892. The Schmidt reaction with aromatic ketones

Evans, D.; Lockhart, I. M.

doi:10.1039/jr9650004806

Cited by 31 publications

(18 citation statements)

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“…Similar effects 41 were seen with 6-methoxy-1-tetralone 8 where the ether oxygen atom is para with respect to the ketone functionality. [62] The resonance structures presented by Evans and Lockhart [61] below ( Fig. 9) do explain the prevention of the aryl migration in 4-chromanone 6; however, they do little in justifying why alkyl migration should occur, as the formation of the antiiminodiazonium ion 39 is still favoured based on the steric effects of the aryl group.…”

Section: Mechanistic Discussion: Schmidt Reactionmentioning

confidence: 94%

“…The only reference to the formation of 21 is by Kamei et al, [60] where it was isolated as a minor product in 2.6% yield. Evans and Lockhart [61] proposed that the preference of alkyl migration is due to the electronic effects of the 'ortho' cyclic ether oxygen and presented a resonance structure of 4-chromanone (Fig. 10), which shows a partial double-bond character between the two carbon atoms (C4 and C4a) 40 making it difficult to migrate.…”

Section: Mechanistic Discussion: Schmidt Reactionmentioning

confidence: 99%

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The Application of the Schmidt Reaction and Beckmann Rearrangement to the Synthesis of Bicyclic Lactams: Some Mechanistic Considerations

2010

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The syntheses of some methoxy-substituted bicyclic lactams, of the types 3 and 4, are reported employing two different conditions for the Schmidt reaction of appropriate ketones and employing two different conditions for the Beckmann rearrangement of the corresponding ketoximes. The alkyl to aryl migration ratios of the reactions were determined by high-performance liquid chromatography analysis of the reactions. The mechanisms of the reactions reported are discussed, some limitations of the reported mechanisms identified, and an alternative mechanism proposed in light of the outcomes of the various reactions. Application of the Schmidt reaction and Beckmann rearrangement was used for the synthesis of some chloro bicyclic lactams, of the types 3 and 4.

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Section: Mechanistic Discussion: Schmidt Reactionmentioning

confidence: 94%

Section: Mechanistic Discussion: Schmidt Reactionmentioning

confidence: 99%

The Application of the Schmidt Reaction and Beckmann Rearrangement to the Synthesis of Bicyclic Lactams: Some Mechanistic Considerations

2010

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“…The Schmidt reaction, according to the literature, gives benzolactam 3 as the major product; however, by changing the reaction medium from trichloroacetic acid, 16 polyphosphoric acid 17 or sulfuric acid 18 to concentrated hydrochloric acid, 19 the desired benzolactams 2 can be obtained in moderate yields (42%). This reaction was optimized by adding two equivalents of the sodium azide, 20 and it resulted in a 75-85% yield of the benzolactam type 2.…”

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confidence: 99%

Synthesis, binding affinity and SAR of new benzolactam derivatives as dopamine D3 receptor ligands

Ortega

Raviña

Masaguer

et al. 2009

Bioorganic & Medicinal Chemistry Letters

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a b s t r a c tA series of new benzolactam derivatives was synthesized and the derivatives were evaluated for their affinities at the dopamine D 1 , D 2 , and D 3 receptors. Some of these compounds showed high D 2 and/or D 3 affinity and selectivity over the D 1 receptor. The SAR study of these compounds revealed structural characteristics that decisively influenced their D 2 and D 3 affinities. Structural models of the complexes between some of the most representative compounds of this series and the D 2 and D 3 receptors were obtained with the aim of rationalizing the observed experimental results. Moreover, selected compounds showed moderate binding affinity on 5-HT 2A which could contribute to reducing the occurrence of extrapyramidal side effects as potential antipsychotics.Ó 2009 Elsevier Ltd. All rights reserved.Dopamine (DA) is a major neurotransmitter in the central nervous system (CNS) that plays important roles in behaviour and cognition, ranging from movement to emotion, sensitization to addiction, and development to plasticity. All DA receptors belong to a superfamily of large peptides that are coupled to G-proteins and modified by attached carbohydrate, lipid-ester or phosphate groups. They are characterized by having seven hydrophobic transmembrane-spanning regions, as well as a functionally critical third intracytoplasmic loop that interacts with G-proteins and other effector molecules to mediate the physiological and neurochemical effects of the receptors. Based on their pharmacological profiles, including their effects on different signal transduction cascades, these receptors are currently divided into two families: the D 1 -like family or adenylyl-cyclase stimulators, which includes D 1 and D 5 receptors, and the D 2 -like family or adenylyl-cyclase inhibitors, which includes D 2 , D 3 and D 4 receptors. 1 The D 3 dopamine receptor was first identified and clonated by Sokoloff et al. 2 in 1990 and has been shown to be an interesting target for different CNS diseases. Although its structure and pharmacology are very similar to dopamine D 2 , the D 3 receptor is generally less abundant than the D 2 receptor, and the difference is particularly striking in the caudate putamen, where D 2 receptors are densest and D 3 receptors are poorly represented. 3 Moreover, D 3 -binding sites and mRNA encoding D 3 receptors are concentrated in the limbic brain areas known to be associated with cognitive and emotional functions. 4 Due to this, the D 3 receptor has been suggested to be a potential target in the treatment of neurological disorders such as schizophrenia, and drug abuse. 5 In schizophrenia, a blockade of D 2 receptors has been considered to be the main mechanism responsible for the efficacy of antipsychotics, 6 but the complex profiles of some atypical drugs challenged this assumption, that is, clozapine exhibits activity at multiple receptors. 7 Now there is an increasing body of clinical evidence that supports the notion that multi-target ligands may be more efficacious than strictly selective ...

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“…Some years ago, Evans and Lockhart (7) had studied a series of tetralones l a and contrasted their behavior in the Schmidt reaction with that of the analogous chromanones 16. They concluded that the preference for the formation of cyclic benzamide derivatives (by alkyl rather than aryl migration) in the heterocyclic series could be attributed to the electronreleasing effect of oxygen.…”

Section: Introductionmentioning

confidence: 99%

The Behavior of Thiochromanone and Isothiochromanone Sulfoxides in the Schmidt Reaction: Isolation of a Novel Azide Product from Thiochromone Sulfone

Still¹,

Thomas²,

Clish³

1975

Can. J. Chem.

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. Can. J . Chem. 53,276(1975).The Schmidt reaction has been carried out on thiochroman-4-one 1-oxide and a number of related sulfoxides. In all cases lactam formation by attack of HN3 on the carbonyl group of the keto sulfoxide appears to predominate, with no evidence for sulfoximine formation. The question of aryl vs. alkyl migration, as in other systems, is dependent on the degree of substitution of the alkyl group. When the Schmidt reaction was carried out upon thiochromone 1,l-dioxide two products, the lactam resulting from preferential vinyl migration and a novel a-azido sulfone resulting from 1,4-addition, were obtained. On a effectue la reaction de Schmidt sur la thiochromanone-4 oxyde-1 et un certainnombre de sulfoxydes qui lui sont apparent&. Dans tous les cas, il y a formation de lactame par attaque de HN3 sur le groupement carbonyle du cCto-sulfoxyde et cette riaction semble predominante; on n'a trouve aucune preuve expirimentale pour la formation d'une sulfoxymine. La question de la migration des groupes aryles par opposition a la migration a des groupes alkyles depend d u degre de substitution en accord avec ce qui a CtC observe dans d'autres systkmes. Lorsque I'on effectue la rtaction de Schmidt sur la thiochromonedioxyde-1

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892. The Schmidt reaction with aromatic ketones

Cited by 31 publications

References 0 publications

The Application of the Schmidt Reaction and Beckmann Rearrangement to the Synthesis of Bicyclic Lactams: Some Mechanistic Considerations

The Application of the Schmidt Reaction and Beckmann Rearrangement to the Synthesis of Bicyclic Lactams: Some Mechanistic Considerations

Synthesis, binding affinity and SAR of new benzolactam derivatives as dopamine D3 receptor ligands

The Behavior of Thiochromanone and Isothiochromanone Sulfoxides in the Schmidt Reaction: Isolation of a Novel Azide Product from Thiochromone Sulfone

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