Ammonia, reaction with sulfonate esters

Ammonia and unhindered amines are good nucleophiles. Therefore, it would appear that amines should be readily prepared by reacting these nucleophiles with the appropriate alkyl halide or sulfonate ester in an SN2 reaction, according to the following general equations ... 

The resistance of the furoxan ring to chemical attack allows derivatives to be prepared via the reactions of the substituents (Section 4.22.3.4). Carboxylic acids are available by permanganate oxidation of methyl derivatives or by hydrolysis of the corresponding esters reaction with ammonia affords carboxamides. Acylfuroxans provide a source of hydroxyalkyl compounds by reduction, and oximes, for example, via nucleophilic addition. Acylation and oxidation of aminofuroxans allows the amide and nitro derivatives to be prepared. Nucleophilic displacements of nitro substituents can take place, but can be somewhat hazardous on account of the explosive nature of these compounds. Alkoxy derivatives are formed with sodium alkoxide, while reaction with thiolate anions yields sulfides, from which sulfones can be synthesized by peracid oxidation. Nitrofuroxans have also been reduced to... 

Sulfate ions are excellent leaving groups. Like sulfonate esters, sulfate esters are good electrophiles. Nucleophiles react with sulfate esters to give alkylated products. For example, the reaction of dimethyl sulfate with ammonia gives a sulfate salt of methylamine, CH3NH CH3OSO3. 

The most interesting behavior of the three dianhydrides is found in the displacement reactions of their 0-sulfonyl derivatives, and at present it seems that the reported results may be covered by three general rules. (1) Displacement of sulfonyloxy groups from the 0-sulfonates may be achieved under certain conditions, and occurs with inversion of configuration at the point of displacement. (2) Ammonia and halide ions displace sulfonyloxy groups, but alkali hydroxides (and perhaps alkoxides) merely hydrolyze the sulfonate esters by 0-sulfonyl fission, with retention of configuration. (3) Displacements by halide ions are possible only for endo sulfonyloxy groups. These rules are only tentative, and may be modified when more sulfonyloxy compounds, and their behavior to a wider variety of anions, have been studied. 

Sulfonyl chlorides as well as esters and amides of sulfonic acids can be hydrolyzed to the corresponding acids. Sulfonyl chlorides can by hydrolyzed with water or with an alcohol in the absence of acid or base. Basic catalysis is also used, though of course the salt is the product obtained. Esters are readily hydrolyzed, many with water or dilute alkali. This is the same reaction as 10-4, and usually involves R —O cleavage, except when R is aryl. However, in some cases retention of configuration has been shown at alkyl R, indicating S—O cleavage in these cases. Sulfonamides are generally not hydrolyzed by alkaline treatment, not even with hot concentrated alkali. Acids, however, do hydrolyze sulfonamides, but less readily than they do sulfonyl halides or sulfonic esters. Of course, ammonia or the amine appears as the salt. However, sulfonamides can be hydrolyzed with base if the solvent is HMPA. ... 

The sodium acetylide solution thus prepared may be used for a variety of organic syntheses by the addition of alkyl halides, sulfates, sulfonates, ketones, aldehydes, and esters. Where a fine suspension of the dry acetylide is desired in an inert solvent such as ether or a hydrocarbon, the solvent is added to the ammonia solution and the mixture is stirred whde the ammonia is evaporated. Extra solvent must be used to replace that entrained by the ammonia, the last traces of which are removed by a period of refluxing. Such a suspension gives better yields of, for example, propiolic acid (by the reaction with carbon dioxide) than sodium acetylide prepared in any other way. 

When the base is hydroxide and the reaction is done in water, as in the preparation of 189, this reaction is known as the Schotten-Baumann reaction, after Carl Schotten (Germany 1853-1910) and Eugen Baumann (Germany 1846-1896). Just as amides are prepared from the reaction of carboxylic acid esters with amines or ammonia, so sulfonamides are prepared from sulfonate esters. An example is the reaction of ethyl butanesulfonate (190) with ammonia to give butanesulfonamide, 191. 

Both ammonia or ammonium hydroxide (often these are used in a reaction bomb) react with an alkyl halide or sulfonate ester to give an amine. If the molecule also has a carboxyl substituent or an acid surrogate, the product is an amino acid or can be converted to one. 1-Bromononanoic acid (1.9), for example, was converted to 9-aminononanoic acid (1.7) by this procedure. There are many examples of this type... 

In 1978, Bartlett published a study of the reaction of esters and acid chlorides to produce P-keto sulfones (467), which could be converted to the enol phosphinates (468) and reduced with sodium in ammonia to the alkyne (469 Scheme 61). The overall yields for the process are good. As discussed in... 

Chlorobenzene is employed in the synthesis of certain amino-containing vat dye intermediates. When reacted with phthalic anhydride, the product is 2-chloroanthraquinone, which, with ammonia, is converted readily into 2-aminoanthraquinone (61). Other routes include replacement of halogen by amino groups, with ammonia or ammonium salts of urea, and alkyl- and aryl amines to afford secondary amines. Modification of the amino group by alkylation, with dimethyl sulfate, alkyl halides or esters of toluenesul-fonic acids, is of synthetic value. Arylation of the amino groups is of importance only in the reaction between aminoanthraquinones and nitro- or chloroanthraquinones to yield dianthraquinonylamines, or anthrimides48. For example, the reaction between 62 and 63 yields 64, which can then be converted into carbazole 65, Cl Vat Brown R (Scheme 14). Amination of haloanthraquinones such as l-amino-4-bromoanthraquinone-2-sulfonic acid (bromamine acid) (66), prepared from 1-aminoanthraquinone, is of industrial use. 

Homoeyelic ring closures. Bunnett and Skorcz31 found that several aliphatic esters, nitriles, sulfones, and ketones bearing an m-o-chlorophenyl group react with potassium amide in liquid ammonia to form homocyclic products of ring closure by way of a benzyne intermediate. The procedure has since been modified to use sodium amide (commercially available).32 The reaction is probably the method of choice for synthesis of 1 -substituted benzcyclobutenes. 

The reactions of enolized keto carboxylic esters with ammonia and amines are described on page 507, and those of a-amino alcohols, cyanohydrins, and a-hydroxy sulfonic acids on pages 516-520. 

To avoid the B-elimi nation neopentyl alkyl sulfonates were subjected to the alkyl nitration. The results summarized in Table XI indicate that the yields of nitration decrease with lengthening of the chain. To obtain optimun yields of a-nitrosulfonate esters containing 8-12 carbons in the chain more concentrated reaction mixtures had to be employed (instead of 250 ml, only 100 ml of liquid ammonia was used). In the case of the C-]2"Sulfonate the yield was only 3% when the nitration was carried out in 250 ml of liquid ammonia. The yield increased ten-fold to 33% when the reaction was performed in only 100 ml of ammonia. It is likely that the low yield was due to a slower rate of anion formation. In fact the yield was increased from 33% to 47% when the anion of the Ci2 Sulfonate was generated with KNH2 in THF at 65° and then nitrated at -40. The Ci6-sulfonate did not undergo nitration at all. This was due to a lack of anion formation. Even when the compound was treated with KNH2 in THF at 65 , no deuterium was... 

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