A novel synthetic method for the preparation of aliphatic aldehydes from the corresponding carboxylic acids

Article abstract of DOI:10.1002/cjoc.201190110

A novel synthetic method for the preparation of aliphatic aldehydes from the corresponding carboxylic acids via 1,3-dimethylbenzimidazolium salts is provided. 1,3-Dimethylbenzimidazolium salts were rapidly reduced with sodium/ethanol and then hydrolyzed with hydrochloric acid to obtain aliphatic aldehydes, in which the 1,3-dimethylbenzimidazolium salts can be readily achieved from the corresponding carboxylic acids. The mechanism for the reductive reaction of 1,3-dimethylbenzimidazolium salts with sodium/ethanol was discussed.

Full text of DOI:10.1002/cjoc.201190110

FULL PAPER
A Novel Synthetic Method for the Preparation of Aliphatic Al-
dehydes from the Corresponding Carboxylic Acids
Guo, Yuan*,a,b(郭媛)
Lu, Zhenhuanb(陆振欢)
Yao, Liboa(药立波)
Shi, Zhenb(史真)
a Department of Biochemistry and Molecular Biology, The Fourth Military Medical University,
Xi'an, Shaanxi 710032, China
b College of Chemistry and Materials Science, Northwest University, Xi'an, Shaanxi 710069, China
A novel synthetic method for the preparation of aliphatic aldehydes from the corresponding carboxylic acids via
1,3-dimethylbenzimidazolium salts is provided. 1,3-Dimethylbenzimidazolium salts were rapidly reduced with so-
dium/ethanol and then hydrolyzed with hydrochloric acid to obtain aliphatic aldehydes, in which the
1,3-dimethylbenzimidazolium salts can be readily achieved from the corresponding carboxylic acids. The mecha-
nism for the reductive reaction of 1,3-dimethylbenzimidazolium salts with sodium/ethanol was discussed.
Keywords aliphatic aldehydes, 1,3-dimethylbenzimidazolium salts, reduction, sodium, synthetic method
Introduction
Scheme 1 General synthetic method of aliphatic aldehydes
from the corresponding carboxylic acids in literature
Aldehydes are an important class of compounds in
view of their distinct structural feature and wide utility
in organic synthesis.1 Many of the straight-chain "fatty"
aldehydes have been recognized as odor-imparting
components in natural compounds.2 A common ap-
proach to obtain aldehydes is in fact the oxidation of
primary alcohols or the reduction of carboxylic acids
and their derivatives. However, aldehydes are very sen-
sitive toward further oxidation to the corresponding
carboxylic acids or reduction to the corresponding al-
cohols. Therefore, a large number of aldehydes are not
available by direct oxidation or reduction. The devel-
opment of general, facile and convenient methods for
transformation of alcohols or carboxylic acids and their
derivatives into the corresponding aldehydes is one of
the most desirable subjects in organic synthesis.3
Scheme 2 The route of the novel synthetic method for prepara-
tion of aliphatic aldehydes
General synthetic method (Scheme 1) of aliphatic
aldehydes from the corresponding carboxylic acids in
literature involves the step of transformation of the car-
boxylic acids into the corresponding carboxylic acid
derivatives which subsequently are reduced.4
In this paper, we first converted carboxylic acids to
the corresponding aldehydes via the quaternary 1,3-
dimethylbenzimidazolium salts which were rapidly re-
duced with sodium/ethanol and then hydrolyzed with
hydrochloric acid to obtain aliphatic aldehydes. The
mechanism for the reductive reaction of 1,3-dimethyl-
benzimidazolium salts with sodium/ethanol was di-
scussed. A novel synthetic method for the preparation of
straight-chain “fatty” aldehydes is provided. The route
of the new synthetic method is shown in Scheme 2.
In our experiments, 2-substituted benzimidazoles
(1a— 1f) were effectively synthesized in few minutes
from the corresponding carboxylic acids and o-phenyl-
enediamine under microwave irradiation.5
1,3-Dimethylbenzimidazolium salts (2a— 2f) can be
*
E-mail: yuanorganic@163.com; Tel./Fax: 0086-029-88302122
Received September 28, 2010; revised January 7, 2011; accepted Jaunary 28, 2011.
Project supported by the National Natural Science Foundation of China (No. 21072158), the China Postdoctoral Science Foundation (No.
20070421139), the Special Foundation of the Education Committee of Shaanxi Province (No. 09JK750).
Chin. J. Chem. 2011, 29, 489— 492
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
489

Guo et al.
FULL PAPER
prepared via quaternization of the benzimidazoles (1a—
1f) with iodomethane in benzene.6 The quaternary ben-
zimidazolium salts (2a— 2f) were rapidly reduced with
sodium/ethanol and then hydrolyzed with hydrochloric
acid to obtain aliphatic aldehydes (3a— 3f), which were
directly converted into the corresponding 2,4-dinitro-
phenylhydrazones due to instability of aldehyde. Thus a
novel synthetic method for aliphatic aldehydes from the
corresponding carboxylic acids was accomplished.
Compound 2d White solid, yield 90%, m.p.
1
172—174 ℃; H NMR (CDCl3, 400 MHz) δ: 0.88 (t,
J＝6.8 Hz, 3H, CH3), 1.27—1.74 (m, 14H, 7×CH2),
3.57 (t, J＝8.2 Hz, 2H, N＝CCH2), 4.12 (s, 6H, 2×
NCH3), 7.61—7.70 (m, 4H, 4×Ar-H); IR (KBr) ν
:
max
3015, 2956, 2925, 2854, 1616 (νC=N), 1533, 1478, 1258,
＋
－1
767 cm ; MS m/z: 273 (M －I).
Compound 2e White solid, yield 88%, m.p.
1
167—168 ℃; H NMR (CDCl3, 400 MHz) δ: 0.88 (t,
J＝6.8 Hz, 3H, CH3), 1.25—1.74 (m, 18H, 9×CH2),
3.55 (t, J＝8.0 Hz, 2H, N＝CCH2), 4.12 (s, 6H, 2×
Experimental
NCH3), 7.61—7.72 (m, 4H, 4×Ar-H); IR (KBr) ν
:
max
Apparatus and materials
3015, 2953, 2924, 2852, 1615 (νC=N), 1534, 1479, 1262,
＋
－1
767 cm ; MS m/z: 301 (M －I).
Melting points were taken on an XT-4 micro-melting
apparatus (Beijing) and uncorrected. TLC analysis was
carried out on glass plates coated with silica gel-G, and
spots were visualized using an ultraviolet (UV) lamp.
Infrared (IR) spectra were recorded on a Bruck
EQUIOX-55 spectrometer (Germany). 1Proton magnetic
resonance (1H NMR) spectra were recorded at 400 MHz
on a Varian INOVA-400 spectrometer (USA), and
chemical shifts were reported relative to internal Me4Si.
All reagants of analytical grade were obtained from a
commercial source and used without further purifica-
tion.
Compound 2f White solid, yield 83%, m.p. 173—
1
174 ℃; H NMR (CDCl3, 400 MHz) δ: 0.88 (t, J＝6.6
Hz, 3H, CH3), 1.25—1.77 (m, 30H, 15×CH2), 3.53 (t,
J＝8.0 Hz, 2H, N＝CCH2), 4.12 (s, 6H, 2×NCH3),
7.60—7.75 (m, 4H, 4×Ar-H); IR (KBr) νmax: 3014,
2922, 2850, 1614 (νC=N), 1532, 1468, 1356, 1263, 765
－1
＋
cm ; MS m/z: 385 (M －I).
General procedure for the preparation of aliphatic
aldehydes (3a— 3f)
A solution of benzimidazolium salts (2 mmol) (2a—
2f) in ethanol (50 mL) was stirred in three-necked flask
under a nitrogen atmosphere. Small particles of sodium
(10 mmol) were added to the solution in batches at room
temperature under stirring. After 45 min, The reaction
mixture was quenched by 10 mL water and then acidify
by hydrochloric acid to pH＝4—5. The resulting mix-
ture was stirred at 60 ℃ for 1 h, then 2,4-dinitro-
phenylhydrazine reagent was added. Yellow precipitate
was appeared, filtered off and recrystallized from 95%
ethanol to give compounds 3a— 3f 2,4-dinitrophenyl-
hydrazone.
General procedure for the preparation of benzimi-
dazolium salts (2a—2f)
The 2-substituted benzimidazoles (1a — 1f) were
prepared from o-phenylenediamine and the corres-
ponding carboxylic acids under microwave irradiation
according to the literature.5 A solution of sodium (0.01
mol) in ethanol was treated with benzimidazoles (0.01
mol) (1a— 1f), iodomethane (0.03 mol) and benzene (12
mL), then the mixture was refluxed for 18 h. The sol-
vent was removed and the residue was recrystallized
from water (2a— 2d) or water-ethanol (V/V, 1∶ 1) (2e,
2f) to give benzimidazolium salts (2a— 2f).
Propionaldehyde (3a) 2,4-dinitrophenylhydra-
zone Yellow solid, yield 51.4%, m.p. 153—154 ℃
1
(Lit.7 154—155 ℃); H NMR (CDCl3, 400 MHz) δ:
Compound 2a White solid, yield 95%, m.p. 252
1
℃ (Lit.6 252 ℃); H NMR (CDCl3, 400 MHz) δ: 1.43
1.22 (t, J＝7.4 Hz, 3H, CH3), 2.44—2.51 (m, 2H, N＝
CCH2), 7.58 (t, J＝4.8 Hz, 1H, N＝CH), 7.93—9.13 (m,
3H, 3×Ar-H), 11.03 (s, 1H, NH); IR (KBr) νmax: 3423,
3292, 3109, 2984, 2924, 1616 (νC=N), 1585, 1510, 1453,
(t, J＝8.0 Hz, 3H, CH3), 3.63 (q, J＝7.7 Hz, 2H, N＝
CCH2), 4.14 (s, 6H, 2×NCH3), 7.26—7.70 (m, 4H, 4×
Ar-H); IR (KBr) νmax: 3020, 2962, 2935, 28＋50, 1608
－1
－1
1413, 1329, 1258, 850, 743, 716 cm ; MS m/z: 238
(νC=N), 1531, 1479, 768 cm ; MS m/z: 175 (M －I).
(M＋).
Compound 2b White solid, yield 91%, m.p.
1
Butyraldehyde (3b) 2,4-dinitrophenylhydrazone
230— 232 ℃; H NMR (CDCl3, 400 MHz) δ: 1.14 (t,
Yellow solid, yield 58.7%, m.p. 121—122 ℃ (Lit.8
J＝7.4 Hz, 3H, CH3), 1.80—1.89 (m, 2H, CH2), 3.57 (t,
J＝8.0 Hz, 2H, N＝CCH2), 4.14 (s, 6H, 2×NCH3),
7.61—7.72 (m, 4H, 4×Ar-H); IR (KBr) νmax: 3010,
1
122—123 ℃); H NMR (CDCl3, 400 MHz) δ: 1.03 (t,
J＝7.4 Hz, 3H, CH3), 1.62—1.71 (m, 2H, CH2), 2.40—
2.44 (m, 2H, N＝CCH2), 7.54 (t, J＝5.2 Hz, 1H, N＝
CH), 7.92—9.13 (m, 3H, 3×Ar-H), 11.03 (s, 1H, NH);
IR (KBr) νmax: 3449, 3296, 3088, 2954, 2928, 2869,
1620 (νC=N), 1590, 1518, 1422, 1331, 1218, 827, 763,
－1
2960, 2925, 2866, 1612 (νC=N), 1530, 1473, 760 cm ;
MS m/z: 189 (M＋－I).
Compound 2c White solid, yield 90%, m.p.
1
186—188 ℃ (Lit.6 182—184 ℃); H NMR (CDCl3,
＋
－1
742 cm ; MS m/z: 252 (M ).
400 MHz) δ: 0.90 (t, J＝7.0 Hz, 3H, CH3), 1.30—1.78
(m, 8H, 4×CH2), 3.54 (t, J＝8.0 Hz, 2H, N＝CCH2),
4.12 (s, 6H, 2×NCH3), 7.60—7.74 (m, 4H, 4×Ar-H);
IR (KBr) νmax: 3013, 2953, 2925, 2854, 16＋14 (νC=N),
Heptaldehyde (3c) 2,4-dinitrophenylhydrazone
Yellow solid, yield 68.5%, m.p. 107—108 ℃ (Lit.9
1
107—108 ℃); H NMR (CDCl3, 400 MHz) δ: 0.91 (t,
－1
J＝6.4 Hz, 3H, CH3), 1.33—1.42 (m, 6H, 3×CH2),
1532, 1475, 1251, 766 cm ; MS m/z: 231 (M －I).
490
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Chin. J. Chem. 2011, 29, 489— 492

A Novel Synthetic Method for the Preparation of Aliphatic Aldehydes
1.58—1.65 (m, 2H, CH2), 2.41—2.46 (m, 2H, N＝
CCH2), 7.54 (t, J＝5.2 Hz, 1H, N＝CH), 7.92—9.13 (m,
3H, 3×Ar-H), 11.03 (s, 1H, NH); IR (KBr) νmax: 3448,
3295, 3089, 2926, 2851, 1621 (νC=N), 1592, 1518, 1424,
Table 1 Yields of the compound 3d at different reductive reac-
tion temperatures
Entry
Temperature/℃
5—10
Yielda/%
73.8
＋
－1
1
2
3
4
1331, 1220, 829, 743, 723 cm ; MS m/z: 294 (M ).
Capraldehyde (3d) 2,4-dinitrophenylhydrazone
Yellow solid, yield 75.3%, m.p. 106—107 ℃ (Lit.10
104 ℃); 1H NMR (CDCl3, 400 MHz) δ: 0.88 (t, J＝6.8
Hz, 3H, CH3), 1.28—1.39 (m, 12H, 6×CH2), 1.58—
1.65 (m, 2H, CH2), 2.40—2.46 (m, 2H, N＝CCH2), 7.54
(t, J＝5.0 Hz, 1H, N＝CH), 7.92—9.13 (m, 3H, 3×
Ar-H), 11.02 (s, 1H, NH); IR (KBr) νmax: 3446, 3295,
3088, 2913, 2847, 1622 (νC=N), 1593, 1518, 1425, 1332,
20—25
74.5
40—45
75.3
70—75
75.6
a Yield of isolated 2,4-dinitrophenylhydrazone (3d); reaction time
is 45 min.
imidazolium salt described in this paper can be
reasonably explained by Scheme 3.
－1
＋
1221, 829, 743, 722 cm ; MS m/z: 336 (M ).
Lauraldehyde (3e) 2,4-dinitrophenylhydrazone
Scheme 3
Possible reaction mechanism of reduction of
Yellow solid, yield 78.0%, m.p. 105—106 ℃ (Lit.11
1,3-dimethylbenzimidazolium salt with sodium/ethanol
1
105—106 ℃); H NMR (CDCl3, 400 MHz) δ: 0.88 (t,
J＝6.6 Hz, 3H, CH3), 1.27—1.41 (m, 16H, 8×CH2),
1.58—1.65 (m, 2H, CH2), 2.41—2.46 (m, 2H, N＝
CCH2), 7.54 (t, J＝5.4 Hz, 1H, N＝CH), 7.92—9.13 (m,
3H, 3×Ar-H), 11.03 (s, 1H, NH); IR (KBr) νmax: 3295,
3090, 2914, 2847, 1621 (νC=N), 1593, 1518, 1466, 1425,
＋
－1
1331, 1221, 829, 763, 743 cm ; MS m/z: 364 (M ).
Stearaldehyde (3f) 2,4-dinitrophenylhydrazone
1
Yellow solid, yield 65.6%, m.p. 98—99 ℃; H NMR
(CDCl3, 400 MHz) δ: 0.88 (t, J＝6.6 Hz, 3H, CH3),
1.26—1.41 (m, 28H, 14×CH2), 1.58—1.65 (m, 2H,
CH2), 2.41—2.46 (m, 2H, N＝CCH2), 7.54 (t, J＝5.4
Hz, 1H, N＝CH), 7.92—9.13 (m, 3H, 3×Ar-H), 11.02
(s, 1H, NH); IR (KBr) νmax: 3295, 3090, 2916, 2848,
1620 (νC=N), 1592, 1518, 1467, ＋1425, 1330, 1220, 828,
The polarized C＝N bond of benzimidazolium salt
was first added two electron from two free radicals of
sodium to give a carbanion, followed by protonation
with ethanol to give benzimidazolidine, which can be
hydrolyzed in acidic solution to give the corresponding
aldehyde.
－1
764, 743 cm ; MS m/z: 448 (M ).
Results and discussion
The mechanism for the reductive reaction of ben-
zimidazolium salt
Two mechanisms universally accepted for the reduc-
tion of ketones with sodium/ethanol were suggested.12
One is thermodynamic control mechanism involving
carbanion intermediate. The other one is kinetic control
mechanism involving free radical intermediate.
The mechanism for the reductive reaction of ben-
zimidazolium salt with sodium/ethanol has not been
reported in literature. However, the reaction can be rea-
sonably explained by the above two mechanisms be-
cause the properties of the polarized C＝N bond of ben-
zimidazolium salt which belongs to good electron ac-
ceptor13 are similar to those of the C＝O bond of ke-
tone.
Conclusion
In conclusion, a novel synthetic method for aliphatic
aldehydes from the corresponding carboxylic acids was
provided. A reasonable mechanism for the reductive
reaction of 1,3-dimethylbenzimidazolium salts with so-
dium/ethanol was proposed. The present results will
help to facilitate the synthesis of various aldehydes.
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Chin. J. Chem. 2011, 29, 489— 492