Schmidt reaction acids

SCHMIDT REACTION. Acid catalyzed addition of hydrazonic acid to carboxylic acids, aldehydes, and ketones to give amines, nitriles, and amides, respectively. 

The conversion of a carboxylic acid into an amine by treatment with hydrazoic acid in concentrated sulphuric acid is known as the Schmidt reaction or rearrangement ... 

Benzilic acid rearrangement Benzoin reaction (condensation) Blanc chloromethylation reaction Bouveault-Blanc reduction Bucherer hydantoin synthesis Bucherer reaction Cannizzaro reaction Claisen aldoi condensation Claisen condensation Claisen-Schmidt reaction. Clemmensen reduction Darzens glycidic ester condensation Diazoamino-aminoazo rearrangement Dieckmann reaction Diels-Alder reaction Doebner reaction Erlenmeyer azlactone synthesis Fischer indole synthesis Fischer-Speior esterification Friedel-Crafts reaction... 

The intermediates in making amines are isocyanates (0==C==N) just like the Hofmann Rearrangement. The isocyanates are decomposed with water, just like the Hofmann. In fact, there is a lot of similarity between the Hofmann and the Schmidt reactions. Before I detail the synthesis steps, I should note that if you wish to generate the Hydrazoic Acid in the flask by adding Sodium Azide, you might need a powder addition funnel. This bit of equipment is quite pricey and it s likely you won t have one, so the first part of the synthesis details how to make the Hydrazoic Acid separately. 

Alkylphenols undergo a carboxylation reaction known as the Kolbe Schmidt reaction. In the following example, the phenolate anion of /)-nonylphenol (15) reacts with carbon dioxide under pressure. Neutralization generates a sahcyhc acid (16) (10). 

Unlike saUcyhc acid, > -hydroxyben2oic acid does not undergo the Friedel-Crafts reaction. It can be converted in 80% yield to y -aminophenol by the Schmidt reaction, which involves treating the acid with hydra2oic acid in trichloroethylene in the presence of sulfuric acid at 40°C (47). 

Schmidt reaction is the reaction between carbonyl compounds and hydrazoic acid in the presence of e.g. concentrated sulphuric acid... 

A potential advantage of the Schmidt reaction is illustrated by the conversion of progesterone to the 17j5-acetylamino derivative, without affecting the A-ring. A 35 % yield is obtained when 1 mole of sodium azide in polyphos-phoric acid is used. With excess azide the A-ring is transformed into an a,jS-unsaturated lactam ... 

In the Schmidt reaction of fluonnated dicarboxyhc acids, the appropnate amides can be obtained in fairly good yield [48] Complications arise from possible cychzation if the fluorine atom is in the 8 position relative to the newly formed amino group [/] Fluonnated aromatic ethers, upon heating in dimethylformamide, undergo Smiles rearrangement to give diarylamines [49, 50] (equation 11)... 

Among other reactions proceeding with the retention of the heterocyclic nucleus may be noted the synthesis of amino acids of the isoxazole series from isoxazole-5-aldehydes/ the successful extension of the Schmidt reaction to 3-acylisoxazoles, and the synthesis of various polycyclic heterocycles, e.g. 101 102, involving the isoxa-... 

The reaction of carboxylic acids, aldehydes or ketones with hydrazoic acid in the presence of a strong acid is known as the Schmidt reaction A common application is the conversion of a carboxylic acid 1 into an amine 2 with concomitant chain degradation by one carbon atom. The reaction of hydrazoic acid with a ketone 3 does not lead to chain degradation, but rather to formation of an amide 4 by formal insertion of an NH-group. 

Intermolecular Schmidt reactions of alkyl azides and hydroxyalkyl azides with cycloketones in the presence of a Lewis acid, lead to formation of iV-alkyl lactams and A-hydroxyalkyl lactams respectively in good yield. The synthesis of chiral lactams by an asymmetric Schmidt reaction has also been reported. ... 

By application of the Schmidt reaction, the conversion of a carboxylic acid into an amine that has one carbon atom less than the carboxylic acid, can be achieved in one step. This may be of advantage when compared to the Curtius reaction or the Hofmann rearrangement, however the reaction conditions are more drastic. With long-chain, aliphatic carboxylic acids yields are generally good, while with aryl derivatives yields are often low. 

The Schmidt reaction of ketones works best with aliphatic and alicyclic ketones alkyl aryl ketones and diaryl ketones are considerably less reactive. The reaction is only seldom applied to aldehydes as starting materials. The hydrazoic acid used as reagent is usually prepared in situ by treatment of sodium azide with sulfuric acid. Hydrazoic acid is highly toxic, and can detonate upon contact with hot laboratory equipment. 

Pure hydrazoic acid in a condensed state has been reported in several instances to explode violently without apparent inducement, but explosions during Schmidt reactions do not seem to have been observed. Nevertheless, it is recommended that this reaction be carried out behind a safety shield. 

There are actually three reactions called by the name Schmidt reaction, involving the addition of hydrazoic acid to carboxylic acids, aldehydes and ketones, and alcohols and alkenes. The most common is the reaction with carboxylic acids, illustrated above.Sulfuric acid is the most common catalyst, but Lewis acids have also been used. Good results are obtained for aliphatic R, especially for long chains. When R is aryl, the yields are variable, being best for sterically hindered compounds like mesi-toic acid. This method has the advantage over 18-13 and 18-14 that it is just one laboratory step from the acid to the amine, but conditions are more drastic. Under the acid conditions employed, the isocyanate is virtually never isolated. 

In the first step of the mechanism, the OH group is converted by the reagent to a better leaving group (e.g., proton acids convert it to OHj). After that, the mecha-nism follows a course analogous to that for the Schmidt reaction of ketones (18-16) from the formation of 71 on ... 

Sadvilkar et al. (1995) have studied condensation of benzaldehydes with acetophenones (Claisen-Schmidt reaction) in an aqueous medium, containing sodium butylmonoglycol sulphate and sodium salts of aromaticsulphonic acids as hydrotropes. A substantial improvement in the rate of reaction was realized, while product recovery was facilitated. 

Carboxylic acids and esters can also be converted to amines with loss of the carbonyl group by reaction with hydrazoic acid, HN3, which is known as the Schmidt reaction,278 The mechanism is related to that of the Curtius reaction. An azido intermediate is generated by addition of hydrazoic acid to the carbonyl group. The migrating group retains its stereochemical configuration. 

Section C of Scheme 10.15 shows some Schmidt reactions. Entry 14 is a procedure using polyphosphoric acid, whereas Entry 15 was done in H2S04. Entry 16 is a case of conversion of a cyclic ketone, adamantanone, to the corresponding lactam. 

Nitrilium salts, e.g., 66, prepared from the alkylation of nitriles, react with sodium azide to yield 1,5-disubstituted tetrazoles, e.g., 67 (Scheme 7).121 The Schmidt reaction,122 a versatile method for the preparation of 1,5-disubstituted tetrazoles from ketones and hydrazoic acid, can now be regarded as a special case of azide addition to nitrilium salts.123... 

The Curtius and Schmidt reactions both involve N2 as the leaving group from the azide intermediate (67), and here again the migration of R occurs in a concerted process. The azide may be obtained either by nitrosation of an acid hydrazide (65)—Curtius reaction—or by the reaction of hydrazoic acid, HN3, on a carboxylic acid (66)—the Schmidt reaction. 

It occurs with the alkyls, aryls or acetylides of metals more electropositive than magnesium, but including Grignard reagents, and is often carried out by adding a solution of the organometallic compound in an inert solvent to a large excess of powdered, solid C02 it is a particularly useful method for the preparation of acetylenic acids. The Kolbe-Schmidt reaction (p. 291) is another example of carbanion carbonation. 

The Schmidt reaction of ketones with hydrazoic acid is believed to be a similar rearrangement, again with concerted trans migration and elimination of nitrogen. 

The rate of the Schmidt reaction of para-substituted benzoic acids is governed by the electron-releasing character of the substituent, the value of the Hammett p parameter being the same as that needed to correlate product ratios in the related reaction of 1,1-diarylethylenes.807 The latter reaction is believed to go by a similar mechanism. 

In addition to the present method,2 1-amino-1-methylcyclo-hexane has been synthesized by the following procedures Ritter reaction, e.g., with 1-methylcyclohexanol (76%, 67%)3i 4 or 1-methylcyclohexene (35%,) 4 5 Hofmann reaction with 1-methyl-cyclohexanecarboxamide (80% as hydrochloride) 6 reduction of 1-methyl-l-nitrocyclohexane (63%) 6 Schmidt reaction with 1-methylcyclohexanecarboxylic acid (42%).6... 

KOH plants, environmental awareness in, 20 634. See also Potassium hydroxide KOH solution, 12 215 meta-Koksowy coal grade (Poland), 6 713t Kolbe-Schmidt reaction, 2 208 of salicylic acid synthesis, 22 7-8 Kolmogoroff microscale, 16 697 Konica Dry Color System, 19 348 Konjac glucomannan, 4 7241... 

The most widely used route to l-benzazepin-2-ones involves the Beckmann or Schmidt reaction of the easily accessible 1-tetralones. Many biologically active compounds described in this review have been prepared on the basis of these reactions they have been fully reviewed [2], In the Beckmann reaction of 1-tetralone oximes, polyphosphoric acid is used as a catalyst-solvent in most instances. Aryl migration generally takes precedence over alkyl migration under these reaction conditions, and various 1-tetralone oximes substituted on the aromatic and/or aliphatic rings can be converted to the appropriate 2,3,4,5-tetrahydro-l//-l-benzazepin-2-ones (51) [5, 20-23, 36, 59, 65, 80, 107-112]. Both courses of the rearrangement occur in some instances, yielding l-benzazepin-2-ones (51) and the isomeric 2-benzazepine-l-ones, probably due to electronic effects of the substituents [90, 113, 114]. 

The Schmidt reaction is also applied to a variety of 1-tetralones, yielding (51). The use of sodium azide in acetic acid and sulphuric acid [7, 12, 13, 30, 34, 36, 37, 72, 73, 84] is preferable to the procedure in the earlier stage, in which hydrazoic acid, sulphuric acid and chloroform are employed [115]. Other acidic reagents such as polyphosphoric acid [116, 117], sulphuric acid [116, 118], methasulphonic acid [119] and trichloroacetic acid [116] are used in some cases. Variation of substituents affects the course of the rearrangement 6-methoxytetralones are rather liable to afford the isomeric 2-benzazepine-l-ones in preference to the desired (51) [ 7, 116, 118]. The Schmidt reaction is also conveniently applied to various 1,4-naphthoquinones and yields a wide range of 2,5-dihydro-l-benzazepin-2,5-diones [85, 120-122]. 

This is the first example of a direct coupling of a diazo compound in a / position of the thiophene nucleus. The Beckmann rearrangement with the ketoxime of 2-thienylketone was found to give poor yields of the aceto-2-thiopheneamide. Furthermore, the Schmidt reaction using hydrazoic and sulphuric acids was investigated and did give rise to aceto-2-thiopheneamide but probably as an eutectic with the isomeric 2-thenoylmethylamide. 

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