Gary M.

Lampman,'
Jennifer Andrews,
Wayne Bratz, Otto Hanssen, The Preparation of Vanillin from Eugenol
Kenneth Kelley, Dana Perry,
and Anthony Ridgeway
Western Washmgton State College and Sawdust
Belhngham, Washmgton 98225

F o r t h e l a s t several years, o u r organic lahoratory classes

have been isolating t h e fragrant liquid eugenol from cloves by
s t e a m distillation ( I ) . It occurred to us that s t u d e n t s might
b e interested i n converting eugenol to a n equally fragrant
solid, vanillin. W e felt that s t u d e n t s would enjoy making t h e
substance used i n ~. r e.~ a r-i vanilla
na a n d , at t h e s a m e time,
learn s o m e interesting chemistry. EUGENOL ISOEUGENOL VANILLIN
The process, shown in Figure 1,involves t h e basic isomer- Figure 1. Preparation of vanillin from eugenol
ization of t h e douhle bond i n eugenol to give isoeugenol, and
t h e n a n oxidation of t h e rearranged double bond to vanillin.
In this paper, two procedures are described for the conversion
of eucenol to vanillin: (1) a direct one-container reaction where
the i&eugenol i s n o t isolated; (2) a two-step reaction where
the isoeugenol is isolated as a n intermediate.

In the first experiment eugenol, wdium hydruxidr, nnd nitn~hen-

rencnredtawlved indimethyl iulfoxidc \l)hlS01and t h ~ m ~ x r u r e ~ s
hrntrd to 120-1.39°(.'f~,r:I hr. Nnn,bewmc ir a urcful ux~dtnml:?cent Figure 2.Isolation and purification scheme for vanillin
widely used in structural studies involving lignins and lignin-like
model eomoounds (2).It has iust the rieht oxidizine. .Dower and does
not d r s t n ~ )the
. phenolic functional y n m p llni~~rrunntdy. the m i -
datiun i i very slow, snd thu* the WdClNlII is usunll) mndutted in &
sealed stainlrsi i t t r l tuhe at IT(, 18U0C 131.As nn cqwrimmt. the
reaction was conducted in aqueous base with nitrobenzene in an open
glassvessel to see if a satisfactory yield could he obtained. However,
it was found that two days of heating were required just t o obtain a
small amount of product. This two-day reaction period is unsatis-
factory for a laboratory preparation and, in addition, the flasks were
nearly destroyed by the base. By using the high boiling solvent, (A)
DMSO, mentioned above, the rates of isomerization and oxidation CllOH CHO
were increased significantly and satisfactory yields of vanillin could
be ohtained. The time period is relatively convenient for a typical
organic laboratory and the glassware is nnt damaged.
The isolation and purification scheme for vanillin is shown in Figure
2. The process requires about two 3-hr labratary periods, with several
blocks of time where other experiments may be conducted simulta- 0 Oil
+
neously. The use of sodium bisulfite for purification of an aldehyde
as the addition product is one of the unique features of the scheme. tH3CH0 % CH3C02H
The crude vanillin obtained after decomposition of the addition Figure 3. Mechanism of me oxidation of isoeugenol wRh nitrobenzene
product is purified readily with cyclohexane which leaves the im-
purities behind. The yield is certainly not spectacular (5.3% yield),
but the amount of the light-fluffy vanillin obtained (0.4 g) from 8 g
of eugenol is large enough for a student to prepare the anil derivative, Using nitrobenzene as the oxidizing agent, and the same procedure
sublime a sample, and determine an nmr spectrum. The vanillin as described for eugenol, a 35% yield of nearly pure vanillin is obtained
sublimes easily to give colorless needle-like crystals. from isoeugenol. Colorless needle-like crystals are obtained from
In the second experiment, eugenol is first isomerized to isoeugenol waterfNorit. The main limitation t o an increased yield is the rate of
and the isolated product is oxidized tovanillin in asecond step. The oxidation. However, the 3-hr reaction period is probably the maxi-
isomerization reaction is carried out for 1.5 hr a t 150°C with base in mum one would desire for a laboratory class.
diethylene glycol solvent t o giw a 75% yield of completely isomerized The mechanism of the oxidation of isoeugenol with nitrobenzene
product. The purity of the product is determined easily by nmr isshown in Figure 3 ( 2 )As . shown in themechanism, it is necessary
spectroscopy by observing the absence of a doublet for the benzylic t o have a paro-hydroxyl group on the ring in order to obtain the
methylene group in eugenol, and the appearanceof ndauhlet for the quinone methide intermediate (A). If the hydroxyl group is removed
allylic methyl group in isoeugenol. or methylated, the yield of vanillin drops tozero (6). It has been ob-
Numerous oxidation methods were tried to convert isoeugenol to served that nitrobenzene has extreme specificity for isoeugenol and
vanillin in high ~ i e l dIncluded
. here are: (1) chromium trioxide or materials related t o them such as lignins or lignin-like model com-
vanadium pentoxide with hydrogen peroxide in t-butyl alcohol ( 4 )
gives from 6% (Cr03 reaction) to 18% (V205 reaction) for 12-20 hr
nnunds i2b 7).
7 ~ . . Nitrobenzene is reduced hv a series of two electron
~ ~ ~ ~ ~ ~ ,

transfers to nitrosobenzene, phenylhydrouylamine, and aniline. These

reaction times; (2) isoeugenol is converted to the acetate (49% yield) intermediates are then converted to the condensation products
and oxidized with osmium tetroxide/sodium periodate ( 5 ) to give,
" . ..
after removal of acetate moUD in the work-uo orocedure. 23% vield
of vanillin. The problems with these procedures are considerahl'. For
example in the chromium trioxide/vsnadium pentoxide procedures,
the reaction time is too long, and the preparation time is great because
of the need t o standardize the peroxide reagents. Likewise, the os- fornia, September 1976.
mium tetrovide reactions involve the use of this expensive and poi- 'Correspondence may be addressed to this author. Detailed ex-
sonous reagent. perimental procedures are available upon request.

776 / Journal of Chemical Education

m,xyhrnzene, arohrnzene, and p-h>dnmgnmhenrenr t 2 h 1 Thrrc
latter mntrrislsarr nut isdatrd in theexprr~menhdcscr~bed in this
paper.
Vanillin (actually the conjugate base) is quite stable in the strongly
basic reaction mixture and does not undergo the Cannizaro reaction.
,
In contrast, veratraldehvde (3.4-dimethoxvhenzaldehvdel ~ readilv.
undrrgwc the Cannizaru rrartmn undrr the samr eonditim-. The
pnra.phen<,xy inn redtaw thr clertruphil~ccharacter of the carbunvl
".. - ,. ..
In the last experiment dcvrilwd in this pnjxr, vonilhn ma). he
isolated irum lot'twotd saudust nftcr hearing the wocd with nitro-
h m r r n r in n hasicsdu!~<mof I IMSO for .I hr nt 12YY" The bields of
vanillin are very low, but the product purity is high. For example, 15
e of sawdust rives 32 me of vanillin. Even with this small amount of
~ ~
matrrinl, an umr spwtrwm can I~.ohtaintd,andthe mawrdsutdimcd
to p u r ~ f yi t . I'ndrr tht. rcsctiun nlnditionc thp hgnins present in the
wwd are derradrrl uith Law fnm thrir inirmll) cornplmted poly.
meric structures (9)to lower molecular weight compounds by reverse
aldol condensation reactions and elimination reactions (2e). These
lower molecular weight compounds are then oxidized to vanillin.
Other aldehydes are produced hut only to the extent of about 8% of
the total (2a, b), and they are removed easily in the purification
scheme described in this paper. I t is important touse softwood saw-
dust uncontaminated with hardwoodssince thelatter materialgives
large amounts of syringaldehyde which cannot be removed easily. The
sawdust, most of which came from fir plywood, was obtained from the
departmental woodshop. No care was taken in separating glue or dirt
from the remaining wood. The remaining component in wood, cellu-
lose, may also be isolated from the sawdust and converted into a low
grade paper. Since cellulose fibers are short-lengthed, they do not
make a good quality paper.
The isolation of vanillin from sawdust would only be recommended
for a student with good technique or for a more advanced class. Its
beauty is that it gives some idea to students how most of the synthetic
vanilla is prepared. It is prepared as a by-product of the pulp and
paper industry from the sulfite liquor obtained after pulping (10).
Procedure
lsomerization of Eugenol to lsoeugenol
Place 50.0g of potassium hydroxide, 200 ml of 23-oxydiethanol,
and 47.0 g of eugenolz in a 500-ml round bottom flask. Assemhle a
reflux apparatus with a thermometer inserted into the reflux con-
denser and projected below the surface of the mixture. Heat the
mixture with occasional swirling until the bailing point is attained
(150°C). When the solution starts to bubble slightly (about 138"C),
it must be watched carefully so that the mixture will not bump. Once
the mixture has stabilized a t the hoilingpoint (150°C), allow the so-
lution to reflux for 1.5 hr. When the hoilingaction isstabilized suffi-
ciently, the thermometer may he removed.
Dilute the cooled reaction mixture with 450 ml of water and acidify
it with concd hydrochloric acid (about 61 ml required) to a p H of 2
to 3. Extract the isaeugenol from the mixture with three 75-ml por-
tions of petroleum ether (hp 3040°C), add 25 ml of diethyl ether to
the combined extracts to make the mixture homogeneous, and dry
the combined extracts with 2.5 g of anhydrous magnesium sulfate.
Remove the solvent on a steam bath to ohtain35.3 g (75.1%yield) of
dark brown isoeugenol. The mixture should be stored in a refrigerator
to prevent polymerization. It is of suitable purity for conversion to
vanillin and enough is prepared for four students. The nmr spectrum
may be determined in CDCIa; 61.9 (d, C=CHd, 63.7 (s, OCHs), 66.0
(m, vinyl and OH), 66.8 (s,arom.). There is no evidence of any eugenol
in the spectrum. The spectrum of eugenol shows absorptions a t 63.4
(d, ArCHz), 63.7 (s, OCH:,), 65.1 (d, C=CHz), 65.8 (6, OH), 66.0 (m,
vinyl), 66.8 (m, arom.).
Oxidation of lsoeugenol or Eugenol
Heat 19.0 g of potassium hydroxide, 80 ml of dimethyl sulfoxide,
and 25 ml of water until the base dissolves. Place this mixture together
with 40 ml of nitrobenzene and 8.0 g (0.049 mole) of isoeugenol or
eugenn12 in a 500-ml round bottom flask. Assemble a reflux apparatus
as described ahove and reflux the mixture for 3 hr after the mixture
begins to hnil (136139°C). Once the temperature stabilizes, the
thermometer may be removed from the reaction flask. After the reflux
period, dilute the cooled mixture with 200 ml of water, acidify with
concd hydrochloric acid (ahout 27 ml required) t o a p H of 2 to 3, and
filter the mixture through a I-cm bed of Celite to remove any sus-
pended solids.
Isolation of Vanillin. Extract the mixture with four 75-ml portions
of diethyl ether" and allow the combined ether layers to stand for
approximately 45 min4 so that any solid material will settle to the
bottom of the flask. Decant the majority of the ether extracts away
from the solid and filter5 the remainine solution through a cotton
plug.
Extract the combined ether layers with four 50-ml portions of a
~ bisulfite.solution (20 g sodium bisulfite/100 mi water). It is
sadium
extremely important during each extraction t o shake the separatory
funnel vigorously for a minimum of 1 to 1%min. Gravity filter the
comhined bisulfite extracts through fast fluted filter paper and de-
compose them slowly with stirring with 27 ml of concd sulfuric acid
in a hood. After adding the acid, heat the mixture for 40 min to50 t u
60'C in a hood while .. eentlv . buhbline air throueh the mixture tore-
move the rrmnmmg sulfur dimide. Extract the < w l r daquwus phnar
with threr 50-ml portions irf dirrhgl ~ t h r rdry , the cornl~mrdcrhw
layers nith 1.5 r: d.mhydrr,us mngnwium wlfatr, and remore the
e r h ~ r u nastpnm Iuth untd a n oil remain.. I'nr erd t o m e o i t h r f d
Inwingp~~riflrati<en p n r d u r e s depending on tht. starring mstrri:ll.
P L r i i w n r i m I,/ I'onrlhn /nrm l s o r ugvn 11 The crudr \nnilliu
K O ohtainrd m the above idation prmtdure ha- a dark rtddish-bmun
&or and completely crystallizesat room temperature. Add 84 ml of
hot cyclohexane (25 ml/l.Ogcrude vanillin) to the crude vanillin and
swirl and scrape the vanillin with heatingfor a5-min period. Decant
the hot solution, allow it to stand until crystallization is complete
(ahout 2 hr), and collect the pale yellow needhlike crystals; 0.98 g,
mp 80-83'C. Repeat the above procedure twice more to obtain 0.98
g (mp 80-83'C) and 0.70 g (mp 80-82W of vanillin. The combined
weight of vanillin is 2.66 g (35.7% yield). Dissolve 1g of the pale yellow
cyclohexane purified vanillin in 35 mlof bailing water, decolorize the
solution with 0.2 g of Norit A, and collect the colorless crystals from
the cooled solution; 0.63 g, mp 80-82T.
Purification of Vanillin from Eugenol: The crude vanillin (1.80 g)
obtained in the ahove isolation procedure has a dark reddish-brown
color anddoes not crystallize upon standing. Add 45 mlof hot cyclo-
hexane (25 mlll.0 g crude vanillin) t o the crude vanillin and treat it
as desmihed ahove to give 0.18 gof vanillin (mp 78-80DC).Repeat with
another 45 ml of hot cyclohexane to obtain 0.21 g of vanillin (mp
7678'C); combined weight 0.39 g (5.3% yield); nmr (CDCI:J, 64.0 (s,
OCHd, 66.3 (h, OH), 67.1, 67.4 (m, arom.), 69.8 ( 8 , CHO). A small
sample (0.05 g) of vanillin may he sublimedQt 85°C (16 mm Hg) to
give colorless crystals; mp 80-82%.
To prepare the vanillin anil derivative, place 0.1 g (0.66 mole) of
cyclohexane purified vanillin and 0.09 ml (0.092 g, 0.87 mmole) of
aniline i n a flask. After 5 minadd 1ml of 95% ethanol to the mixture
and heat the solution until the solid dissolves. Cool with scratching
and collect the light yellow crystals (0.06 g, 38% yield, m p 147-
153'C).
Preparation of Vanillin From Sawdust
Substitute 15 g af softwood sawdust7 for the isoeugenol/eugenol
in the ahnve procedure. After the reaction period, remove the cellulose,
wash i t with small portions of water, and continue the procedure as
above.
Purification of Vanillin from Sawdust: Extract the crude vanillin
(0.94 g) with 25 ml of hot cyclohexane and decant the solution away
from the aiL8 As the solution cools it will appear cloudy but no crystals
will form. Evaporate the cyclohexane to dryness under partial vacu-
um, and dissolve the majority of the resulting product in 13 ml of
cyclohexane. Decant the solution away from the ail, coal for about 2
hr, and collect the vanillin; 0.0328 g, m p 78-80% The nmr spectrum
may heobtained and the sample recovered and sublimed to givecal-
orless crystals; mp 80-82°C.
2Catalog No. E5, 179-1, Aldrich Chemical Co., Inc., Milwaukee,
Wis.
"0 avoid a potentially troublesome emulsion problem in the
sawdust reaction, add the first 75 ml portion of ether t o the beaker
containing the mixture with stirring and if an emulsion is formed the
mixture must be filtered through a cotton plug into a separatory
funnel.
'Far the sawdust reection, i t is recommended that the solution
stand until the next laboratory period.
Tor the eugenol and sawdust reactions, the solid adheres strongly
t o the bottom of the flask and filtration may not he required.
Tavia, D. L., Lempman, G. M., Kriz, G. S., "Introduction to Or-
ganic Laboratory Techniques," W. B. Saunders Co., Philadelphia,
1976, p. 630. Fig. 13-2A.
?Fermented sulfite spent liquor from the el ling ham, Washington
Division of the Georgia-Pacific Corporation has also been used.
RFurther extractions with hot cyclohexane yield insignificant
amounts of vanillin.
Volume 54, Number 12, December 1977 / 777
 Wash the crude cellulose successively with two 60-ml portions of 12) is1 Leupuld.B.,~cto chpmscond., 6,88119~21.(h) PW.I.C ...I . A ~ W I. W
., .siil.
ether and two 120-ml portions of 50:50 acetone-water tu give 7.5 g of 17.2881 1 1 9 M I . ~ c ~ C h m ~ . H . ~ M . , sAllan.U.C..in
nd "l.irnin~."lt.'dil~~r~:S;~rkn~~~n.
K . V..snd Ludwir.C. H I , Wiley-lntorrcience, New Vcwk. l'J?I,l:hn[~. II.
which gives a MO1ischtest'g To prepare paper,add 18) Leopold. 8.Ac1n C h r m Srond.. 4.1523 1195U):Kavsnagh. K. Il..ntd IPel,pcr..I. M..
0.5 g of cellulose to 100 ml of water, break up any lumps, and collect con. J chom.. 33.24 119551.
the well-stirred mixture on a small Buehner funnel. Press the sample 141 Mi1aa.N A . J . Amrr. Chroi. Soa.. 59,2912 119:171.
between two pieces ,,f heavy hlattingpaperand dry the with 15) PBPW, R., Allen, D.S.. Lcrnieux. R. U.. .lohna,n. W. S., J O r * . i'lwa.. 21. 478
(1956).
a hot iron. 161 waeek, and ~ r a t z lK.. , ?hem. ~ e r .77,616 , (19441and relerencrr therein.
. L.. AcLo Chcm. Srand.. 5,9:!6 llY51): l.e~pc,ld. H . 6 ,
171 Leopsld. B..snd M a l r n r t r ~ m1.
Acknowledgment 1898(19511:6.55119521.
181 B S ' k m n . W..l.,and Purves.C. B.,J Amsr Chem Sue., 75,4386 119531.
T h e authors wish to thank Dr. Charles H.Ludwig for his 19) Reference ( 2 ~ 1p.< , Pearl. 1. A,. "Lienin CherniLry: A Cenlury~OldPuzzle." Chrm.
helpful comments during t h e course of t h i s project. E ~ ZN. ~ ~81SIJUI~ . 6, 1sfi41.
I101 Reference 12~1,p. 800.
Literature Cited
11) Pavia. D. L..Lsrnprnsn, G.M.. Krir, G. S.. " l n t n d u e l i ~A
! ~ O r ~ a n i rI.nl,c~m~~mry
w
T ~ c ~ ~ I ~ ~ u ~ sB.. 'saunders
' co,philaddphia. 1976, P. 152. gFootnote 6, p. 437.

778 1 Journal of Chemical Education