Tetrabromo hydrogenated cardanol: Efficient and renewable brominating agent

Article abstract of DOI:10.1021/ol061637b

(Chemical Equation Presented) 2,4,4,6-Tetrabromo-3-n-pentadecyl-2,5- cyclohexadienone (TBPCO) has been synthesized and used as a new efficient, convenient, and environmentally friendly brominating agent.

Full text of DOI:10.1021/ol061637b

ORGANIC
LETTERS
2006
Vol. 8, No. 19
4291-4293
Tetrabromo Hydrogenated Cardanol:
Efficient and Renewable Brominating
Agent
Orazio A. Attanasi,*,† Stefano Berretta,† Gianfranco Favi,† Paolino Filippone,*,†
Giuseppe Mele,‡ Giada Moscatelli,† and Raffaele Saladino§
Centro di Sudio delle Sostanze Organiche di Origine Naturale, UniVersita` di Urbino
“Carlo Bo”, Via Sasso 75, 61029 Urbino, Italy, Dipartimento di Ingegneria
dell’InnoVazione, UniVersita` di Lecce, Via Arnesano, 73100 Lecce, Italy, and
Dipartimento di Agrobiologia ed Agrochimica, UniVersita` della Tuscia,
Via S. Camillo de Lellis, 01100 Viterbo, Italy
attanasi@uniurb.it; filippone@uniurb.it
Received July 4, 2006
ABSTRACT
2,4,4,6-Tetrabromo-3-n-pentadecyl-2,5-cyclohexadienone (TBPCO) has been synthesized and used as
environmentally friendly brominating agent.
a
new efficient, convenient, and
The spongy mesocarp of a cashew nut shell (Anacardium
occidentale L.) contains, in nearly 25-30% of the total nut
weight, an alkyl phenolic oil internationally known as
“cashew nut shell liquid” (CNSL). This oil derives as a
byproduct from mechanical processing for edible use of the
cashew kernel presently in some 350 000 tons per annum
worldwide with the expectation to rise up to 600 000 tons
per annum soon.1-3 Therefore, CNSL represents a renewable,
widely available, and relatively low-cost organic natural raw
material useful for several applications in fine chemistry or
for production of varnishes, resins, surfactants, pesticides,
etc.4 Chemically, CNSL is a mixture of anacardic acid,
cardanol, and a smaller amount of cardol and 2-methylcardol,
with the polyketide long chain being saturated, monoolefinic
(8), diolefinic (8,11), and triolefinic (8,11,14) with an average
value of two double bonds per molecule (Figure 1).1-3
However, anacardic acid undergoes ready thermal decar-
boxylation. Thus, the distillation of CNSL provides cardanol
in high yield and good purity. The subsequent catalytic
hydrogenation of distilled cardanol gives rise to 3-n-penta-
decylphenol (1).5
* To whom correspondence should be addressed. Fax: +390722303441.
† Universita` di Urbino.
‡ Universita` di Lecce.
§ Universita` della Tuscia.
(1) Tyman, J. H. P. Synthetic and Natural Phenols; Elsevier: Amsterdam,
1966 and references therein.
(2) Attanasi, O. A.; Buratti, S.; Filippone, P. Chim. Ind. (Milan) 2003,
85, 11.
(3) Paramashivappa, R.; Kumar, P. P.; Vithayathil, P. J.; Rao, A. S. J.
Agric. Food Chem. 2001, 49, 2548.
(4) (a) Sethi, S. C.; Subba Rao, B. C. Indian J. Technol. 1963, 1, 218.
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27, 645. (c) Lubi, M. C.; Thachil, E. T. Des. Monomers Polym. 2000, 3,
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(5) Oltremare SpA, Bologna (Italy).
10.1021/ol061637b CCC: $33.50
© 2006 American Chemical Society
Published on Web 08/22/2006

al. reported the synthesis of 1,2-dipyridiniumditribromide-
ethane (DPTBE) as a new efficient brominating reagent.19
Despite the variety of reagents available for bromination,
low selectivity and formation of undesired side products
under mild reaction conditions continue to be problematic.
To find an alternative, environmentally friendly, mild,
clean, efficient, regioselective, simple workup, and cost-
effective procedure, we investigated the use of hydrogenated
cardanol as starting material for the preparation of such a
brominating reagent, as part of our ongoing program for the
utilization of this compound in fine chemistry. First, 2,4,6-
tribromo-3-n-pentadecylphenol 2 was easily obtained in 4 h
by reaction of 3-n-pentadecylphenol 1 in carbon tetrachloride
under reflux with 3 equiv of bromine (1.0 M solution in
CH3COOH). The fourth bromine atom in position 4 of the
phenolic ring of 2 was introduced by treatment of this latter
compound in carbon tetrachloride with a fourth bromine
equivalent (1.0 M solution in CCl4) in the presence of ZnCl2
in a catalytic amount producing 2,4,4,6-tetrabromo-3-n-
pentadecyl-2,5-cyclohexadienone 3 (TBPCO) in nearly quan-
titative yield (Scheme 1).4b
Figure 1. Components of CNSL.
During the past few years, allylation,6 cyclocarbonylation,6
and nitration7 of hydrogenated cardanol, as well as the
synthesis of phthalocyanines,8 porphyrins,9 and fullerene10
derivatives of cardanol, have been investigated in our
laboratories.
Scheme 1. Preparation of TBPCO and Bromination of
Organic Substrates
The general importance of halogenation reactions in
organic chemistry11 and, in particular, the role of bromina-
tion12 in the synthesis of organic intermediates or antitumor,
antifungal, antibacterial, antineoplastic, and antiviral com-
pounds have drawn our attention.13 The most commonly used
reagents for such a reaction include elemental bromine,14
organic ammonium tribromides (OATB),15 copper(II) bro-
mide,16 N-bromosuccinimmide (NBS),17 and 2,4,4,6-tetra-
bromo-2,5-cyclohexadienone (TBCO).18 Recently, Patel et
This brominating agent easily and inexpensively made in
multigram quantity is a crystalline solid, facile to handle,
and stable for extended periods when stored in a refrigerator.
The presence of the long alkyl chain in the meta position
of the phenole ring gives to TBPCO a lower melting point
and a higher solubility in apolar organic solvents than those
of similar products lacking a long alkyl side chain (i.e.,
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G. J.; Vasapollo, G. J. Porphyrins Phthalocyanines 2003, 7, 52. (b) Attanasi,
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4292
Org. Lett., Vol. 8, No. 19, 2006

TBCO). For the same reason, its precursor 2,4,6-tribromo-
3-n-pentadecylphenol 2 is soluble in most organic solvents
but is highly insoluble in water, methanol, and acetonitrile
thus facilitating its recovery by separation from brominated
products at the end of the reaction.20 These properties repre-
sent a further advantage of this reagent in respect to other
known organic tetrabromides together with the smooth regen-
eration of TBPCO and the natural origin of these reagents.
The results of bromination at room temperature of
activated aromatic amines and phenols, â-naphthol, and
sensitive substrates such as carbonyl compounds are sum-
marized in Table 1. TBPCO works well with both aromatic
agent in which “positive” bromine is transferred to release
aromatic phenolate anions.
In conclusion, this paper reports the synthesis of new
tetrabromide reagent TBPCO obtained from natural and
largely available CNSL. [TBPCO demonstrates an excellent
bromine carrier that is able to brominate different organic
substrates.] The reaction generally occurs under mild condi-
tions, requires a simple workup procedure, and permits both
the recovery and the regeneration of the brominating reagent.
Therefore, the whole reaction may be considered environ-
mentally friendly. On the basis of preliminary findings, the
regioselective monobromination of TBPCO seems more
favored than that of TBCO. Moreover, investigations are in
progress by computational calculations able to quantify the
effect of the steric hindrance of an alkyl side chain on the
ortho-bromine atoms of TBPCO. Kinetics measurements
will be made also to exactly determine the peculiar prop-
erties of TBPCO in respect to the other similar brominating
agents.
Table 1. Bromination of Organic Substrates with TBPCO
At present, further investigations are in progress to find
additional applications of this reagent in organic synthesis.
Acknowledgment. This work was supported by the
financial assistance from the Ministero dell’Universita`,
dell’Istruzione e della Ricerca (MIUR)-Roma, and the
Universita` degli Studi di Urbino “Carlo Bo”.
Supporting Information Available: Experimental pro-
cedures including characterization of all compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL061637B
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(20) General Experimental Procedure for Bromination of Organic
Substrates. To a stirred solution of organic substrate (0.5 mmol) dissolved
in the appropriate solvent (10 mL) (Table 1) was added in small portions
2,4,4,6-tetrabromo-3-n-pentadecyl-2,5-cyclohexadienone (0.55 mmol). The
reaction mixture was magnetically stirred until the disappearance of the
starting organic substrate (monitored by TLC). After completion of the
reaction, the reaction mixture was concentrated under reduced pressure and
was purified by crystallization of 2,4,6-tribromo-3-n-pentadecylphenol from
CH3OH. The brominated organic substrate was obtained in satisfactory yield
and purity.
a All the bromo derivatives are known compounds reported in the
literature. Their identities and purities were confirmed by 1H NMR spectra.
b Yields of isolated product by crystallization with methanol of the 2,4,6-
tribromo-3-n-pentadecylphenol 2. c Reaction performed under reflux.
(entries 1-5) and aliphatic (entries 6-12) substrates as well
as with different polarity solvents.
2,4,4,6-Tetrabromo-3-n-pentadecyl-2,5-cyclohexadi-
enone 3 (TBPCO) seems to be an electrophilic brominating
Org. Lett., Vol. 8, No. 19, 2006
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