Acids direct introduction

Alkylation a.ndAryla.tion, The direct introduction of carbon—carbon bonds in quinoline rings takes place in low yield and with Htde selectivity. The most promising report involves carboxyHc acids with ammonium persulfate and silver nitrate (31). 

Some time ago Tedder (1957) recommended a process which he called direct introduction of the diazonium group , because it replaces the steps of nitration, reduction, and diazotization of an aromatic compound by a one-pot operation with three equivalents of a nitrosating reagent in acidic solution. The first step (Scheme 2-35) is a C-nitrosation and the following steps (Scheme 2-36) are the reduction of the nitroso-arene. 

The techniques based on the direct introduction of the sample in the mass spectrometer can also be used with CL This allows just a small amount of fragmentation. Due to the fact that less energy is used than in the El mode, Cl produces relatively stable molecular ions and ion fragments, and does not give as extensive fragmentation as readily as El does. Figure 3.8 compares the mass spectra of 7-oxo-dehydroabietic acid obtained by DE-MS using El at 70 eV and Cl with isobutane. In both these... 

Chiral butenolides are valuable synthons towards y-butyrolactone natural products [37] and have also been successfully applied to the synthesis of paraconic acids. The lactone 91, readily available from the hydroxyamide (rac)-90 by enzymatic resolution [38] followed by iodolactonization, proved to be an especially versatile key intermediate. Copper(I)-catalyzed cross coupling reactions with Grignard reagents allowed the direct introduction of alkyl side chains, as depicted in 92a and 92b (Scheme 13) [39, 40]. Further... 

Direct introduction of a diazo group upon treatment with an excess of nitrites was also an effective method to synthesize 4-diazopyrazoles. The dimethyl derivative was prepared in good yield in strong acid [61CI(L)1163], whereas the diphenyl derivative was only obtained in acetic acid in the presence of acetic anhydride (63JCS4589). Catalysis by mercuric acetate was also observed (63JCS4589). Direct introduction of a... 

Carbethoxy-4-diazo-l-phenylpyrazol-5-one (22a) (Scheme 88) was synthesized in 76% yield under mild conditions by direct introduction of the diazo group with the azidium salt 293 in sulfuric acid at room temperature [78H(10)199]. The easy introduction of the diazo group probably occurred because the a position of the ester was activated. On the contrary, tosyl azide failed to give the diazo derivative under the same conditions. Diazo transfer with this reagent only takes place under alkaline conditions, but in these reaction conditions, the diazo compound couples with the starting material. 

However, it is not impossible that at platinum mmdeH a direct introduction of hydroxyl groups into the benzene nucleus, i.e. a primary formation of hydroquinone fakes place, especially if concentrated sulphuric acid is chosen as the electrolyte. Chemical as well as -electrochemical experiences indicate this. Thus, by means of persulphuric acid or its salts, obtained by the electrolysis of sulphuric acid or its salts, nitrophonol can be directly converted into mtrohydro-quinone, salicylic acid into hydroquinonecarboxylle add,... 

In this category, only the chlorides have been used recently. Their usual preparative route from pyrazinecarboxylic acids has been discussed in Section 8.1.2. However, some 1/4-piperazinecarbonyl chlorides have been made by direct introduction or displacement, as illustrated in the following examples ... 

The direct introduction of functional groups into the oxadiazole nucleus is possible in only a few cases. The protonation of the nuclear nitrogen in acidic media reduces extremely strongly the possibility of electrophilic attack.119 Thus no nitrations or sulfonations of unsubstituted oxadiazoles are known in the literature. Halogenation also has not so far been described although in this case the deactivating effect of the oxadiazole nucleus is not so important.47,61... 

Mass spectra can only be obtained from compounds which are in the vapor-phase. The vapor pressure required to obtain a spectrum depends on the kind of sample introduction system if the sample is first evaporated in the gas container of the spectrometer and from there introduced into the ion source, a vapor pressure of about 10-2 mm Hg is necessary, while for direct introduction of the substance into the ion source a vapor pressure of only 10-6 mm is needed,2 usually sufficient to obtain spectra of very polar and nearly nonvolatile compounds, e.g., amino acids. Therefore, direct introduction systems2-9 (see also Biemann,10 p. 33) available since the pioneering work of Reed2 in all commercial instruments should be used in spite of experimental difficulties, if thermal or catalytic decomposition of the sample is to be expected. If the vapor pressure is so low that the sample cannot be vaporized sufficiently in the ion source, protecting of polar OH and NH groups by methylation or acetylation may produce a derivative of volatility enough to obtain a spectrum. 

Several medio are available for the intnxluction of sulfenyl groups a to carbonyl derivatives and these have been reviewed. - The most versatile procedure involves reaction of the enolate with an appropriate thiol derivative, but the preferred m od is largely dependent on the nature of the substrate employed (see below). In most instances, sulfur has been introduced in the divalent state and subsequently oxidized, although the oxidative step has been avoided by the direct introduction of sulfur at the S oxidation level. The oxidation of sulfides to sulfoxides is a trivial procedure that can be effected by a variety of reagents. Sodium metaperiodate, m-chloroperbenzoic acid and hydrogen peroxide are the most common oxidants, but r-butyl hydroperoxide, r-butyl hypochlorite, N-chlorobenzotriazole,... 

Direct introduction of the carboxyl group into an aromatic ring is accomplished with urea hydrochloride, phosgene, oxalyl chloride, or carbon dioxide. Carboxylation of benzene is effected in 15-58% yields by treating with liquid phosgene and aluminum chloride. No catalyst is required in the conversion of dimethylaniline and phosgene to p-dimethyl-aminobenzoic acid (50%). 9-Anthroic acid (67%) is prepared from anthracene by heating to 240° with oxalyl chloride and nitrobenzene. ... 

The synthetic potential of a simple method for the direct introduction of nitrogen into the 5-position of the pyrimidine ring is illustrated by the synthesis of 1,3-dimethyluric acid (15) from 1,3-dimethyluracil-6-amine by reaction with diethyl azodicarboxylate, reduction to 5-[(ethoxycarbonyl)amino]-l,3-dimethyluracil-6-amine, and thermal ring closure. "... 

Direct introduction of a carboxyl group can be achieved via the Grignard reagent or lithiated imidazole (see Section 7.2.2). This approach is especially valid for making 2-carboxylic acids, but 4- and/or 5-carboxylation is possible when C-2 is blocked (see Scheme 7.2.2), and if the differential reactivities of anions at these positions are utilized by careful control of reaction conditions. An example has been included in Section 7.2.2, and many others are listed in Iddon and Ngochindo s recent review [2]. 

In all of these cases the carboxyl group results from the direct introduction of carbon dioxide in front of a hydrogen or sodium atom. Now the sodium compound of phenol, viz., sodium phenolate, CeHg—ONa, undergoes a similar reaction yielding first a phenyl ester of carbonic acid which rearranges into salicylic acid. 

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