Acid-catalyzed Reactions of Aliphatic Azides<sup>1</sup>

Boyer, J. H.; Canter, F. C.; Hamer, Jan; Putney, Richard K.

doi:10.1021/ja01583a021

Cited by 62 publications

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“…Nevertheless, the photoreactive azido group was introduced into position 4, since the specificity requirements of the interaction with the binding site does allow some modification in this position. Furthermore, we surmized that substitution of the hydroxyl group with an azido group would still permit some hydrogen bonding at this position during the dark reaction, as azido groups have been reported to accept hydrogen bonds [25]. However, we did find a limited loss in binding energy (in the dark, approximately 1.7 kcal mol-', [ 11).…”

Section: Resultsmentioning

confidence: 85%

Photoaffinity labeling and identification of (a component of) the small‐intestinal Na⁺, D‐glucose transporter using 4‐azidophlorizin

et al. 1981

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Section: Resultsmentioning

confidence: 85%

Photoaffinity labeling and identification of (a component of) the small‐intestinal Na⁺, D‐glucose transporter using 4‐azidophlorizin

et al. 1981

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“…12 Moreover, they found that aromatic aldehydes, when treated with β -or γ -hydroxy azides in the presence of sulfuric acid, provided oxazoline products in good yield. 13 At the time, the latter reaction was proposed to occur by direct azide attack onto the carbonyl; the differences in yield were ascribed to greater acid stability of the starting hydroxyalkyl azides thanks to hydrogen bonding (mechanism not shown). However, hindsight helped workers nearly fi fty years later 14 to formulate a more satisfying explanation involving initial oxygen attack to form an oxonium ion.…”

Section: Introduction and Early Attempts (1940 -60)mentioning

confidence: 99%

Schmidt Rearrangement Reactions with Alkyl Azides

Grecian¹,

Aubé

2009

Organic Azides

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The sobriquet ' Schmidt reaction ' refers to a number of related processes in which hydrazoic acid or an alkyl azide reacts with an electrophile. 1 -6 The product obtained will depend on the reaction partner (carboxylic acids generate amines, aldehydes give nitriles and formamides, and ketones provide amides, respectively) but all of these reactions have certain features in common. They are the initial nucleophilic addition of the azide component to an electrophile (usually promoted by acid) eventually followed by a rearrangement step driven by the energetically favorable loss of nitrogen. The classical Schmidt reaction of hydrazoic acid with ketones is generally considered to involve an intermediate dehydration step. 7,8 Despite the diversity of reactions that comprise the Schmidt family, its single most common variant is shown in Scheme 7.1 . This overall process can be regarded as an insertion of NH between the carbonyl and an α alkyl group. 9 The development of this version of the Schmidt reaction predates the experience of anyone working in organic chemistry today (Schmidt ' s original report was in 1924) but the extension of the concept to nucleophilic alkyl azides is a decidedly contemporary development. For example, if one compares the two reactions shown in Scheme 7.2 , it is clear that the direct insertion of an alkyl azide into cyclohexanone allows for the introduction of additional nitrogen atom substitution and, in the case of an alkyl azide tethered to a carbonyl substrate, the possibility of an intramolecular reaction. The goal of this chapter

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“…Treatment of azide V with trifluoroacetic acid induced intramolecular Schmidt reaction leading to the formation of a new heterocyclic system. The product,4,7,8,9,4]diazepine-2-carboxylate (VI) was isolated in 24% yield after chromatographic purification.The discovered reaction attracts interest from the practical viewpoint, taking into account that it leads to fused diazepine derivatives which are known as pharmacologically important heterocyclic systems. Examples are zolazepam [11] (anticonvulsant and anesthetic agent), anxiolytic ripazepam [12,13], and antidepressant zometapine [14].…”

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confidence: 99%

“…It was found that the Schmidt reaction of aromatic aldehydes and cyclohexanone can be performed with the use of alkyl azides in the presence of strong acids; as a result, substituted arenecarboxamides [3] or N-substituted lactams [4] were obtained. Aube and Milligan [5] were the first to report intramolecular Schmidt reaction of azido ketone I with trifluoroacetic acid, which produced 91% of tricyclic lactam II (Scheme 1).…”

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Intramolecular Schmidt reaction of tert-butyl 3-(3-azidopropyl)-4-oxopiperidine-1-carboxylate as a synthetic route to saturated fused aza heterocycles

Moskalenko

Boev

2014

Russ J Org Chem

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Treatment of the title compound with trifluoroacetic acid induced intramolecular Schmidt reaction with formation of a saturated fused heterocyclic system, tert-butyl 5-oxo-2, 3,4,5,7,8,9,9a-octahydro-1H-pyrrolo[1,2-a][1,4]diazepine-2-carboxylate. The latter was reduced with lithium tetrahydridoaluminate, and subsequent treatment with hydrogen chloride in dioxane gave 2, 3,4,5,7,8,9,9a-octahydro-1H-pyrrolo[1,2-a][1,4]-diazepine dihydrochloride which is a promising intermediate product for the synthesis of N-substituted diazepines with a fused pyrrole ring.The Schmidt reaction, i.e., the reaction of carbonyl compounds with hydrazoic acid underlies an important method of synthesis of amines from carboxylic acids, amides from ketones, and nitriles from aldehydes [1,2]. It was found that the Schmidt reaction of aromatic aldehydes and cyclohexanone can be performed with the use of alkyl azides in the presence of strong acids; as a result, substituted arenecarboxamides [3] or N-substituted lactams [4] were obtained. Aube and Milligan [5] were the first to report intramolecular Schmidt reaction of azido ketone I with trifluoroacetic acid, which produced 91% of tricyclic lactam II (Scheme 1). Subsequently, analogous intramolecular cyclizations of various cyclic and aromatic azido ketones were studied, and fused polycyclic N-substituted lactams [6,7] and N-aryl-substituted lactams [8] were thus obtained. Apart from trifluoroacetic acid, titanium(IV) chloride, trifluoromethanesulfonic acid, and boron trifluoride-diethyl ether complex were used as catalysts.In continuation of our studies on the Schmidt reaction in the series of nitrogen-containing heterocyclic ketones [9], in the present work we made an attempt to accomplish intramolecular version of this reaction, as reported for analogous carbocyclic azido ketones [6]. For this purpose, we have synthesized azido ester V by alkylation of dimethylhydrazone III with 1-chloro-3-iodopropane [10] and subsequent nucleophilic substitution of the chlorine atom in IV by azido group on heating with sodium azide in DMSO (Scheme 2). Treatment of azide V with trifluoroacetic acid induced intramolecular Schmidt reaction leading to the formation of a new heterocyclic system. The product,4,7,8,9,4]diazepine-2-carboxylate (VI) was isolated in 24% yield after chromatographic purification.The discovered reaction attracts interest from the practical viewpoint, taking into account that it leads to fused diazepine derivatives which are known as pharmacologically important heterocyclic systems. Examples are zolazepam [11] (anticonvulsant and anesthetic agent), anxiolytic ripazepam [12,13], and antidepressant zometapine [14].Compound VI was subjected to chemical transformations to obtain a series of fused diazepine heterocycles. In particular, the carbonyl group in VI was reduced according to the procedure described in [15],

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Acid-catalyzed Reactions of Aliphatic Azides¹

Cited by 62 publications

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Photoaffinity labeling and identification of (a component of) the small‐intestinal Na⁺, D‐glucose transporter using 4‐azidophlorizin

Photoaffinity labeling and identification of (a component of) the small‐intestinal Na⁺, D‐glucose transporter using 4‐azidophlorizin

Schmidt Rearrangement Reactions with Alkyl Azides

Intramolecular Schmidt reaction of tert-butyl 3-(3-azidopropyl)-4-oxopiperidine-1-carboxylate as a synthetic route to saturated fused aza heterocycles

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Acid-catalyzed Reactions of Aliphatic Azides1

Cited by 62 publications

References 0 publications

Photoaffinity labeling and identification of (a component of) the small‐intestinal Na+, D‐glucose transporter using 4‐azidophlorizin

Photoaffinity labeling and identification of (a component of) the small‐intestinal Na+, D‐glucose transporter using 4‐azidophlorizin

Schmidt Rearrangement Reactions with Alkyl Azides

Intramolecular Schmidt reaction of tert-butyl 3-(3-azidopropyl)-4-oxopiperidine-1-carboxylate as a synthetic route to saturated fused aza heterocycles

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Acid-catalyzed Reactions of Aliphatic Azides¹

Photoaffinity labeling and identification of (a component of) the small‐intestinal Na⁺, D‐glucose transporter using 4‐azidophlorizin

Photoaffinity labeling and identification of (a component of) the small‐intestinal Na⁺, D‐glucose transporter using 4‐azidophlorizin