Convenient syntheses of unsymmetrical imidazolidines

Article abstract of DOI:10.1021/jo010868n

Unsymmetrical imidazolidines 10-14, optically active imidazolidines 20-22, and 2,3-dihydro-1H benzimidazoles 28 and 29 were synthesized in good to excellent yields by Mannich reactions of 1,2-ethanediamines 8a-c, 18a-c, or N-methyl-1,2-benzenediamine (26a) with benzotriazole and formaldehyde, followed by the nucleophilic substitution of the benzotriazolyl group with C- nucleophiles (Grignard reagents, sodium cyanide), an S-nucleophile (benzenethiol), and a P-nucleophile (triethyl phosphite).

Full text of DOI:10.1021/jo010868n

J . Org. Chem. 2002, 67, 3109-3114
3109
Con ven ien t Syn th eses of Un sym m etr ica l Im id a zolid in es
Alan R. Katritzky,* Kazuyuki Suzuki, and Hai-Ying He
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida,
Gainesville, Florida 32611-7200
katritzky@chem.ufl.edu
Received August 24, 2001
Unsymmetrical imidazolidines 10-14, optically active imidazolidines 20-22, and 2,3-dihydro-1H-
benzimidazoles 28 and 29 were synthesized in good to excellent yields by Mannich reactions of
1,2-ethanediamines 8a -c, 18a -c, or N-methyl-1,2-benzenediamine (26a ) with benzotriazole and
formaldehyde, followed by the nucleophilic substitution of the benzotriazolyl group with C-
nucleophiles (Grignard reagents, sodium cyanide), an S-nucleophile (benzenethiol), and a P-
nucleophile (triethyl phosphite).
Sch em e 1
In tr od u ction
Imidazolidines 1 are important building blocks in
biologically active compounds,1 and carriers of pharma-
cologically active carbonyl compounds.2 Symmetrical
imidazolidines 1 (R1 ) R2 ) Ar) were prepared early, by
Bischoff3a in 1898 and by Scholtz3b in 1901, by condensa-
tions of N,N′-diaryl-1,2-ethanediamines 2 with formal-
dehyde (Scheme 1). The same methodology was applied
to synthesize other symmetrical 1,3-diarylimidazolidines
1 (R1 ) R2 ) Ar)4 and 1,3-dialkylimidazolidines 1 (R1 )
R2 ) alkyl or allyl) from N,N′-dialkyl-1,2-ethanediamines
2.5 Another route to symmetrical imidazolidines 1 in-
volves the reduction of symmetrical cyclic ureas with
LiAlH4.6 Reactions of 1,3,6,8-tetraazatricyclo[4.4.1.13,8]-
dodecane with para-substituted phenols afford sym-
metrical 1 in about 21-28% yields.7 Mannich reactions
of 1,2-ethanediamine, benzotriazole, and formaldehyde
led to 1,3-bis(benzotriazolylmethyl)imidazolidine (3), which
easily undergoes nucleophilic substitutions with Grignard
reagents to afford symmetrical 1 (Scheme 1).8
tained three 1-phenyl-3-alkylimidazolidines 1 (R1 ) Ph,
R2 ) alkyl) by the reaction of formaldehyde with N-alkyl-
N′-phenyl-1,2-ethanediamines 4 (Scheme 1), obtained by
the condensation of â-aminosulfonic acids (need to be
prepared) and primary amines.10 Lambert synthesized
three unsymmetrical imidazolidines 1 (in ca. 25% overall
yields) from diethyl oxalate (5) via selective amidations
of 5 with primary amines, LiAlH4 reduction of the
corresponding oxamides to unsymmetrical N,N′-disub-
stituted 1,2-ethanediamines, and final reactions with
formaldehyde (Scheme 1).9 Perillo11 recently prepared two
1-benzyl-3-arylimidazolidines from formaldehyde and
N-benzyl-N′-aryl-1,2-ethanediamines 6, produced by the
BH3 reduction of the corresponding N-benzoyl-N′-aryl-
1,2-ethanediamines 7 (Scheme 1).12
These and other reported methods generally introduce
R1 and R2 (alkyl or aryl) groups into the imidazolidine
ring directly from N,N′-disubstituted 1,2-ethanediamines.
It is difficult to convert such N-alkyl or N-aryl substit-
uents into other functionalities. We have shown that the
weak C-N bond of N-substituted benzotriazoles allows
easy replacement of the benzotriazolyl group via nucleo-
philic substitution, elimination, reduction, cyclization,
etc.13 We now report a simple and efficient way to prepare
novel unsymmetrical imidazolidines 10-14 and optically
active imidazolidines 20-22 in good to excellent yields
As pointed out by Lambert,9 relatively few papers have
been published on the preparation of unsymmetrical
N,N′-disubstituted imidazolidines. In 1977, Kliegel ob-
* To whom correspondence should be addressed.
(1) (a) Sharma, V.; Crankshaw, C. L.; Piwnica-Worms, D. J . Med.
Chem. 1996, 39, 3483. (b) Sage, C. R.; Michelitsch, M. D.; Stout, T. J .;
Biermann, D.; Nissen, R.; Finer-Moore, J .; Stroud, R. M. Biochemistry
1998, 37, 13893. (c) Olmos, G.; Ribera, J .; Garcia-Sevilla, J . A. Eur. J .
Pharm. 1996, 310, 273. (d) Chang-Fong, J .; Benamour, K.; Szymonski,
B.; Thomasson, F.; Morand, J .-M.; Cussac, M. Chem. Pharm. Bull.
2000, 48, 729. (e) Rogers, J . A.; Choi, Y. W. Pharm. Res. 1993, 10,
913. (f) Sakuta, H.; Okamoto, K. Eur. J . Pharm. 1994, 259, 223.
(2) (a) Crank, G.; Harding, D. R. K.; Szinai, S. S. J . Med. Chem.
1970, 13, 1212. (b) Crank, G.; Harding, D. R. K.; Szinai, S. S. J . Med.
Chem. 1970, 13, 1215.
(3) (a) Bischoff, C. A. Chem. Ber. 1898, 31, 3248. (b) Scholtz, M.;
J aross, K. Chem. Ber. 1901, 34, 1504.
(4) J aenicke, L.; Brode, E. Liebigs Ann. Chem. 1959, 624, 120.
(5) (a) Donia, R. A.; Shotton, J . A.; Bentz, L. O.; Smith, G. E. P., J r.
J . Org. Chem. 1949, 14, 952. (b) Heaney, H.; Papageorgiou, G.; Wilkins,
R. F. Tetrahedron 1997, 53, 14381.
(6) Bates, H. A.; Condulis, N.; Stein, N. L. J . Org. Chem. 1986, 51,
2228.
(7) Rivera, A.; Gallo, G. I.; Gayon, M. E.; J oseph-Nathan, P. Synth.
Commun. 1993, 23, 2921.
(8) Katritzky, A. R.; Pilarski, B.; Urogdi, L. J . Chem. Soc., Perkin
Trans. 1 1990, 541.
(10) Kliegel, W.; Franckenstein, G.-H. Liebigs Ann. Chem. 1977, 956.
(11) Salerno, A.; Hedrera, M. E.; D’Accorso, N. B.; Alho, M. M.;
Perillo, I. A. J . Heterocycl. Chem. 2000, 37, 57.
(9) Lambert, J . B.; Huseland, D. E.; Wang, G.-T. Synthesis 1986,
657.
(12) Orelli, L. R.; Salerno, A.; Hedrera, M. E.; Perillo, I. A. Synth.
Commun. 1998, 28, 1625.
10.1021/jo010868n CCC: $22.00 © 2002 American Chemical Society
Published on Web 04/06/2002

3110 J . Org. Chem., Vol. 67, No. 9, 2002
Katritzky et al.
Sch em e 2a ,b
Ta ble 1. P r ep a r a tion of 1,3-Disu bstitu ted Im id a zolid in es
11a -l
yield
(%)
11
R1
Ph
Ph
Ph
Ph
Ph
Ph
Et
R2 a
n-Bu
CH2CH2Ph
CH2Ph
C6H4OMe-p
CtCPh
CHdCH2
CH2Ph
C6H4Me-p
CH2Ph
CHdCH2
CtCPh
methodb
a
b
c
d
e
f
g
h
i
80
96
96
81
80
75
75
71
79
63
65
80
A, 1.4 equiv of GRc
A, 1.2 equiv of GR
A, 2.0 equiv of GR
A, 1.2 equiv of GR
A, 1.2 equiv of GR
A, 1.2 equiv of GR
B, 2.0 equiv of GR
B, 2.0 equiv of GR
B, 2.0 equiv of GR
B, 2.0 equiv of GR
B, 1.2 equiv of GR
B, 1.6 equiv of GR
Et
PhCH2
PhCH2
PhCH2
PhCH2
j
k
l
n-C5H11
a
R2MgBr was used except in the case of 11c,g,i when
b
PhCH2MgCl was used. Method A: in THF (10 mL), rt 0.5 h and
then reflux 1 h. Method B: in toluene (10 mL), rt 0.5 h and then
1 h at 50 °C. c GR ) Grignard reagent.
a
Reagents and conditions: (i) NaBH4 (R1 ) Ph); (ii) R2MgX;
(iii) NaCN; (iv) PhSH/NaH (R1 ) Ph); (v) P(OEt)3/ZnBr2 (R1 ) Ph).
Bt ) benzotriazol-1-yl and -2-yl.
benzylmagnesium chloride in dry THF or toluene fur-
nished novel unsymmetrical 1,3-disubstituted imidazo-
lidines 11a -l in 63-96% yields. The isolated yields and
the reaction conditions for 11 are summarized in Table
1. Compounds 11g-l easily decompose on silica gel, so
they were isolated by neutral aluminum oxide column
chromatography. The structures of 11a -l were clearly
b
and extend this methodology for the preparation of 2,3-
dihydro-1H-benzimidazoles 28 and 29 using benzotria-
zole as a synthetic auxiliary.
Resu lts a n d Discu ssion
1
supported by their H and 13C NMR spectra and micro-
analyses or HRMS results. The methylene protons be-
tween the two nitrogens in 11a -f appear at around 4.0
ppm as singlets.
P r ep a r a tion of 1-Su bstitu ted 3-(ben zotr ia zolyl-
m eth yl)im id a zolid in es 9a -c. Mannich condensations
of N-substituted 1,2-ethanediamines 8a -c with 1 equiv
of benzotriazole and 2 equiv of formaldehyde (37%
aqueous solution) in MeOH/H2O at room temperature
gave 1-substituted 3-(benzotriazolylmethyl)imidazol-
idines 9a -c in 96%, 85%, and 92% yields, respectively
(Scheme 2). Compound 9a was initially obtained as a sole
Bt1 isomer; in CDCl3, it gradually changes to a mixture
of Bt1 and Bt2 isomers in a ca. 5.6:1 ratio after 3 days.
Compounds 9b,c were obtained as mixtures of Bt1 and
Bt2 isomers, each in a ca. 5:1 ratio. On the bais of our
previous results showing a small difference in the
reactivity of the Bt1 and Bt2 isomers,14 9b,c were used
directly as mixtures for the subsequent reactions. In the
13C NMR spectrum of 9a , the 145.8 ppm peak is believed
to contain two carbons, since it changes to two signals
(145.0 and 146.0 ppm, respectively) in DMSO-d6. Benzo-
triazolyl intermediates 9a -c were used as crude products
for the subsequent reactions.
Nu cleop h ilic Su bstitu tion s of 9a -c w ith Na BH4,
Gr ign a r d Rea gen ts, Sod iu m Cya n id e, Ben zen eth i-
ol, a n d Tr ieth yl P h osp h ite. (Cf. Scheme 2.) Treatment
of 9a with 2 equiv of sodium borohydride in refluxing
THF replaced the Bt group with hydrogen to give
1-phenyl-3-methylimidazolidine (10) in 96% yield. The
methylene protons between the two nitrogen atoms in
10 appear at 3.97 ppm as a singlet.
We previously reported that the benzotriazolyl group
attached to the R-position to a nitrogen is easily replaced
by nucleophilic reagents.15 Nucleophilic substitutions
of 9a -c with alkyl-, vinyl-, aryl-, and (phenylethynyl)-
magnesium bromide and, for the preparation of 11c,g,i,
The benzotriazolyl group in 9a -c can be substituted
by a cyano anion to furnish 2-(3-substituted 1-imidazo-
lidinyl)acetonitriles 12a -c in 77-97% yields. Reaction
of 9a with benzenethiol in the presence of sodium hydride
produced 1-phenyl-3-(phenylthiomethyl)imidazolidine (13)
in 66% yield. The benzotriazolyl group in 9a was replaced
in the presence of ZnBr2 by a P-nucleophile (triethyl
phosphite) to afford diethyl (3-phenyl-1-imidazolidinyl)-
methylphosphonate (14) in 70% yield. The Lewis acid
ZnBr2 facilitates loss of the benzotriazolyl anion to form
an iminium cation, which is then attacked by the
P-nucleophile.15c Thus, various useful functionalities were
introduced to the imidazolidine ring system via the
nucleophilic substitutions of the benzotriazolyl group as
a synthetic auxiliary.
Syn th eses of Op tica lly Active Im id a zolid in es. (Cf.
Scheme 3.) We further investigated the preparation of
optically active imidazolidines starting from commercially
available N-Boc-R-amino acids 15a -c. On the basis of
our recent paper,16 R-amino amides 17a -c were easily
obtained in two steps from the optically active N-Boc-R-
amino acids 15a -c (R3 ) Me, i-Bu, or PhCH2) and
4-methylphenylamine. Crombie and Hooper reduced
2-amino-N-phenylpropanamide with LiAlH4 to 2-amino-
propylaniline without reporting a detailed procedure.17
We found that refluxing of 17b (R3 ) i-Bu) with 3 equiv
of LiAlH4 in dry THF for 1 day gave a 1:1 mixture of 17b
and 18b. When 6 equiv of LiAlH4 in dry THF for 2 days
was used, reduction of 17a -c afforded chiral diamines
(15) (a) Katritzky, A. R.; Yannakopoulou, K.; Lue, P.; Rasala, D.;
Urogdi, L. J . Chem. Soc., Perkin Trans. 1 1989, 225. (b) Katritzky, A.
R.; Mehta, S.; He, H.-Y.; Cui, X. J . Org. Chem. 2000, 65, 4364. (c)
Katritzky, A. R.; Qiu, G.; He, H.-Y.; Yang, B. J . Org. Chem. 2000, 65,
3683.
(13) For a review of using benzotriazole as an auxiliary for organic
syntheses, see: Katritzky, A. R.; Lan, X.; Yang J . Z.; Denisko, O. V.
Chem. Rev. 1998, 98, 409.
(14) (a) Katritzky, A. R.; Rachwal, S.; Hitchings, G. J . Tetrahedron
1991, 47, 2683. (b) Katritzky, A. R.; Mehta, S.; He, H.-Y. J . Org. Chem.
2001, 66, 148.
(16) Katritzky, A. R.; Xu, Y.-J .; He, H.-Y.; Steel, P. J . J . Chem. Soc.,
Perkin Trans. 1 2001, 1767.
(17) Crombie, L.; Hooper, K. C. J . Chem. Soc. 1955, 3010.

Convenient Syntheses of Unsymmetrical Imidazolidines
J . Org. Chem., Vol. 67, No. 9, 2002 3111
Sch em e 3a
Sch em e 4a
a
Reagents and conditions: (i) p-O2NC6H4CHO; (ii) BtH, HCHO.
Sch em e 5
a
Reagents and conditions: (i) ClCOOBu-i, N-methylmorpholine;
(ii) HCl/Et2O (2 M); (iii) aq NaOH.
18a -c in more than 90% yields. Intermediates 16a -c,
17a -c, and 18a -c were all used as crude products
without further purification for subsequent reactions.
Reaction of diamines 18a -c with benzotriazole and
formaldehyde generated benzotriazol-1-yl intermediates
19a -c in 85%, 93%, and 93% yields, respectively. Nu-
cleophilic substitutions of 19a -c by Grignard reagents,
triethyl phosphite, or sodium cyanide gave optically
active imidazolidines 20a -d , 21, or 22 in 66-99% yields.
ther treated with sodium cyanide to afford 2-[3-ethyl-2-
(4-nitrophenyl)-1-imidazolidinyl]acetonitrile (25) in 92%
yield (Scheme 4).
P r ep a r a tion of 3-Su bstitu ted 1-Meth yl-2,3-d ih y-
d r o-1H-ben zim id a zoles 28 a n d 29. 2,3-Dihydro-1H-
benzimidazoles are usually prepared by the condensa-
tions of the corresponding N,N′-disubstituted 1,2-benzene-
diamines with formaldehyde.19 We previously reported
the formation of 1,3-bis(benzotriazolylmethyl)-2,3-dihy-
dro-1H-benzimidazole on the treatment of 1,2-benzene-
diamines with benzotriazole and formaldehyde.20 We now
find that condensation of N-methyl-1,2-benzenediamine
(26a ) with benzotriazole and 2 equiv of formaldehyde
produces Bt intermediate 27 in 85% yield (Scheme 5).
Compound 27 was obtained as a mixture of Bt1 and Bt2
isomers in a ca. 5.9:1 ratio, which was used directly for
the subsequent reactions.
1
The structures of 20-22 are supported by their H and
13C NMR spectra and microanalyses. The two diaste-
reotopic methylene hydrogens at the 5-position appear
at different chemical shifts due to the 4-postion chirality.
For 20a and 21, irradiation of the annular CH3 caused a
distinct positive NOE effect for one of the methylene
hydrogens at the 5-position; thus, this hydrogen at a
higher field is assigned to be the anti-hydrogen Ha. We
did not attempt to assign Ha and Hb for 20b-d and 22
because of their overlapping with other protons; however,
we believe that their anti-Ha would be upfield by analogy
to what was observed for 20a and 21.
Reaction of 27 with vinylmagnesium bromide was
found to give unidentifiable products probably opening
the five-membered ring. The weaker nucleophile vinyl-
zinc bromide (prepared from vinylmagnesium bromide
and zinc chloride) gave 1-allyl-3-methyl-2,3-dihydro-1H-
benzimidazole (28) in 83% yield. Compound 28 is ex-
tremely sensitive to silica gel or neutral Al2O3; it was
finally purified by flash column chromatography on basic
Al2O3. It also easily decomposes in CDCl3 with disap-
pearance of the NCH2N methylene group, so its NMR
Mod ifica tion of th e 2-P osition of th e Im id a zoli-
d in e Rin g. Following a previously reported procedure,18
a 4-nitrophenyl group was introduced onto the imidazo-
lidine ring at the 2-position by the reaction of N-ethyl-
1,2-ethanediamine with 4-nitrobenzaldehyde using azeo-
tropic distillation. To avoid the formation of chain
tautomers due to possible ring-chain tautomerism,18 we
did not attempt using N-phenyl-1,2-ethanediamine (8a )
as the starting material. Compound 23 exists only in its
cyclic form since no spectral evidence for the open
tautomer was observed.
Reaction of 23 with 1 equiv of benzotriazole and
formaldehyde gave Bt intermediate 24, which was fur-
(19) (a) Morgan, G. T.; Challenor, W. A. P. J . Chem. Soc. 1921, 1537.
(b) Harvey, I. W.; McFarlane, M. D.; Moody, D. J .; Smith, D. M. J .
Chem. Soc., Perkin Trans. 1 1988, 1939.
(20) Katritzky, A. R.; Rachwal, S.; Wu. J . Can. J . Chem. 1990, 68,
446.
(18) Parrinello, G.; Mu¨lhaupt, R. J . Org. Chem. 1990, 55, 1772.

3112 J . Org. Chem., Vol. 67, No. 9, 2002
Katritzky et al.
colorless flakes (from Et2O); yield 96%; mp 33-34 °C (lit.10 mp
spectra were recorded in DMSO-d6. Treatment of 27 with
2 equiv of NaCN produced a 94% yield of 2-(3-methyl-
2,3-dihydro-1H-benzimidazol-1-yl)acetonitrile (29), which
was also purified by flash basic Al2O3 column chroma-
tography. Compounds 28 and 29 are both labile to air,
so they may be used in situ for other transformations,
since their crude NMR spectra and GC analyses show
more than 90% purity. In the absence of mechanistic
studies, a possible reason for instability is that com-
pounds 28 and 29 are readily oxidized.
Condensation of 26b (R ) Ph) with benzotriazole and
formaldehyde (1 or 2 equiv) only generated the acyclic
intermediate 30 possibly due to the increased steric
hindrance caused by the PhNHAr fragment. The Bt
group in 30 was further substituted by cyano anion to
furnish 2-(2-anilinoanilino)acetonitrile (31) in 77% yield.
In summary, a short and efficient method has been
developed for the preparation of unsymmetrical imida-
zolidines and 2,3-dihydro-1H-benzimidazoles via Man-
nich reactions of diamines with benzotriazole and form-
aldehyde, followed by the nucleophilic substitutions of
the benzotriazolyl group with other functionalities. Com-
pared to the previous methods (multiple steps and low
yields) for the preparation of unsymmetrical imidazoli-
dines,9-11 our method needs only two steps, utilizes easily
available starting materials, and generally affords the
desired products in good to excellent yields.
1
32-34 °C); H NMR δ 2.48 (s, 3H), 2.96 (t, J ) 6.3 Hz, 2H),
3.42 (t, J ) 6.3 Hz, 2H), 3.97 (s, 2H), 6.53 (d, J ) 7.8 Hz, 2H),
6.69 (t, J ) 7.3 Hz, 1H), 7.23 (t, J ) 7.3 Hz, 2H); 13C NMR δ
40.8, 46.3, 54.8, 71.8, 111.4, 116.1, 129.2, 146.4.
Gen er a l P r oced u r e for th e Nu cleop h ilic Su bstitu tion s
of 9a -c w ith Gr ign a r d Rea gen ts. To a solution of 1-sub-
stituted 3-(benzotriazolylmethyl)imidazolidine 9a-c (1.0 mmol)
in dry THF or toluene (10 mL) at 0 °C was added dropwise an
appropriate Grignard reagent. The amount of the Grignard
reagent and the subsequent reaction conditions are collected
in Table 1. After being cooled, the mixture was quenched with
water and extracted with Et2O. The combined extracts were
washed with 1 M NaOH and brine and dried over anhyd
MgSO4. After removal of the solvents in vacuo, the residue
was purified by column chromatography (silica gel) with
hexanes/EtOAc as an eluent to give 1,3-disubstituted imida-
zolidine 11a -f. Compounds 11g-l were purified by neutral
Al2O3 column chromatography.
Da ta for 1-P en tyl-3-p h en ylim id a zolid in e (11a ): color-
1
less oil; yield 80%; H NMR δ 0.91 (t, J ) 6.3 Hz, 3H), 1.34-
1.40 (m, 4H), 1.53-1.58 (m, 2H), 2.55 (t, J ) 7.5 Hz, 2H), 2.95
(t, J ) 6.3 Hz, 2H), 3.40 (t, J ) 6.3 Hz, 2H), 3.98 (s, 2H), 6.48
(d, J ) 8.2 Hz, 2H), 6.68 (t, J ) 7.3 Hz, 1H), 7.22 (t, J ) 7.7
Hz, 2H); 13C NMR δ 14.0, 22.6, 28.5, 29.6, 46.1, 52.9, 54.7, 70.3,
111.3, 116.0, 129.1, 146.4. Anal. Calcd for C14H22N2: C, 77.01;
H, 10.16; N, 12.83. Found: C, 77.30; H, 10.49; N, 13.14.
Da ta for 1-Eth yl-3-p h en eth ylim id a zolid in e (11g): color-
less oil; yield 75%; 1H NMR δ 1.10 (t, J ) 7.5 Hz, 3H), 2.56 (q,
J ) 7.4 Hz, 2H), 2.78-2.86 (m, 8H), 3.46 (s, 2H), 7.19-7.31
(m, 5H); 13C NMR δ 14.1, 35.8, 49.3, 52.2, 52.5, 57.4, 76.4,
126.0, 128.3, 128.6, 140.1. Anal. Calcd for C13H20N2: C, 76.42;
H, 9.87. Found: C, 76.53; H, 9.77.
Exp er im en ta l Section
Da ta for 1-Ben zyl-3-p h en eth ylim id a zolid in e (11i): col-
orless oil; yield 79%; 1H NMR δ 2.76 (br s, 4H), 2.84 (br s, 4H),
3.44 (s, 2H), 3.70 (s, 2H), 7.19-7.33 (m, 10H); 13C NMR δ 35.8,
52.3, 52.5, 57.1, 59.5, 76.5, 126.0, 126.9, 128.2, 128.3, 128.4,
128.5, 139.2, 140.1. Anal. Calcd for C18H22N2: C, 81.16; H, 8.32;
N, 10.52. Found: C, 81.21; H, 8.63; N, 10.31.
Gen er a l P r oced u r e for t h e R ea ct ion of 9a -c w it h
Na CN. A mixture of 9a -c (1.0 mmol) and NaCN (0.050 g, 1.0
mmol) in DMSO (5 mL) was stirred at 25 °C for 20 h. The
mixture was poured into 20 mL of water. For 12a , the
precipitate formed was filtered to give a white powder, which
was recrystallized from EtOH. For 12b,c, the mixture was
extracted with CH2Cl2, and the organic extracts were washed
with 1 M NaOH, water, and brine and dried over anhyd
MgSO4. After removal of the solvent in vacuo, the residue was
purified by column chromatography to give 12b,c.
THF or toluene was distilled from sodium-benzophenone
prior to use. Melting points are uncorrected. 1H and 13C NMR
spectra were recorded (300 and 75 MHz, respectively) in CDCl3
(with TMS for 1H and chloroform-d for 13C as the internal
reference), unless otherwise stated. Elemental analyses were
performed on a Carlo Erba-1106 instrument. Optical rotation
values were measured with the use of the sodium D line.
Column chromatography was performed on silica gel (200-
425 mesh), neutral alumina (60-325 mesh), or basic alumina
(60-325 mesh). All of the reactions were carried out under
N2.
Gen er a l P r oced u r e for th e P r ep a r a tion of 1-Su bsti-
tu ted 3-(Ben zotr ia zolylm eth yl)im id a zolid in es 9a -c. A
mixture of an N-substituted 1,2-ethanediamine, 8a -c (3.0
mmol), BtH (0.36 g, 3.0 mmol), and formaldehyde (37%
aqueous solution, 0.49 g, 6 mmol) in CH3OH/H2O (10 mL/5
mL) was stirred for 4 h at 20 °C. For 9a , the precipitate formed
was filtered and washed with cool Et2O. For 9b,c, the mixture
was extracted with EtOAc, and the organic fraction was
washed with 1 M NaOH and brine and dried over anhyd Na2-
SO4. Removal of the solvents in vacuo gave 9b,c as an oil. Bt
intermediates 9a -c were used as crude products for the
subsequent reactions.
Data for 2-(3-P h en yl-1-im idazolidin yl)aceton itr ile (12a):
white microcrystals (from EtOH); yield 77%; mp 65-66 °C;
1H NMR δ 3.15 (t, J ) 6.2 Hz, 2H), 3.49 (t, J ) 6.2 Hz, 2H),
3.74 (s, 2H), 4.15 (s, 2H), 6.51 (d, J ) 8.1 Hz, 2H), 6.75 (t, J )
7.3 Hz, 1H), 7.25 (t, J ) 7.9 Hz, 2H); 13C NMR δ 40.6, 46.2,
51.3, 68.6, 111.7, 114.9, 117.0, 129.3, 145.9. Anal. Calcd for
C
11H13N3: C, 70.56; H, 7.00; N, 22.44. Found: C, 70.31; H,
7.14; N, 22.45.
Data for 1-(1H-1,2,3-Ben zotr iazolylm eth yl)-3-ph en ylim -
id a zolid in e (9a ): white microcrystals (from CHCl3/hexanes);
yield 96%; mp 123-124 °C; 1H NMR δ 3.20 (t, J ) 6.1 Hz,
2H), 3.35 (t, J ) 6.1 Hz, 2H), 4.24 (s, 2H), 5.62 (s, 2H, Bt1-
CH2), 6.43 (d, J ) 7.9 Hz, 2H), 6.70 (t, J ) 7.2 Hz, 1H), 7.19
(t, J ) 7.7 Hz, 2H), 7.37 (t, J ) 7.5 Hz, 1H), 7.51 (t, J ) 7.5
P r oced u r e for th e Nu cleop h ilic Su bstitu tion of 9a
w ith Ben zen eth iol. To a solution of benzenethiol (0.13 g, 1.2
mmol) in dry THF (10 mL) was added NaH (60% in mineral
oil, 0.05 g, 1.3 mmol), and the mixture was stirred at 20 °C
for 10 min. One drop of methanol was added to quench excess
NaH, and then 9a (0.28 g, 1.0 mmol) was added. The mixture
was refluxed for 38 h. After removal of THF in vacuo, the
residue was extracted with Et2O. The organic extracts were
washed with 2 M NaOH and brine and dried over anhyd
MgSO4. The desired compound was purified by column chro-
matography with hexanes/EtOAc (4:1) as an eluent.
Da ta for 1-P h en yl-3-(p h en ylth iom eth yl)im id a zolid in e
(13): white flakes (from CH3OH); yield 66%; mp 64-65 °C;
1H NMR δ 3.12 (t, J ) 6.2 Hz, 2H), 3.99 (t, J ) 6.3 Hz, 2H),
4.14 (s, 2H), 4.55 (s, 2H), 6.43-6.46 (m, 2H), 6.70 (t, J ) 7.3
Hz, 1H), 7.18-7.30 (m, 5H), 7.45-7.48 (m, 2H); 13C NMR δ
46.3, 49.6, 60.2, 67.1, 111.6, 116.4, 126.6, 129.0, 129.2, 130.9,
Hz, 1H), 7.65 (d, J ) 8.2 Hz, 1H), 8.06 (d, J ) 8.4 Hz, 1H); 13
C
NMR δ 45.9, 49.6, 64.4, 67.0 (Bt1CH2), 109.6, 111.6, 116.8,
119.9, 124.1, 127.7, 129.1, 133.4, 145.8, 145.8. Anal. Calcd for
C
16H17N5: C, 68.79; H, 6.13; N, 25.07. Found: C, 68.96; H,
6.18; N, 25.13.
P r oced u r e for th e Red u ction of 9a w ith Na BH 4. A
mixture of 9a (0.28 g, 1.0 mmol) and NaBH4 (0.076 g, 2.0
mmol) was refluxed in dry THF (10 mL) overnight. After
removal of the solvent in vacuo, the residue was diluted with
EtOAc. The organic extracts were washed with 1 M NaOH
and brine and dried over anhyd MgSO4. Evaporation of the
solvent in vacuo gave 1-methyl-3-phenylimidazolidine (10):

Convenient Syntheses of Unsymmetrical Imidazolidines
J . Org. Chem., Vol. 67, No. 9, 2002 3113
137.1, 146.2. Anal. Calcd for C16H18N2S: C, 71.07; H, 6.71; N,
10.36. Found: C, 71.09; H, 6.88; N, 10.30.
(d, J ) 8.2 Hz, 2H); 13C NMR δ 16.8, 20.2, 33.2, 51.8, 53.9,
58.7, 70.8, 111.3, 115.8, 125.1, 129.6, 136.3, 144.3. Anal. Calcd
for C15H22N2: C, 78.21; H, 9.63; N, 12.16. Found: C, 78.05; H,
9.63; N, 11.99.
P r oced u r e for th e Nu cleop h ilic Su bstitu tion of 9a
w ith Tr ieth yl P h osp h ite. To a solution of 9a (0.28 g, 1.0
mmol) in dry CH2Cl2 (20 mL) at 0 °C were sequentially added
ZnBr2 (0.22 g, 1.0 mmol) and triethyl phosphite (0.34 mL, 2.0
mmol). The reaction mixture was stirred at 0 °C for 2 h and
at room temperature overnight. After extraction with CH2Cl2,
the combined organic layers were washed with 1 M NaOH and
brine and dried over anhyd MgSO4. After removal of the
solvent in vacuo, the desired product was purified by column
chromatography with hexanes/EtOAc (4:1) as an eluent.
Da ta for Dieth yl (3-P h en yl-1-im id a zolid in yl)m eth yl-
Da ta for Dieth yl [(5S)-5-Meth yl-3-(4-m eth ylp h en yl)-
tetr ah ydr o-1H-im idazol-1-yl]m eth ylph osph on ate (21): yel-
1
low oil; yield 90%; [R]25 ) +50.6 (c 1.58, CHCl3); H NMR δ
D
1.22 (d, J ) 5.4 Hz, 3H), 1.35 (t, J ) 7.0 Hz, 6H), 2.24 (s, 3H),
2.77 (dd, J ) 15.1, 6.6 Hz, 1H, Ha), 2.98-3.02 (m, 2H), 3.20
(dd, J ) 17.7, 15.1 Hz, 1H, Hb), 3.46-3.47 (m, 1H), 3.87, 4.65
(AB, J ) 4.7 Hz, 2H), 4.12-4.22 (m, 4H), 6.42 (d, J ) 8.4 Hz,
2H), 7.03 (d, J ) 8.4 Hz, 2H); 13C NMR δ 16.4 (d, J ) 5.7 Hz),
16.5 (d, J ) 5.7 Hz), 16.7, 20.2, 47.8 (d, J ) 167.2 Hz), 53.4,
60.1 (d, J ) 17.8 Hz), 61.9 (d, J ) 6.3 Hz), 62.5 (d, J ) 6.3
Hz), 71.9 (d, J ) 2.3 Hz), 111.5, 125.4, 129.6, 144.2. Anal. Calcd
for C16H27N2O3P: C, 58.88; H, 8.34; N, 8.58. Found: C, 58.58;
H, 8.33; N, 8.60.
1
p h osp h on a te (14): yellow oil; yield 70%; H NMR δ 1.36 (t,
J ) 7.0 Hz, 6H), 3.02 (d, J ) 12.5 Hz, 2H), 3.17 (t, J ) 6.3 Hz,
2H), 3.41 (t, J ) 6.1 Hz, 2H), 4.05-4.23 (m, 6H), 6.50 (d, J )
8.2 Hz, 2H), 6.71 (t, J ) 7.3 Hz, 1H), 7.23 (t, J ) 7.7 Hz, 2H);
13C NMR δ 16.5 (d, J ) 5.3 Hz), 45.8, 50.2 (d, J ) 167.3 Hz),
54.7 (d, J ) 10.6 Hz), 62.3 (d, J ) 6.4 Hz), 71.5 (d, J ) 12.7
Hz), 111.5, 116.4, 129.2, 146.2. Anal. Calcd for C14H23N2O3P:
C, 56.37; H, 7.77; N, 9.39. Found: C, 56.39; H, 7.89; N, 9.59.
Gen er a l P r oced u r e for th e P r ep a r a tion of Ch ir a l
Diam in es 18a-c fr om N-Boc-r-am in o Acids 15a-c. R-Ami-
no amides 17a -c were obtained according to our recent
paper.16
Da ta for 2-[(5S)-5-Ben zyl-3-(4-m eth ylp h en yl)tetr a h y-
d r o-1H-im id a zol-1-yl]a ceton itr ile (22): yellow flakes (from
EtOH); yield 99%; mp 76-77 °C; [R]25D ) +40.4 (c 1.98, CHCl3);
1H NMR δ 2.23 (s, 3H), 2.71 (dd, J ) 13.0, 7.1 Hz, 1H), 2.98
(dd, J ) 13.3, 5.1 Hz, 1H), 3.14 (br s, 1H), 3.36-3.41 (m, 2H),
3.63 (s, 2H), 4.05, 4.37 (AB, J ) 4.0 Hz, 2H), 6.38 (d, J ) 8.4
Hz, 2H), 7.02 (d, J ) 8.2 Hz, 2H), 7.21-7.35 (m, 5H); 13C NMR
δ 20.2, 38.6, 38.9, 52.3, 62.1, 69.9, 111.9, 114.8, 126.2, 126.7,
128.6, 128.8, 129.6, 137.5, 143.7. Anal. Calcd for C19H21N3: C,
78.31; H, 7.26; N, 14.42. Found: C, 78.45; H, 7.45; N, 14.11.
P r oced u r e for th e P r ep a r a tion of th e Bt In ter m ed ia te
24 a n d Its Su bstitu tion w ith Na CN. A mixture of 1-ethyl-
2-(4-nitrophenyl)imidazolidine (23; 0.66 g, 3.0 mmol), BtH
(0.36 g, 3.0 mmol), formaldehyde (37% aq solution; 0.25 g, 3.0
mmol) in CH3OH/H2O (10/4 mL) was stirred at room temper-
ature for 24 h. The precipitate formed was filtered and
recrystallized from EtOH to give 24.
A mixture of 24 (0.35 g, 1.0 mmol) and NaCN (0.10 g, 2.0
mmol) was stirred in DMSO (3 mL) at 25 °C for 24 h. The
mixture was diluted with CH2Cl2, washed with water, and
dried over anhyd MgSO4. After removal of the solvent in vacuo,
the residue was purified by flash basic Al2O3 column chroma-
tography with hexanes/EtOAc (6:4) as an eluent to afford 25.
Da ta for 1-{[3-Eth yl-2-(4-n itr op h en yl)-1-im id a zolid i-
n yl]m eth yl}-1H-1,2,3-ben zotr ia zole (24): pale yellow mi-
crocrystals (from EtOH); yield 85%; mp 121-122 °C; 1H NMR
δ 0.92 (t, J ) 7.2 Hz, 3H), 2.06-2.13 (m, 1H), 2.29-2.42 (m,
2H), 3.10-3.17 (m, 1H), 3.33-3.40 (m, 1H), 3.51 (q, J ) 7.4
Hz, 1H), 4.11 (s, 1H), 5.29, 5.45 (AB, J ) 14.0 Hz, 2H), 7.34-
7.39 (m, 2H), 7.48 (t, J ) 7.1 Hz, 1H), 7.75 (d, J ) 8.5 Hz,
2H), 8.04 (d, J ) 7.4 Hz, 1H), 8.21 (d, J ) 8.7 Hz, 2H); 13C
NMR δ 13.4, 46.4, 48.1, 50.6, 62.2, 83.4, 109.4, 119.9, 123.4,
124.0, 127.6, 130.2, 133.6, 145.6, 147.4, 148.3. Anal. Calcd for
A mixture of 17a -c (3 mmol) and LiAlH4 (powder, 0.68 g,
18 mmol) in dry THF (30 mL) was refluxed for 2 days. The
mixture was slowly quenched with water under an ice bath.
The precipitate formed was filtered off and washed with CH2-
Cl2. The combined filtrate was washed with 1 M NaOH and
brine and dried over anhyd K2CO3. Removal of the solvents
afforded diamine 18a -c, which was directly used for the
subsequent reaction. GC analyses show that the purity of
18a -c is more than 90%.
Data for (2S)-N1-(4-Meth ylph en yl)-1,2-pr opan ediam in e
1
(18a ): yellow oil; yield 96%; H NMR δ 1.20 (d, J ) 7.1 Hz,
3H), 1.20-1.80 (br s, 2H), 2.31 (s, 3H), 2.90 (dd, J ) 12.1, 8.0
Hz, 1H), 3.14-3.22 (m, 2H), 3.80-4.25 (br s, 1H), 6.62 (d, J )
8.4 Hz, 2H), 7.05 (d, J ) 8.1 Hz, 2H); 13C NMR δ 20.1, 21.8,
45.9, 52.3, 112.8, 126.1, 129.5, 146.0.
Gen er a l P r oced u r e for th e P r ep a r a tion of Op tica lly
Active Im id a zolid in es 20a -d , 21, a n d 22. A mixture of a
diamine, 18a -c (3.0 mmol), BtH (0.36 g, 3.0 mmol), and
formaldehyde (37% aq solution; 0.49 g, 6.0 mmol) in CH3OH/
H2O (10 mL/5 mL) was stirred for 4 h at 20 °C. The precipitate
formed was filtered and washed with cool Et2O to give 19a -
c.
To a solution of 19a -c (1.0 mmol) in dry THF (15 mL) was
added dropwise an appropriate Grignard reagent (1.2 mmol)
in THF. The reaction mixture was stirred at room temperature
for 30 min and then refluxed for 1 h. The same workup as
used for the preparation of 11 gave 20a -d , which was purified
by flash column chromatography (silica gel).
C
18H20N6O2: C, 61.35; H, 5.72; N, 23.85. Found: C, 61.29; H,
5.83; N, 23.90.
Da ta for 2-[3-Eth yl-2-(4-n itr op h en yl)-1-im id a zolid in yl]-
1
The same procedure as used for the preparation of 14 and
12b afforded 21 and 22, respectively.
Da ta for 1-{[(5S)-5-Meth yl-3-(4-m eth ylp h en yl)tetr a -
h yd r o-1H-im id a zol-1-yl]m et h yl}-1H-1,2,3-b en zot r ia zole
a ceton itr ile (25): brown oil; yield 92%; H NMR δ 1.00 (t, J
) 7.2 Hz, 3H), 2.22-2.34 (m, 1H), 2.42-2.54 (m, 1H), 2.62-
2.71 (m, 1H), 2.99-3.06 (m, 1H), 3.24 (d, J ) 17.6 Hz, 1H),
3.39-3.54 (m, 2H), 3.57 (d, J ) 17.7 Hz, 1H), 3.92 (s, 1H),
7.67 (d, J ) 8.6 Hz, 2H), 8.23 (d, J ) 8.6 Hz, 2H); 13C NMR δ
13.4, 39.0, 46.5, 49.5, 50.2, 85.4, 115.0, 123.7, 129.9, 146.4,
148.6. Anal. Calcd for C13H16N4O2: C, 59.99; H, 6.20; N, 21.52.
Found: C, 59.93; H, 6.17; N, 21.80.
(19a ): colorless microcrystals (from EtOH); yield 85%; mp
1
129-130 °C; [R]25 ) -16.2 (c 1.71, CHCl3); H NMR δ 1.41
D
(d, J ) 6.1 Hz, 3H), 2.21 (s, 3H), 3.02 (t, J ) 8.1 Hz, 1H), 3.25-
3.31 (m, 1H), 3.45 (t, J ) 7.3 Hz, 1H), 4.13, 4.38 (AB, J ) 4.1
Hz, 2H), 5.64 (d, J ) 3.5 Hz, 2H), 6.34 (d, J ) 8.5 Hz, 2H),
7.00 (d, J ) 8.2 Hz, 2H), 7.38 (t, J ) 7.2 Hz, 1H), 7.52 (t, J )
7.5 Hz, 1H), 7.65 (d, J ) 8.4 Hz, 1H), 8.07 (d, J ) 8.4 Hz, 1H);
13C NMR δ 16.9, 20.2, 54.1, 54.6, 61.8, 68.1, 109.5, 111.7, 120.0,
124.0, 126.0, 127.7, 129.7, 133.6, 143.9, 145.9. Anal. Calcd for
P r ocedu r e for th e P r epar ation of 1-Su bstitu ted 3-Meth -
yl-2,3-d ih yd r o-1H-ben zim id a zoles 28 a n d 29. A mixture
of N-(2-aminophenyl)-N-methylamine (26a ; 0.37 g, 3.0 mmol),
BtH (0.36 g, 3.0 mmol), and formaldehyde (37% aq solution;
0.49 g, 6.0 mmol) in CH3OH/H2O (10 mL/4 mL) was stirred at
room temperature overnight. Then an additional 10 mL of
water was added, and the mixture was stirred for 1 h. The
precipitate formed was filtered and washed with cool ethanol
to give 27.
To a solution of vinylmagnesium bromide (2.0 M in THF;
0.7 mL, 1.4 mmol) at 0 °C was added dropwise ZnCl2 (0.5 M
in Et2O; 3.0 mL, 1.5 mmol). After the mixture was stirred for
15 min, a solution of 27 (0.26 g, 1.0 mmol) in dry THF (10
mL) was added dropwise. The reaction mixture was stirred
C
18H21N5: C, 70.33; H, 6.89; N, 22.78. Found: C, 70.24; H,
7.11; N, 22.95.
Da ta for (4S)-3-(3-Bu ten yl)-4-m eth yl-1-(4-m eth ylp h en -
yl)tetr a h yd r o-1H-im id a zole (20a ): yellow oil; yield 94%;
[R]25 ) +111 (c 2.17, CHCl3); 1H NMR δ 1.20 (d, J ) 6.0 Hz,
D
3H), 2.24 (s, 3H), 2.30-2.37 (m, 3H), 2.82-2.94 (m, 2H), 3.02
(t, J ) 8.2 Hz, 1H, Ha), 3.44 (t, J ) 7.4 Hz, 1H, Hb), 3.68, 4.43
(AB, J ) 4.1 Hz, 2H), 5.04 (d, J ) 10.2 Hz, 1H), 5.11 (d, J )
17.0 Hz, 1H), 5.79-5.92 (m, 1H), 6.40 (d, J ) 8.4 Hz, 2H), 7.02

3114 J . Org. Chem., Vol. 67, No. 9, 2002
Katritzky et al.
for 20 min at room temperature and then refluxed for 2 h.
After being cooled, the mixture was quenched with water and
extracted with CH2Cl2. The organic extracts were washed with
1 M NaOH, water, and brine and dried over anhyd K2CO3.
Evaporation of the solvent in vacuo gave the crude product
28, which was purified by flash basic Al2O3 column chroma-
tography with hexanes/EtOAc (8:2) as an eluent.
NMR (DMSO-d6) δ 2.72 (s, 3H), 4.38 (s, 2H), 4.46 (s, 2H), 6.55
(d, J ) 7.2 Hz, 1H), 6.65-6.78 (m, 3H); 13C NMR (DMSO-d6)
δ 34.0, 35.4, 76.7, 106.7, 115.9, 118.7, 120.8, 139.4, 143.3; GC-
MS (EI) m/z 173 (M+). Anal. Calcd for C10H11N3: H, 6.40; N,
24.26. Found: H, 6.54; N, 24.16.
P r oced u r e for th e P r ep a r a tion of 2-(2-An ilin oa n ilin o)-
a ceton itr ile (31). The same procedure as used for the
preparation of 24 and 25 gave compounds 30 and 31, respec-
tively.
The same procedure as used for the preparation of 25
afforded 29.
Da ta for 1-(Ben zotr ia zolylm eth yl)-3-m eth yl-2,3-d ih y-
d r o-1H-ben zim id a zole (27): obtained as a mixture of Bt1
and Bt2 isomers in a ca. 6:1 ratio (1H and 13C NMR data for
the Bt1 isomer only are presented); white microcrystals (from
CH3OH); yield 85%; mp 122-124 °C; 1H NMR δ (Bt1) 2.66 (s,
3H), 4.61 (s, 2H), 5.96 (s, 2H), 6.38-6.41 (m, 1H), 6.67-6.77
(m, 2H), 6.81-6.83 (m, 1H), 7.34-7.39 (m, 1H), 7.46 (t, J )
7.2 Hz, 1H), 7.58 (d, J ) 8.0 Hz, 1H), 8.06 (d, J ) 8.3 Hz, 1H);
13C NMR δ (Bt1) 34.0, 60.2, 76.0, 106.6, 106.7, 109.7, 118.8,
119.9, 120.8, 124.1, 127.8, 132.7, 138.6, 142.9, 146.1. Anal.
Calcd for C15H15N5: C, 67.90; H, 5.70; N, 26.40. Found: C,
67.72; H, 5.46; N, 26.40.
Da ta for 1-Allyl-3-m eth yl-2,3-d ih yd r o-1H-ben zim id a -
zole (28): Rf ) 0.70 [eluent hexanes/CH2Cl2, 7:3; Al2O3 TLC
plate (Aldrich, Catalog No. Z23421-4)]; extremely labile to air;
yellow oil; yield 83%; 1H NMR (DMSO-d6) δ 2.64 (s, 3H), 2.79
(d, J ) 6.1 Hz, 2H), 4.29 (s, 2H), 5.19 (d, J ) 12.1, 2.1 Hz,
1H), 5.30 (dd, J ) 17.2, 2.0 Hz, 1H), 5.84-5.94 (m, 1H), 6.38-
6.45 (m, 2H), 6.50-6.55 (m, 2H); 13C NMR (DMSO-d6) δ 34.0,
50.4, 77.5, 105.8, 106.2, 117.5, 118.5, 118.7, 134.1, 141.9, 143.2;
GC-MS (EI) m/z 174 (M+).
Data for N-(1H-1,2,3-Ben zotr iazol-1-ylm eth yl)-N′-ph en -
yl-1,2-ben zen ed ia m in e (30): white microcrystals; yield 92%;
mp 146-147 °C; H NMR δ 5.18 (s, 1H), 5.51 (t, J ) 6.8 Hz,
1H), 6.07 (d, J ) 7.0 Hz, 2H), 6.85 (d, J ) 7.9 Hz, 2H), 6.78-
6.85 (m, 2H), 7.05-7.16 (m, 5H), 7.31-7.42 (m, 2H), 7.49 (d,
J ) 7.9 Hz, 1H), 8.03 (d, J ) 8.2 Hz, 1H); 13C NMR δ 57.9,
109.9, 112.8, 115.2, 119.6, 120.0, 120.1, 124.0, 126.1, 126.8,
127.4, 128.8, 129.3, 132.3, 141.2, 145.6, 146.4. Anal. Calcd for
1
C
19H17N5: C, 72.36; H, 5.43; N, 22.21. Found: C, 72.47; H,
5.79; N, 22.27.
Da ta for 31: separated by basic Al2O3 flash column chro-
matography; yellow plates (from ethanol/hexanes); yield 77%;
1
mp 102-103 °C; H NMR δ 4.08 (d, J ) 7.0 Hz, 2H), 4.55 (t,
J ) 6.7 Hz, 1H), 5.13 (s, 1H), 6.68 (d, J ) 7.8 Hz, 2H), 6.81-
6.90 (m, 3H), 7.15-7.25 (m, 4H); 13C NMR δ 32.4, 111.9, 115.2,
116.8, 119.8, 120.2, 125.7, 126.5, 129.3, 129.4, 141.2, 145.3.
Anal. Calcd for C14H13N3: C, 75.31; H, 5.87; N, 18.82. Found:
C, 75.60; H, 5.65; N, 18.89.
Su p p or tin g In for m a tion Ava ila ble: Characterization
data for compounds 9b,c, 11b-f,h ,j-l, 12b,c, 18b,c, 19b,c,
20b-d . This material is available free of charge via the
Internet at http://pubs.acs.org.
Da ta for 2-(3-Meth yl-2,3-d ih yd r o-1H-ben zim id a zol-1-
yl)a ceton itr ile (29): Rf ) 0.70 [eluent hexanes/CH2Cl2, 7:3;
Al2O3 TLC plate (Aldrich, Catalog No. Z23421-4)]; separated
by flash basic Al2O3 column chromatography with CH2Cl2 as
an eluent; extremely labile to air; brown oil; yield 94%; 1H
J O010868N