Apr.

1970 269

Trifluoromethylfurans I1

R . E. Bambury and L. F. Miller

Hem & Clark Division of Richardson-Merrell, Inc.

Ethyl acetoacetate reacted with 3-bromo-1,l ,l-trifluoro-2-propanone in the presence of base

to give 3-carbethoxy-4,5-dihydro-4-hydroxy-2-methyl-4-trifluoromethylfuran (I). Acid catalyzed
dehydration of I gave the corresponding furan (111). Saponification of 111 gave 2-methyl-4-
trifluoromethyl-3-furoic acid which was decarboxylated to yield 2-methyl-4-trifluoromethylfuran
(V) for which a structure proof is presented. Conversion of the methyl groups of 111 and V t o
formyl groups is described.

In a previous paper (1) the preparation of some 5-tri- closely related condensations in which a-haloketoesters
fluoromethylfuran derivatives was described. This report are condensed with 0-ketoesters (4). In order to defi-
discusses the synthesis of several 4-trifluoromethyIfurans. nitely establish the structure of V i t was condensed with
Addition of one equivalent of sodium ethoxide to a diethyl acetylenedicarboxylate to give the Diels-Alder ad-
benzene solution of ethyl acetoacetate and 3-bromo-1,I , I - duct, VI. The adduct was hydrogenated over palladium
trifluoro-Z-propanone gave a product (I) which was readily on charcoal and then heated at 180", effecting a retro-
dehydrated under acidic conditions to give an ester, 111. On grade Diels-Alder reaction. Comparison of the product
saponification and decarboxylation of 111 a compound (V) with an authentic sample of diethyl 2-methylfuran-3,4-
was obtained which analyzed as a methyltrifluoromethyl- dicarboxylate (5) showed them to be identical. The for-
furan. If the initial reaction to produce I was similar to mation of this compound established the structure of V as
previously reported ( 1,2) condensations of a-halopropan- 2-methyl-4-trifluoromethylfuran.
ones with ethyl acetoacetate using strong base, the product, Comparison of the NMR of V with the N M R of the
V, should have been 2-methyl-5-trifluoromethylfuran. acid (IV) from which it was formed showed that when the
However, comparison of the infrared and NMK spectra of carboxyl group was present the signal due to the upfield
V with spectra obtained from an authentic sample of proton on the three position of the furan ring disappeared.
2-methyl-5-trifluoromethylfuran( I ) indicated that the This observation established the structure of IV and its
compounds were not the same. Examination of the NMR ethyl ester (111) as 2-methyl-4-trifluoromethyl-3-furoic
acid
of V showed, in addition to the signal from the methyl and ethyl Z-methyl-4-trifluorornethyl-3-furoate, respec-
group at 6 2.24, one-proton singlets at 6 6.12 and 6 tively.
7.55, a pattern which suggested that V was a 2,4-disiib- These findings left only the structure of the initial
stituted furan. This type of product is typical of those condensation product, I, to be established. Dunlop and
isolated from the Feist-Benary synthesis (3) and other Hurd (4) were the first to question the postulate that

CHART I
270 It. 14:. I{anibriry and L. F. Miller Vol. 7

CHART II

CF3COCHzBr

Hp.111 + I e-

0-alkylation was tliv initial step in the Feist-1ji:niit-y syti- TABLE I ( I )

t l i v h i s atid related reactions of a-lialokctoc.stc~rs with p-
hetorstc.rs. They felt that an aldol-type c~ondensationwas Compound Solvent ( 2 ) u , c=o,/l v, O H , M
the initial step, giving a product which siibseqiiently cy-
I none 5.9 (b) 2.9 ( b )
clizrd and dehydratr:d t o give the furan. This hypothesis
tiah been substantiated in part by the work of Cantlon, cc14 (3) 5.80 2.86
Cockr:r and McMnrry (7) who studied the reaction o f ethyl 5.90 2.92
bromopyruvatc: with othyl sodio-osalooc.et~iti~ and the Lro- THF 5.85 3.05 ( b )
niination of c.thyl so(lio-oxaloacetati.. ‘1‘hc.y w i w able t o 5.95 (w,s)
identify thc- initial prodirrts from t h t w rc:ac-tionh its triethyl
CH3CN 5.85 2.95 ( b )
-I.,5-dihydro-4-hydr~~xy-2,~~,4-furantricart~oxylate anti tetra-
5 . 9 3 (w,s)
f: t h y l 4.5-d i h y d ro-4-hydroxy-2,~1,4,~-fur;intetracarboxyl-

ate, rc:spectivcly. Ihinlop and Hnrd (4) had t:arlic:r sug- 11 cc14 5.85
gested the same strncturc:s for t h w : prodiic:ts. They had THF 5.85
also suggc:str:d the cpoxidcs, which woiiltl rc:siilt i f a
Darzt:ns-type reaction had oc:c:irrrtd, as i t 1 tmiatc: possibili- ( I ) b=broad, w=weak, s=shoulder. (2) Spectra were determined
tics for the produc:ts. Uascd on t1ic:sc: c:orisidt:ratioris a at a concentration of 5-10 mg./ml. in a 1.0 mm. cell except where
rcasonabli: st:quc:ncc: (:an be drawn for thi: formation o f 111 noted. (3) Determined over a concentration range of 3.0-50.0
(Chart 11). mg./ml.
Analytical arid spwtral data clirninated the cpoxidr:
(XI) and the halohydrin (XIT) as possibilitiw for thc. struc- The spectrum obtained from I (neat) showed a broad,
tura o f I . Thi: hydroxy dihydro-fiiran striictiirc:, however, hydrogen bonded, 0 - H stretching band a t 2.9 p and a
fit the dataquite well. The NMK spectrum of1 in dimethyl- broad ester carbonyl absorption, also hydrogen bondid,
sitlfoxide-d6 cxhibitcci a broad siriglct a t 6 0. I 0 and addi- a t 5.9 p . These bands arc: typical for intermolecularly
tion o f di:uti:riuni oxide indic:atc:tl that thc: proton was hydrogen bonded groups (8). However, when the spectruni
r c d i l y c:xc:hangc:abli:. ‘J’he signals l’rorri the: two ring prtr of I was determined in carbon tetrachloride solution,
tons a t position five appc:arc:tl as ari A H qrrartc:t c:c:nt(*rc:tl carbonyl absorption bands a t 5.80 p and 5.90 p and
at 6 4.43. ‘lhc rnc:ttiyI group and ttic: (:thy1 fragnic:rit of ttic hydroxyl absorption bands a t 2.86 p and 2.92 p w i n :
vstcr group gavi: the. c:xpc:c:tt:d signals. obst:rved. The positions arid relative intensities of tht:st:
Attcnipts to acxtylatt: o r hnzoylati: I met with little bands were independent of concentration ( 3 t o 50
success; mild cwndi tions gavc: n o reaction arid more vig- mg./ml.) which suggested the presence of two hydrogen
orous c:onditions I d t o tli:hydration. tlowt:vc:r, it was bonded conformations in carbon tetrachloride. In order to
possibli: to obtain the methyl c:thvr (11) i n 54%)yield by determine the position of the non-bonded ester carbonyl
trc.atmr:nt o f 1 with methyl iodide and barium hydroxide absorption of I its spectrum was determined in tetrahydro-
i n dimc:thylformaniid(: (0). The NMIt spwtrum of I I e x - fnran (1HF) and acetonitrile. Both of these solvrrits
hihited the c:xprc:tt:d peaks with the ring protons a t position contain excellent hydrogen bond acceptor groups which
fivr appearing as a singlet a t 6 4.53. ‘J’rc:atrncwt of II witti could be expected to successfully compcte with the 1:stt.r
acid causr:ti tht: l o s s of mt:thanol and gave thc: fiiraii, 111. group for the alcohol proton. The spectra determined i n
‘l’ablt: I lists thi: infrared data obtainc:d with c:ompoitnds these solvents showed sharp non-bonded carbonyl absorp-
I and 11. tion bands a t 5.85 p with weak, bonded bands a t 5.05 p .
 ,\pr. 1070 'J'rifliiorotnrtliylfurans 11 27 1

1he h!-tlroxyl bantlh a t ;{.05p (TlIE') and 2.05 p (Cl13CN)

r 1
EXPERIMENTAL
+I t'rv qiiitc liroad. inilicativi* o f s t r o n g intermoli:c:iilar bond-
ing \+it11 thc. solvvnt. 'J'hv assignment o f 5.85 p t o i~ non- Melting points were determined with a Thomas-Hoover melting
point apparatus and are uncorrected. The infrared spectra, unless
t , o n t l ~ ~ tahsorption
l tiatid for thi: cstcr c.art)onyl a g r w d wc,ll
indicated otherwise, were determined with a Beckman IR-5 infra-
M ith Lhc posi~ioriof the- csstc:r c a r t m i y l a b so r p t i o n tiand red spectrophotometer as thin liquid films o r potassium bromide
(5.85 p ) obtairit:tl w h i m thi: h y d r o x y l groiip o f 1 w'as r c - pellets. GLC analyses were done with an F & M model 500 gas
placwl b y a m e t h o x y g r o u p , as in c:onipoiiiid II. 'I'ht:rc:fort:, chromatograph equipped with a 1609 flame ionization detector
\4 ith cwmpound 1 in c a r b o n tctrachloridt: t w o inLramoli:c:u-
using a column )/4 in. in diameter by 48 in. long packed with 5%
SE-30 on Anakrom ABS. NMR spectra were recorded with a
l a d y hydrogcn 1)otidt:d cwnforniaLioris w w : obsc:rvc:tl; om: Varian A-60 spectrometer using TMS as an internal standard.
i n w l i i c ~ l i tlic: c:artionyl t)and was sliift(:d to ;I longcr wave Elemental analyses were performed by Spang Microanalytical Labo-
Itvigtli (5.00 p ) ant1 ont: w h m : tlicrc: was a shift to a ratory, Ann Arbor, Michigan or Galbraith Laboratories, Knoxville,
s h o r t r r wiivt' Irngtli ( 5 . 8 0 p ) . 'Tennessee.
I1yilrogi:n honding to thv carhonyl oxygcn o f an cstcr 3-Carbethoxy-4,5-d i h y d ro-4-hydroxy-2-methyl-4-trifluoromethyl-
i h w v I I knowri to ( ~ a i i s ca shift of the c,arlionyl atJsorption furan (I).
band t o 1oiigc.r wave Icngths (0). A s h i f t o f an c.stt:r Sodium (15.8 g., 0.688 mole) dissolved in 300 ml. of absolute
c.art)on);l absorption hanil t o s h o r tc r wave lengths has o n l y ethanol was slowly added with stirring to a solution of 89.5 g.
h : n o h : r v i d in a fcw c:asc:s. tlc:nbt:st antl I,ovc:ll (0) (0.688 mole) of ethyl acetoacetate, 131.5 g. (0.688 mole) of 3-
bromo-1,l ,l-trifluoro-2-propanone (13) in 350 ml. of benzene.
werv the I'irst to o1)sc:rvc: this i:fft:c:t arid asc-rit)c:d it to
The temperature of the reaction mixture was maintained below
1iytlrogc:n liontling to tlict "i:thi:r" oxygt:ri of thc: w t v r func- 10' throughout the 4 hour addition period. Next, 700 mi. of
tion. l'his c:fl'c:c:t has h c : n obsc:rvc:d by t w o o t h c r groups water was added and the benzene phase separated. The aqueous
( 10). 'J'hus, the t w o c o n f o r m a t io n s o f 1 p r t xen t in car b o n phase was extracted twice with ether; organic phases were then
tetrachloridi. arc: pro1,ably : combined. dried over magnesium sulfate and the solvent evaporated.
The residual oil was fractionated with a 20 cm. column packed with
glass helices to give 107 g. (65% yield) of product (b.p. 48-50' at
0.06 mm.). A center cut (pure by GLC) was sent for analysis.
Infrared, v max (neat), 5.9 p broad (C=O); 2.91 p(OH); 8.1-8.8
g broad (CF3). NMR (DMSO-d,), 6 1.23 (3H, triplet, J=7cps,
CH,CH,O-); S 2.25 (3H, singlet, methyl group 2 pos.); 6 4.15
(2H, quartet, J=7cps, CH~CHZO-);6 4.45 (2H, AB quartet, ring
protons 5 pos., overlaps with quartet at 6 4.15); 6 6.16 ( l H ,
r . broad singlet, exchangeable with deuterium oxide, OH).
1hi> appears t o tw the first t:xamplc o f a c o n f o r m at i o n al Anal. Calcd. for Cg H l l F3 0 4 : C, 45.00; H, 4.62; F, 23.75.
equilibrium of this typv. Found: C, 44.89; H, 4.63; F, 23.81.
Bwausc. o f o u r p r w i o u s ly di:scribt:ti (I) intt:rt:st in tri-
e t h y I-4-trifluorome thyl-
3-Carbe thoxy-4,5dihydro-4-methoxy-2-m
t~uoromc.thylfrirfiiral dvrivativr:s, c:ornpoiinds [I1 and 1' furan (11).
Men' cvrivc.rtc:tl t o aldt:liydi:s. Bromiriation of 111 and V with
A mixture of 2.0 g. (0.008 mole) of I, 15 ml. of methyl iodide,
!\'-bromosiic.c:ininiitli. gavc the b r o m o n i e t h y l dwivativeh in 15 g. of barium oxide, 40 ml. of dimethylformamide and 0.2 ml. of
07% antl 70%)yit:ld. respc:c:tively. Treatment of t h c b r o m o water was stirred for 2 hours. The mixture was then poured into
c o m p o u n d s with s o d i u m Zpropanr: nitroriati: according t o 200 ml. of water and the resulting mixture was extracted twice with
thv method o f Hass and B e n d e r ( 1 I) gavc t h c desired ether. The extracts were combined, dried over magnesium sulfate
and evaporated to give 2.2 g. of crude oil. The crude oil was
ald(:hydes, IX and X . purified by preparative GLC using an F & M model 776 Prep-
master Junior. A column 3/4 in. in diameter by 80 in. long
packed with 20% UCW-98 silicone rubber o n Chromosorb P was
used. The compound had a retention time of 4.5 minutes using a
carrier gas ( N , ) flow rate of 0.52 Ipm. at 150'. A 54% yield (1.1
8.) of the ether was obtained. Rechromatography under the same
conditions gave an analytical sample. Infrared, v max (neat), 5.86
111 R=CO&HS VII R=CO&,H, IX R=CW,H, g (C=O); 6.13 p (C=C). NMR (deuteriochloroform), 6 1.33(3H3,
V R=H Vlll R = H x R=H triplet, J=7cps, CH3CH20-); 6 2.39 (3H, singlet, methyl group 2
pos.); 6 3.32 (3H, singlet, -OCH3); 6 4.30 (2H, quartet, J=7cps,
' J ' h c s sc:mic:arbaxont: o f X was tt:stt:d as an anticoccidial
CH~CHZO-), S 4.52 (2H, singlet, ring protons 5 pos., overlaps with
agent and found to bi: devoid of activity. An isomer of quartet at 6 4.30).
this c:ompound, 5-trifliioromc:thyl-2-fiirfural sc:mic:arba- Anal. Calcd. for C10H13F304: C, 47.25; H, 5.15; F, 22.42.
x o n c ~ . had prc:viorisly s h o w n this typc: ol' activity ( I ) . Found: C, 47.09; H, 5.23; F, 22.63.
Thi:rt:i'orc, thc trifhioromethyl g r o u p m u s t bc in t h e five Treatment of I1 with Acid.
position f o r biologic:al activity, which is also the casc: with A 1 g. sample of II was warmed on the steam bath for 30
the corresponding n i tr o h i r a n s (12). minutes with a few crystals of p-toluenesulfonic acid. The mixture
27 2 R. E. Bambury a n d L. F. Miller VOl. 7

was neutralized with aqueous sodium bicarbonate and extracted A mixture of 10.6 g. (0.070 mole) of V and 12.0 g. (0.071
with ether, The ether extract was dried over magnesium sulfate, mole) of diethyl acetylenedicarboxylate was heated for 5.5 hours.
filtered and evaporated to give a colorless oil. The infrared spec- The temperature of the heating bath was raised gradually from
trum and GLC retention time of the oil showed it to be ethyl 2- 125 to 160' during the heating period. The reaction mixture was
methyl-4-trifluoromethyl-3-furoate (111), described below. fractionated at 0.1 mm. using a 10 em. Vigreaux column. Material
boiling from 75 to 85' was collected to give 15.9 g. (70% yield) of
Ethyl 2-Methyl-4-trifluoromethyl-3-furoate
(111).
product. A center cut from the distillation, b.p. 82.5-84', was
The dihydrofuran, I (80.0 g., 0.33 mole), was heated on a submitted for analysis. Infrared, v max (neat), 5.8 p ( C = O ) ; 6.1
steam bath, under a slight vacuum, with 1.3 g. of p-toluenesulfonic p (C=C); 8.5-9.0 p broad (CF3). NMR (deuteriochloroform), 6
acid. After one hour an additional 1.3 g. of p-toluenesulfonic acid 1.30 and 6 1.35 (6H, two overlapping triplets, C H ~ C H Z O - )6; 1.92
was added and the heating was continued until GLC analysis indi- (3H, singlet, methyl group 4 pos.); 6 4.28 and 6 4.38 (4H, two
cated that the starting material was gone (approximately 30 min- overlapping quartets, CH3CH20-); 6 5.76 (IH, singlet, ring proton
utes). Water (50 ml.) was added, the mixture neutralized with 1 pos.); 6 7.45 (IH, quartet, J=2.5cps, ring proton 5 pos.).
excess sodium bicarbonate and extracted with ether. The ether Anal. Calcd. for C14H15F305: C, 52.50; H, 4.72; F, 17.80.
extracts were dried over magnesium sulfate and evaporated to give Found: C, 52.54; H, 4.88; F, 17.56.
72.0 g. of oil (95% pure by GLC). An analytical sample (b.p.
60°) was prepared by fractionating the material at 5 mm. using a Hydrogenation and Thermal Decomposition of VI.
10 cm. column packed with Raschig rings. Infrared, v max (neat), A mixture of 9.6 g. (0.03 mole) of VI, 25 ml. of ethyl acetate
5.8 p (C=O); 6.35 p (ring stretching); 8.4-8.9 p (CF3). NMR (deu- and 0.1 g. of 10%palladium on charcoal was stirred under one
teriochloroform), 6 1.36 (3H, triplet, J=7cps, CHBCH~O-);6 2.59 atmosphere of hydrogen at room temperature. Within one hour
(3H, singlet, methyl group 2 pos.); 6 4.33 (2H, quartet, J=7cps, the calculated amount of hydrogen was absorbed. The mixture
CH,CH2O-); 6 7.69 (IH, singlet, ring proton 5 pos.). was filtered and the solvent evaporated. The residual oil was heated
Anal. Calcd. for C&F303: C, 48.65; H, 4.08; F, 25.65. at 180' for 1 5 minutes in an open flask and then fractionated at
Found: C, 48.51; H, 4.21; F, 25.56. 5 mm. using a 4 em. Vigreaux column. The material boiling at
129-131', nZ5 1.4683 (3.6 g., 55% yield), was collected and found
Acid (IV).
2-Methyl-4-trifluoromethyl-3-furoic
to be pure by GLC analysis. The index of refraction, GLC retention
The ester, I11 (60.0 g., 0.27 mole), was refluxed for 30 minutes time, and infrared spectrum of the material were identical with
with 10.8 g. (0.27 mole) of sodium hydroxide, 140 ml. of water those of an authentic sample of diethyl 2-methylfuran-3,4-dicar-
and 425 ml. of ethanol. The mixture was then neutralized with boxylate prepared by the method of Alder and Rickert (5).
hydrochloric acid and evaporated to one-third of its original volume.
E thy1 2-Bromomethyl-4-trifluoromethyl-3-furoate
(VII).
The solution was basified with 10%sodium hydroxide and 9 g. of
unreacted starting ester was recovered by extraction with ether. A mixture of 103.1 g. (0.464 mole) of III,82.6 g. (0.464 mole)
The aqueous phase was re-acidified with concentrated hydrochloric of N-bromosuccinimide and 650 ml. of carbon tetrachloride was
acid and extracted with ether. The ether extract was dried over heated to reflux and the reaction initiated with a 275 watt sun
magnesium sulfate and evaporated to give 38.0 g. of crude acid. lamp. The lamp was removed and the heating maintained until the
The unreacted starting material was hydrolyzed in the same fashion refluxing mixture became colorless. After cooling, the mixture was
to give an additional 6.0 g. of acid to bring the total yield to 80%. filtered to remove the succinimide and the solvent distilled under
Recrystallization of the acid from cyclohexane gave an analytical reduced pressure using a 15 cm. Vigreaux column. The residual oil
sample, m.p. 140-141'. Infrared, u max (potassium bromide), was fractionated at 0.05 mm. using a 20 cm. column packed with
3.1-4.2 p broad (OH); 5.95 p (C=O); 6.35 p (ring stretching); Raschig rings, to give 109.0 g. (78% yield) of product, b.p. 70°.
8.5-8.9 p broad (CF3); NMR (deuteriochloroform), 6 2.69 (3H, A center cut (pure by GLC) was submitted for analysis. Infrared,
singlet, methyl group 2 pos.); 6 7.70 (IH, singlet, ring proton 5 u max (neat), 5.8 p (C=O); 6.38 p (ring stretching); 8.3-9.0
pos.); 6 12.0 ( l H , singlet, -COOH). (CF3); NMR (deuteriochloroform), 6 1.49 (3H, triplet, J=7cps,
Anal. Calcd. for CTHSF303: C, 43.29; H, 2.59; F, 29.35. CH3CHzO-); 6 4.40 (2H, quartet, J=7cps, CH~CHZO-);6 4.83
Found: C, 43.13; H, 2.63; F, 29.50. (2H, singlet, -CH2Br); 6 7.84 ( l H , singlet, ring proton 5 pos.).
Anal. Calcd. for C9H*BrF3O3: C, 35.89; H, 2.68; Br, 26.54;
2-Methyl-4-trifluoromethylfuran(V).
F, 18.93. Found: C, 36.01; H, 2.80; Br, 26.43; F, 18.80.
The acid, IV (49.5 g., 0.255 mole), 35 ml. of quinoline and 2
g. of anhydrous cupric sulfate were placed in a flask equipped with 2-Bromomethyl-4.trifluoromethylfuran(VIII).
a 10 em. column, packed with glass helices, and an efficient con- Using the Same procedure as outlined for the preparation of
denser. The flask was heated at 230' with a Meeker burner and VII, 28.6 g. (0.19 mole) of 2-methyl-4-trifluoromethylfuran was
swept with a slow stream of nitrogen until all low boiling material converted to 29.2 g. (67% yield) of the bromo compound, b.p.
had distilled. The distillate (34.3 9.) was dried over sodium sulfate 82.5-84' at 0.1 mm. A center cut from the fractionation was taken
and redistilled using a 10 cm. Vigreaux column to give 28.5 g. for analysis. Infrared, v max (neat), 6.43 p (ring stretching); 8.4-
(75% yield) of pure furan, b.p. 84-85'. Infrared, u max (neat), 9.1 p (CF3). NMR (deuteriochloroform), 6 4.47 (2H, singlet,
6.37 p (ring stretching); 8.4-9.1 p broad (CF3); NMR (deuterio- -CH2Br); 6 6.58 (lH, singlet, ring proton 3 pos.); 6 7.78 (LH,
chloroform), 6 2.24 (3H, singlet, methyl group 2 pos.); 6 6.12 singlet, ring proton 5 pos.).
( l H , singlet, ring proton 4 pos.); 6 7.55 ( l H , singlet, ring proton A d . Calcd. for C6H4BrF30: C, 31.47; H, 1.76; Br, 34.90;
2 pos.). F, 24.89. Found: C, 31.58; H, 1.90; Br, 34.80; F, 25.00.
Anal. Calcd. for C6H5F30: C, 47.97; H, 3.35; F, 37.95. (IX).
3-Carbethoxy-4-trifluoromethyl-2-furfural
Found: C, 47.78; H, 3.16; F, 37.83.
A solution containing 7.4 g. (0.323 mole) of sodium and 36.5
2.2.1 ] -
2,3- Dicarbethoxy-4-methyl-6-triuoromethyl-7-oxabicyclo[ g. of 2-nitropropane in 450 ml. of absolute ethanol was slowly
hepta-2,5-diene (VI). added to a stirred solution of 97.4 g. (0.323 mole) of VII in 50 ml.
Apr. 1970 Trifluoromethylfurans I1 273

of absolute ethanol. The temperature of the reaction mixture was stretching); 8.2-9.0 p (CF3); NMR (deuteriochloroform), 6 7.51
maintained at 50’ during the three hour addition period and for (IH, singlet, ring proton 3 pos.); 6 8.16 ( l H , singlet, ring proton 5
one hour thereafter. One liter of water was added and the mixture pos.); 6 9.85 ( l H , singlet, -CHO).
extracted three times with ether. The extracts were combined, dried Anal. Calcd. for C6H3F302: C, 43.91; H, 1.84; F, 34.74.
over magnesium sulfate, decolorized with charcoal and evaporated. Found: C, 43.91; H, 1.90; F, 34.96.
The residual oil was dissolved in ether, washed with 1% sodium A semicarbazone was prepared from X in the usual fashion and
hydroxide solution and then water. After drying over magnesium recrystallized from acetonitrile to give material, m.p. 208-211”.
sulfate the ether was evaporated. The residual oil was fractionated Anal. Calcd. for C ~ H ~ F ~ N C, Z : H, 2.74; F, 25.78;
~ O38.02;
at 0.045 mm. using a 10 cm. column packed with glass helices to N , 19.00. Found: C, 38.03; H, 2.80; F, 25.70; N, 18.86.
give 35 g. (45% yield) of aldehyde, b.p. 95-100’. An analytical
sample (m.p. 55-56.5”) was prepared by recrystallizing the aldehyde REFERENCES
from hexane. Infrared, u max (potassium bromide), 5.82 p
(C02C2H5); 5.95 p (CHO); 6.46 p (ring stretching); 8.5-8.9 p (1) R. E. Bambury, H. K. Yaktin and K. K. Wyckoff, J.
(CF3), NMR (deuteriochloroform), 6 1.44 (3H, triplet, J=7cps. Heterocyclic Chem., 5 , 9 5 (1968).
CH3CH20-); 6 4.50 (2H, quartet, J=7cps, CH~CHZO-);6 8.06 (2) 0. Dann, H. Distler and H. Merkel, Chem. Ber., 85, 457
(IH, singlet, ring proton 5 pos.); 6 10.3 (lH,singlet, -CHO). (1957).
Anal. Calcd. for C9H7F304: C, 4.5.77; H, 2.99; F, 24.14. (3) R. C. Elderfield and T. N . Dodd, in “Heterocyclic Com-
Found: C, 45.72; H, 2.85; F, 24.51. pounds,” Vol. I, R. C. Elderfield, Ed., John Wiley & Sons, Inc.,
A semicarbazone was prepared from I X in the usual fashion and New York, N. Y., 1950, Chapter 4, p. 132.
recrystallized from ethanol to give material, m.p. 243-246’; (4) A. P. Dunlop and C. D. Hurd, J. Org. Chem., 15, 1160
Anal. Calcd. for C10H10F3N304: C, 40.96; H, 3.44; F, (1950).
19.44; N, 14.33. Found: C, 41.15; H, 3.40; F, 19.34; N , 14.20. (5) K. Alder and H. F. Rickert, Chem. Ber., 70, 1354 (1937).
(6) R. Kuhn and H. Trischmann, ibid., 94,2258 (1961).
4-Trifluoromethyl-2-furfural( X ) .
(7) I. J. Cantlon, W. Cocker and T. B. H. McMurry, Tetra-
To a cooled solution of sodium ethoxide prepared from 5.86 g. hedron, 15, 46 (1961).
(0.255 g.-atom) of sodium and 450 ml. of absolute ethanol was ( 8 ) L. J. Bellamy, “The Infrared Spectra of Complex Mole-
added 28.0 g. of 2-nitropropane. The resulting solution was added cules,” 2nd Ed., John Wiley & Sons, Inc., New York, N. Y., 1958,
slowly to a well stirred solution of 58.3 g. (0.255 mole) of VIII and p.180.
50 mi. of absolute ethanol maintained at 55’. Addition required (9) H. B. Henbest and B. J. Lovel1,J. Chem. SOC.,1957 (1965).
3.5 hours and the heating was continued for an additional hour. (10) R. West, J. J. Korst and W. S. Johnson,J. Org. Chem., 25,
After adding 1.2 1. of water, the mixture was extracted three times 1976 (1960); T. C. Bruice and T. H. Fife,J. Am. Chem. SOC., 84,
with ether. The ether was evaporated and a sodium bisulfite com- 1973 (1962).
plex was prepared by treating the residual oil with e x c e s aqueous (11) H. B. Hass and M. L. Bender, ibid., 71,1767 (1949).
sodium bisulfite. The complex was collected by filtration, washed (12) K. Miura and H. K. Reckendorf, in “Progress in Medicinal
with ether and then decomposed with aqueous sodium bicarbonate. Chemistry”, G. P. Ellis and G. B. West, Ed., Plenum Press, New
Continuous extraction of the aqueous bicarbonate solution with York, N. Y., 1967, Chapter 6.
ether for four days yielded 14 g. (34%)of aldehyde. An analytical (13) E. T. McBee and T. M. Burton, J. A m . Chem. SOC., 74,
sample, b.p. 37-38’ at 19 mm., was prepared by distillation of the 3902 (1952).
aldehyde using a short path distillation apparatus. Infrared, v max
(neat), 3.55 p (CHO); 5.91 p (CHO); 6.22 p and 6.54 p (ring Received October 9. 1969 Ashland, Ohio 44805