Addition of halocarboxylic acids esters and halohydrocarbons to pentafluorobenzaldehyde promoted by iron pentacarbonyl

Article abstract of DOI:10.1007/s11178-006-0007-y

Iron pentacarbonyl is an efficient promoter of addition to the carbonyl group of pentafluorobenzene of alkyl α-halocarboxylates and alkyl halides. The electron-acceptor character of the pentafluorophenyl group essentially affects the course of reaction an

Full text of DOI:10.1007/s11178-006-0007-y

Russian Journal of Organic Chemistry, Vol. 41, No. 11, 2005, pp. 1615-1618. Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 11, 2005,
pp. 1649-1652.
Original Russian Text Copyright Ó 2005 by Terent’ev, Vasil’eva, Chakhovskaya, Mysova, Kochetkov.
.
Addition of Halocarboxylic Acids Esters and Halohydrocarbons
to Pentafluorobenzaldehyde Promoted by Iron Pentacarbonyl
A.B. Terent’ev, T.T. Vasil’eva, O.V. Chakhovskaya,
N.E. Mysova, and K.A. Kochetkov
Nesmeyanov Institute of Organoelemental Compounds, Russian Academy of Sciences, Moscow, 119991Russia
mail: terent@ineos.ac.ru
Received November 4, 2004
Abstract—Iron pentacarbonyl is an efficient promoter of addition to the carbonyl group of pentafluorobenzene of
alkyl a-halocarboxylates and alkyl halides. The electron-acceptor character of the pentafluorophenyl group
essentially affects the course of reaction and the nature of the arising products.
In reaction of nitrile IIa with aldehyde I at room
temperature we succeeded in detecting the formation of
bromohydroxynitrile IVa confirming the above scheme.
Note that both these reactions in the yields and the
character of products obtained proved to be similar to
the analogous reactions with benzaldehyde [5, 6].
Apparently due to the high efficiency of the functionally
substituted dibromo derivatives of esters or nitriles the
difference in the reactivity of benzaldehyde and penta-
fluorobenzaldehyde does not considerably affect the
course of the process.
We showed formerly [1–3] that Fe(CO)5 was an
efficient promotor of processes of Reformatsky and
Barbier type, and in some cases the yield of adducts
attained 80–95%. The reactions proceed under homo-
geneous conditions, do not require application of
anhydrous solvents and inert atmosphere. It was besides
established that the polar character of substituents in the
substrates (both in the aldehyde and in the organohalogen
compound) significantly affected the yield of the final
products and the direction of the reactions [3, 4]. The
involving into these reactions of pentafluorobenzaldehyde
(I) with a strong electron-acceptor pentafluorophenyl
group provides a possibility, on the one hand, to extend
the range of studies of the effect on the process of polar
characteristics of substituents in the aldehyde, and on the
other hand, taking into account the ready occurrence of
the reaction in the presence of Fe(CO)5 and the good
yields of adducts, to develop sufficiently efficient
preparative method of introducing the pentafluorophenyl
group into various polyfunctional compounds.
The reaction of aldehyde I with methyl 2-bromo-
propionate (Va), with the corresponding nitrile Vb, methyl
trichloroacetate (VI), and bromoform (VII) occurred
along another pattern yielding hydroxyester VIIIa and
hydroxynitrile VIIIb respectively. From the reaction
products obtained from aldehyde I and ester Va 1,2-di-
(pentafluorophenyl)-1,2-ethanediol (IX) was isolated
alongside hydroxyester VIIIa. The formation of product
like diol IX was not previously observed in this type
reactions.
The reactions of pentafluorobenzaldehyde (I) with
dibromoacetonitrile (IIa) or diethyl dibromomalonate (IIb)
proceeded in benzene at 80°C to give the corresponding
unsaturated compounds IIIa and IIIb whose structure
was confirmed by 1H, 19F, 13C NMR and mass spectra.
)Hꢁ&2ꢂ
,ꢀꢁꢀ0H&+ꢁ%Uꢂ5
& ) &+ꢁ2+ꢂ&+ꢁ0Hꢂ5
9 ꢂꢀ9E
9,,, ꢂꢀ9,,,E
& ) &+ꢀ2+ꢁ&+ꢀ2+ꢁ& )
,;
)Hꢁ&2ꢂ
R = CO2Me (a), CN (b).
& ) &+2ꢀꢀꢀ&%U ;<
>& ) &+ꢁ2+ꢂ&%U;<@
It is presumable that because of the strong electron-
withdrawing effect of the pentafluorophenyl group
aldehyde I is reduced a lot easier than the other aldehydes
with an electron transfer from the iron pentacarbonyl to
afford diol IX.
,9 ꢁꢂ,9E
,, ꢁꢂ,,E
,
& ) &+ &;<
+2%U
,,, ꢁꢂ,,,E
X = H, Y = CN (a), X = Y = CO Et (b).
2
1070-4280/05/4111-1615Ó2005 Pleiades Publishing, Inc.

TERENT'EV et al.
1616
The considerable competing process of diol IX forma-
These compounds were detected in the reaction
mixture by GC-MS method. The main product of the
reaction was diol IX in the form of two diastereomers in
a ~1:1 ratio. Allyl iodide (XV) with aldehyde I in the
presence of Fe(CO)5 furnished adduct XVI in a quanti-
tative yield; therewith at raising the temperature from
60°C to 80°C common for these processes the yield of
the product was reduced from 95 to 60%. It is possible
that at the higher temperature iodide XV partially
decomposed in the presence of Fe(CO)5.
tion reduces naturally the yield of the target hydroxyester
VIIIa. For instance, at the molar ratio of the reagents
(I):(Va) equal to 1:1 adduct VIIIa formed in a ~70%
yield, and diol IX in a 20% yield. At the same time using
the double amount of aldehyde I we obtained adduct
VIIIa in a quantitative yield and ~30% of compound IX
(calculated on the excess aldehyde).
It should be noted that 2-bromopropionitrile (Vb), more
reactive than ester Va, reacted with aldehyde I selectively
giving only adduct VIIIb.
)Hꢁ&2ꢂ
In reaction of ester VI with aldehyde I alongside the
formation of addition product X and unsaturated ester
XI we observed for the first time a second stage reaction
of adduct X with the second aldehyde I molecule to afford
«diadduct» XII.
&+ &+&+ ,
& ) &+ꢁ2+ꢂ&+ &+ &+
,ꢀꢀ
;9
;9,
This reaction does not take place at room temperature.
Note that in analogous reactions with the benzaldehyde
and p-chlorobenzaldehyde the yield of adducts did not
exceed 15–20%. We believe that here also the favorable
combination of polar factors plays the main role: The
pentafluorophenyl group sharply increases the
electrophilic character of aldehyde I considerably
facilitating its reaction with the allyl anion in the transition
iron-carbonyl complex A.
)Hꢁ&2ꢂ
& ) &+ꢁ2+ꢂ&&O &2 0H
,ꢀꢀꢀ&&O &2 0H
9,
;
& ) &+ &&O&2 0H
;,
)Hꢁ&2ꢂ
>& ) &+ꢁ2+ꢂ@ &&O&2 0H
,ꢀꢀꢀ;
;,,
)
)
;
)H
&
Ester XII can be obtained as the main product (yield
80–85%) applying 2 moles of aldehyde I per 1 mole of
ester VI.
2
&
)
+
+
+
)
)
Hydroxydichloroester X whose formation confirms the
above mentioned scheme can be obtained in a low yield
only in reaction in DMF at room temperature; at 80°C
only compounds XI and XII form in an overall yield ~80%.
The reaction with the benzaldehyde furnished only the
corresponding unsaturated ester of XI type in a 35%
yield [2].
&+ &+
$
The reactions with allyl bromide (XVII) are less
efficient and more complicated. At 60°C in benzene
adduct XVI formed in a 35% yield. However, the reaction
carried out in the presence of HMPAgave rise alongside
compound XVI with a terminal double bond also to its
isomer XVIII with a double bond in the position 2. This
fact is illustrated by comparison of the mass spectra. The
characteristic ion of compound XVI 197 [M – C3H5]+
(100) corresponds to the rupture of the C–allyl bond,
whereas in the mass spectrum of isomer XVIII ion 233
[M – Me]+ (100) arises in the first stage by elimination
The use of aldehyde I in Barbier reactions in the
presence of Fe(CO)5 also resulted in significantly different
behavior as compared to analogous processes with the
benzaldehyde. The reaction with bromoform (VII) gave
rise to adducts in keeping with the Barbier type process
affording hydroxydibromide XIII that partially underwent
elimination of a HOBr group giving unsaturated bromide
XIV.
)Hꢁ&2ꢂ
)Hꢂ&2ꢃ
;9,
&+ &+&+ %U
,ꢀꢀ
+03$
,ꢀꢁꢀ&+%U
& ) &+ꢂ2+ꢃ&+%U
;9,,
9,,
;,,,
& ) &+ꢁ2+ꢂ&+ &+&+
& ) &+ &+%U
+2%U
;9,,,
;,9
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 11 2005

ADDITION OF HALOCARBOXYLIC ACIDS ESTERS
1617
of a methyl group neighboring to the C=C bond. In the
reaction mixture was also identified diol IX.
chloric acid, washed with water, and dried on MgSO4.
The reaction products were isolated either by preparative
GLC or TLC (eluent petroleum ether–chloroform–ethyl
acetate, 8:1:1). Yields were determined by GLC using
standards.
In reaction of aldehyde I with perfluorobutyl iodide
(XIX) performed in the presence of pyridine the GC-MS
method revealed the formation of adduct XX in a low
yield (10–15%).
3-Pentafluorophenylacrylonitrile (IIIa). Reaction
1
temperature 80°C, yield 75%, mp 96–98°C. H NMR
)Hꢂ&2ꢃ ꢀ3\
spectrum, d, ppm (J, Hz): trans-isomer – 6.21, 6.29 d
(1H, =CHCN, J 17), 7.29, 7.37 d (1H, C6F5CH=, J 16);
cis-isomer – 5.88, 5.94 d (1H, =CHCN, J 12), 7.01,
7.07 d (1H, C6F5CH=, J 12). Mass spectrum, m/z (Irel,
,ꢀꢁꢀ&) ꢂ&) ꢃ ,
& ) &+ꢂ2+ꢃꢂ&) ꢃ &)
;;
;,;
The comparison of results obtained with those for the
corresponding reactions with the benzaldehyde [1, 2]
permits a conclusion that as a rule aldehyde I reacts more
efficiently than benzaldehyde: With allyl iodide the adduct
forms in a quantitative yield, aldehyde I reacts with
bromoform, the process with methyl trichloroacetate is
accompanied by side reactions and 1,3-diol formation; in
some cases 1,2-diol is obtained as a product of reductive
dimerization of aldehyde I.
%): 219 [M]+ (100), 192 [M – CN–H]+ (10), 168
.
+
+
.
.
[C6F5H] (12), 52 [M – C6F5] (3). Found, %: C 49.20;
H 1.20; F 43.4; N 6.25. C9H7F5N. Calculated, %: C 49.3;
H 1.0; F 43.4; N 6.4.
2-Bromo-3-hydroxy-3-pentafluorophenyl-
propionitrile (IVa). Reaction temperature 20°C, yield
16%. Mass spectrum, m/z (Irel, %): 315, 317 [M]+ (0.5),
219 [M – BrOH]+ (0.2), 197 [C6F5CH(OH)]+ (100).
Nitrile (IIIa), yield 6%.
It should be emphasized that Reformatsky and Barbier
reactions with the use of aldehyde I in some cases
provided preparative yields of products in the presence
of an uncommon for these reactions agent like iron
entacarbonyl.
Diethyl (pentafluorobenzylidene)malonate (IIIb).
1
Reaction temperature 80°C, yield 35%. H NMR
spectrum, d, ppm (J, Hz): 7.45 s (1H, CH=), 4.10 q (2H,
CH2O, J 18), 1.18 t (3H, CH3CH2, J 16). 13C NMR
spectrum, d, ppm: 163.6 (COO), 133.9–146.9 (Ar), 128.3
(C=), 62.7 (CH2O), 53.6 (CH=), 14.5 (CH3). Mass
EXPERIMENTAL
+
+
.
.
spectrum, m/z (Irel, %): 338 [M] (35), 310 [M – C2H4]
Mass spectra were measured on a GC-MS instrument
Finnigan Mat Magnum, column 25 m long (Ultra-2),
temperature programmed from 30 to 220°C at a rate
2.5 deg/min. GLC analysis was carried out on a chromato-
graph LKhM, steel column (1300 ´ 3 mm), stationary
phase 15% SKTFT-50X on Chromaton-N-AW, carrier
gas helium (60 ml/min), detector thermal-conductivity
detector, temperature programmed from 50 to 250°C at
+
+
.
(30), 293 [M – C2H5O] (78), 264 [M – HCO2Et] (100),
192 [M – 2CO2Et] (85), 143 [M – C6F5CH–CH3] (30),
+
+
.
45 [C2H5O]+ (40).
Methyl 2-methyl-3-hydroxy-3-pentafluoro-
phenylpropionate (VIIIa). Reaction temperature 80°C,
ratio of ester to aldehyde 1:1, yield 71%, nD20 1.4541, d240
1.4761. 1H NMR spectrum, d, ppm (J, Hz): 5.19 m (1H,
CHOH), 3.06 m (1H, CHCOO), 3.72 s, 3.56 s (3H,
CH3O), 3.00 m (1H, OH), 1.31, 1.27; 0.98 d, 0.94 d (3H,
CH3, J 16). 13C NMR spectrum, d, ppm: 174.5 (COO),
136.7–147.0 (Ar), 68.1 (CHO), 52.5 (CH3O), 45.3
(CHCOO), 14.0 (CH3C). Mass spectrum, m/z (Irel, %):
197 [C6F5CHOH]+ (63), 88 [CH3CH2CO2CH3]+ (100).
Found, %: C 46.25; H 3.20; F 33.8. C11H9F5O3.
Calculated, %: C 46.5; H 3.2; F 33.4.
a rate of 6 deg/min.
1H and 13C NMR spectra were
registered on a spectrom-eter Bruker WP-200 (200 MHz),
solvent CDCl3, chemical shifts were presented with
respect to TMS.
All organic reagents were subjected to distillation;
Fe(CO)5 purchased from Fluka was used without addi-
tional purification.
Reaction of pentafluorobenzaldehyde (I) with
halogen derivatives IIa, IIb, Va, Vb, VI, VII, XV,
XVII, and XIX. A solution of a mixture of 1 mmol of
halocompound, 1 mmol of aldehyde, 2 mmol of Fe(CO)5,
4 mmol of HMPA, and 1–2 drops of CCl3Br in 1 ml of
benzene was heated for 3–4 h at 80°C or kept for 3–5
days at room temperature. Then the reaction mixture was
diluted with 2 ml of benzene, treated with 1 N hydro-
1,2-Dipentafluorophenyl-1,2-ethanediol (IX).
1
Yield 21%, mp 152°C. H NMR spectrum, d, ppm
(J, Hz): 5.45 br.s (2H, CH), 3.15 s (2H, OH). Calculated:
5.32 (+/– 0.29), 3.97(+/– 0.97).
Ester VIIIa, reaction temperature 80°C, ratio of ester
to aldehyde 1:2, yield 95%; diol IX, yield 30% (calculated
on excess aldehyde).
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 11 2005

TERENT'EV et al.
1618
1H NMR spectrum, d, ppm (J, Hz): 5.60–5.81 m (1H,
CH=), 5.02–5.16 m (3H, CH2=, CH), 2.48–2.80 m (2H,
CH2), 2.38, 2.41 d (1H, OH, J 12). Mass spectrum, m/z
(Irel,%): 197 [M – C3H5]+ (100). Found, %: C 50.20;
H 3.14; F 39.60. C10H7F5O. Calculated, %: C 50.43;
H 2.96; F 39.88.
3-Hydroxy-2-methyl-3-pentafluorophenyl-
propionitrile (VIIIb). Reaction temperature 80°C, yield
75%, nD20 1.4611, d240 1.4774. 1H NMR spectrum, d, ppm
(J, Hz): 5.01 m (1H, CHOH), 3.20 m (1H, CHCN),
3.55 br.s (1H, OH), 1.47, 1.43; 1.18 d, 1.14 d (3H, CH3,
J 16). Found, %: C 47.6; H 2.6; F 37.6; N 5.6.
C10H6F5NO. Calculated, %: C 47.8; H 2.4; F 37.8;
N 5.6.
Adduct (XVI), reaction temperature 60°C, yield 95%;
reaction temperature 60°C, solvent benzene, yield 35%;
reaction temperature 60°C, solvent HMPA, yield 12%.
Mass spectrum, m/z (Irel, %): 197 [M – C3H5]+ (100); 1-
pentafluorophenyl-2-buten-1-ol (XVIII), yield 7%.
Mass spectrum, m/z (Irel, %): 238 [M]+. (95), 223 [M –
CH3]+ (100), 197 [M – C3H5]+ (35), 195 [M – C3H7]+
(75), 43 [C3H7]+ (85); diol IX, yield 11%.
Methyl di[hydroxy(pentafluorophenyl)methyl]-
chloroacetate (XII). Reaction temperature 80°C, ratio
of ester to aldehyde 1:1, yield 57%, mp 180°C. 1H NMR
spectrum, d, ppm (J, Hz): 5.47 s (2H, CHOH), 3.68 br.s
(2H, OH), 3.36 s (3H, CH3O). Mass spectrum, m/z (Irel,
%): 304 [M –C6F5C(OH)]+ (10), 286 [M–C6F5C(OH)–
OH, 1Cl]+ (100), 251 [M – C6F5C(OH) – OH – Cl]+
(75), 197 [C6F5CH(OH)]+ (80), 59 [CO2CH3]+ (25).
Found, %: C 41.20; H 1.35; Cl 6.90; F 36.60.
C17H7ClF10O4. Calculated, %: C 40.8; H 1.4; Cl 7.0;
F 38.0.
Adduct (XVI), reaction temperature 60°C, solvent
HMPA, reaction time 72 h, yield 10%; diol IX, yield
17%; adduct XVIII virtually absent.
1-Pentafluorophenyl-2,2,3,3,4,4,5,5,5-nona-
fluoropentan-1-ol (XX). Reaction temperature 65°C,
in the presence of 4 mmol of pyridine, yield ~15%. Mass
Methyl 3-pentafluorophenyl-2-chloroacrylate
(XI), yield 25%. Mass spectrum, m/z (Irel, %): 286 [M]+
.
+
+
.
.
spectrum, m/z (Irel, %): 416 [M] (1.8), 397 [M – F]
+
+
.
(85), 251 [M – Cl] (100), 192 [M – Cl – CO2Me] (90),
+
+
.
(1.05), 197 [M – C4F9] (100), 69 [CF3] (13.2).
59 [CO2Me]+ (35).
Ester XII, reaction temperature 80°C, ratio of ester
to aldehyde 2:1, yield 82%; ester XI, yield 11%.
REFERENCES
1. Terentiev,A.B., Vasilieva, T.T., Kuzmina, N.A., Mysov, E.I.,
Kuznetsov, N.Yu., and Belokon, Yu.N., J. Chem. Res. S., 1998,
pp. 306, 1281.
2. Terent’ev,A.B., Vasil’eva, T.T., Kuz’mina, N.A., Mysov, E.I.,
Kuznetsov, N.Yu., and Belokon’, Yu.N., Izv. Akad. Nauk,
Ser. Khim., 1999, p. 1132.
Methyl 3-hydroxy-3-pentafluorophenyl-2,2-
dichloropropionate (X). Reaction temperature 20°C,
+
.
yield 12%. Mass spectrum, m/z (Irel, %): 338 [M] (0),
+
+
.
251 [M – HOCl – Cl] (7), 197 [C6F5CH(OH)] (82),
142 [CHCl2CO2Me, 2Cl]+ (100); ester XII, yield 5%.
1,1-Dibromo-2-pentafluorophenylethanol (XIII).
Reaction temperature 80°C. Mass spectrum, m/z (Irel,
%): 370 [M]+ (0.9), 274 [M – BrOH]+ (0.7), 197
[C6F5CHOH]+ (100).
3. Vasil’eva, T., Mysova, N.E., Chakhovskaya, O.V., and
Terent’ev,A.B., Zh. Org. Khim., 2002, vol. 38, 1056.
4. Terent’ev, A.B., Vasil’eva, T.T., Kuz’mina, N.A., Myso-
va, N.E., and Chakhovskaya, O.V., Zh. Org. Khim., 2001,
vol. 37, p. 1341.
1-Bromo-2-pentafluorophenylethene (XIV). Mass
+
+
.
spectrum, m/z (Irel, %): 272 [M] (55), 193 [M – Br]
(100). Diol IX, diastereomers mixture at a ratio ~1:1,
yield 87%. 1H NMR spectrum, d, ppm (J, Hz): 5.45 br.s
(CH), 3.02 s (OH).
5. Vasil’eva, T.T., Kuz’mina, N.A., Chakhovskaya, O.V.,
Mysova, N.E., and Terent’ev, A.B., Zh. Org. Khim., 2004,
vol. 40, p. 199.
1-Pentafluorophenyl-3-buten-1-ol (XVI). Reaction
temperature 80°C, yield 60%, nD20 1.4580, d240 1.4220.
6. Terent’ev, A.B., Vasil’eva, T.T., Mysova, N.E., and
Chakhovskaya, O.V., Zh. Org. Khim., 2004, vol. 40, p. 965.
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 11 2005