Aromatic Experimental Procedure

Experimental procedures have been described in which the desired reactions have been carried out either by whole microbial cells or by enzymes (1—3). These involve carbohydrates (qv) (4,5) steroids (qv), sterols, and bile acids (6—11) nonsteroid cycHc compounds (12) ahcycHc and alkane hydroxylations (13—16) alkaloids (7,17,18) various pharmaceuticals (qv) (19—21), including antibiotics (19—24) and miscellaneous natural products (25—27). Reviews of the microbial oxidation of aUphatic and aromatic hydrocarbons (qv) (28), monoterpenes (29,30), pesticides (qv) (31,32), lignin (qv) (33,34), flavors and fragrances (35), and other organic molecules (8,12,36,37) have been pubflshed (see Enzyp applications, industrial Enzyt s in organic synthesis Elavors AND spices). 

Many reagents are able to chlorinate aromatic pyrazole derivatives chlorine-water, chlorine in carbon tetrachloride, hypochlorous acid, chlorine in acetic acid (one of the best experimental procedures), hydrochloric acid and hydrogen peroxide in acetic acid, sulfuryl chloride (another useful procedure), etc. iV-Unsubstituted pyrazoles are often used as silver salts. When methyl groups are present they are sometimes chlorinated yielding CCI3 groups. Formation of dimers and trimers (308 R = C1) has also been observed. 

Two reactions of the non-aromatic 4,4-disubstituted pyrazolones are worthy of mention. Carpino discovered that 4,4-dihalogenopyrazolones (365) and 4-substituted 4-halogenopyrazolones (366) when treated with bases yield a, 8-alkynic and -alkenic acids, respectively (66JOC2867). The reaction proceeds through an oxopyrazolenine (2,3-diazacyc-lopentadienone (367) (B-74M140408). A modification of the experimental procedure transforms (365) into bimanes (368) (82JOC214), which are formed from (367 R = X),... 

The synthetic procedure described is based on that reported earlier for the synthesis on a smaller scale of anthracene, benz[a]anthracene, chrysene, dibenz[a,c]anthracene, and phenanthrene in excellent yields from the corresponding quinones. Although reduction of quinones with HI and phosphorus was described in the older literature, relatively drastic conditions were employed and mixtures of polyhydrogenated derivatives were the principal products. The relatively milder experimental procedure employed herein appears generally applicable to the reduction of both ortho- and para-quinones directly to the fully aromatic polycyclic arenes. The method is apparently inapplicable to quinones having an olefinic bond, such as o-naphthoquinone, since an analogous reaction of the latter provides a product of undetermined structure (unpublished result). As shown previously, phenols and hydro-quinones, implicated as intermediates in the reduction of quinones by HI, can also be smoothly deoxygenated to fully aromatic polycyclic arenes under conditions similar to those described herein. 

A solution of estradiol (38, 15 mg) in methanol-OD (4 ml) and one drop of 10% deuteriosulfuric acid in deuterium oxide is heated under reflux for 5 days. After cooling the reaction mixture is diluted with ether, washed with dilute sodium bicarbonate solution and water, then dried over anhydrous sodium sulfate. Evaporation of the ether gives crystalline 2,4-d2-estradiol (39, 15 mg, 99%), mp 173-175° (ether-hexane), exhibiting 82% isotopic purity and only one aromatic hydrogen by NMR. (For an experimental procedure describing the exchange of aromatic protons under Clemmensen conditions, see section III-D.)... 

Primary aromatic amines (aniline, 3-toluidine, 4-anisidine and 3-chloroanilinc) react with 4 to give 2-[2-(arylamino)-l-cyanoviny]]benzimidazoles9 (see Houben-Weyl, Vol.E8c, p 314 with an experimental procedure).289... 

Of course the structural changes represented in Table 1 are much more complex than the simple bond angle plus electronic effect analysis reveals. For example, solvation of the carbene may depend on the details of its structure, and solvation undoubtedly influences chemical and physical properties (Langan et al., 1984). Nonetheless, it is possible to develop a good grasp of the most important properties of aromatic carbenes from the simple considerations described above. Before we proceed to examine these relationships in more detail, the carbene properties of interest must be identified, and the experimental procedures available for measurement of these properties must be critically considered. 

The preparation of macrocyclic diimines and endocyclic enamines are represented by the procedures for the formation of 1,10-DIAZA-CYCLOOCTADECANE and N-METHYL-2-PHENYL-A2-TETRA-HYDROPYRIDINE. Other procedures representative of alkylation reactions and aromaticity (TRI-i-BUTYLCYCLOPROPENYL FLUOROBORATE) round out a volume of tested experimental procedures of general value. 

On the other hand, the method of Mukaiyama can be succesfully applied to silyl enol ethers of acetic and propionic acid derivatives. For example, perfect stereochemical control is attained in the reaction of silyl enol ether of 5-ethyl propanethioate with several aldehydes including aromatic, aliphatic and a,j5-unsaturated aldehydes, with syir.anti ratios of 100 0 and an ee >98%, provided that a polar solvent, such as propionitrile, and the "slow addition procedure " are used. Thus, a typical experimental procedure is as follows [32e] to a solution of tin(II) triflate (0.08 mmol, 20 mol%) in propionitrile (1 ml) was added (5)-l-methyl-2-[(iV-l-naphthylamino)methyl]pyrrolidine (97b. 0.088 mmol) in propionitrile (1 ml). The mixture was cooled at -78 °C, then a mixture of silyl enol ether of 5-ethyl propanethioate (99, 0.44 mmol) and an aldehyde (0.4 mmol) was slowly added to this solution over a period of 3 h, and the mixture stirred for a further 2 h. After work-up the aldol adduct was isolated as the corresponding trimethylsilyl ether. Most probably the catalytic cycle is that shown in Scheme 9.30. 

Considering that the described reaction is feasible for both aromatic and aliphatic aldehydes, that the experimental procedure is very easy, that the yields, in spite of moderate, are not far from the theoretical, the described method is certainly a useful contribution for the synthesis of symmetrical divinyl tellurides. 

Catalytic hydrogenation is hardly ever used for this purpose since the reaction by-product - hydrogen chloride - poses some inconveniences in the experimental procedures. Most transformations of acyl chlorides to alcohols are effected by hydrides or complex hydrides. Addition of acyl chlorides to ethereal solutions of lithium aluminum hydride under gentle refluxing produced alcohols from aliphatic, aromatic and unsaturated acyl chlorides in 72-99% yields [5i]. The reaction is suitable even for the preparation of halogenated alcohols. Dichloroacetyl chloride was converted to dichloro-... 

The technically most important polysulfide is poly thiophenylene or poly(p-phe-nylene sulfide), PPS. It is obtained by reacting sodium sulfide and p-dichlo-robenzene in a polar solvent, for example, l-methyl-2-pyrrolidone at about 280 °C under pressure. The mechanism of the reaction is very complex and cannot be described by a simple aromatic substitution. This synthesis requires special autoclaves and is therefore not suitable for a laboratory course (for an experimental procedure see Table 2.3). 

The technical production of poly(benzimidazole) (PBI) is also carried out in two steps. In the first step an aromatic tetramine is condensed with the diphenyl ester of an aromatic dicarboxylic acid at 220-260 °C, yielding a poly(amino amid) with elimination of phenol. Ring closure with elimination of water occurs in the second step (solid-phase polycyclocondensation), conducted at 400 °C and yielding the polybenzimidazole (experimental procedure, see Table 2.3). 

Non-activated aryl bromides (but not fluorides) can be used as substrates for palla-dium(0)-catalyzed aromatic nucleophilic substitutions with aliphatic or aromatic amines. These reactions require sodium alcoholates or cesium carbonate as a base, and sterically demanding phosphines as ligands. Moreover, high reaction temperatures are often necessary to achieve complete conversion (Entries 7 and 8, Table 10.4 Experimental Procedure 10.1). Unfortunately, the choice of substituents on the amine... 

The phenolic group is activating and ortho-para directing. The electrophilic substitution reactions in the nucleus in (a) nitrosation and nitration (b) halogenation and (c) acylation and alkylation, are therefore particularly facile, and various experimental procedures need to be adopted to control the extent of substitution (cf. substitution reactions of aromatic amines and their acylated derivatives, Sections 6.6.1 and 6.6.2, pp. 906 and 916 respectively). 

Nitration. These may generally be prepared as detailed under Aromatic hydrocarbons, Section 9.6.3, p. 1238 the following experimental procedure for anisole may be regarded as typical. Add 0.5 g of anisole to a mixture of equal volumes of concentrated nitric acid and concentrated sulphuric acid keeping the temperature below 25 °C by cooling in an ice bath. Finally warm to 40 °C until dilution of a small portion with water gives a solid product. Pour the whole of the reaction mixture into water collect the resulting 2,4-dinitroanisole and recrystallise from ethanol. 

The present overview deals with the application of Fischer chromium carbene complexes in the benzannulation reaction for the preparation of highly substituted aromatic compounds. Before focussing on specific arenes (Section 8.5), details of the mechanism are given (Section 8.2), and the scope and limitations of the reaction are defined (Section 8.3). A short description of the experimental procedure is given thereafter (Section 8.4). Finally, the contribution deals with the application of the chromium carbene benzannulation to natural compounds and molecules with biological activity (Section 8.6). 

Yen and co-workers [54] have reported an efficient one-pot procedure for the synthesis of 4,6-diaryl-2-pyridinones 3 based on a cyclocondensation reaction of iV-ethoxycarbonyl-methylpyridinium chloride or iV-carbamoylmethyl p3Tidinium chloride with an aromatic aldehyde and a substituted acetophenone. The MCR was performed under microwave irradiation (domestic oven) with NTUOAc/AcOH as the reaction medium. The nature of the substituents on the aromatic aldehyde and ketone seem to have little influence on the obtained yields. The highlights of this approach include a convenient and simple experimental procedure with easy product isolation (Scheme 3). 

Both theoretical and experimental studies show that not only are aromatic ladder polymers more thermally stable but they are also more highly conducting than analogously structured nonladder systems.In this communication, we report the synthesis and electronic properties of a ladder aromatic polymer, poly(8-methyl, 2.3-6,7-quinolino) (PMQ). The experimental procedures for preparation and characterization of PMQ are described in refs. 5 and 6. 

The condensation of aldehydes and ketones with ethyl chloroacetate in the presence of sodium ethoxide or sodium amide produces a,/3-epoxy esters (Darzens). The scope, limitations, typical experimental procedures, and examples have been given. Briefly, aliphatic and aromatic ketones, and aromatic aldehydes react satisfactorily, whereas aliphatic aldehydes give poor yields. a-Halopropionic and a-halobutyric... 

The foregoing experimental procedures were successful only with primary aromatic amines. Weygand added water to his reaction mixtures, but such practice cannot be recommended with strongly basic amines because W-gly-cosyl derivatives of the latter are easily hydrolyzed. -Hydrolysis in strongly basic, aqueous media results in alkaline degradation of the sugar. ... 

The first step in the experimental procedure consists of preparative electrolysis of the aromatic compound A to A . The preparative potentiostat is then disconnected and a UME is inserted into the cathodic compartment. The steady-state oxidation current of A is recorded as a function of time for a certain time period to ascertain that the stability of A is high. If this is indeed the case, the alkyl halide RX is added to the solution while it is stirred for a few seconds to assure that homogeneous conditions apply for the reaction of Eq. 90. The recorded current is observed to decay exponentially towards zero. A plot of In / versus t is shown in Figure 16 for four different combinations of aromatic compounds and sterically hindered alkyl halides. From the slopes of the straight lines, -2A etCrx, A et values can readily be obtained. The method is useful for the study of relatively slow reactions with kET < 10 M- s-. ... 

Ferrocene behaves like an aromatic compound activated for electrophilic substitution reactions. Thus, only minor modifications of experimental procedures developed for aromatics are necessary to obtain ferrocene derivatives (a useful review on general methods is given by Schldgl and Falk [42]). For central chiral ferrocenes, resolution of the racemate is a frequently applied technique. Traditionally, resolutions are best achieved by salt formation between a chiral acid or base and the... 

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