A Facile and Green Synthesis of Sulforaphane

HO HO
HO
HO
Tong Jian DING et al. 1153
Figure 1 SFN enzymatically hydrolysed from GRA
O
OH
-O3SO 2
myrosinase
rearrangement
1
N
S
O
S
S
C
N
Scheme 1 Synthesis of SFN
OH
a Br
OH
b N3 3 4 5
N3 OTs
d
N3 S e S
C
N
S
f
1
6 7 8
Reagents: a. HBr (40%), benzene, 53% yield; b. NaN3, DMF, 61% yield; c. TsCl, Py, CH2Cl2, 95%
yield; d. MeSNa, DMF; e. PPh3, ether, then CS2; f. oxone, CH2Cl2, 80% yield (from 6 to 1).
As shown in Scheme 1, a mixture of 1,4-butanediol 3 and aqueous hydrobromic
acid (HBr, 40%) in benzene was refluxed for 20 hs, removing the water at the same time,
to afford monobromoalkanol 4 as an oil in 53% yield purified by Kugelrohr distillation 7 .
Then alcohol 4 was reacted with sodium azide (NaN3) at 70°C for 24 hs in dry
N,N-dimethylformamide (DMF) to afford 4-azido-1-butanol 5 as an oil in 61% yield 8 .
Treatment of 5 with p-toluenesulfonyl chloride (TsCl) in the presence of pyridine in
dichloromethane (CH2Cl2) gave the protected alcohol 6 as an oil in 95% yield. Then a
solution of compound 6 in DMF was added into the mixture of NaSMe in dry DMF
under argon atmosphere at 0°C, the SN2 type reaction proceeded to give 4-azidobutyl
methyl sulfide 7 6a , which was easy to loss in the process of distillation of solvent in
vaccum, fortunately, the existence of a little solvent did not affect the next step reaction.
7 was reacted with triphenylphosphine (PPh3) in ether for 3 hs. After removing the
solvent, carbon disulfide (CS2) was added to the reaction system, the resulting mixture
was refluxed for another 1 h to afford the compound 8 6a . The crude 8 was subjected to
oxone oxidation to give SFN 1 as a yellow oil purified by silica gel chromatography in
80% yield based on the compound 6 (last three steps from 6 to 1). The structures of the
compounds were confirmed by the spectra (NMR and MS) 9 . The spectral data of 1 H
and 13 C NMR coincided with that of reported SFN 10 .
Our synthetic strategy avoided the use of KCN 2,4 and thiophosgene 2,4,5 . Because
the isothiocyanate group was introduced by NaN3, PPh3/CS2 on the basis of references 6 ,
the yield was excellent. Moreover the complicated operation was avoided such as
strictly anhydrous and low temperature to introduce the methylsulfinyl group 6a . All of
the reactions involved in our route were very easy to control as to the synthesis of the
racemic SFN. All of the reagents used were not expensive.
In summary, SFN had been synthesized via a facile method based on the general
modification of previous routes. The advantages of the past strategies had been applied
and disadvantages discarded. The synthetic transformation utilized readily available
OH
c
O
S