Treatment With Acid Classical Procedure

The Nef reaction was originally carried out under acidic conditions using strong acid such as aqueous HC1.1-3 However, the use of base followed by acid is incompatible with polyfunctional substrates in addition, some compounds are prone to undergo side reactions or fail to react, as discussed in the references.1-3 Thus, various modified methods have been developed, and they 

Silica gel can be used as an acid for the Nef reaction. The basic silica gel impregnated with sodium methoxide has been used very conveniently for the Nef reaction (Eq. 6.1).4 

In general, the acid-catalyzed Nef reaction is carried out in water or water-containing solvents. If the reaction is carried out in methanol, nitro compounds are converted into the corresponding dimethylacetals. This process has merits over the conventional one due to the wider applicability of the Nef reaction (Eq. 6.2).5 

The Nef reaction is accelerated by the presence of silicon atom at y-position of nitro functions, as shown in Eq. 6.3. The presence of the y-silicon is essential for such smooth reaction.6 The conversion of 5-nitrobicyclo[2.2.1]heptenes to the corresponding ketones via the Nef reaction is very complicated by the degradation of the product. Thus, (3-trimethylsilyl ketones can be prepared by a one-flask method via the addition of Grignard reagents containing trimethylsilyl groups to nitroalkenes and the subsequent hydrolysis, as shown in Eq. 6.4. 

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Omission of the phenolic group from cyclazocine results in a molecule which retains analgesic activity. In a classical application of the Grewe synthesis,15 the methylated pyridinium salt 54 is condensed with benzylmagnesium bromide. There is thus obtained the dihydropyridine 55. Treatment of that intermediate with sodium borohydride results in reduction of the iminium function to afford the tetrahydro derivative 56. Cyclization of 56 on treatment with acid leads to the desired benzomorphan nucleus. The cis compound (57) is separated from the mixture of isomers and demethylated by the cyanogen bromide procedure (58,... 

Certain starting materials may give rise to the non-selective formation of regioisomeric enolates, leading to a mixture of isomeric products. Furthermore a ,/3-unsaturated carbonyl compounds tend to polymerize. The classical Michael procedure (i.e. polar solvent, catalytic amount of base) thus has some disadvantages, some of which can be avoided by use of preformed enolates. The CH-acidic carbonyl compound is converted to the corresponding enolate by treatment with an equimolar amount of a strong base, and in a second step the a ,/3-unsaturated carbonyl compound is added—often at low temperature. A similar procedure is applied for variants of the aldol reaction. 

Scheme 2.12 shows some representative Mannich reactions. Entries 1 and 2 show the preparation of typical Mannich bases from a ketone, formaldehyde, and a dialkylamine following the classical procedure. Alternatively, formaldehyde equivalents may be used, such as l>is-(di methyl ami no)methane in Entry 3. On treatment with trifluoroacetic acid, this aminal generates the iminium trifluoroacetate as a reactive electrophile. lV,A-(Dimethyl)methylene ammonium iodide is commercially available and is known as Eschenmoser s salt.192 This compound is sufficiently electrophilic to react directly with silyl enol ethers in neutral solution.183 The reagent can be added to a solution of an enolate or enolate precursor, which permits the reaction to be carried out under nonacidic conditions. Entries 4 and 5 illustrate the preparation of Mannich bases using Eschenmoser s salt in reactions with preformed enolates. 

Entries 1 and 2 in Scheme 2.11 show the preparation of Mannich bases from a ketone, formaldehyde, and a dialkylamine following the classical procedure. Alternatively, formaldehyde equivalents may be used, such as bis(dimethylamino)methane in entry 3. On treatment with trifluoroacetic acid, this aminal generates the iminium trifluoroacetate as a reactive electrophile. 

Chemat et al. [14] found the ]oint use of US and microwaves for the treatment of edible oils for the determination of copper to shorten the time taken by this step to about a half that was required in the classical procedure (heating in a Buchi digester) or with microwave assistance, nitric acid and hydrogen peroxide. However, they did not state the specific medium where the microwave-US-assisted method was implemented and assumed US to have mechanical effects only, even though they mentioned a cavitational effect. This is a very common mistake in working with US that is clarified in an extensive discussion by Chanon and Luche [15] of the division of sonochemistry applications into reactions which were the result of true and false effects. Essentially, these terms refer to real chemical effects induced by cavitation and those effects that can be ascribed to the mechanical impact of bubble collapse. The presence of one of these phenomena only has not been demonstrated in the work of Chemat et al. [14] — despite the illustrative figure in their article — so their ascribing the results to purely mechanical effects of US was unwarranted. 

As described earlier (Section 4.4.1.1), the intermediates of the Curtius reaction are acyl azides, which themially rearrange to isocyanates. One of the classical procedures for the preparation of acyl azides consists of the formation of hydrazides from esters and hydrazine, followed by treatment of the hydrazides with nitrous acid, generated from sodium nitrite and acetic, hydrochloric or sulfuric acid. Acyl azides are commonly used in the crude state or in solution since they are thermally unstable and potentially explosive. 

Duff reaction (1, 430). Review.1 In the classical procedure highly activated aromatic compounds are converted into their formyl derivatives by treatment with hexamethylenetetramine and glyceroboric acid yields are generally low. Smith2 finds that a variety of aromatic compounds, including simple hydrocarbons, when treated with hexamethylenetetramine in conjunction with trifluoroacetic acid at reflux temperature (82-90°) are converted into inline products which yield aldehydes on hydrolysis ... 

Non-terpenoid Alkaloids.—De-A-methylation of lysergic acid and derivatives can be achieved using a variant14 of the classical von Braun procedure which involves successive treatments with cyanogen bromide and zinc-acetic acid (or hydrogen-Raney nickel). 

Aryl-3,4-dihydroisoquinolines.2 Isoquinolines are generally prepared by the Bis-chlcr-Napicralski reaction, but this classical route is not useful in the case of 3-aryl-isoquinolincs. In a modified procedure, the precursor, (phenylcthyl)amidc (1), is treated with oxalyl chloride to form a, which on treatment with FeCI, forms an N-acy-liminium ion b. This ion cyclizes to 2, which is converted into 3,4-dihydroisoquinolinc 3 by treatment with sulfuric acid in methanol. Overall yields of 3 are in the range 55-90%. 

The Nef reaction1 2 is the conversion of nitroalkanes to ketones and aldehydes through treatment with base followed by acid.3 4,5,6 For example, deprotonation of 1-nitrobutane (1) with aqueous NaOH followed by addition of excess aqueous sulfuric acid afforded butyraldehyde (2) in 85% yield (isolated as the oxime derivative).7 These reactions proceed via intermediate nitronate anions, which are subsequently hydrolyzed to afford the carbonyl products. The overall transformation leads to formal polarity reversal of the carbon bearing the nitro group from a nucleophilic species to an electrophilic carbonyl carbon. Although the classical conditions for this process are quite harsh, a number of alternative procedures that employ mild reaction conditions have been developed. 

Few exponents of the art of enzymic analysis of polysaccharide structure would claim that it replaces the classical, nonenzymic methods. One of the purposes of this article is to illustrate how the two types of method, enzymic and nonenzymic, may usefully complement each other. This result may be achieved in several ways. In its simplest form, it merely involves nonenzymic characterization of products of enzymic hydrolysis or, more commonly, characterization, by simple enzymic procedures, of products of low molecular weight that have been obtained by nonenzymic methods. In their most sophisticated form, enzymic methods alone are used for analysis of fine structure after a nonenzymic determination of the gross structural features of a polysaccharide has been made. Another variation is the consecutive use of enzymic and nonenzjonic treatments at the polysaccharide level for example, enzymic degradation after periodate oxidation, or after mild hydrolysis with acid to remove labile residues. Examples of all of these types of application will be considered. Contrary to some misconceptions, enzymic analysis does not result solely in qualitative information instead, the most important uses of enzymes... 

A classical procedure of Carpenter for the preparation of (difluoroiodo)arenes involves a one-step reaction of (dichloroiodo)arenes with yellow mercuric oxide and 48% aqueous hydrofluoric acid in dichloromethane [56]. The resulting solution of (difluoroiodo)arenes in dichloromethane can be used in subsequent reactions without additional purification. A drawback of this method is the use of a large quantity of harmful HgO to remove the chloride ion from the reaction mixture. A convenient modified procedure without the use of HgO consists of the treatment of iodosylarenes 5 with 40-46% aqueous hydrofluoric acid (Scheme 2.2) followed by crystallization of products 6 from hexane [30,31]. It is important that the freshly prepared iodosylarenes 5 are used in this procedure. 

With nitrous acid, ethyl [3- C]acetoacetate forms the corresponding isonitroso derivative, which is readily hydrolyzed to give ethyl 2,3-dioxo[3- " C]butyrate 13341. This compound served as a key intermediate in one of the classical preparation procedures of p- Cllactic acid, which was accessible in two steps through treatment with aqueous sodium hydroxide and thermolytic decarboxylation . ... 

The classical method for the determination of iodide in seawater was described by Sugawara [5]. Various workers [6,7] have improved the original method. Matthews and Riley [6] modified the method by concentrating iodide by means of coprecipitation with chloride using silver nitrate (0.23 g per 500 ml seawater). Treatment of the precipitate with aqueous bromine and ultrasonic agitation promote recovery of iodide as iodate which [15] when reacted with excess of iodide ions under acid conditions, yields Ij, which are determined either spectrophotometrically or by photometric titration with sodium thiosulfate. Photometric titration gave a recovery of 99.0 0.4% and a coefficient of variation of 0.4% compared with 98.5 0.6% and 0.8%, respectively, for the spectrophotometric procedure. 

A method for the preparation of olefins from primary amines is shown in equation 120. Treatment of 2-(4-bromophenyl)ethylamine (358) with acetic acid, acetic anhydride and sodium nitrite generates the nitroso amide 359, which decomposes to 4-bromostyrene in the presence of rhodium(II) acetate. The procedure is thus a mild, non-basic alternative to the classical Hofmann elimination of amines396,397. 

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