Ultrasound effect on the synthesis of 4-alkyl-(aryl)aminobenzaldehydes

Article abstract of DOI:10.1016/S0040-4020(01)00403-3

The sonochemical nucleophilic aromatic substitutions on 4-fluorobenzaldehyde with different azacycloalkanes and azoles have been studied. A beneficial ultrasound effect was observed, reactions were clean and high yields of the products were isolated after 15 min sonication.

Full text of DOI:10.1016/S0040-4020(01)00403-3

TETRAHEDRON
Pergamon
Tetrahedron 57 ;2001) 4781±4785
Ultrasound effect on the synthesis of
4-alkyl-ꢀaryl)aminobenzaldehydes
p
Ï
Peter Magdolen, Maria Meciarova and Stefan Toma
Â
Ï
Â
Department of Organic Chemistry, Faculty of Natural Sciences, Comenius University, 842 15 Bratislava, Slovakia
Received 18 October 2000; revised 19 March2001; accepted 5 April 2001
AbstractÐThe sonochemical nucleophilic aromatic substitutions on 4-¯uorobenzaldehyde with different azacycloalkanes and azoles have
been studied. A bene®cial ultrasound effect was observed, reactions were clean and high yields of the products were isolated after 15 min
sonication. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
described by Cozzi et al.,3 using dimethylsulfoxide
;DMSO) as the solvent and potassium carbonate as the
base. We found out that a long reaction time is necessary
to achieve reasonable yields, and the reaction resulted in
rather impure products which were dif®cult to purify.
Exchange of potassium carbonate for dimethylaniline as
the base did not improve the achieved results. We therefore
decided to perform the sonochemical SNAr reactions of
4-¯uorobenzaldehyde with different azacycloalkanes and
azoles. Dimethylsulfoxide was used as the solvent and
potassium carbonate as the base ;Scheme 1). Control experi-
ments with some amines under thermal heating were also
performed. For all sonochemical experiments it was
characteristic that the temperature of the reaction mixture
rose very sharply up to 100±1408C during the ®rst 5±8 min
of sonication. Prolonging the sonication did not cause
further temperature rise, and in some cases even a drop in
reaction temperature was observed. From this observation it
follows that an exothermic reaction was started by sonica-
tion and further, that the reaction was, possibly, completed
after 8±10 min of sonication.
The synthesis of 4-alkylaminoacetophenones via the SNAr
reaction of 4-¯uoroacetophenone with appropriate amines
under potassium carbonate catalysis was described by Bader
et al.1 and Gale et al.2 Cozzi et al.3 claimed that SNAr
reactions on the haloarenes having mild electron-
withdrawing groups such as the formyl group needs rather
harsh conditions.
On the other hand Smith et al.4 described the ultrasound
acceleration of Ullmann diarylether synthesis, Hanoun et
al.5 described the ultrasound acceleration of Ullmann±
Goldberg synthesis of N-arylanthranilic acids and Cerrada
et al.6 described ultrasound acceleration of the SNAr
reaction of 4-nitro¯uorobenzene witha range of azoles.
The main aim of this work was to examine the
possible bene®cial ultrasound effect on the SNAr reactions
of 4-¯uorobenzaldehyde with different alicyclic as well as
aromatic amines.
Application of ultrasound shortened the reaction time from
5 hunder classical conditions to 15 min, and the yields of
the products were 15±30% higher than in the experiments
with 5 h thermal heating of the reaction mixture at 1008C.
2. Results and discussion
At the beginning of our work we checked the procedure
Scheme 1. Thermal heating plus stirring, 3±5 h 50±60% yields; sonochemical reaction, 15 min 70±95% yields.
Keywords: ultrasound; 4-dialkylaminobezaldehydes; nucleophilic aromatic substitutions.
Corresponding author. Tel.: 1421-7-60296208; fax: 1421-7-60296690; e-mail: toma@fns.uniba.sk
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020;01)00403-3

4782
P. Magdolen et al. / Tetrahedron 57 +2001) 4781±4785
Scheme 2.
Lower yields of the products in experiments with aziridine
or 1-methylaziridine ;24%) were due to the low stability of
the three-membered ring. Indirect proof of this was the
formation of tarry material. Lower yields in the case of
N-monoalkylpiperazines can be caused by the fact that
products are oils and an extraction procedure has to be
implemented for their isolation.
reaction withpyrrole. The potential intermediate of this
reaction ;aminoalcohol) underwent reaction with a second
molecule of 4-¯uorobenzaldehyde and gave 10% of 4-;4-
¯uoro-a-pyrrol-1-ylbenzyloxy)benzaldehyde. This reaction
route is depicted in Scheme 2.
Our results ;Table 1) indicate that ultrasound considerably
enhances the SNAr substitution of the ¯uorine on 4-¯uoro-
benzaldehyde with different alicyclic as well as aromatic
amines, catalyzed by potassium carbonate. One can assume
that catalysis is caused by very powerful micro-streaming,
which accompanies implosions of micro-bubbles and
provides effective mass transfer. Potassium carbonate
particles are disrupted and its active surface is therefore
considerably enlarged, which means that the catalytic
activity of potassium carbonate is also enhanced. This
hypothesis is con®rmed by the experiment when potassium
carbonate was sonicated 15 min in DMSO, then 4-¯uoro-
benzaldehyde and azetidine were added and the reaction
was performed under heating at 1008C and magnetic stirring
for 15 min. The yield of this reaction was 78% instead of
95% ;the yield of the sonochemical reaction). The yield of
the silent reaction without ultrasonic activation of potassium
carbonate was 58% after 5 h. If this is the case then a similar
effect should be observed if the reaction is performed in
UltraTurax, as foreseen by Reisse.7
Ultrasound had also another positive effectÐthe products
were very pure. Usual work-up of the reaction mixture with
water afforded, in many cases, analytically pure materials.
Chromatographic separation of the product was necessary
just in the case of the reactions with aziridine or 1-methyl-
aziridine and 1,2,3-benzotriazole, when a 3:1 mixture of
positional isomers is formed. Unsuccessful experiments of
SNAr substitution withindole and pyrrole were also
obtained. No substitution product was detected by 1H
NMR spectroscopy in the experiments with indole and
just approximately 10% of the product was isolated in the
Table 1. 4-Alkyl-;aryl)aminobenzaldehydes
Entry
R
Yield ;%)
1
2
Aziridin-1-yl
Azetidin-1-yl
24
81
3. Conclusion
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
2-Methylaziridin-1-yl
Pyrrolidin-1-yl
Piperidin-1-yl
Hexamethylenimin-1-yl
Morpholin-4-yl
Thiomorpholin-4-yl
4-Methylpiperazin-1-yl
4-Heptylpiperazin-1-yl
4-Octylpiperazin-1-yl
4-Ethoxycarbonylpiperazin-1-yl
7,15-Diazadispiro[5.1.5.3]hexadecane-15-yl
Pyrrol-1-yl
Imidazol-1-yl
1,2,4-Triazol-1-yl
5-Methylsulfanyltetrazol-1-yl
3,5-Bis-methylsulfanyl-1,2,4-triazol-1-yl
Benzimidazol-1-yl
24
92 ;62a)
85 ;48a)
Application of ultrasonic irradiation in the nucleophilic
aromatic substitutions of 4-¯uorobenzaldehyde with
different azacycloalkanes and azoles allows ;i) a shortening
of the reaction time from 5 h to 15 min, ;ii) increased yields
and ;iii) simpli®cation of work-up of the reaction mixtures
after the reactions.
95 ;58a, 78b)
60 ;60a)
45
73 ;57a)
64
51
39 ;70a)
72 ;31a)
10
75
49
2
4. Experimental
The 1H NMR spectra were recorded at 300 MHz on a Varian
Gemini spectrometer in CDCl3 withtetramethylsilane as an
internal standard. The 13C NMR spectra were recorded at
75 MHz in CDCl3. The IR spectra were recorded on a
Perkin±Elmer 1600 FT-IR instrument as 2% solutions in
chloroform and the elemental analyses were recorded on a
Carlo-Erba instrument. Melting points were determined on
a Ko¯er hot stage and uncorrected. All sonochemical
2
80
17
55
Benzotriazol-1-yl
Benzotriazol-2-yl
a
Yields of classical SNAr reactions.
b
Reaction performed under classical conditions ;heating at 1008C,
magnetic stirring for 15 min) withsonocehmically activated K 2CO3
;K2CO3 was sonicated 15 min in DMSO).

P. Magdolen et al. / Tetrahedron 57 +2001) 4781±4785
4783
experiments were carried out in a glass reactor ®tted to an
ultrasonic horn ULTRAGEN ;20 kHz, 300 W) for 15 min
under an air atmosphere.
4.4. Synthesis of 4-ꢀbenzotriazol-1-yl)benzaldehyde and
4-ꢀbenzotriazol-2-yl)benzaldehyde
Potassium carbonate ;4.42 g; 0.032 mol) was added to
the solution of 1,2,3-benzotriazole ;3.57 g; 0.03 mol) and
4-¯uorobenzaldehyde ;3.72 g; 0.03 mol) in DMSO
;20 mL). The reaction mixture was sonicated for 10 min
and then cooled to room temperature. The solid reaction
mixture was suspended in distilled water ;200 mL) and
the crude product ;5.9 g; mp 138±1488C) was ®ltered off
with suction. This product was puri®ed by chromatography
on silica using isohexane:ethyl acetate 1:1, and later with
pure chloroform as the eluent.
Starting materials were either commercially available or
prepared according to literature procedures. Aziridine and
1-methylaziridine were prepared according to Ref. 8,
azetidine according to Ref. 9 and N-ethoxycarbonylpipera-
zine according to Ref. 10. N-Alkylpiperazines were
prepared by the following procedure.
4.1. Synthesis of N-alkylpiperazines
The appropriate iodoalkane ;0.1 mol) was added dropwise
over 10 min to a solution of anhydrous piperazine ;21.5 g,
0.25 mol) in anhydrous methanol ;60 mL). The reaction
mixture was left for one day at room temperature and the
solid piperazine hydrogeniodide was ®ltered off and
the ®ltrate was concentrated under reduced pressure. The
residual oil was dissolved in diethyl ether ;150 mL) and
washed twice with aqueous 3 M sodium hydroxide
;100 mL). The ether solution was dried over Na2SO4, and
ether evaporated on a rotary vacuum evaporator, with the
residue being distilled bulb to bulb on a Buchi instrument at
8 mmHg pressure.
4.4.1. 4-ꢀAziridin-1-yl)benzaldehyde. Pale yellow solid,
0.71 g, 24%, mp 31±328C; [Found: C, 73.2; H, 6.1; N,
9.6. C9H9NO requires C, 73.45; H, 6.16; N, 9.52%]; Rf
;ethyl acetate) 0.49; nmax ;CHCl3) 2998, 2739, 1694,
1665, 1602, 1574, 1508, 1335, 1305, 1153, 907,
843 cm21; dH ;300 MHz CDCl3) 9.88 ;1H, s, CHO), 7.77
;2H, d, Jˆ8.7 Hz, ArZH), 7.11 ;2H, d, Jˆ8.7 Hz, ArZH),
2.22 ;4H, s, 2£CH2 aziridin); dC ;75 MHz, CDCl3) 191.3,
161.3, 131.5, 121.5, 27.9.
4.4.2. 4-ꢀAzetidin-1-yl)benzaldehyde. Yellow solid,
2.61 g, 81%, mp 33±348C; [Found: C, 74.4; H, 6.7; N,
8.8. C10H11NO requires C, 74.51; H, 6.88; N, 8.69%]; Rf
;ethyl acetate) 0.6; nmax ;CHCl3) 2865, 2745, 1678, 1598,
1557, 1528, 1481, 1391, 1305, 1159, 834, 823 cm21; dH
;300 MHz CDCl3) 9.72 ;1H, s, CHO), 7.70 ;2H, d,
Jˆ8.7 Hz, ArZH), 6.38 ;2H, d, Jˆ8.7 Hz, ArZH), 4.03
;4H, t, Jˆ7.5 Hz, 2£CH2 azetidin), 2.44 ;2H, m, CH2 azeti-
din); dC ;75 MHz, CDCl3) 190.4, 155.1, 132.0, 125.7, 109.7,
51.4, 16.5.
4.2. The general procedure for classical SNAr reactions
on 4-¯uorobenzaldehyde
Potassium carbonate ;3.04 g; 0.022 mol) was added to the
solution of appropriate secondary cyclic amine ;0.02 mol)
and 4-¯uorobenzaldehyde ;2.48 g; 0.22 mol) in DMSO
;20 mL). The reaction mixture was heated at 1008C for
3±5 h. The reaction mixture was then poured into water
;400 mL) and the emulsion formed was extracted three
times into diethyl ether ;75 mL). The ether solution was
washed with water, dried over anhydrous Na2SO4, ether
was distilled off on a rotary vacuum evaporator and the
crude product was chromatographed on silica using
isohexane:ethyl acetate 9:1±2:1 as the eluent.
4.4.3. 4-ꢀ2-Methylaziridin-1-yl)benzaldehyde. Colourless
oil, 0.77 g, 24%; [Found: C, 74.3; H, 6.9; N, 8.7. C10H11NO
requires C, 74.51; H, 6.88; N, 8.69%]; Rf ;ethyl acetate)
0.59; nmax ;CHCl3) 2978, 2799, 1700, 1605, 1587, 1513,
1410, 1308, 1245, 1162, 846 cm21; dH ;300 MHz CDCl3)
9.86 ;1H, s, CHO), 7.76 ;2H, d, Jˆ8.4 Hz, ArZH), 7.07
;2H, d, Jˆ8.4 Hz, ArZH), 2.29 ;1H, m, CH3CH methyl-
aziridin), 2.18 ;1H, d, Jˆ6.0 Hz, NCHaHb, methylaziridin),
2.13 ;1H, d, Jˆ3.3 Hz, NCHaHb, methylaziridin), 1.40 ;3H,
d, Jˆ5.7 Hz, CHCH3); dC ;75 MHz, CDCl3) 190.8, 160.7,
131.2, 121.0, 35.4, 34.9, 18.1.
4.3. The general procedure for sonochemical SNAr
reactions on 4-¯uorobenzaldehyde
Potassium carbonate ;3.04 g; 0.022 mol) was added to the
solution of appropriate secondary cyclic amine ;0.02 mol)
and 4-¯uorobenzaldehyde ;2.48 g; 0.022 mol) in DMSO
;20 mL). The reaction mixture was sonicated for 15 min.
The temperature of the reaction mixture attained 1508C at
the end of sonication. The reaction mixture was cooled
down to 608C and then poured into distilled water
;400 mL). The emulsion formed was extracted three times
into diethyl ether ;75 mL). The ether solution was washed
withwater, dried over anyhdrous Na 2SO4, ether was
distilled off on a rotary vacuum evaporator and the product
was collected by ®ltration with suction. In the case where
the product was an oil or not pure enough ;TLC) it was
puri®ed by chromatography on silica using isohexane:ethyl
acetate 9:1±2:1 as the eluent. The results are given in the
Table 1.
4.4.4. 4-ꢀPyrrolidin-1-yl)benzaldehyde. White solid,
3.22 g, 92%, mp 79±828C, lit.11 84±858C; [Found: C,
75.5; H, 7.6; N, 8.1. C11H13NO requires C, 75.39; H, 7.48;
N, 8.00%]; Rf ;ethyl acetate) 0.62; nmax ;CHCl3) 2978, 2856,
2739, 1675, 1597, 1553, 1530, 1485, 1393, 1351, 1187,
1168 cm21; dH ;300 MHz CDCl3) 9.72 ;1H, s, CHO), 7.73
;2H, d, Jˆ8.7 Hz, ArZH), 6.57 ;2H, d, Jˆ8.7 Hz, ArZH),
3.39 ;4H, m, 2£H2, 2£H5 pyrrolidin), 2.05 ;4H, m, 2£H3,
2£H4 pyrrolidin); dC ;75 MHz, CDCl3) 190.3, 152.0, 132.2,
124.8, 111.2, 47.7, 25.4.
4.4.5. 4-ꢀPiperidin-1-yl)benzaldehyde. White solid,
3.22 g, 85%, mp 60±618C, lit.11 62±648C; [Found: C,
76.2; H, 8.1; N, 7.3. C12H15NO requires C, 76.14; H, 7.99;
N, 7.40%]; Rf ;ethyl acetate) 0.64; nmax ;CHCl3) 2939, 2928,
2741, 1664, 1592, 1560, 1518, 1436, 1393, 1361, 1172,

4784
P. Magdolen et al. / Tetrahedron 57 +2001) 4781±4785
1
12
1127, 1024, 919 cm21; H NMR data consistent withlit.;
dC ;75 MHz, CDCl3) 190.4, 155.2, 132.0, 126.1, 113.3,
48.4, 25.4, 24.4.
1080, 1002 cm21; dH ;300 MHz CDCl3) 9.82 ;1H, s,
CHO), 7.79 ;2H, d, Jˆ8.5 Hz, ArZH), 6.93 ;2H, d,
Jˆ8.5 Hz, ArZH), 4.19 ;2H, q, Jˆ7.2 Hz, CH2CH3), 3.66
;4H, m, 2£CH2 piperazin), 3.41 ;4H, m, 2£CH2 piperazin),
1.29 ;3H, t, Jˆ7.2 Hz, CH2CH3); dC;75 MHz, CDCl3)
190.5, 155.4, 154.8, 131.9, 127.6, 113.9, 61.7, 47.1, 43.1,
14.7.
4.4.6. 4-ꢀHexamethylenimin-1-yl)benzaldehyde. Yellow
solid, 3.86 g, 95%, mp 358C; [Found: C, 76.7; H, 8.4; N,
6.7. C13H17NO requires C, 76.80; H, 8.43; N, 6.89%]; Rf
;ethyl acetate) 0.65; IR data constistent with lit.;13 1H
12
NMR data consistent withlit.;
190.2, 155.2, 131.9, 126.1, 113.0, 48.3, 27.7, 26.0.
dC ;75 MHz, CDCl3)
4.4.13. 4-ꢀ7,15-Diazodispiro[5.1.5.3]hexadecan-15-yl)-
benzaldehyde. Yellow solid, 4.70 g, 72%, mp 85±868C;
[Found: C, 77.4; H, 9.4; N, 8.6. C21H30N2O requires C,
77.26; H, 9.26; N, 8.58%]; Rf ;ethyl acetate) 0.32; nmax
;CHCl3) 2930, 2857, 1602, 1508, 1477, 1444, 1425, 1047,
929 cm21; dH ;300 MHz CDCl3) 9.72 ;1H, s, CHO), 7.72
;2H, d, Jˆ9.1 Hz, ArZH), 6.83 ;2H, d, Jˆ9.1 Hz, ArZH),
3.28 ;4H, s, NCH2C), 1.50 ;20H, sb, 5£CH2 cykl); dC
;75 MHz, CDCl3) 190.0, 149.8, 131.0, 125.9, 110.5, 58.9,
48.9, 32.6, 25.3, 21.7.
4.4.7. 4-ꢀMorpholin-4-yl)benzaldehyde. White solid,
2.29 g, 60%, mp 62±648C, lit.11 61±638C; [Found: C,
69.2; H, 6.9; N, 7.2. C11H13NO2 requires C, 69.08; H,
6.86; N, 7.33%]; Rf ;ethyl acetate) 0.52; nmax ;CHCl3)
2839, 2750, 1690, 1666, 1600, 1566, 1519, 1450, 1382,
1
2
1173, 1122, 929 cm21; H NMR data consistent withlit.;
dC ;75 MHz, CDCl3) 190.5, 155.2, 131.8, 127.7, 113.5,
66.5, 47.3.
4.4.14. 4-ꢀPyrrol-1-yl)benzaldehyde. White solid, 0.34 g,
10%, mp 92±948C, lit.16 94±958C; [Found: C, 77.0; H, 5.2;
N, 8.3. C11H9NO requires C, 77.17; H, 5.30; N, 8.18%]; Rf
4.4.8. 4-ꢀThiomorpholin-4-yl)benzaldehyde. Yellow solid,
1.87 g, 45%, mp 35±408C; [Found: C, 63.6; H, 6.1; N, 6.6;
S, 15.3. C11H13NOS requires C, 63.75; H, 6.33; N, 6.76; S,
15.44%]; Rf ;ethyl acetate) 0.64; nmax ;CHCl3) 2741, 1688,
;ethyl acetate) 0.15; IR data consistent with lit.;14 1H NMR
14
data consistent withlit.;
145.3, 133.3, 131.6, 120.0, 119.1, 112.0.
dC ;75 MHz, CDCl3) 190.9,
1666, 1598, 1561, 1519, 1433, 1393, 1359, 1170, 954 cm21
;
dH ;300 MHz CDCl3) 9.78 ;1H, s, CHO), 7.75 ;2H, d,
Jˆ9.0 Hz, ArZH), 6.87 ;2H, d, Jˆ9.0 Hz, ArZH), 3.84
;4H, m, CH2ZSZCH2), 2.71 ;4H, m, CH2ZNZCH2); dC
;75 MHz, CDCl3) 190.3, 153.8, 132.1, 126.4, 113.7, 50.3,
25.8.
4.4.15. 4-ꢀImidazol-1-yl)benzaldehyde. White solid,
2.58 g, 75%, mp 1508C, lit.17 146±1478C, lit.18 149±
1508C; [Found: C, 69.5; H, 4.8; N, 16.1. C10H8N2O requires
C, 69.76; H, 4.68; N, 16.27%]; Rf ;ethyl acetate) 0.14; nmax
;CHCl3) 2988, 2737, 1704, 1607, 1585, 1519, 1485, 1302,
1170, 1110, 1054, 835 cm21; 1H NMR data consistent with
lit.;14 dC ;75 MHz, CDCl3) 191.0, 142.0, 135.7, 135.3,
131.9, 131.6, 121.4, 117.9.
4.4.9. 4-ꢀ4-Methylpiperazin-1-yl)benzaldehyde. Yellow
solid, 2.98 g, 73%, mp 57±608C; [Found: C, 70.4; H, 8.0;
N, 13.6. C12H16N2O requires C, 70.56; H, 7.89; N, 13.71%];
Rf ;ethyl acetate) 0.09; nmax ;CHCl3) 2945, 2808, 2751,
1687, 1666, 1599, 1563, 1519, 1450, 1393, 1381, 1292,
4.4.16. 4-ꢀ1,2,4-Triazol-1-yl)benzaldehyde. White solid,
1.70 g, 49%, mp 146±148C, lit.19 148±1498C; [Found: C,
62.3; H, 3.9; N, 24.1. C9H7N3O requires C, 64.42; H, 4.07;
N, 24.26%]; Rf ;ethyl acetate) 0.33; nmax ;CHCl3) 2744,
1705, 1607, 1590, 1519, 1501, 1408, 1303, 1281, 1168,
1173, 1143, 1007, 923 cm21 1H NMR data consistent
;
14
withlit.;
127.1, 113.5, 54.7, 47.1, 46.1.
dC ;75 MHz, CDCl3) 190.4, 155.0, 131.9,
1
4.4.10. 4-ꢀ4-Heptylpiperazin-1-yl)benzaldehyde. Pale
yellow solid, 3.69 g, 64%, mp 27±308C; [Found: C, 75.1;
H, 9.7; N, 9.6. C18H28N2O requires C, 74.96; H, 9.78; N,
9.71%]; Rf ;ethyl acetate) 0.45; nmax ;CHCl3) 2931, 2855,
1690, 1667, 1599, 1563, 1519, 1453, 1390, 1312, 1173,
1142, 1048, 980, 953, 835 cm21; H NMR data consistent
14
withlit.; dC ;75 MHz, CDCl3) 190.3, 152.8, 140.8, 1407,
135.1, 131.0, 119.5.
4.4.17. 4-ꢀ5-Methylsulfanyltetrazol-1-yl)benzaldehyde.
White solid, 90 mg, 2%, mp 96±978C; [Found: C, 49.0;
H, 3.5; N, 25.3; S, 14.4. C9H8N4OS requires C, 49.08; H,
3.66; N, 25.44, S, 14.56%]; Rf ;hexane/ethyl acetate 3:1)
0.26; nmax ;CHCl3) 2962, 2932, 2860, 2742, 1706, 1605,
1510, 1413, 1399, 1285, 1164, 1130, 1075, 1040, 991,
837 cm21; dH ;300 MHz CDCl3) 10.10 ;1H, s, CHO), 8.31
;2H, d, Jˆ8.9 Hz, ArZH), 8.09 ;2H, d, Jˆ8.9 Hz, ArZH),
2.78 ;3H, s, SCH3); dC ;75 MHz, CDCl3) 191.0, 142.6,
141.0, 133.8, 131.0, 130.4, 17.0.
1
15
1129, 1005; H NMR data consistent withthe lit.;
;75 MHz, CDCl3) 190.4, 155.1, 131.9, 127.0, 113.4, 58.7,
dC
52.9, 47.1, 31.8, 29.3, 27.5, 26.9, 22.7, 14.1.
4.4.11. 4-ꢀ4-Octylpiperazin-1-yl)benzaldehyde. Yellow
solid, 3.09 g, 51%, mp 22±258C; [Found: C, 75.3; H, 9.9;
N, 9.4. C19H30N2O requires C, 75.45; H, 10.00; N, 9.26%];
Rf ;ethyl acetate) 0.46; nmax ;CHCl3) 2929, 2856, 1683,
1668, 1600, 1563, 1519, 1455, 1389, 1292, 1173, 1129,
1
15
1006; H NMR data consistent withlit.;
dC ;75 MHz,
CDCl3) 190.4, 155.1, 131.9, 127.0, 113.4, 58.7, 52.9, 47.1,
31.9, 29.5, 29.3, 27.6, 26.9, 22.7, 14.1.
4.4.18. 4-ꢀ3,5-Bis-methylsulfanyl-1,2,4-triazol-1-yl)benz-
aldehyde. White solid, 0.11 g, 2%, mp 84±858C; [Found: C,
49.9; H, 4.0; N, 16.00; S, 24.0. C11H11N3OS2 requires C,
49.79; H, 4.18; N, 15.84; S, 24.16%]; Rf ;hexane/ethyl
acetate 3:1) 0.20; nmax ;CHCl3) 2934, 2740, 1704, 1604,
1512, 1454, 1434, 1363, 1302, 1275, 1168, 1009,
841 cm21; dH ;300 MHz CDCl3) 10.06 ;1H, s, CHO), 8.01
;2H, d, Jˆ8.7 Hz, ArZH), 7.83 ;2H, d, Jˆ8.7 Hz, ArZH),
4.4.12. 4-ꢀEthoxycarbonylpiperazin-1-yl)benzaldehyde.
White solid, 2.05 g, 39%, mp 49±518C; [Found: 64.2; H,
6.8; N, 10.6. C14H18N2O3 requires C, 64.11; H, 6.92; N,
10.68%]; Rf ;ethyl acetate) 0.52; nmax ;CHCl3) 2747,
1689, 1600, 1565, 1518, 1433, 1386, 1287, 1172, 1127,

P. Magdolen et al. / Tetrahedron 57 +2001) 4781±4785
4785
2.76 ;3H, s, SCH3), 2.65 ;3H, s, SZCH3); dC ;75 MHz,
CDCl3) 191.1, 163.1, 155.4, 142.0, 135.5, 131.1, 123.1,
16.0, 14.4.
Institute of Chemistry of Comenius University for 1H
NMR analyses. This work was supported by VEGAÐ
Grant Agency, Grant No 1/4166/97Ðand the auspicies
COSTÐChemistry Project No D-10/0008/98.
4.4.19. 4-ꢀBenzimidazol-1-yl)benzaldehyde. White solid,
3.56 g, 80%, mp 106±1088C, lit.20 100±1018C; [Found: C,
75.5; H, 4.4; N, 12.6. C14H10N2O requires C, 75.66; H, 4.54;
N, 12.60%]; Rf ;ethyl acetate) 0.32; nmax ;CHCl3) 2966,
2741, 1705, 1603, 1578, 1516, 1494, 1455, 1377, 1292,
1169, 976, 835 cm21; dH ;300 MHz CDCl3) 10.12 ;1H, s,
CHO), 8.21 ;1H, s, H2 benzimidazol), 8.13 ;2H, d,
Jˆ8.4 Hz, ArZH), 7.92 ;1H, m, H4 benzimidazol), 7.75
;2H, d, Jˆ8.4 Hz, ArZH), 7.64 ;1H, m, H benzimidazol),
7.40 ;2H, m, H5, H6 benzimidazol); dC ;75 MHz, CDCl3)
190.7, 141.8, 135.3, 131.7, 123.7, 124.3, 123.5, 121.1,
110.5, 144.4, 133.0.
References
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3.69 g, 55%, mp 159±1608C, lit.19 156±1588C; [Found: C,
70.0; H, 4.1; N, 18.6. C13H9N3O requires C, 69.95; H, 4.06;
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837 cm21
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4.4.21. 4-ꢀBenzotriazol-2-yl)benzaldehyde. White solid,
1.14 g, 17%, mp 189±1918C, lit.19 193±1958C; [Found: C,
70.1; H, 4.0; N, 18.6. C13H9N3O requires C, 69.95; H, 4.06;
N, 18.82%]; Rf ;chloroform) 0.36; IR data consistent with
2
lit.;2 1H NMR data consistent withlit.; dC ;75 MHz,
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CDCl3) 191.0, 145.4, 144.2, 136.1, 131.0, 128.0, 120.9,
118.6.
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4.4.22. 4-ꢀ4-Fluoro-a-pyrrol-1-ylbenzyloxy)benzalde-
hyde. White solid, 0.24 g, 10%; mp 126±1278C ;from
cyclohexane) [Found: C, 73.3; H, 4.7; N, 4.8; F, 6.5.
C18H14FNO2 requires C, 73.16; H, 4.75; N, 4.75; F,
6.44%]; Rf ;hexane/ethyl acetate 3:1) 0.27; nmax ;CHCl3)
2742, 1697, 1599, 1582, 1511, 1305, 1159, 1083, 1015,
833; dH ;300 MHz CDCl3) 9.90 ;1H, s, CHO), 7.82 ;2H,
d, Jˆ8.7 Hz, ArZH), 7.36 ;2H, d, Jˆ9.0 Hz, ArZH), 7.14
;2H, d, Jˆ8.7 Hz, ArZH), 7.09 ;2H, d, Jˆ9.0 Hz, ArZH),
6.93 ;1H, s, NCHO), 6.83 ;2H, t, Jˆ2.4 Hz, H2, H5 pyrrol),
6.25 ;2H, t, Jˆ2.4 Hz, H3, H4 pyrrol); dC ;75 MHz, CDCl3)
191.0, 163.5, 161.7, 133.6, 132.2, 128.4, 119.7, 117.1,
116.1, 110.2, 86.9; dF ;282 MHz, CDCl3) 2111.8.
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Acknowledgements
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The authors thank Dr E. Solcaniova and her staff of the