one product is isolated vide infra). The reaction can be promoted by acid catalysis, sometimes with improved results. 

Some interesting organic chemistry is involved in the synthesis of chlorite-resistant brighteners for acrylic fibres. None of these compounds is easy to make and methods for preparation of the starting materials can be complex. Much manufacturing know-how is involved. One route for introduction of the benzimidazole nucleus into structure 11.55 is shown in Scheme 11.22. Preparation of the chemically rather simpler benzoxazole grouping in product 11.56 is shown in Scheme 11.23. 

Compound 146 was converted to 147 (relative stereochemistry is shown in Scheme 68) by addition of a series of aldehydes, and other isomers were also obtained which were easily purified. But attempts to liberate a dihydrofuran from 147 were unsuccessful, which is believed to be due to decarbonylation by rhenium.306 Alternative approaches can be envisaged, although the authors noted the difficulty in the preparation of the starting material as a serious barrier to this.306... 

Preparation of the starting materials Mn(CO)5(CH3) and the phosphine-substituted derivative [cis-Mn(CO)4(PPh3)(CH3)] follow those from the literature.7,8 Solvents are dried over 4A molecular sieves and purged with nitrogen before use (except for chromatography). Silica gel for chromatography was obtained from Baker/ All reactions should be carried out under an inert atmosphere but after cooling may be worked up in air (however, solutions of the products slowly decompose in air). 

The intramolecular carbon-carbon bond-forming reactions considered in this section are based on the aldol condensation (see Section 5.18.2, p. 799), the Claisen-Schmidt reaction (see Section 6.12.2, p. 1032), the Claisen ester condensation (see Section 5.14.3, p. 736), and the Claisen reaction (see Section 6.12.2, p. 1032). Since these carbonyl addition reactions are reversible, the methods of synthesis are most successful for the formation of the thermodynamically stable five- and six-membered ring systems. The preparation of the starting materials for some of these cyclisation reactions further illustrates the utility of the Michael reaction (see Section, 5.11.6, p. 681). 

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... 

Fig. 11.7. trans-Selective Wittig olefination of aldehydes I—Preparation of a trans-configured a,j8-unsaturated ester (preparation of the starting material Figure 17.24). 

Fig. 14.50. Frans-selective Ireland-Claisen rearrangements with 1,4-chirality transfer. (See Figures 13.47 and 13.48, respectively, with R = vinyl in both cases, for preparations of the starting materials syn-A and anti-k, respectively.)...

The addition of two nucleophiles to a coordinated //6-arene is a synthetically important goal. A one-pot synthesis of 1,3-disubstituted cyclohexadienes involving an initial ipso addition to fluoroarene complexes is possible. Indeed, p-fluorotoluenetricarbonylchromium complex 22c reacts with isobutyronitrile carbanion (2 equiv.) in THF to give, after 5 days at —30 °C and acidic treatment under CO atmosphere, the cyclohexadiene 66 in 47 % yield (Scheme 31) [53] the yield can reach 75 % after several weeks Carbon monoxide was used in order to decoordinate the // -cyclohexadiene intermediate and to recover Cr(CO)6 needed for the preparation of the starting material [54]. 

The oxy-Cope rearrangement has also been used in synthesis of ( )-peripla-none-B (V/38), the sex excitant pheromone of the American cockroach (Peri-planeta americana) [24]. Scheme V/7 gives the preparation of the starting material, V/43, for the rearrangement step. The divinylcyclohexenol derivative, V/43, smoothly underwent an oxy-Cope rearrangement after conversion to its potassium salt. The reaction mixture was cooled to —78°, treated with (CH3)3SiCl and finally oxidized with m-chloroperbenzoic acid [24]. 

The preparation of the starting material is worth a closer look because it too involved a cross-condensation between two esters, Here it is in full. You have met all of these reactions in earlier chapters of this book. 

In a short known reaction sequence, enal 250 was obtained from commercially available material 184). With methylamine and magnesium sulfate imine 251 was formed and combined with acyl chloride 252 185) (>4 steps). The use of low temperatures for this acylation led exclusively to the less substituted dienamide 253. The desired basic skeleton of dendrobine 254 was obtained by cyclizing 253 at 180°C in an acceptable 50% yield, Adduct 254 was accompanied by small amounts of the exo-adduct. Epoxidation led exclusively to exo-epoxide 255, which by means of trimethylsilyltriflate was converted into the allylic silyl ether. Acid treatment liberated the hydroxy group and subsequent oxidation of alcohol 256 led to enone 163, an intermediate of Inubushi s dendrobine synthesis and thus concluded this formal synthesis. The intermediate 163 was obtained from commercially not available materials in seven steps in 22.5% overall yield. To reach ( )-dendrobine according to Inubushi et al. would afford six additional steps, reducing the overall yield to 0.4% without including the preparation of the starting materials from commercially available compounds. 

Treatment of methyl N-nitroso- -alkylaminoisobutyl ketones with sodium isopropoxide or sodium cyclohexoxide furnishes a third method (equation 3)- The preparation of the starting materials involves simply the addition of an amine to mesityl oxide with subsequent nitrosation. In this case the starting material (equation 3, R=H) for diazomethane is more stable than nitrosomethylurea and does not have an irritating action like methyinitrosourethane. ... 

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