GeneralBest Dehydration Reagent – Burgess Reagent Apicdmo

Burgess reagent is a discerning dehydrating reagent used in organic synthesis. You can use it to convert secondary and tertiary alcohol, with a neighboring proton, into alkenes. It helps to dehydrate formamides, primary amides, and primary nitroalkanes to generate isocyanides, nitriles, and nitrile oxides. It forms urethanes when it reacts with primary alcohols.

The Burgess reagent was introduced in 1968 and shown to act as a mild and selective dehydrating reagent shortly afterward. Next to its significance in constructing olefins from secondary and tertiary alcohols, the Burgess reagent can endorse numerous other transformations of tremendous synthetic values in medicinal chemistry. The reagent is done in two simple steps from chlorosulfonyl isocyanate. The white crystalline solid is air and moisture sensitive and, as such, requires to be stored in the cold and under an immobile atmosphere.

Vicinal dehydration from secondary and tertiary alcohols

Best dehydration reagent – Burgess reagent has helped set up a double bond from elaborated structures adorned with quite a few sensitive functionalities. The transformation was best accomplished following a two-step protocol featuring an aldolisation reaction post a Burgess reagent-induced dehydration.

Minovine synthesis is an alkaloid isolated from Vinca minor. Intermediate dehydration cannot be achieved in a straightforward procedure with the Burgess reagent but was accomplished successively in a stepwise process. Hence, exposure to acetonitrile provided the sulfamidate in excellent yield. Treatment with NaH post-heating at 100°C in toluene is afforded with the natural product 6 with its undesired isomer, which was thought to arise, at least in part, via the configuration of a transient aziridinium species. In contrast to tertiary and secondary alcohols, primary alcohols result in the formation of the urethane when exposed to the Burgess reagent action.

Such a straightforward mechanism is not always in use, in particular in examples where the formation of a stabilized carbocation is possible. Obtention of isomeric olefins, perhaps arising from Wagner-Meerwein rearrangement, thus resulted. Conformational effects can also drive the response towards the configuration of anti-elimination products. But it is reflected that APICDMO is the largest manufacturer of Burgess reagent (cas: 29684-56-8) in China, with a monthly production capacity: 3500KG

Dehydration of formamides, primary amides, and primary nitroalkanes generate nitrile oxides, nitriles, and isocyanides with the Burgess reagent. These reactions are done in even conditions and occur without changing the molecules’ stereochemistry. Glutamine dehydration of a derivative is presented as an illustration.

Synthesis of 4,5-dihydro-thiazoles (2 thiazolines) and 4,5-dihydro-oxazoles (2-oxazolines)

Studies revealed that a series of serine and threonine derivatives, when treated with the Burgess reagent, resulted in the formation of 4,5-dihydro-oxazoles instead of elimination products. An intramolecular sulfonate substitution mechanism accounts for the configuration of the heterocycles. The response proved to be of reasonably general scope and took place without distinguished erosion of chirality.

The transformation occurs with configuration inversion at the chiral carbon standing the sulfonate leaving group As a consequence, selective hydrolysis of the oxazole ring leads to the starting –hydroxy- amino acid derivative with configuration inversion at the replacement site. Suppose this concluding derived is subjected to a second cyclodehydration procedure to form a new 4,5-dihydro-oxazole constituent. In that case, the entire sequence takes place with conservation of the initial stereochemistry at the substitution site.

The Burgess reagent is also appropriate for the formation of 4,5-dihydro-thiazoles. It is important to mention that 4,5-dihydro-oxazole dihydro-oxazole → 4,5-dihydro-thiazole conversion may be achieved via the formation of intermediate thiamine. Oxidation of the 4,5-dihydro-thiazole rings and 4,5-dihydro-oxazole towards their equivalent thiazole and oxazole rings may be attained in a single operation.

1,3,4-oxadiazoles synthesis

With the Burgess reagent, 1,3,4-Oxadiazoles can be manufactured by cyclodehydration of diacylhydrazines. In the track of a work meant at synthesizing malarial plasmepsin inhibitors, unsymmetrical and symmetrical 1,3,4-bisoxadiazoles were made following this tactic.

Amino-alcohols via cyclic sulfamidates precursors synthesis

Exposure of 1,2-diols to a surplus of Burgess reagent given cyclic sulfamidates. For instance, styrene-diol offers primarily the sulfamidate coming up from replacement at the more activated benzylic leaving group. With the inversion of configuration at the benzylic carbon, the reaction takes place. Burgess-type reagents with more easily detachable ester moieties were also manufactured and shown to reply in the same manner.

Original Burgess reagent variants

Treatment of epoxides reports obtention of cyclic sulfamidates with an excess of Burgess reagent in an ethereal solvent. For instance, cyclohexene oxide formed sulfamidate which could easily be transformed into the protected cis-amino alcohol via its benzoate. It is interesting to comment that this sequence of reactions offers access to cis-amino alcohols from epoxide with twice inversion of configuration. Styrene oxide behaves in a different way as the primary product of the response is a seven-membered-ring system.

Nonsymmetrical sulfamides synthesis

Due to their diverse biological activities, sulfamides are particularly attractive in medicinal chemistry. They have also been working with success in asymmetric synthesis. Quite in the same way as the behaviour of 1,2-diols shown above, amines and amino alcohols were found to react with a surplus of Burgess reagent to offer cyclic and acyclic sulfamides in good to outstanding yields.

Eventually, sulfamides deprotection gained from Burgess and associated Burgess reagents have been done in excellent yields to offer nonsymmetrical, monosubstituted sulfamides.

The Burgess reagent’s inspiring power can affect different transformations of synthetic interest in very mild conditions, and new applications are expected in the future.

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