3-Bromofuran

Synthesis

3-Bromofuran was obtained in minor amounts in 1887 as a by-product in a reaction of 3-bromofuroic acid with calcium hydroxide. Four decades later, it was prepared deliberately and in higher yield. 3-bromofuran has since also been prepared from 3,4-dibromofuran via ortho-metalation with butyllithium in good yield. A synthesis of 3-bromofuran is due to Fechtel who prepared this compound via a Diels Alder-bromination-reverse Diels Alder sequence.

Applications

3-Bromofuran is a useful starting material for 3-substituted furans, a structural motif widespread in chemotherapy agents, HIV drugs, type 2 diabetes treatments, drugs for osteoporosisZhi-Cai Shi, et al., " Preparation of 4-[6-(2,2,2-trifluoro-1-phenylethoxy)pyrimidin-4-yl]-(S)-phenylalanine derivative tryptophan hydroxylase inhibitors for treating osteoporosis ", US PCT Int. Appl. (2010), WO 2010065333 A1 20100610. and experimental drugs for Alzheimer's disease. For example, the total synthesis of (+)Cacospongionolide B, a sesterterpene with anti-inflammatory properties, has been accomplished using 3-bromofuran as a starting compound. It was also used to synthesize Rosefuran, a constituent chemical of the odor of the rose and an insect sex attractant. 3-bromofuran was reacted with 3,3-dimethylallyl bromide and lithium diisopropylamide, followed by reaction at with iodomethane and N-butyllithium.

The total synthesis of (−)-neothiobinupharidine, a bioactive alkaloid isolated from Nuphar pumila (the small yellow pond-lily) was accomplished in eight steps employing two moles of 3-bromofuran. Similarly, one of the steps of the total synthesis of Salvinorin A, the primary hallucinogenic compound in Salvia divinorum, a Mexican plant used by Mazatec shamans, used 3-bromofuran as a reactant.

References

References

1. Conzoneri. (1887). "none".
2. A. F. Shepard. (1930). "The simple halogen derivatives of furan". J. Am. Chem. Soc..
3. Carlos Alvarez-Ibarra. (1996). "Synthesis of polysubstituted 3-thiofurans by regiospecific mono-ipso-substitution and ortho-metallation from 3,4-dibromofuran.". Tetrahedron.
4. Guenter Fechtel, "Preparation of furan and cyclopentadiene derivatives as biocides and drug intermediates" East Ger. Patent 246,107 (1987)
5. Han-Zhong Zhang. (2005). "Discovery and Structure-Activity Relationship of 3-Aryl-5-aryl-1,2,4-oxadiazoles as a New Series of Apoptosis Inducers and Potential Anticancer Agents.". Journal of Medicinal Chemistry.
6. Susan E. Hagen. (2001). "4-Hydroxy-5,6-dihydropyrones as inhibitors of HIV protease: the effect of heterocyclic substituents at C-6 on antiviral potency and pharmacokinetic parameters". Journal of Medicinal Chemistry.
7. Qun Dang. (2009). "Fructose-1,6-bisphosphatase Inhibitors. 1. Purine Phosphonic Acids as Novel AMP Mimics". Journal of Medicinal Chemistry.
8. Zhi-Cai Shi, et al., " Preparation of a (((1,2,4-oxadiazolyl)phenyl)morpholino)pyrimidin-4-one compound as a therapeutic tau protein kinase inhibitor ", PCT Int. Appl. (2009), WO 2009035162 A1 20090319.
9. Inmaculada Posadas. (2003). "Cacospongionolide B suppresses the expression of inflammatory enzymes and tumour necrosis factor-α by inhibiting nuclear factor-κB activation". Br J Pharmacol.
10. Motoko Oshida. (2010). "Total synthesis of (+)-cacospongionolide B". Heterocycles.
11. Peter Weyerstahl. (1995). "Structure-odor correlation. Part XXI. Olfactory properties and convenient synthesis of furans and thiophenes related to rosefuran and perillene and their isomers". Liebigs Annalen.
12. Daniel J. Jansen. (2013). "Synthesis of (−)-Neothiobinupharidine". Journal of the American Chemical Society.
13. Hisahiro Hagiwara. (2005). "Second-generation synthesis of salvinorin A". Tetrahedron.