Modular synthesis of heterocyclic carbene precursors

Article abstract of DOI:10.1021/jo060594+

A series of N-heterocyclic carbene precursors, containing an imidazoline or tetrahydropyrimidine framework, were prepared from ω-chloroalkanoyl chlorides. The sequential attachment of nitrogen nucleophiles and subsequent ring closure gave, depending on the reagents used, either the desired dihydroimidazolium and tetrahydropyrimidinium salts or their parent heterocycles. In this latter case, the second substituent was introduced in an alkylation step. The preparation of carbene precursors bearing chiral or bulky substituents was achieved with comparable efficiency.

Full text of DOI:10.1021/jo060594+

Modular Synthesis of Heterocyclic Carbene Precursors
Attila Paczal,† Attila C. Be´nyei,‡ and Andra´s Kotschy*,†
Institute of Chemistry, Eo¨tVo¨s Lora´nd UniVersity, Pa´zma´ny Pe´ter s. 1/A, H-1117 Budapest, Hungary, and
Department of Chemistry, Laboratory for X-ray Diffraction, UniVersity of Debrecen, P.O. Box 7,
H-4010 Debrecen, Hungary
kotschy@chem.elte.hu
ReceiVed March 17, 2006
A series of N-heterocyclic carbene precursors, containing an imidazoline or tetrahydropyrimidine
framework, were prepared from ω-chloroalkanoyl chlorides. The sequential attachment of nitrogen
nucleophiles and subsequent ring closure gave, depending on the reagents used, either the desired
dihydroimidazolium and tetrahydropyrimidinium salts or their parent heterocycles. In this latter case, the
second substituent was introduced in an alkylation step. The preparation of carbene precursors bearing
chiral or bulky substituents was acieved with comparable efficiency.
Introduction
and olefin metathesis, both achiral11 and enantioselective.12
Some of the chiral NHC ligands were also successful in other
catalytic asymmetric transformations,13 and besides their role
as ligands in metal complexes, certain NHCs also act as efficient
organocatalysts.14
It is thus probably not surprising that the preparation of
N-heterocyclic carbene precursors15,16 and their metal com-
plexes17 has been extensively studied recently. The chemistry
of the parent imidazole system and its analogues (oxazoles,
triazoles, pyrimidines, and annulated derivatives) is well
Following the original reports of O¨ fele1 and Wanzlick2 on
the existence of N-heterocyclic carbene (NHC)-metal com-
plexes in 1968 and the seminal paper of Arduengo3 describing
stable NHCs, N-heterocyclic carbenes have had a spectacular
career in synthetic chemistry,4 principally as supporting ligands
in transition-metal complexes. Such NHC-metal complexes
have been successfully utilized in cross-coupling reactions5 and
related processes, including hydrogenation,6 hydrosilylation,7
hydroformylation,8 oxidation,9 and Pauson-Khand reactions10
(9) Jensen, D. R.; Schultz, M. J.; Mueller, J. A.; Sigman, M. S. Angew.
Chem., Int. Ed. 2003, 42, 3810-3813.
* To whom correspondence should be addressed. Tel: +36-1-372-2910.
Fax: +36-1-372-2909.
† Eo¨tvo¨s Lora´nd University.
(10) Gibson, S. E.; Johnstone, C.; Loch, J. A.; Steed, J. W.; Stevenazzi,
A. Organometallics 2003, 22, 5374-5377.
‡ University of Debrecen.
(1) O¨ fele, K. J. Organomet. Chem. 1968, 12, P4-P43.
(2) Wanzlick, H.-W.; Scho¨nherr, H. J. Angew. Chem., Int. Ed. Engl. 1968,
7, 141-142.
(3) Arduengo, A. J.; Harlow, R. L.; Kline, M. J. Am. Chem. Soc. 1991,
113, 361-363.
(11) Selected examples include: (a) Trnka, T. M.; Morgan, J. P.; Sanford,
M. S.; Wilhelm, T. E.; Scholl, M.; Choi, T.-L.; Ding, S.; Day, M. W.;
Grubbs, R. H. J. Am. Chem. Soc. 2003, 125, 2546-2558. (b) Garber, S.
B.; Kingsbury, J. S.; Gray, B. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2000,
122, 8168-8179. (c) Bujok, R.; Bieniek, M.; Masnyk, M.; Michrowska,
A.; Sarosiek, A.; Stepowska, H.; Arlt, D.; Grela, K. J. Org. Chem. 2004,
69, 6894-6896. (d) Wakamatsu, H.; Blechert, S. Angew. Chem., Int. Ed.
2002, 41, 2403-2405. (e) Weskamp, T.; Schattenmann, W. C.; Spiegler,
M.; Herrmann, W. A. Angew. Chem., Int. Ed. 1998, 37, 2490-2493. (f)
Huang, J.; Stevens, E. D.; Nolan, S. P.; Petersen, J. L. J. Am. Chem. Soc.
1999, 121, 2674-2678. (g) Fu¨rstner, A.; Ackermann, L.; Gabor, B.;
Goddard, R.; Lehmann, C. W.; Mynott, R.; Stelzer, F.; Thiel, O. R. Chem.s
Eur. J. 2001, 7, 3236-3253.
(12) (a) Seiders, T. J.; Ward, D. W.; Grubbs, R. H. Org. Lett. 2001, 3,
3225-3228. (b) Van Veldhuizen, J. J.; Garber, S. B.; Kingsbury, J. S.;
Hoveyda, A. H. J. Am. Chem. Soc. 2002, 124, 4954-4955. (c) Van
Veldhuizen, J. J.; Gillingham, D. G.; Garber, S. B.; Kataoka, O.; Hoveyda,
A. H. J. Am. Chem. Soc. 2003, 125, 12502-12508. (d) Gillingham, D. G.;
Kataoka, O.; Garber, S. B.; Hoveyda, A. H. J. Am. Chem. Soc. 2004, 126,
12288-12290. (e) Funk, T. W.; Berlin, J. M.; Grubbs, R. H. J. Am. Chem.
Soc. 2006, 128, 1840-1846.
(4) The rapid expansion of the field was greatly facilitated by earlier
contributions on stable nonheterocyclic carbenes and their metal complexes.
For a comprehensive review of the related literature, see: Bourissou, D.;
Guerret, O.; Gabbai, F. P.; Bertrand, G. Chem. ReV. 2000, 100, 39-91.
(5) Selected examples include: (a) Bohm, V. P.; Weskamp, T.; Gstott-
mayr, C. W.; Herrmann, W. A. Angew. Chem., Int. Ed. 2000, 39, 1602-
1604. (b) Grasa, G. A.; Viciu, M. S.; Huang, J.; Zhang, C.; Trudell, M. L.;
Nolan, S. P. Organometallics 2002, 21, 2866-2873. (c) Stauffer, S. R.;
Lee, S.; Stambuli, J. P.; Hauck, S. I.; Hartwig, J. F. Org. Lett. 2000, 2,
1423-1426.
(6) Perry, M. C.; Cui, X.; Powell, M. T.; Reibenspies, J. H.; Bugess, K.
J. Am. Chem. Soc. 2003, 125, 113-123.
(7) Enders, D.; Gielen, H. J. Organomet. Chem. 2001, 617-618, 70-
80.
(8) Ko¨cher, C.; Herrmann, W. A. J. Organomet. Chem. 1997, 532, 261-
265.
10.1021/jo060594+ CCC: $33.50 © 2006 American Chemical Society
Published on Web 06/30/2006
J. Org. Chem. 2006, 71, 5969-5979
5969

Paczal et al.
SCHEME 1
established, the preparation of tailor-made NHC precursors
bearing less common substituent combinations, however, is still
a challenge attracting much attention.
The aim of our research was the establishment of a modular
synthetic protocol, which enables the preparation of a wide range
(13) (a) Powell, M. T.; Hou, D.-R.; Perry, M. C.; Cui, X.; Burgess, K.
J. Am. Chem. Soc. 2001, 123, 8878-8879. (b) Ma, Y.; Song, C.; Ma, C.;
Sun, Z.; Chai, Q.; Andrus, M. B. Angew. Chem., Int. Ed. 2003, 42, 5871-
5874. (c) Bonnet, L. C.; Douthwaite, R. E.; Kariuki, B. M. Organometallics
2003, 22, 4187-4189. (d) Alexakis, A.; Winn, C. L.; Guillen, F.; Pytkowicz,
J.; Roland, S.; Mangeney, P. AdV. Synth. Catal. 2003, 345, 345-348. (e)
Jensen, D. R.; Sigman, M. S. Org. Lett. 2003, 5, 63-65. (f) Larsen, A. O.;
Leu, W.; Oberhuber, C. N.; Campbell, J. E.; Hoveyda, A. H. J. Am. Chem.
Soc. 2004, 126, 11130-11131. (g) Gade, L. H.; Cesar, V.; Bellemin-
Laponnaz, S. Angew. Chem., Int. Ed. 2004, 43, 1014-1017. (h) Bappert,
E.; Helmchen, G. Synlett 2004, 1789-1793. (i) Arnold, P. L.; Rodden, M.;
Davis, K. M.; Scarisbrick, A. C.; Blake, A. J.; Wilson, C. Chem. Commun.
2004, 1612-1613. (j) Tominaga, S.; Oi, Y.; Kato, T.; An, D. K.; Okamoto,
S. Tetrahedron Lett. 2004, 45, 5585-5588.
of dihydroimidazolium salts, since this compound class gives
very effective ligands both in ruthenium and palladium catalyzed
transformations. Besides being carbene precursors themselves,
the dihydroimidazolium salts might also be oxidized, providing
access to the corresponding imidazolium salts.18 Substituents
attached to the ring nitrogen atoms included chiral groups, bulky
alkyl and aryl moieties, or substituents offering additional centers
for attachment or coordination of transition metals.
(14) Selected recent examples include: (a) Csihony, Sz.; Culkin, D. A.;
Sentman, A. C.; Dove, A. P.; Waymouth, R. M.; Hedrick, J. L. J. Am.
Chem. Soc. 2005, 127, 9079-9084. (b) Kano, T.; Sasaki, K.; Maruoka, K.
Org. Lett. 2005, 7, 1347-1349. (c) Movassaghi, M.; Schmidt, M. A. Org.
Lett. 2005, 7, 2453-2456. (d) Nair, V.; Bindu, S.; Sreekumar, V. Angew.
Chem., Int. Ed. 2004, 43, 5130-5135. (e) Enders, D.; Balensiefer, T. Acc.
Chem. Res. 2004, 37, 534-541. (f) Singh, R.; Kissling, R. M.; Letellier,
M. A.; Nolan, S. P. J. Org. Chem. 2004, 69, 209-212. (g) Reynolds, N.
T.; de Alaniz, J. R.; Rovis, T. J. Am. Chem. Soc. 2004, 126, 9518-9519.
(h) Sohn, S. S.; Rosen, E. L.; Bode, J. W. J. Am. Chem. Soc. 2004, 126,
14370-14371. (i) Duong, H. A.; Cross, M. J.; Louie, J. Org. Lett. 2004, 6,
4679-4681. (j) Canac, Y.; Soleilhavoup, M.; Conejero, S.; Bertrand, G. J.
Organomet. Chem. 2004, 689, 3857-3865. (k) Nair, V.; Vellalath, S.;
Poononth, M.; Mohan, R.; Suresh, E. Org. Lett. 2006, 8, 507-509. (l) Chan,
A.; Scheidt, K. A. Org. Lett. 2005, 7, 905-908.
Results and Discussion
Our synthetic strategy was based on the construction of the
heterocyclic core from readily available building blocks. Our
choice for the introduction of the carbon backbone of the
imidazole ring was chloroacetyl chloride (1a). This approach
was expected to offer some advantages over reported routes
utilizing the alkylation of ethylenediamine,19 starting from
oxallyl chloride and amines, as described recently by Dinger,20
or glyoxal and amines,21 which are biased by mediocre
selectivity in the opening step. The acylation of different amines
(2a-e) with 1a under standard conditions,22 as expected, led
to the isolation of the desired amides in good yield (Scheme 1)
and complete chemoselectivity. Using 3-chloropropionyl chlo-
ride (1b), which opens up the way to tetrahydropyrimidinium
salts, amide 3f was also prepared in somewhat lower yield.
Our first approach to NHC precursors relied on the use of
N,N′-disubstituted ethylenediamine derivatives as key intermedi-
ates, since their well-established ring closure with trialkyl
orthoformates was expected to give the desired dihydroimida-
zolium salts efficiently. The preparation of the selected diamines
(5a-c) followed a two-step nucleophilic substitution-reduction
sequence (Scheme 2). Amine-chloroamide combinations were
chosen to provide diamines with one chiral substituent. The
reaction of chloroacetamide derivatives (3a,c,e) with the enan-
tiomer-enriched R-phenylethylamine (2c) or O-benzylethanol-
amine (2f) gave the desired R-aminoacetamides (4a-c) in good
yield. The reduction of the resulting aminoamides (4a-c) to
the corresponding ethylenediamine derivatives (5a-c) was
achieved using lithium aluminum hydride: the diamines were
obtained in analytical purity. Treatment of the diamines (5a-
(15) Research in this direction has recently been further fuelled by the
fact that several NHC precursors are ionic liquids, which offers new
applications.
(16) (a) Toshihisa, O.; Kazuyuki, T.; Kaoru S. Heterocycles 1988, 27,
2815-2824. (b) Shahrokh, S.; Brescia, A. M.; Kaloustian, M. K. Tetra-
hedron Lett. 1991, 32, 5031-5034. (c) Lloyd, D.; Reichardt, C.; Struthers,
M. Liebigs Ann. Chem. 1986, 8, 1368-1379. (d) Arduengo, A. J.; Krafczyk,
R.; Schmutzler, R.; Craig, H. A.; Goerlich, J. R.; Marshall, W. J.; Unverzagt,
M. Tetrahedron 1999, 55, 14523-14534. (e) Alder, R. W.; Blake, M. E.;
Bufali, S.; Butts, C. P.; Orpen, A. G.; Schuetz, J.; Stuart, J. W. J. Chem.
Soc., Perkin Trans. 1 2001, 14, 1586-1593. (f) Sanwoo, L.; Hartwing J.
F. Org. Chem. 2001, 66, 3402-3415. (g) Veldhuizen, J. J.; Garber, S. B.;
Kingsbury, J. S.; Hoveyda, A. H. J. Am. Chem. Soc. 2002, 124, 4954-
4955. (h) Mehnert, C. P.; Cook, R. A.; Dispenziere, N. C.; Afeworki, M.
J. Am. Chem. Soc. 2002, 124, 12932-12933. (i) Ma, Y.; Song, C.; Ma, C.;
Sun, Z.; Chai, Q.; Andrus, M. B. Angew. Chem., Int. Ed. 2003, 42, 5871-
5874. (j) Alcarazo, M.; Roseblade, S. J.; Alonso, E.; Fernandez, R.; Alvarez,
E.; Lahoz, F. J.; Lassaletta, J. M. J. Am. Chem. Soc. 2004, 126, 13242-
13243. (k) Guillen, F.; Winn, C. L.; Alexakis, A. Tetrahedron: Asymmetry
2001, 12, 2083-2086. (l) Garber, S. B.; Kingsbury, J. S.; Gray, B. L.;
Hoveyda, A. H. J. Am. Chem. Soc. 2000, 122, 8168-8179.
(17) Selected examples include: (a) Ketz, B. E.; Cole, A. P.; Waymouth,
R. M. Organometallics 2004, 23, 2835-2837. (b) Viciu, M. S.; Stevens,
E. D.; Petersen, J. L.; Nolan, S. P. Organometallics 2004, 23, 3752-3755.
(c) Viciu, M. S.; Germaneau, R. F.; Nolan, S. P. Org. Lett. 2002, 4, 4053-
4056. (d) Jensen, D. R.; Sigman, M. S.; Org. Lett. 2003, 5, 63-65. (e)
Clement, N. D.; Cavell, K. J.; Jones, C.; Elsevier, C. J. Angew. Chem., Int.
Ed. 2004, 43, 1277-1279. (f) Jensen, D. R.; Schultz, M. J.; Ueller, J. A.;
Sigman, M. S.; Angew. Chem., Int. Ed. 2003, 42, 3810-3813. (g) Coleman,
K. S.; Chamberlayne, H. T.; Turberville, S.; Green, M. L. H.; Cowley, A.
R. Dalton Trans. 2003, 2917-2922. (h) Lebel, H.; Janes, M. K.; Charette,
A. B.; Nolan, S. P. J. Am. Chem. Soc. 2004, 126, 5046-5047. (i) Viciu,
M. S.; Navarro, O.; Germaneau, R. F.; Kelly, R. A.; Sommer, W.; Marion,
N.; Stevens, E. D.; Cavallo, L.; Nolan, S. P. Organometallics 2004, 23,
1629-1635. (j) Buchgraber, P.; Toupet, L.; Guerchais, V. Organometallics
2003, 22, 5144-5147. (k) Lee, H. M.; Jiang, T.; Stevens, E. D.; Nolan, S.
P. Organometallics 2001, 20, 1255-1258. (l) Gessler, S.; Randl, S.;
Blechert, S. Tetrahedron Lett. 2000, 41, 9973-9976. (m) Dorta, R.; Stevens,
E. D.; Hoff, C. D.; Nolan, S. P. J. Am. Chem. Soc. 2003, 125, 10490-
10491. (n) Trnka, T. M.; Day, M. W.; Grubbs, R. H. Organometallics 2001,
20, 3845-3847. (o) Sanford, M. S.; Love, J. A.; Grubbs, R. H. Organo-
metallics 2001, 20, 5314-5318. (p) Grela, K.; Harutyunyan, S.; Michrow-
ska, A. Angew. Chem. Int. Ed. 2002, 41, 4038-4040. (q) O¨ zdemir, I.;
Gu¨rbu¨z, N.; Sec¸kin, T.; C¸ etinkaya, B. Appl. Organomet. Chem. 2000, 19,
633-638.
(18) Ge´nisson, Y.; Lauth-de Viguerie, N.; Chantal Andre´, C.; Baltas,
M. Tetrahedron: Asymmetry 2005, 16, 1017-1023.
(19) Frost, A. E.; Carlson, A. A. J. Org. Chem. 1959, 24, 1581-1582.
(20) Dinger, M. B.; Nieczypor, P.; Mol, J. C. Organometallics 2003,
22, 5291-5296.
(21) Grasa, G. A.; Viciu, M. S.; Huang, J.; Nolan, S. P. J. Org. Chem.
2001, 66, 7729-7737.
(22) Orena, M.; Porzi, G.; Sandri, S. J. Org. Chem. 1992, 57, 6532-
6536.
5970 J. Org. Chem., Vol. 71, No. 16, 2006

Modular Synthesis of Heterocyclic Carbene Precursors
SCHEME 2
SCHEME 3
SCHEME 4. Alkylating Agents Used in the Synthesis of NHC Precursors
c) with trimethyl orthoformate in the presence of ammonium
tetrafluoroborate gave the expected dihydroimidazolium salts
(6a-c) in good to excellent yield; these were isolated as
tetrafluoroborates. It is interesting to note that 6b and 6c are
both chiral room-temperature ionic liquids.23
in the case of the aryl-substituted amines 8a,b and 8f substantial
amounts of the ring closure intermediate were present in the
crude product. In these reactions complete conversion of the
diamines to the ring-closed products was achieved using triethyl
orthoformate25 in the presence of catalytic amounts of concen-
trated hydroiodic acid. The ethylenediamine derivatives gave
the arylimidazolines (9a,b) in good yield, while the analogous
ring closure of 8f was somewhat less efficient, giving the desired
N-mesityl-1,2,3,4-tetrahydropyrimidine (9f) in acceptable yield.
In our second approach preparation of the appropriate
monosubstituted dihydroimidazoles was followed by the at-
tachment of the desired side chain in the concluding alkylation
step. Transformation of the ω-chloroacetamide (3a-e) and
propionamide (3f) derivatives to dihydroimidazoles started
(Scheme 3) by their conversion to the appropriate azides (7a-
f) which in most cases proceeded in excellent yield. Concomitant
reduction of the azide and amide groups by lithium aluminum
hydride led to the formation of the N-substituted ethylenedi-
amine derivatives (8a-f) in good yield. An alternative route to
8a-f is offered by the direct amination of the chloroamides
(3a-f) but our attempts in this direction gave only low yields.
The conversion of the monosubstituted ethylenediamines 8a-f
to the desired dihydroimidazoles (9a-f) was attempted by using
N,N-dimethylformamide dimethyl acetal,24 which worked very
efficiently for the alkylimidazolines 8c-e and furnished the
desired ring closed products 9c-e in excellent yield; however
In the final step the heterocycles (9a-f) were alkylated. Some
of the alkylating agents of our choice (Scheme 4) were
commercially available (11e-g), while others (11a-d) were
prepared by us. These latter reagents, bearing a pendant olefin
moiety, were selected on the basis of their inherent potential to
act as weakly coordinating ligands or alkylidene sources in
transition metal complexes. Besides its ability to be attached to
a metal center, the unsaturated bond in ligands derived from
11a-d also offers the possibility of further functionalization.
The preparation of 11a-d followed a straightforward strategy:
alkylation of salicylaldehide with R,ω-dihalogenoalkanes gave
the O-alkylated aldehydes (10a-d), whose carbonyl group was
converted to the olefin moiety (11a-d) in a classical Wittig
reaction.26 During the Wittig reaction, which gave a 60:40
mixture of E- and Z-isomers in all cases,27 we also observed
the partial exchange of the pendant halogen by iodine, so in
(23) On the basis of chemical precedent, we presume that the utilized
transformations do not erode the R/S enantiomer ratio introduced with the
commercial amines (97:3 for 2c and >99.5:0.5 for 2e), but so far we were
unable to prove this hypothesis by measuring the enantiomer ratio of the
formed salts.
(24) (a) Dominianni, S. J. Y.; Terence T. J. Med. Chem. 1989, 32, 2301-
2306. (b) Athey, P. S.; Kiefer, G. E. J. Org. Chem. 2002, 67, 4081-4085.
(c) Cetinkaya, B.; Hitchcock, E.; Peter, B.; Lappert, M. F., Oezdemir, I. J.
Chem. Soc., Dalton Trans. 1997, 1359-1362.
(25) Saba, S.; Brescia, A. M.; Kaloustian, M. K. Tetrahedron Lett. 1991,
32, 5031-5034
(26) (a) Wehrli, R.; et al. HelV. Chim. Acta 1977, 60, 2034-2061. (b)
Hollywood, F.; Suschitzky, H. Synthesis 1982, 662-665.
J. Org. Chem, Vol. 71, No. 16, 2006 5971

Paczal et al.
TABLE 1. 1,3-Disubstituted 4,5-Dihydroimidazolium (6d-m) and 3,4,5,6-Tetrahydropyrimidinium (6n-p) Salts Prepared by the Alkylation of
the Appropriate Heterocycles (9a-f)
diethyl,30 and dimesityl31 tetrahydropyrimidinium salts were
SCHEME 5
investigated and the anion (BF4- or PF6-) was often disordered.
The more interesting structural features of 6o are the proximity
of C2 and I1 (3.251(4) Å) resulting in a weak C2-H2-I1
hydrogen bond, as well as the repulsion between the allylic
methyl group of C39 and the disordered methylene group of
C5 resulting a short C38-C39 bond (1.297(12) Å). A strong
electrostatic interaction between the iodide anion and tetrahy-
dropyrimidinium cation stabilizes the structure and the iodide
ion is also close to the neighboring tetrahydropyrimidinium
rings. Solution NMR results show that the compound is a
mixture of E and Z isomers and it was also supported by the
X-ray analysis. Based on the X-ray data and large atomic
displacement parameters, the amount of the E isomer is
estimated to be less than 10% in the single crystalline solid
phase.
Besides their conversion to the neutral heterocycles, the
N-substituted diamines (8a-f) might also be utilized in the
preparation of such systems where the two nitrogen atoms bear
different aryl moieties (Scheme 6). Buchwald-Hartwig coupling
order to complete the process, the crude product was converted
to the iodo derivative in a Finkelstein reaction using NaI as
reagent.
Alkylation of the heterocycles 9a-f proceeded smoothly in
DMF at elevated temperatures and the desired dihydroimida-
zolium (6d-m) and tetrahydropyrimidinium salts (6n-p) were
isolated in good yield (Scheme 5, Table 1). The chiral
dihydroimidazolium salts 6k and 6m are by definition also ionic
liquids, having their melting points below 100 °C. The structure
of the products was verified unambiguously by 1H and 13C NMR
measurements, and in the case of 6o, we observed the formation
of “cubic” crystals, which were suitable for X-ray analysis. The
ORTEP diagram of the unit cell of the crystal and its packing
diagram are placed in the Supporting Information.
Search of the Cambridge Structural Database (Version 5.26
update Aug. 2005)28 revealed that X-ray structure of 1,3-
disubstituted 3,4,5,6-tetrahydropyrimidinium salts has been
reported only for a few symmetrical systems: diisopropyl,29
(29) Alder, R. W.; Blake, M. E.; Bortolotti, C.; Bufali, S.; Butts, C. P.;
Linehan, E.; Oliva, J. M.; Orpen, G. A.; Quayle, M. J. Chem. Commun.
1999, 241-242.
(30) Alder, R. W.; Blake, M. E.; Bufali, S.; Butts, C. P.; Orpen, G. A.;
Schutz, J.; Williams, S. J. J. Chem. Soc., Perkin Trans. 1 2001, 1586-
1593.
(27) Since the envisaged application of NHCs prepared from 11a-d was
not influenced by the geometry of the olefin side chain, no further attempts
were made to improve the E/Z selectivity of the Wittig reaction.
(28) Allen, F. H. Acta Crystallogr. 2002, B58, 380-388.
(31) (a) Hermann, W. A.; Schneider, S. K.; Ofele, K.; Sakamoto, M.;
Herdtweck, E. J. Organomet. Chem. 2004, 689, 2441-2449. (b) Paulsen,
A. L.; Madsen, R. Heterocycles 2004, 63, 2051-2056.
5972 J. Org. Chem., Vol. 71, No. 16, 2006

Modular Synthesis of Heterocyclic Carbene Precursors
SCHEME 6
SCHEME 7
the appropriate solvent. Reactions were monitored by GC and TLC
and were run until completion. In the cases of 3a-d,f, the K2CO3
was removed by filtration, the MeCN was evaporated under reduced
pressure, and the crude products were recrystallized from DCM-
hexane. In the case of 3e, the volume of the solvent was reduced
to half, and following the addition of DCM the organic layer was
washed with water and brine and dried over MgSO4. Following
the evaporation of the solvent, 3e was obtained as white crystals.
N-Chloroacetylmesitylamine (3a).34 Starting from 2a (10 mL,
9.63 g, 71.2 mmol), K2CO3 (19,6 g, 142.4 mmol), and 1a (6.8 mL,
85.4 mmol) in 200 mL of MeCN, 3a was obtained (14.31 g, 67.61
mmol, 95%) as a white solid: mp 178-178.5 °C; 1H NMR (CDCl3,
250 MHz) δ 7.83 (s, 1H), 6.9 (s, 2H), 4.21 (s, 2H), 2.27 (s, 3H),
2.18 (s, 6H); 13C NMR (CDCl3, 62.5 MHz) δ 164.5, 137.5, 134.9,
129.9, 128.9, 42.6, 20.8, 18.1. IR (KBr) 3228, 2921, 2104, 1669,
1536, 1240 cm-1. Anal. Calcd for C11H14ClNO: C, 62.41; H, 6.67;
N, 6.62. Found: C, 62.15; H, 6.42; N, 6.72.
N-Chloroacetyl-2,6-diisopropylaniline (3b).35 Starting from 2b
(10 mL, 9.39 g, 52.9 mmol), K2CO3 (14,6 g, 105.8 mmol), and 1a
(4.21 mL, 52.9 mmol) in 200 mL of MeCN, 3b was obtained (12.48
g, 49.18 mmol, 93%) as a white solid: mp 148-149 °C; 1H NMR
(CDCl3, 250 MHz) δ 7.83 (s, 1H), 7.36-7.19 (m, 3H), 4.26 (s,
2H), 3.11-2.94 (m, 2H), 1.22 (d, 12H, J ) 6.9 Hz); 13C NMR
(CDCl3, 62.5 MHz) δ 165.3, 145.9, 129.9, 128.8, 123.6, 42.7, 28.8,
23.5. IR (KBr) 3251, 2960, 2105, 1680, 1658, 1530 cm-1. Anal.
Calcd for C14H20ClNO: C, 66.26; H, 7.94; N, 5.52. Found: C,
66.73; H, 7.66; N, 5.28.
N-Chloroacetyl-(1R)-(+)-1-phenylethylamine (3c).22 Starting
from 2c (9.65 g, 10 mL, 77.5 mmol), K2CO3 (21.39 g, 155 mmol),
and 1a (6.14 mL, 77.5 mmol) in 200 mL of MeCN, 3c was obtained
(15.01 g, 75.95 mmol, 98%) as a white solid: mp 101-102 °C;
1H NMR (CDCl3, 250 MHz) δ 7.38-7.25 (m, 5H), 6.85 (s, 1H),
5.12 (quint., 1H, J ) 7.0 Hz), 4.02 (dd, 2H, J ) 15.2 Hz, J ) 2.5
Hz), 1.52 (d, 3H, J ) 6.9); 13C NMR (CDCl3, 62.5 MHz) δ 164.9,
142.2, 128.7, 127.5, 126.0, 49.2, 42.5, 21.6; [R]546 ) +64.8 (c 5.09,
CH2Cl2); IR (KBr) 3261, 2978, 1650, 1548, 1233 cm-1. Anal. Calcd
for C10H12ClNO: C, 60.76; H, 6.12; N, 7.09. Found: C, 60.96; H,
5.98; N, 6.92.
of 8b with 1-iodo 2-methoxynaphthalene gave the N,N′-
diarylethylenediamine derivative 5d, while the coupling of the
analogous 8f with 2-bromotoluene also proceeded readily to give
the appropriate propylenediamine derivative 5e.32 The moderate
yields are due to the fact that these reaction conditions were
not optimized.33 Ring closure of the diamines (5d,e) with
trimethyl orthoformate gave the desired N,N′-diaryldihydroimi-
dazolium (6q) and tetrahydropyrimidinium (6r) salts in varying
yields, the formation of the six-membered ring proceeding less
efficiently, as previously observed in other cases.
The monoarylated ethylenediamine 8b was also used to
prepare a ferrocenylmethyl substituted NHC precursor (Scheme
7). Condensation of 8b with acetylferrocene, followed by the
reduction of the crude imine gave the diamine 5f in good yield.
Attempts to isolate the ferrocenylimine in pure form were
unsuccessful, due to the instability of this compound, while the
diamine was stable and easy to purify by column chromatog-
raphy. Treatment of 5f with trimethyl orthoformate gave the
desired ferrocenylmethyldihydroimidazolium salt (6s) as a
brownish yellow solid in acceptable yield.
Conclusion
In summary, we elaborated a series of synthetic protocols
that enable the preparation of dihydromidazolium and tetrahy-
dropyrimidinium salts bearing different substituents in positions
1 and 3. These routes rely on the use of easily available starting
materials and allow for the efficient preparation of the target
systems with different substituent combinations, which include
chiral and achiral alkyl groups, as well as different aryl moieties;
the introduction of bulky substituents, e.g., 2,6-diisopropylphen-
yl, posed no difficulty either. Some of the new chiral dihy-
droimidazolium salts were found to be ionic liquids. Study of
the prepared carbene precursors as supporting ligands in metal
complexes or as organocatalysts is in progress in our labora-
tories.
N-Chloroacetyl-1-aminoadamantane (3d).36 Starting from 2d
(10.0 g, 66.1 mmol), K2CO3 (18.24 g, 132 mmol), and 1a (5.26
mL, 66.1 mmol) in 200 mL of MeCN, 3d was obtained (10.53 g,
46.24 mmol, 70%) as an off-white solid: mp 119-120 °C; 1H NMR
Experimental Section
General Procedure for the Preparation of Amides 3a-f. The
acylating agent (1a or 1b) was added dropwise with vigorous
stirring to the mixture of the corresponding amine and K2CO3 in
(34) Lebedeva, A. S.; Chernyakova, I. V.; Likhosherstov, A. M.; Sipilina,
N. M.; Ivanova, T. I.; Zagorevskii, V. A.; Vinokurov, V. G.; Zhukov, V.
N.; Skoldinov, A. P. Khim.-Farm. Zh. 1991, 25, 13-15; Chem. Abstr. 1991,
115, 8551.
(35) Phillips, G. B.; Morgan, T. K.; Nickisch, K.; Lind, J. M.; Gomez,
R. P.; et al. J. Med. Chem. 1990, 33, 627-633.
(36) Sztaricskai, F.; Pelyvas, I.; Dinya, Z.; Szilagyi, L.; Gyorgydeak,
Z.; Hadhazy, Gy.; Vaczi, L.; Bognar, R. Pharmazie 1975, 30, 571-581.
(32) van Veldhuizen, J. J.; Campbell, J. E.; Giudici, R. E.; Hoveyda, A.
H. J. Am. Chem. Soc. 2005, 127, 6877-6882.
(33) The same N,N′-disubstituted diamines might also be prepared in
comparable yields in the reaction of the chloroacetamide 3b or chloropro-
pionamide 3f and the appropriate aromatic amines. Paczal, A.; Kotschy,
A. Unpublished results.
J. Org. Chem, Vol. 71, No. 16, 2006 5973

Paczal et al.
(CDCl3, 250 MHz) δ 6.22 (s, 1H), 3.90 (s, 2H), 2.12-2.03 (m,
3H), 2.03-1.95 (m, 6H), 1.66 (t, 6H, J ) 2.8 Hz); 13C NMR
(CDCl3, 62.5 MHz) δ 164.5, 52.3, 42.8, 41.1, 36.1, 29.3; IR (KBr)
3238, 3082, 2905, 2105, 1661, 1567, 1236 cm-1. Anal. Calcd for
C12H18ClNO: C, 63.29; H, 7.97; N, 6.15. Found: C, 63.12; H,
7.85; N, 6.32.
amine (1.82 g, 12 mmol), and K2CO3 (1.65 g, 12 mmol) in 50 mL
of MeCN, 4c was obtained (1.58 g, 5.05 mmol, 85%) as a yellow
oil: 1H NMR (DMSO-d6, 250 MHz) δ 8.2 (d, 1H, J ) 8.2 Hz),
7.34-7.16 (m, 10H), 4.95 (quint., 1H, J ) 7.0 Hz), 4.46 (s, 2H),
3.48 (t, 2H, J ) 5.4 Hz), 3.13 (s, 2H), 2.67 (t, 2H, J ) 5.4 Hz)
2.4-2.2 (br s, 1H), 1.34 (d, 3H, J ) 7.0 Hz); 13C NMR (DMSO-
d6, 62.5 MHz) δ 170.2, 144.4, 138.4, 128.2, 128.1, 127.4, 127.3,
126.5, 125.8, 71.8, 69.3, 51.9, 48.5, 47.4, 22.3; [R]546 ) +38.9 (c
1.98, CH2Cl2); IR (KBr) 3313, 2862, 1655, 1603, 1095, 738, 697
cm-1. Anal. Calcd for C19H24N2O2: C, 73.05; H, 7.74; N, 8.97.
Found: C, 72.92; H, 7.59; N, 8.78.
N-Chloroacetyl-(2R)-(-)-3,3-dimethyl-2-aminobutane (3e).37
Starting from 2e (5 mL, 3.62 g, 35.8 mmol), K2CO3 (9.88 g, 71.4
mmol), and 1a (2.84 mL, 35.8 mmol) in 100 mL of MeCN and 25
mL of H2O, 3e was obtained (6.10 g, 34.36 mmol, 96%) as a white
1
solid: mp 71-71.5 °C; H NMR (CDCl3, 250 MHz) δ 6.46 (s,
General Procedures for the Preparation of Ethylenediamine
Derivatives. By Reduction of Aminoacetamides (5a-c). The
mixture of the aminoamide (4a-c) and 4 equiv of LiAlH4 was
refluxed in freshly distilled THF under Ar until the reaction was
judged complete by GC or TLC. The compounds were used in the
next steps without purification.
In Buchwald-Hartwig Coupling (5d,e). A mixture of the
monosubstituted ethylenediamine (8b,f), 1 equiv of aryl halide, 4
equiv of KOtBu, 10 mol % of Pd(OAc)2, and 20 mol % of (()-
BINAP in 10 mL of toluene/mmol substrate was heated under Ar
atmosphere at 100 °C until the reaction was judged complete by
GC. The reaction mixtures were filtered trough Celite, and after
evaporation of the volatiles in vacuo the crude product was purified
by column chromatography (Hex/EtOAc as eluent).
N-Mesityl-N′-((1R)-1-phenylethyl)ethylenediamine (5a). Start-
ing from 4a (1.5 g, 7.08 mmol) and LiAlH4 (1.07 g, 28.32 mmol)
in 100 mL of THF, 5a was obtained (1.01 g, 3.6 mmol, 71%) as
yellow oil: 1H NMR (CDCl3, 250 MHz) δ 7.32-7.19 (m, 5H.),
6.79 (s, 2H), 3.77 (q, 1H, J ) 6.6 Hz), 3.00-2.95 (m, 2H), 2.75-
2.58 (m, 2H), 2.24 (s, 6H), 2.21 (s, 3H), 1.37 (d, 3H, J ) 6.6 Hz);
13C NMR (CDCl3, 62.5 MHz) δ 145.7, 143.8, 129.4, 128.4, 126.8,
126.5, 58.2, 48.6, 47.9, 24.3, 20.5, 18.4; [R]546 ) +26.8 (c 3.06,
CH2Cl2); IR (KBr) 3359, 2971, 2922, 2848, 1484, 1434, 1242, 1119,
762, 700 cm-1 Anal. Calcd for C19H26N2: C, 80.80; H, 9.28; N,
9.92. Found: C, 80.68; H, 9.46; N, 9.69.
1H), 4.03 (s, 2H), 3.90-3.78 (m, 1H), 1.07 (d, 3H, J ) 6.8 Hz),
0.89 (s, 9H); 13C NMR (CDCl3, 62.5 MHz) δ 164.9, 53.3, 42.8,
34.1, 26.0, 15.8; [R]546 ) -33 (c 5.00, CH2Cl2); IR (KBr) 3292,
2966, 1649, 1554 cm-1. Anal. Calcd for C8H16ClNO: C, 54.08;
H, 9.08; N, 7.88. Found: C, 54.34; H, 9.22; N, 7.81.
N-(3′-Chloropropionyl)mesitylamine (3f).38 Starting from 2a
(10 mL, 9.63 g, 71.2 mmol), K2CO3 (19,6 g, 142.4 mmol), and 1b
(6.8 mL, 71.2 mmol) in 200 mL of MeCN, 3f was obtained (11.73
g, 51.97 mmol, 73%) as a light yellow solid: mp 130-131 °C;
1
obtained as a 9:1 mixture of syn/anti amide rotamers; H NMR
(CDCl3, 250 MHz) syn δ 7.64 (s, 1H), 6.76 (s, 2H), 3.76 (t, 2H, J
) 6.2 Hz), 2.67 (t, 2H, J ) 6.2 Hz), 2.22 (s, 3H), 2.05 (s, 6H); anti
δ 7.64 (s, 1H), 6.93 (s, 2H), 3.72 (t, 2H, J ) 6.4 Hz), 2.35 (t, 2H,
J ) 6.4 Hz), 2.30 (s, 3H), 2.20 (s, 6H); 13C NMR (CDCl3, 62.5
MHz) syn δ 168.5, 136.6, 134.9, 130.9, 128.6, 40.3, 39.1, 20.8,
18.1; anti δ 172.1 138.2, 136.2, 131.1, 129.3, 38.9, 34.9, 20.8, 18.3.
Anal. Calcd for C12H16ClNO: C, 63.85; H, 7.14; N, 6.21. Found:
C, 64.02; H, 6.94; N, 6.33.
General Procedure for the Preparation of Aminoamides 4a-
c. A mixture of the chloroamide (3a,c,f), 2 equiv of the corre-
sponding amine (2c,f), and 2 equiv K2CO3 were refluxed in MeCN
until the reaction was judged complete by GC or TLC. Following
removal of K2CO3 by filtration, the solvent was evaporated under
reduced pressure. The crude products were purified by column
chromatography (4a) or by short path distillation at 190-200 °C,
0.2 mbar (4b and 4c).
N-(2-Benzyloxyethyl)-N′-(2R-3,3-dimethylbut-2-yl)ethylene-
diamine (5b). Starting from 4b (1 g, 3.42 mmol) and LiAlH4 (389
mg, 10.26 mmol) in 50 mL of THF, 5b was obtained (790 mg,
2.84 mmol, 83%) as a yellow oil: 1H NMR (DMSO-d6, 250 MHz)
δ 7.33-7.23 (m, 5H), 4.46 (s, 2H), 3.48 (t, 2H, J ) 5.6 Hz), 2.76-
2.66 (m, 3H), 2.58-2.53 (m, 2H), 2.46-2.37 (m, 1H), 2.10 (q,
1H, J ) 6.5 Hz), 1.8-1.2 (br s, 2H), 0.89 (d, 3H, J ) 6.5 Hz),
0.82 (s, 9H); 13C NMR (DMSO-d6, 62.5 MHz) δ 138.5, 128.0,
127.2, 127.1, 71.8, 69.5, 61.4, 49.2, 48.6, 47.8, 34.1, 26.2, 14.6;
[R]546 ) -40.36 (c 5.5, CH2Cl2); IR (KBr) 3324, 3030, 2866, 1665,
1453, 1362, 1097, 735, 697 cm-1. Anal. Calcd for C17H30N2O: C,
73.33; H, 10.86; N, 10.06. Found: C, 73.11; H, 10.81; N, 9.98.
N-(2-Benziloxyethyl)-N′-((1R)-1-phenylethyl)ethylene-
diamine (5c). Starting from 4c (1.00 g, 3.2 mmol) and LiAlH4 (364
mg, 9.6 mmol) in 50 mL of THF, 5c was obtained (740 mg, 2.49
mmol, 78%) as a yellow oil: 1H NMR (DMSO-d6, 250 MHz) δ
7.37-7.14 (m, 10H), 4.45 (s, 2H), 3.64 (q, 1H, J ) 6.8 Hz), 3.45
(t, 2H, J ) 5.6 Hz), 2.63 (t, 2H, J ) 5.6 Hz), 2.56-2.46 (m, 3H),
2.44-2.28 (m, 3H), 1.20 (d, 3H, J ) 6.8 Hz); 13C NMR (DMSO-
d6, 62.5 MHz) δ 146.3, 138.5, 128.1, 128.0, 127.3, 127.2, 126.3,
71.8, 69.4, 57.5, 49.0, 48.5, 46.8, 24.5; [R]546 ) +23.4 (c 4.99,
CH2Cl2); IR (KBr) 3313, 2862, 1655, 1516, 1452, 1095, 738, 697
cm-1. Anal. Calcd for C19H26N2: C, 76.47; H, 8.78; N, 9.39.
Found: C, 76.22; H, 9.05; N, 9.33.
N-Mesityl-2-((1′R)-1′-phenylethylamino)acetamide (4a). Start-
ing from 3a (1.20 g, 6 mmol), 2c (1.45 g, 12 mmol), and K2CO3
(1.65 g, 12 mmol) in 50 mL of MeCN, 4a was obtained (1.37 g,
1
4.62 mmol, 82%) as a white solid: mp 68 °C; H NMR (CDCl3,
250 MHz) δ 8.63 (s, 1H), 7.36-7.21 (m, 5H), 6.86 (s, 2H), 3.82
(q, 1H, J ) 6.6 Hz), 3.29 (s, 2H), 2.24 (s, 3H), 2.12 (s, 6H), 2.01
(s, 1H), 1.41 (d, 3H, J ) 6.6 Hz); 13C NMR (CDCl3, 62.5 MHz) δ
170.2, 144.2, 136.5, 134.6, 131.0, 128.7, 128.5, 127.3, 126.4, 58.3,
50.2, 23.8, 20.7, 18.2; [R]546 ) +48.7 (c 5.17, CH2Cl2); IR (KBr)
3324, 3285, 2973, 2911, 1674, 1497 cm-1. Anal. Calcd for
C19H24N2O: C, 76.99; H, 8.16; N, 9.45. Found: C, 76.61; H, 8.18;
N, 9.37.
2-(2′-Benzyloxyethylamino)-N-((2R)-3,3-dimethylbut-2-yl)-
acetamide (4b). Starting from 3e (1.20 g, 6.7 mmol), 2-benzyl-
oxyethylamine (2.04 g, 13.4 mmol), and K2CO3 (1.85 g, 13.4 mmol)
in 50 mL of MeCN, 4b was obtained (1.61 g, 5.49 mmol, 82%) as
yellow oil: 1H NMR (DMSO-d6, 250 MHz) δ 7.50 (d, 1H, J )
9.6 Hz), 7.37-7.23 (m, 5H), 4.47 (s, 2H), 3.74-3.62 (m, 1H), 3.47
(t, 2H, J ) 5.6 Hz), 4.4-3.12 (br s, 1H), 2.65 (t, 2H, J ) 5.6 Hz),
0.94 (d, 3H), 0.81 (s, 9H); 13C NMR (DMSO-d6, 62.5 MHz) δ
170.1, 138.4, 128.4, 128.1, 127.4, 127.3, 71.9, 69.4, 51.9, 51.3,
48.6, 33.8, 26.0, 15.7; [R]546 ) -10.4 (c 2.5, CH2Cl2); IR (KBr)
3316, 2962, 2868, 1655, 1521, 1096, 736, 698 cm-1. Anal. Calcd
for C17H28N2O2: C, 69.83; H, 9.65; N, 9.58. Found: C, 69.65; H,
9.88; N, 9.32.
N-(2,6-Diisopropylphenyl)-N′-(2-methoxynaphth-1-yl)ethyl-
enediamine (5d). Starting from 8b (220 mg, 1 mmol) and 1-iodo-
2-methoxynaphthalene (284 mg, 1 mmol), 5d was obtained (169
mg, 0.45 mmol, 45%) as a brown oil: 1H NMR (CDCl3, 250 MHz)
δ 8.17 (d, 1H, J ) 9.0 Hz.), 7.75 (d, 1H, J ) 8.7 Hz), 7.51-7.39
(m, 2H), 7.34-7.21 (m, 2H), 7.14-7.00 (m, 3H), 4.4-3.4 (br s,
2H), 3.92 (s, 3H), 3.53 (t, 2H, J ) 5.4 Hz), 3.30 (hept, 2H, J ) 6.8
Hz), 3.04 (t, 2H, J ) 5.98 Hz), 1.20 (d, 12H, J ) 6.8 Hz); 13C
NMR (CDCl3, 62.5 MHz) δ 147.7, 143.3, 142.5, 131.7, 129.9,
2-(2′-Benzyloxyethylamino)-N-((1R)-1-phenylethyl)acet-
amide (4c). Starting from 3c (1.20 g, 6 mmol), 2-benzyloxyethyl-
(37) Fu, Shou-Cheng J.; Birnbaum, S. M. J. Am. Chem. Soc. 1953, 75,
918-920.
(38) Dofek, R.; Vrba, C. Collect. Czech. Chem. Commun. 1960, 25,
1596-1599.
5974 J. Org. Chem., Vol. 71, No. 16, 2006

Modular Synthesis of Heterocyclic Carbene Precursors
128.3, 128.4, 123.7, 123.6, 123.5, 122.7, 122.6, 113.3, 56.7, 51.9,
50.3, 27.6, 24.2; IR (KBr) 3360, 2959, 1594, 1512, 1460, 1263,
799, 736 cm-1. Anal. Calcd for C25H32N2O: C, 79.75; H, 8.57; N,
7.44. Found: C, 79.98; H, 8.85; N, 7.35.
mg, 0.75 mmol) and NH4BF4 (86.6 mg, 0.82 mmol) in 2 mL of
trimethyl orthoformate, 6b was obtained (241 mg, 0.64 mmol, 85%)
as a colorless liquid: 1H NMR (CDCl3, 250 MHz) δ 8.00 (s, 1H),
7.35-7.23 (m, 5H), 4.50 (s, 2H), 4.00-3.90 (m, 4H), 3.75-3.62
(m, 4H), 3.49 (q, 1H, J ) 7.0 Hz), 1.26 (d, 3H, J ) 7.0 Hz), 0.90
(s, 9H); 13C NMR (CDCl3, 62.5 MHz) δ 157.9, 137.3, 128.2, 127.7,
72.7, 65.9, 63.2, 48.4, 48.1, 47.5, 34.9, 26.3, 13.2; [R]546 ) -21 (c
N-Mesityl-N′-(o-tolyl)propylenediamine (5e). Starting from 8e
(385 mg, 2 mmol) and 2-bromotoluene (342 mg, 2 mmol), 5e was
obtained (366 mg, 1.3 mmol, 65%) as a brown oil: 1H NMR
(CDCl3, 250 MHz) δ 7.14-7.01 (m, 2H), 6.80 (s, 2H), 6.67-6.58
(m, 2H), 3.4 (br s, 2H), 3.28 (t, 2H, J ) 6.6 Hz), 3.05 (t, 2H, J )
6.6 Hz), 2.23 (s, 6H), 2.21 (s, 3H), 2.09 (s, 3H), 1.91 (quint, 2H,
J ) 6.7 Hz); 13C NMR (CDCl3, 62.5 MHz) δ 146.2, 143.3, 131.4,
129.9, 129.7, 129.4, 127.0, 121.8, 116.7, 109.4, 47.2, 42.4, 30.6,
20.5, 18.2, 17.4; IR (KBr) 1666, 1313, 1051, 986 cm-1. Anal. Calcd
for C19H26N2: C, 80.80; H, 9.28; N, 9.92. Found: C, 80.56; H,
9.56; N, 9.90.
N-(2,6-Diisopropylphenyl)-N′-(1-ferrocenylethyl)ethylenedi-
amine (5f). Compound 8b (0.965 g, 4.4 mmol), acetylferrocene
(1.00 g, 4.4 mmol), and a catalytic amount of p-TsOH were
dissolved in 50 mL of toluene and refluxed in a vessel equipped
with a Dean-Stark distillation head for 5 h. The solvent was
removed under reduced pressure to give 1.57 g of the crude product,
which was used without further purification. The reduction of the
Schiff base was carried out in 50 mL of methanol by stirring with
690 mg (18 mmol, 5 equiv) of NaBH4 at room temperature for 2
h. The crude product was purified by flash chromatography using
hexanes-ethyl acetate as eluent. Compound 5f was obtained (1.39
g, 3.22 mmol, 70%) as a brown oil: 1H NMR (CDCl3, 250 MHz)
δ 7.16-7.05 (m, 3H), 4.24-4.15 (m, 9H), 3.62 (q, 1H, J ) 6.6
Hz), 3.58 (hept, 2H, J ) 6.8 Hz), 3.09-2.83 (m, 4H), 1,47 (d, 3H,
J ) 6.6 Hz), 1.58 (d, 12H, J ) 6.8 Hz); 13C NMR (CDCl3, 62.5
MHz) δ 143.6, 142.2, 123.4, 93.8, 68.3, 67.3, 67.2, 67.0, 65.7, 52.1,
51.7, 47.5, 27.5, 24.3, 21.6; IR (KBr) 2965, 1639, 1263, 1145, 1073
cm-1. Anal. Calcd for C26H36FeN2: C, 72.22; H, 8.39; N, 6.48.
Found: C, 72.09; H, 8.25; N, 6.42.
General Procedure for the Preparation of Dihydroimidazo-
lium and Tetrahydropyrimidinium Salts. By the Ring Closure
of Diamines(6a-c,q-s). The appropriate diamine was refluxed in
20 equiv of trimethyl orthoformate in the presence of 1.1 equiv of
NH4BF4 under argon atmosphere until its consumption. The
volatiles were removed under reduced pressure, and the residue
was dissolved in a little DCM and precipitated by the addition of
diethyl ether. The precipitate was filtered and recrystallized from
toluene/butanol except for 6b and 6c, which are liquid at ambient
temperature, and purified by column chromatography using ethyl
acetate-methanol as eluent.
By the Alkylation of Dihydroimidazoles or Tetrahydropyri-
midines (6d-p). A solution of the parent heterocycle and 1 equiv
of the alkylating agent was heated in DMF at 100 °C under argon
until the reaction was judged complete by TLC. After the solution
was cooled to room temperature, the solvent was removed in a
vacuum, and the residue was dissolved in MeCN and stirred with
10 equiv of NaBF4 overnight. After evaporation of the solvent, the
solid was dissolved in DCM. Following removal of the inorganics
by filtration, the products were precipitated by the addition of diethyl
ether and purified by crystallization from DCM-ether.
6.2, CH2Cl2); IR (KBr) 2971, 2876, 1645, 1057, 909, 727 cm-1
.
Anal. Calcd for C18H29BF4N2O: C, 57.46; H, 7.77; N, 7.45.
Found: C, 57.26; H, 7.84; N, 7.32.
3-(2′-Benzyloxyethyl)-1-((1′R)-1′-phenylethyl)-4,5-dihydroimi-
dazolium Tetrafluoroborate (6c). Starting from 5c (500 mg, 1.67
mmol) and NH4BF4 (175 mg, 1.67 mmol) in 5 mL of trimethyl
orthoformate, 6c was obtained (595 mg, 1.5 mmol, 90%) as a
colorless liquid: 1H NMR (CDCl3, 250 MHz) δ 8.19 (s, 1H), 7.41-
7.24 (m, 10H), 4.74 (q, 1H, J ) 7.00 Hz), 4.51 (s, 2H), 3.98-3.83
(m, 2H), 3.76-3.63 (m, 6H), 1.69 (d, 3H, J ) 7 Hz); 13C NMR
(CDCl3, 62.5 MHz) δ 156.5, 137.5, 137.5, 129.3, 128.9, 128.5,
127.9, 127.8, 126.7, 73.0, 66.6, 58.2, 49.0, 48.1, 47.0, 19.3; [R]546
) +6.64 (c 4.02, CH2Cl2); IR (KBr) 3030, 2925, 1646, 1051, 1034,
748, 701 cm-1. Anal. Calcd for C20H25BF4N2O: C, 60.62; H, 6.36;
N, 7.07. Found: C, 60.89; H, 6.36; N, 6.82.
1-Mesityl-3-(4′-[2′′-propenylphenyl]butyl)-4,5-dihydroimida-
zolium Iodide (6d). Starting from 9a (250 mg, 1.32 mmol) and
11b (417 mg, 1.32 mmol) in 10 mL of DMF, 6d was obtained
(514 mg, 1.02 mmol, 78%) as a white solid: mp 132-133 °C; a
1
7:3 mixture of Z and E isomers; H NMR (CDCl3, 250 MHz) E:
δ 8.95 (s, 1H), 7.37-7.09 (m, 2H), 6.90-6.79 (m, 4H), 6.67 (dd,
1H, J ) 15.7 Hz, J ) 1.4 Hz), 6.18 (dq, 1H, J ) 15.7 Hz, J ) 6.4
Hz), 4.33-4.08 (m, 4H), 4.02-3.89 (m, 4H), 2.23 (s, 6H), 2.22 (s,
3H), 2.00-1.72 (m, 7H); Z: δ 8.90 (s, 1H), 7.37-7.09 (m, 2H),
6.90-6.79 (m, 4H), 6.48 (dd, 1H, J ) 11.8 Hz, J ) 1.5 Hz), 5.72
(dq, 1H, J ) 11.8 Hz, J ) 7.1 Hz), 4.33-4.08 (m, 4H), 4.02-3.89
(m, 4H), 2.23 (s, 6H), 2.22 (s, 3H), 2.00-1.72 (m, 7H); 13C NMR
(CDCl3, 62.5 MHz) δ 157.8, 155.8, 154.9, 140.1, 140.0, 135.1,
130.2, 129.9, 129.7, 127.9, 127.7, 126.8, 126.6, 126.2, 126.1, 125.9,
125.3, 125.0, 120.6, 120.0, 111.9, 111.6, 67.2, 67.1, 50.8, 49.0,
48.2, 25.8, 25.7, 23.9, 23.8, 20.9, 20,8, 18.9, 18.2, 14.5; IR (KBr)
3032, 2970, 1642, 1486, 1448, 1243, 1229 cm-1. Anal. Calcd for
C25H33IN2O: C, 59.52; H, 6.59; N, 5.55. Found: C, 59.44; H, 6.42;
N, 5.25.
1-Mesityl-3-(5′-[2′′-propenylphenyl]pentyl)-4,5-dihydroimida-
zolium Iodide (6e). Starting from 9a (500 mg, 2.64 mmol) and
11c (872 mg, 2.64 mmol) in 10 mL of DMF, 6e was obtained (1.16
g, 2.24 mmol) as white solid: mp 153-154 °C; a 90:10 mixture
1
of Z and E isomers; H NMR (CDCl3, 250 MHz) E: δ 8.44 (s,
1H), 7.34 (d, 1H, J ) 7.6 Hz), 7.10 (t, 1H, J ) 7.3 Hz), 6.87-6.78
(m, 4H), 6.66 (d, 1H, J ) 15.9 Hz), 6.24-6.10 (m, 1H), 4.25-
4.09 (m, 4H), 3.93 (t, 2H, J ) 5.8 Hz), 3.75 (t, 2H, 6.4 Hz), 2.22
(s, 3H), 2.20 (6H), 1.89-1.78 (m, 7H), 1.70-1.52 (m, 2H); Z: 8.44
(s, 1H), 7.34 (d, 1H, J ) 7.6 Hz), 7.10 (t, 1H, J ) 7.3 Hz), 6.87-
6.78 (m, 4H), 6.51 (d, 1H, J ) 10.7 Hz), 5.82-5.69 (m, 1H), 4.25-
4.09 (m, 4H), 3.93 (t, 2H, J ) 5.8 Hz), 3.75 (t, 2H, 6.4 Hz), 2.22
(s, 3H), 2.20 (6H), 1.89-1.78 (m, 7H), 1.70-1.52 (m, 2H); 13C
NMR (CDCl3, 62.5 MHz) δ 157.7, 156.0, 155.2, 139.9, 135.1,
130.2, 129.7, 129.6, 127.7, 127.6, 126.7, 126.6, 126.2, 125.9, 125.8,
125.3, 124.9, 120.4, 119.7, 111.8, 111.5, 67.5, 65.5, 50.7, 48.7,
48.2, 28.4, 26.6, 22.6, 20.7, 18.7, 17.6, 15.0, 14.5; IR (KBr) 3015,
2866, 1643, 1488, 1444, 1244, 1055, 763 cm-1. Anal. Calcd for
C26H35IN2O: C, 60.23; H, 6.80; N, 5.40. Found: C, 60.13; H, 6.89;
N, 5.35%.
3-Mesityl-1-((1′R)-1′-phenylethyl)-4,5-dihydroimidazolium Tet-
rafluoroborate (6a). Starting from 5a (500 mg, 1.77 mmol) and
NH4BF4 (185 mg, 1.77 mmol) in 5 mL of trimethyl orthoformate,
6a was obtained (484 mg, 1.27 mmol, 72%) as a white solid: mp
119-120 °C; 1H NMR (CDCl3, 250 MHz) δ 8.02 (s, 1H), 7.39-
7.35 (m, 5H), 6.88 (s, 2H), 5.15 (q, 1H, J ) 6.8 Hz), 4.17-3.99
(m, 4H), 2.24 (s, 3H), 2.22 (s, 6H), 1.75 (d, 3H, J ) 6,8 Hz); 13C
NMR (CDCl3, 62.5 MHz) δ 156.8, 140.2, 137.2, 135.3, 130.6,
129.9, 129.4, 129.1, 127.0, 58.1, 50.8, 46.8, 20.9, 18.6, 17.4; [R]546
) +16.2 (c 2.02, CH2Cl2); IR (KBr) 3415, 2978, 1634, 1455, 1057,
703 cm-1. Anal. Calcd for C20H25N2BF4: C, 63.18; H, 6.63; N,
7.37. Found: C, 62.85; H, 6.66; N, 7.32.
1-Mesityl-3-(6′-[2′′-propenylphenyl]hexyl)-4,5-dihydroimida-
zolium Iodide (6f). Starting from 9a (250 mg, 1.32 mmol) and
11d (454 mg, 1.32 mmol) in 10 mL of DMF, 6f was obtained (575
mg, 1.08 mmol, 82%) as a white solid: mp 114-115 °C; a 7:3
1
mixture of Z and E isomers; H NMR (CDCl3, 250 MHz) E: δ
8.81 (s, 1H), 7.37-7.09 (m, 2H), 6.92-6.80 (m, 4H), 6.69 (d, 1H,
J ) 15.6 Hz), 6.27-6.13 (m, 1H), 4.33-4.12 (m, 4H), 3.94 (t,
2H, J ) 5.8 Hz), 3.83 (t, 2H, J ) 6.3 Hz), 2.25 (s, 9H), 1.89-1.76
3-(2′-Benzyloxyethyl)-1-((2′R)-3′,3′-dimethylbut-2′-yl)-4,5-di-
hydroimidazolium Tetrafluoroborate (6b). Starting from 5b (210
J. Org. Chem, Vol. 71, No. 16, 2006 5975

Paczal et al.
(m, 7H), 1.59-1.43 (m, 4H); Z: δ 8.81 (s, 1H), 7.37-7.09 (m,
2H), 6.92-6.80 (m, 4H), 6.54 (d, 1H, J ) 11.5 Hz), 5.85-5.72
(m, 1H), 4.33-4.12 (m, 4H), 3.94 (t, 2H, J ) 5.8 Hz), 3.83 (t, 2H,
J ) 6.3 Hz), 2.25 (s, 9H), 1.89-1.76 (m, 7H), 1.59-1.43 (m, 4H);
13C NMR (CDCl3, 62.5 MHz) δ 157.6, 156.1, 155.3, 139.9, 135.0,
130.2, 129.7, 129.6, 127.7, 127.5, 126.7, 126.2, 126.1, 126.0, 125.9,
125.4, 124.9, 120.3, 119.6, 111.8, 111.4, 67.7, 67.6, 50.8, 49.0,
48.3, 28.8, 26.8, 25.7, 25.6, 25.3, 20.7, 18.8, 18.0, 14.5; IR (KBr)
3033, 2862, 1645, 1489, 1449, 1239, 1051, 750 cm-1. Anal. Calcd
for C27H37IN2O: C, 60.90; H, 7.00; N, 5.26. Found: C, 60.95; H,
7.09; N, 5.31.
obtained (998 mg, 2.35 mmol, 82%) as a white solid: mp 91-92
°C; a 4:6 mixture of Z and E isomers; 1H NMR (CDCl3, 250 MHz)
E: δ 8.30 (s, 1H), 7.37-7.11 (m, 7H), 6.96-6.86 (m, 2H), 6.63
(dd, 1H, J ) 15.9 Hz, J ) 1.6 Hz), 6.13 (dq, 1H, J ) 15.9 Hz, J
) 6.6 Hz), 4.72-4.63 (m, 1H), 4.13-3.59 (m, 8H), 2.24-2.11
(m, 2H), 1.84 (dd, 3H, J ) 6.6 Hz, J ) 1.8 Hz), 1.60 (d, 3H, J )
7.0 Hz); Z: δ 8.33 (s, 1H), 7.37-7.11 (m, 7H), 6.96-6.86 (m,
2H), 6.45 (dd, 1H, J ) 11.7 Hz, J ) 1.7 Hz), 5.74 (dq, 1H, J )
11.7 Hz, J ) 7.1 Hz), 4.72-4.63 (m, 1H), 4.13-3.59 (m, 8H),
2.24-2.11 (m, 2H), 1.74 (dd, 3H, J ) 7.0 Hz, J ) 1.9 Hz), 1.61
(d, 3H, J ) 7.1 Hz); 13C NMR (CDCl3, 62.5 MHz) δ 155.9, 155.7,
154.8, 137.4, 130.0, 129.1, 128.7, 128.1, 128.0, 126.7, 126.5, 126.2,
126.0, 125.1, 124.8, 121.1, 120.4, 112.1, 111.8, 65.2, 65.1, 58.1,
3-Benzyl-1-mesityl-4,5-dihydroimidazolium Tetrafluorobo-
rate (6g). Starting from 9a (1.00 g, 5.3 mmol) and 11f (672 mg,
5.3 mmol, 0.61 mL) in 25 mL of DMF, 6g was obtained (1.45 g,
58.1, 48.1, 47.1, 46.0, 26.6, 26.6, 19.3, 19.3, 18.8, 14.5; [R]546
)
1
+8.64 (c 1.00, CH2Cl2); IR (KBr) 2972, 2874, 1645, 1450, 1233,
1054, 746 cm-1. Anal. Calcd for C23H29IN2O: C, 57.99; H, 6.14;
N, 5.88. Found: C, 57.65; H, 6.25; N, 5.75.
3.98 mmol, 75%) as a white solid: mp 142-143 °C; H NMR
(CDCl3, 250 MHz) δ 8.14 (s, 1H), 7.44-7.30 (m, 5H), 6.85 (s,
2H), 4.76 (s, 2H), 4.18-3.82 (m, 4H), 2.22 (s, 3H), 2.19 (s, 6H);
13C NMR (CDCl3, 62.5 MHz) δ 157.8, 140.1, 135.3, 132.4, 130.5,
129.8, 129.3, 129.1, 129.0, 52.1, 50.1, 48.2, 20.9, 17.3; IR (KBr)
3019, 1643, 1488, 1218, 1050 cm-1. Anal. Calcd for C19H23-
BF4N2O: C, 62.32; H, 6.33; N, 7.65. Found: C, 62.41; H, 6.19;
N, 7.56.
1-Adamantyl-3-methyl-4,5-dihydroimidazolium Iodide (6l).
Starting from 9d (204 mg, 1 mmol) and 11e (142 mg, 65 µL, 1
mmol) in 5 mL of MeCN, 6l was obtained (263 mg, 0.76 mmol,
1
76%) as a white solid: mp 225-226 °C; H NMR (CDCl3, 250
MHz) δ 9.00 (s, 1H), 4.08 (s, 4H), 3.41 (s, 3H), 2.21 (s, 3H), 2.01
(s, 6H), 1.69 (s, 6H); 13C NMR (CDCl3, 62.5 MHz) δ 154.7, 56.4,
50.0, 43.9, 40.3, 35.0, 34.8, 28.3; IR (KBr) 3020, 2904, 2846, 1648,
1304, 1139 cm-1. Anal. Calcd for C14H23IN2: C, 48.56; H, 6.70;
N, 8.09. Found: C, 48.41; H, 6.65; N, 8.11.
3-Ethoxymethyl-1-mesityl-4,5-dihydroimidazolium Tetrafluo-
roborate (6h). Starting from 9a (200 mg, 1.06 mmol) and 11g
(100 mg, 1.06 mmol, 49.3 µL) in 5 mL of DMF, 6h was obtained
(311 mg, 0.93 mmol, 88%) as a white solid: mp 120-121 °C; 1H
NMR (CDCl3, 250 MHz) δ 8.27 (s, 1H), 6.91 (s, 2H), 5.03 (s,
2H), 4.31-4.12 (m, 4H), 3.58 (q, 2H, J ) 7.0 Hz), 2.28 (s, 3H),
2.23 (s, 6H), 1.23 (t, 3H, J ) 7.0 Hz); 13C NMR (CDCl3, 62.5
MHz) δ 158.8, 140.4, 135.2, 130.1, 129.9, 78.0, 64.9, 51.3, 47.0,
1-Benzyl-3-((2′R)-3′,3′-dimethylbut-2′-yl)-4,5-dihydroimida-
zolium Tetrafluoroborate (6m). Starting from 9e (462 mg, 3
mmol) and 11f (344 µL, 380 mg, 3 mmol) in 10 mL of DMF, 6m
was obtained (847 mg, 2.55 mmol, 85%) as a white solid: mp
21.0, 17.3, 14.8; IR (KBr) 3080, 2981, 1643, 1115, 1070 cm-1
.
1
80-82 °C; H NMR (CDCl3, 250 MHz) δ 8.33 (s, 1H), 7.35-
Anal. Calcd for C15H23BF4N2O: C, 53.91; H, 6.94; N, 8.38.
Found: C, 53.83; H, 6.89; N, 8.52.
7.28 (m, 5H), 4.67 (dd, 2H, J ) 14.7 Hz, J ) 3.0 Hz), 4.08-3.72
(m, 4H), 3.58 (q, 1H, J ) 7.0 Hz), 1.29 (d, 3H, J ) 7.0 Hz), 0.95
(s, 9H); 13C NMR (CDCl3, 250 MHz) δ 157.5, 132.6, 129.2, 128.9,
128.8, 63.6, 51.9, 48.0, 47.2, 35.1, 26.6, 13.3; [R]546 ) -10.2 (c
5.01, CH2Cl2); IR (KBr) 3089, 2978, 1647, 1446, 1210, 1134, 1049
cm-1. Anal. Calcd for C16H25BF4N2: C, 57.85; H, 7.59; N, 8.43.
Found: C, 57.81; H, 7.60; N, 8.29.
1-(2′,6′-Diisopropylphenyl)-3-(5′-[2"-propenylphenyl]pentyl)-
4,5-dihydroimidazolium Iodide (6i). Starting from 9b (200 mg,
0.87 mmol) and 11c (275 mg, 0.87 mmol) in 5 mL of DMF, 6i
was obtained (307 mg, 0.59 mmol, 68%) as a white solid: mp
117-118 °C; a 60:40 mixture of Z and E isomers; 1H NMR (CDCl3,
250 MHz) E: δ 8.96 (s, 1H), 7.42-7.10 (m, 5H), 6.94-6.81 (m,
2H), 6.70 (dd, 1H, J ) 15.9 Hz, J ) 1.7 Hz), 6.20 (dq, 1H, J )
15.9 Hz, J ) 6.6 Hz), 4.40-4.15 (m, 4H), 3.99-3.90 (m, 4H),
2.88 (hept, 2H, J ) 6.7 Hz), 1.95-1.79 (m, 7H), 1.63-1.54 (m,
2H), 1.21 (dd, 12H, J ) 6.6 Hz, J ) 4.8 Hz); Z: δ 8.94 (s, 1H),
7.42-7.10 (m, 5H), 6.94-6.81 (m, 2H), 6.53 (dd, 1H, J ) 11.8
Hz, J ) 1.7 Hz), 5.77 (dq, 1H, J ) 11.8 Hz, J ) 6.5 Hz), 4.40-
4.15 (m, 4H), 3.99-3.90 (m, 4H), 2.88 (hept, 2H, J ) 6.7 Hz),
1.95-1.79 (m, 7H), 1.63-1.54 (m, 2H), 1.21 (dd, 12H, J ) 6.6
Hz, J ) 4.8 Hz); 13C NMR (CDCl3, 62.5 MHz) δ 157.6, 156.2,
155.3, 146.4, 130.9, 129.9, 129.6, 127.8, 127.7, 126.8, 126.3, 126.1,
125.9, 125.5, 125.1, 124.7, 120.5, 119.8, 111.9, 111.6, 67.7, 67.6,
53.3, 49.3, 48.4, 28.6, 28.5, 26.8, 26.7, 25.0, 23.9, 22.7, 18.9, 14.6;
IR (KBr) 2958, 1645, 1447, 1239, 1054, 751 cm-1. Anal. Calcd
for C29H41IN2O: C, 61.53; H, 7.19; N, 5.13. Found: C, 61.61; H,
7.23; N, 5.18.
1-Mesityl-3-(5′-[2′-propenylphenyl]pentyl)-3,4,5,6-tetrahydro-
pyrimidinium Iodide (6n). Starting from 9f (596 mg, 2.95 mmol)
and 11c (974 mg, 2.95 mmol) in 10 mL of DMF, 6n was obtained
(1.42 g, 2.65 mmol, 90%) as a white solid: mp 126-127 °C; a
60:40 mixture of Z and E isomers; 1H NMR (CDCl3, 250 MHz) E:
δ 8.18 (s, 1H), 7.35-7.09 (m, 2H), 6.92-6.80 (m, 4H), 6.66 (d,
1H, J ) 15.8 Hz), 6.17 (dq, 1H, J ) 15.8 Hz, J ) 6.8 Hz), 3.96
(t, 2H, J ) 6.0 Hz), 3.80 (t, 2H, J ) 6.6 Hz), 3.70 (s, 2H), 3.60 (t,
2H, J ) 5.0 Hz), 2.35 (t, 2H, J ) 5.0 Hz), 2.25 (s, 3H), 2.21 (s,
6H), 1.87-1.80 (m, 7H), 1.60-1.41 (m, 2H); Z: δ 8.18 (s, 1H),
7.35-7.09 (m, 2H), 6.92-6.80 (m, 4H), 6.50 (d, 1H, J ) 11.7
Hz), 5.76 (dq, 1H, J ) 11.7 Hz, J ) 7.0 Hz), 3.96 (t, 2H, J ) 6.0
Hz), 3.80 (t, 2H, J ) 6.6 Hz), 3.70 (s, 2H), 3.60 (t, 2H, J ) 5.0
Hz), 2.35 (t, 2H, J ) 5.0 Hz), 2.25 (s, 3H), 2.21 (s, 6H), 1.87-
1.80 (m, 7H), 1.60-1.41 (m, 2H); 13C NMR (CDCl3, 62.5 MHz)
δ 155.9, 155.0, 152.8, 139.5, 136.0, 134.2, 129.6, 127.6, 127.5,
126.5, 126.0, 125.8, 125.7, 125.2, 124.8, 120.3, 119.6, 111.7, 111.4,
67.5, 67.3, 55.6, 45.6, 43.4, 28.3, 26.9, 22.5, 20.6, 18.9, 18.7, 17.8,
14.4; IR (KBr) 2907, 1669, 1487, 1318, 1243, 748 cm-1. Anal.
Calcd for C27H37IN2O: C, 60.90; H, 7.00; N, 5.26. Found: C, 60.81;
H, 7.11; N, 5.38.
1-Benzyl-3-(2′,6′-diisopropylphenyl)-4,5-dihydroimidazoli-
um Tetrafluoroborate (6j). Starting from 9b (500 mg, 2.17 mmol)
and 11f (249 µL, 274 mg, 2.17 mmol) in 10 mL of DMF, 6j was
obtained (647 mg, 1.58 mmol, 73%) as a white solid: mp 182-
1
183 °C; H NMR (CDCl3, 250 MHz) δ 8.21 (s, 1H), 7.43-7.26
(m, 6H), 7.19-7.16 (m, 2H), 4.82 (s, 2H), 4.18-4.07 (m, 4H),
2.84 (hept, 2H, J ) 6.6 Hz), 1.18 (dd, 12H, J ) 12.1 Hz, J ) 7.0
Hz); 13C NMR (CDCl3, 62.5 MHz) δ 157.6, 146.7, 132.4, 131.1,
129.8, 129.4, 129.2, 129.2, 124.8, 53.4, 52.2, 48.6, 28.6, 24.7, 23.9;
IR (KBr) 2964, 1643, 1452, 1269, 1056 cm-1. Anal. Calcd for
C22H29BF4N2: C, 64.72; H, 7.16; N, 6.86. Found: C, 64.81; H,
7.19; N, 6.72.
1-((1′R)-1′-Phenylethyl)-3-(3′-[2′′-propenylphenyl]propyl)-4,5-
dihydroimidazolium Iodide (6k). Starting from 9c (500 mg, 2.87
mmol) and 11a (867 mg, 2.87 mg) in 10 mL of DMF, 6k was
1-Mesityl-3-(6′-[2′′-propenylphenyl]hexyl)-3,4,5,6-tetrahydro-
pyrimidinium Iodide (6o). Starting from 9f (404 mg, 2 mmol)
and 11d (688 mg, 2 mmol) in 10 mL of DMF, 6o was obtained
(799 mg, 1.6 mmol, yield 80%) as a white solid: mp 123-124
1
°C; a 60:40 mixture of Z and E isomers; H NMR (CDCl3, 250
MHz) E: δ 8.22 (s, 1H), 7.36-7.09 (m, 2H), 6.90-6.80 (m, 4H),
6.68 (d, 1H, J ) 15.8 Hz), 6.14 (dq, 1H, J ) 15.8 Hz, J ) 6.7
Hz), 3.95 (t, 2H, J ) 4.4 Hz), 3.81 (t, 2H, J ) 6.7 Hz), 3.71 (t,
2H, J ) 5.0 Hz), 3.62 (s, 2H), 2.37 (t, 2H, J ) 4.6 Hz), 2.26 (s,
3H), 2.24 (s, 6H), 1.90-1.74 (m, 7H), 1.6-1.35 (m, 4H); Z: δ
5976 J. Org. Chem., Vol. 71, No. 16, 2006

Modular Synthesis of Heterocyclic Carbene Precursors
8.22 (s, 1H), 7.36-7.09 (m, 2H), 6.90-6.80 (m, 4H), 6.52 (d, 1H,
J ) 11.6 Hz), 5.78 (dq, 1H, J ) 11.6 Hz, J ) 7.2 Hz), 3.95 (t, 2H,
J ) 4.4 Hz), 3.81 (t, 2H, J ) 6.7 Hz), 3.71 (t, 2H, J ) 5.0 Hz),
3.62 (s, 2H), 2.37 (t, 2H, J ) 4.6 Hz), 2.26 (s, 3H), 2.24 (s, 6H),
1.90-1.74 (m, 7H), 1.6-1.35 (m, 4H); 13C NMR (CDCl3, 62.5
MHz) δ 156.1, 155.2, 152.8, 139.6, 136.0, 134.3, 129.7, 127.6,
127.4, 126.6, 126.1, 126.0, 125.9, 125.7, 125.3, 124.8, 120.2, 119.5,
111.7, 111.4, 67.7, 67.6, 55.7, 45.7, 43.5, 28.7, 28.7, 27.2, 25.5,
25.5, 25.3, 20.7, 19.0, 18.7, 17.9, 14.4; IR (KBr) 2940, 1674, 1488,
1451, 1242, 753 cm-1. Anal. Calcd for C28H39IN2O: C, 61.53; H,
7.19; N, 5.13. Found: C, 61.42; H, 7.23; N, 5.28.
3-Benzyl-1-mesityl-3,4,5,6-tetrahydropyrimidinium Tetraflu-
oroborate (6p). Starting from 9f (404 mg, 2 mmol) and 11f (253
mg, 2 mmol) in 10 mL of DMF, 6p was obtained (608 mg, 1.6
mmol, 80%) as a white solid: mp 135-136 °C; 1H NMR (CDCl3,
250 MHz) δ 7.89 (s, 1H), 7.35-7.27 (m, 5H); 6.89 (s, 2H), 4.74
(s, 2H), 3.50 (q, 4H, J ) 5.0 Hz), 2.24-2.19 (m, 11H); 13C NMR
(CDCl3, 62.5 MHz) δ 153.3, 139.8, 136.5, 134.5, 132.5, 129.8,
129.2, 129.0, 128.7, 58.8, 45.8, 43.0, 20.84, 18.8, 17.3; IR (KBr)
3040, 1574, 1488, 1451, 1241, 754 cm-1. Anal. Calcd for C20H25-
BF4N2: C, 63.18; H, 6.63; N, 7.37. Found: C, 63.19; H, 6.67; N,
7.42.
being cooled to ambient temperature, the product was collected by
filtration (except for 7e which after removal of the solvents was
purified by Kugelrohr distillation at 0.2 Torr at 80 °C).
2-Azido-N-mesitylacetamide (7a). Starting from 3a (10.0 g, 47.2
mmol) and NaN3 (6.14 g, 94.5 mmol) in 250 mL of MeOH, 7a
was obtained (9.48 g, 43.45 mmol, 92%) as a white solid: mp 178-
1
178.5 °C; H NMR (CDCl3, 250 MHz) δ 7.61 (s, 1H), 6.89 (s,
2H), 4.12 (s, 2H), 2.27 (s, 3H), 2.16 (s, 6H); 13C NMR (CDCl3,
62.5 MHz) δ 165.2, 137.4, 134.9, 130.0, 128.9, 52.6, 20.9, 18.1;
IR (KBr) 3235, 3040, 2102, 1666, 1539, 1485, 1245 cm-1. Anal.
Calcd for C11H14N4O: C, 60.53; H, 6.47; N, 25.67. Found: C,
60.54; H, 6.44; N, 25.74.
2-Azido-N-(2′,6′-diisopropylphenyl)acetamide (7b). Starting
from 3b (10.00 g, 39.4 mmol) and NaN3 (5.12 g, 78.8 mmol) in
250 mL of MeOH, 7b was obtained (9.74 g, 37.4 mmol, 95%) as
1
a white solid: mp 129.5-130 °C; H NMR (CDCl3, 250 MHz) δ
7.62 (s, 1H), 7.35-7.18 (m, 3H.), 4.18 (s, 2H), 3.00 (hept, 2H, J )
6.9 Hz), 1.21 (d, 12H, J ) 6.9 Hz); 13C NMR (CDCl3, 62.5 MHz)
δ 165.9, 145.9, 129.9, 128.69, 123.6, 52.7, 28.8, 23.5; IR (KBr)
3281, 2963, 2100, 1658, 1515, 1221 cm-1. Anal. Calcd for
C14H20N4O: C, 64.59; H, 7.74; N, 21.52. Found: C, 64.85; H, 7.78;
N, 21.58.
1-(2′,6′-Diisopropylphenyl)-3-(2′-methoxynaphth-1′-yl)-4,5-di-
hydroimidazolium Tetrafluoroborate (6q). Starting from 4d (376
mg, 1 mmol) and NH4BF4 (115 mg, 1.1 mmol) in 4 mL of trimethyl
orthoformate, 6q was obtained (289 mg, 0.61 mmol, 61%) as a
white solid: mp 211-212 °C; 1H NMR (CDCl3, 250 MHz) δ 8.00
(s, 1H), 7.91 (t, 1H, J ) 8.7 Hz), 7.86 (d, 1H, J ) 8.0 Hz), 7.59
(t, 1H, J ) 7.4 Hz), 7.44-7.14 (m, 6H), 4.51 (br s, 4H), 3.97 (s,
3H), 3.07 (hept, 2H, J ) 6.2 Hz), 1.26 (dd, 12H, J ) 21.9 Hz, J
) 6.6 Hz); 13C NMR (CDCl3, 62.5 MHz) δ 160.7, 152.4, 146.2,
132.3, 131.2, 129.8, 129.4, 129.0, 128.6, 128.4, 124.8, 120.3, 116.7,
112.6, 56.8, 54.2, 52.4, 28.6, 24.7, 23.8; IR (KBr) 3054, 2973, 1671,
1280, 1066, 1051, 1038 cm-1. Anal. Calcd for C26H31BF4N2O: C,
65.83; H, 6.59; N, 5.91. Found: C, 65.89; H, 6.46; N, 5.82.
1-Mesityl-3-(o-tolyl)-3,4,5,6-tetrahydropyrimidinium Tet-
rafluoroborate (6r). Starting from 4e (200 mg, 0.71 mmol) and
NH4BF4 (82 mg, 0.78 mmol) in 2 mL of trimethyl orthoformate,
6r was obtained (105 mg, 0.27 mmol, 39%) as a white solid: mp
209-210 °C; 1H NMR (CDCl3, 250 MHz) δ 7.55 (s, 2H), 7.38-
7.26 (m, 3H), 6.94 (s, 2H), 4.02 (t, 2H, J ) 5.2 Hz), 3.87 (t, 2H,
J ) 5.2 Hz), 2.54 (quint., 2H, J ) 5.5 Hz), 2.36 (s, 3H), 2.32 (s,
6H), 2.28 (s, 3H); 13C NMR (CDCl3, 62.5 MHz) δ 153.5, 140.4,
139.9, 136.5, 134.6, 133.3, 131.8, 130.5, 130.1, 128.3, 127.3, 47.2,
46.3, 20.9, 19.4, 17.6, 17.4; IR (KBr) 3072, 1666, 1352, 1094, 1051
cm-1. Anal. Calcd for C20H25BF4N2: C, 63.18; H, 6.63; N, 7.37.
Found: C, 63.25; H, 6.56; N, 7.81.
1-(2′,6′-Diisopropylphenyl)-3-(1′-ferrocenylethyl)-4,5-dihy-
droimidazolium Tetrafluoroborate (6s). Starting from 4f (1.00
g, 2.31 mmol) and NH4BF4 (267 mg, 2.54 mmol) in 10 mL of
trimethyl orthoformate, 6s was obtained (796 mg, 1.5 mmol, 65%)
as a yellow-brown solid: mp 182-184 °C; 1H NMR (CDCl3, 250
MHz) δ 8.00 (s, 1H), 7.36 (t, 1H, J ) 7.28 Hz), 7.16 (d, 2H, J )
6.6 Hz), 5.29 (q, 1H, J ) 6.5 Hz),4.38 (s, 1H), 4.26-3.87 (m,
12H), 2.75 (dt, 2H, J ) 34.4 Hz, J ) 6.1 Hz), 1.73 (d, 3H, J ) 6.3
Hz), 1.22-1.12 (m, 12H); 13C NMR (CDCl3, 62.5 MHz) δ 156.6,
146.6, 146.2, 130.8, 129.9, 124.7, 124.5, 84.8, 69.5, 69.2, 68.6,
68.1, 65.8, 54.3, 53.0, 45.2, 28.5, 28.4, 24.6, 24.6, 23.8, 23.6, 17.2;
IR (KBr) 3361, 3093, 2961, 2867, 1672, 1457, 1254, 1106, 818,
755, 484 cm-1. Anal. Calcd for C27H36BF4FeN2: C, 61.16; H, 6.65;
N, 5.28. Found: C, 61.06; H, 6.68; N, 5.15.
2-Azido-N-((1′R)-1′-phenylethyl)acetamide (7c). Starting from
3c (5.00 g, 25.3 mmol) and NaN3 (3.28 g, 50.6 mmol) in 125 mL
of MeOH, 7c was obtained (4.85 g, 23.7 mmol, 94%) as a white
1
solid: mp 52.5-53.0 °C; H NMR (CDCl3, 250 MHz) δ 7.38-
7.23 (m, 5H.), 6.65 (s, 1H), 5.12 (quint, 1H, J ) 6.9 Hz), 3.93 (dd,
2H, J ) 16.4 Hz, J ) 2.4 Hz), 1.50 (d, 3H, J ) 6.9 Hz); 13C NMR
(CDCl3, 62.5 MHz) δ 165.6, 142.4, 128.7, 127.5, 126.0, 52.5, 48.7,
21.6; [R]546 ) +78.64 (c 5.15, CH2Cl2); IR (KBr) 3291, 2976, 2095,
1647, 1543, 1282, 1254, 694 cm-1. Anal. Calcd for C10H12N4O:
C, 58.81; H, 5.92; N, 27.43. Found: C, 58.91; H, 5.75; N, 27.28.
2-Azido-N-adamantylacetamide (7d). Starting from 3d (10.00
g, 43.9 mmol) and NaN3 (5.70 g, 87.8 mmol) in 250 mL of MeOH,
7d was obtained (8.33 g, 35.6 mmol, 81%) as a white solid: mp
86-86.5 °C; 1H NMR (CDCl3, 250 MHz) δ 5.96 (s, 1H), 3.79 (s,
2H), 2.08-1.98 (m, 3H), 1.97-1.91 (m, 6H), 1.63 (t, 6H, J ) 2.8
Hz); 13C NMR (CDCl3, 62.5 MHz) δ 165.2, 52.8, 52.0, 41.2, 36.0,
29.2; IR (KBr) 3236, 2906, 2852, 2100, 1661, 1537, 1242 cm-1
.
Anal. Calcd for C10H12N4O: C, 58.81; H, 5.92; N, 27.43. Found:
C, 58.91; H, 5.75; N, 27.28.
2-Azido-N-((2′R)-3′,3′-dimethylbut-2′-yl)acetamide (7e). Start-
ing from 3e (5.00 g, 28.1 mmol) and NaN3 (3.65 g, 56.3 mmol) in
125 mL of MeOH, 7e was obtained (4.82 g, 26.2 mmol, 93% yield)
1
as a white solid: mp 54-55 °C; H NMR (CDCl3, 250 MHz) δ
6.20 (s, 1H), 3.93 (d, 2H, J ) 3.0 Hz), 3.89-3.76 (m, 1H), 1.03
(d, 3H, J ) 6.8 Hz), 0.85 (s, 9H); 13C NMR (CDCl3, 62.5 MHz) δ
165.6, 52.8, 52.6, 33.9, 25.9, 15.8; [R]546 ) -15.33 (c 5.1, CH2-
Cl2); IR (KBr) 3298, 2964, 2096, 1647, 1550, 1284 cm-1. Anal.
Calcd for C10H12N4O: C, 58.81; H, 5.92; N, 27.43. Found: C,
58.91; H, 5.75; N, 27.28.
3-Azido-N-mesitylpropionamide (7f). Starting from 3f (5.00
g, 22.2 mmol) and NaN3 (2.88 g, 44.3 mmol) in 100 mL of DMF,
7f was obtained (3.86 g, 16.6 mmol, yield 75%) as a light yellow
solid: mp 110-112 °C; a 9:1 mixture of syn/anti amide rotamers;
1H NMR (CDCl3, 250 MHz) syn: δ 7.38 (s, 1H), 6.81 (s, 2H),
3.62 (t, 2H, J ) 6.4 Hz), 2.52 (t, 2H, J ) 6.4 Hz), 2.23 (s, 3H),
2.10 (s, 6H); anti: δ 7.38 (s, 1H), 6.93 (s, 2H), 3.53 (t, 2H, J )
6.3 Hz), 2.29 (s, 3H), 2.20 (s, 6H), 2.12 (t, 2H, J ) 6.3 Hz); 13C
NMR (CDCl3, 62.5 MHz) syn: δ 168.8, 136.9, 135.0, 130.9, 128.7,
47.6, 35.5, 20.9, 18.0; anti: δ 172.6, 138.2, 136.3, 131.3, 129.3,
46.6, 31.5, 20.8, 18.2. Anal. Calcd for C12H16ClNO: C, 63.85; H,
7.14; N, 6.21. Found: C, 64.02; H, 6.94; N, 6.33.
General Procedure for the Preparation of N-Substituted
Ethylenediamines 8a-f. The mixture of the appropriate azidoamide
(7a-f) and 5 equiv of LiAlH4 was refluxed in freshly distilled THF
(for 7a-d,f) or diethyl ether (for 7e) under Ar atmosphere until
consumption of the starting material as judged by GC. After the
reaction mixture was cooled to -10 °C, 1 mL of water, 2 mL of 2
General Procedure for the Preparation of Azidoamides 7a-
f. The mixture of the chloroamide (3a-f) and 2 equiv of sodium
azide was heated in MeOH (at reflux for 3a-e) or DMF (at 80 °C
for 3f) until complete conversion as judged by GC. The solvent
was removed under reduced pressure, the residue was dissolved in
DCM, and the inorganic compounds were removed by filtration.
Hexane was added to the filtrate, and the solvent was removed
until the product started to precipitate from the warm solution. After
J. Org. Chem, Vol. 71, No. 16, 2006 5977

Paczal et al.
N NaOH, and another 2 mL of water were added slowly to the
mixture, and it was allowed to warm to room temperature.
Following the addition of some diethyl ether and stirring for a
further 1 h, the white inorganics were removed by filtration. After
evaporation of the combined solvents, all of the diamines were
purified by short path distillation at 0.2 mbar.
General Procedure for the Preparation of N-Substituted 4,5-
Dihydroimidazoles and 3,4,5,6-Tetrahydropyrimidines 9a-f.
Ring Closure of Alkylamines 8c-e. The mixture of the appropriate
amine and 1 equiv of Me2NHC(OCH3)2 in cyclohexane was stirred
at 80 °C under Ar atmosphere until consumption of the starting
material as judged by GC. In the cases of 8c,d, the reaction
proceeded faster (20-25 min), whereas in case of 8e a longer
reaction period was needed. In the latter case, a GC-detectable
intermediate could be observed during the reaction.
N-Mesitylethylenediamine (8a).39 Starting from 7a (5.00 g, 22.9
mmol) and LiAlH4 (4.35 g, 114.5 mmol) in 125 mL of THF, 8a
was obtained (3.18 g, 17.86 mmol, 78%) as a pale yellow oil: 1H
NMR (CDCl3, 250 MHz) δ 6.83 (s, 2H), 3.01-2.87 (m, 4H), 2.29
(s, 6H), 2.24 (s, 3H); 13C NMR (CDCl3, 62.5 MHz) δ 143.5, 131.2,
129.7, 129.3, 51.2, 42.5, 20.5, 18.3; IR (KBr) 3360, 2946, 2861,
2836, 1484, 1230, 853 cm-1. Anal. Calcd for C11H18N2: C, 74.11;
H, 10.18; N, 15.71. Found: C, 74.13; H, 10.21; N, 15.59.
N-(2′,6′-Diisopropylphenyl)ethylenediamine (8b). Starting from
7b (5.00 g, 19.2 mmol) and LiAlH4 (3.64 g, 96 mmol) in 125 mL
of THF, 8b was obtained (3.45 g, 15.7 mmol, 82%) as a pale yellow
oil: 1H NMR (CDCl3, 250 MHz) δ 7.14-7.03 (m, 3H), 3.33 (hept,
2H, J ) 6.8 Hz), 3.00-2.90 (m, 4H), 2.6-1.4 (br s, 3H), 1.26 (d,
12H, J ) 6.9 Hz); 13C NMR (CDCl3, 62.5 MHz) δ 143.1, 142.3,
123.5, 123.3, 54.2, 42.4, 27.4, 24.1; IR (KBr) 3362, 2960, 2867,
1444, 754 cm-1. Anal. Calcd for C14H24N2: C, 76.31; H, 10.98;
N, 12.71. Found: C, 76.13; H, 10.94; N, 12.57.
Ring Closure of Arylamines 8a,b,f. The solution of the
appropriate amine in 20 equiv of trimethyl orthoformate was
refluxed in the presence of a catalytic amount of concd HI under
Ar atmosphere. All of the reactions were followed by GC.
After evaporation of the solvent, all products were purified by
short path distillation at 0.2 bar.
1-Mesityl-4,5-dihydro-1H-imidazole (9a).39 Starting from 8a
(3.00 g, 16.8 mmol) and 30 mL of trimethyl orthoformate, 9a was
obtained (2.53 g, 13.5 mmol, 80%) as a white solid: mp 62-63
1
°C; H NMR (CDCl3, 250 MHz) δ 6.9 (s, 2H), 6.83 (s, 1H), 4.04
(t, 2H, J ) 10.0 Hz), 3.54 (t, 2H, J ) 10.2 Hz), 2.28 (s, 3H), 2.22
(s, 6H); 13C NMR (CDCl3, 62.5 MHz) δ 155.8, 137.2, 136.8, 134.7,
129.3, 55.2, 48.7, 20.8, 18.0; IR (KBr) 2943, 2858, 1590, 1486,
1261, 1205 cm-1. Anal. Calcd for C12H16N2: C, 76.55; H, 8.57;
N, 14.88. Found: C, 76.42; H, 8.75; N, 14.94.
N-((1′R)-1′-Phenylethyl)ethylenediamine (8c).40 Starting from
7c (5.00 g, 24.5 mmol) and LiAlH4 (3.72 g, 98 mmol) in 125 mL
of THF, 8c was obtained (3.41 g, 20.8 mmol, 85%) as a pale yellow
oil: 1H NMR (CDCl3, 250 MHz) δ 7.35-7.18 (m, 5H), 3.75 (q,
1H, J ) 6.7 Hz), 2.77-2.72 (m, 2H), 2.61-2.41 (m, 2H), 1.38 (s,
3H), 1.36 (d, 3H, J ) 6.7 Hz); 13C NMR (CDCl3, 62.5 MHz) δ
145.1, 128.3, 126.7, 126.4, 58.2, 50.3, 41.9, 24.4; [R]546 ) +57.2
(c 5.4, CH2Cl2); IR (KBr) 3287, 2972, 2829, 1657, 1568, 1492,
1450, 761, 700 cm-1. Anal. Calcd for C10H16N2: C, 73.13; H, 9.82;
N, 17.06. Found: C, 73.14; H, 9.94; N, 17.09.
1-(2′,6′-Diisopropylphenyl)-4,5-dihydro-1H-imidazole (9b).
Starting from 8b (3.00 g, 13.6 mmol) and 30 mL of trimethyl
orthoformate, 9b was obtained (2.44 g, 10.6 mmol, 78%) as a white
1
solid: mp 67-68 °C; H NMR (CDCl3, 250 MHz) δ 7.32-7.15
(m, 3H), 6.8 (s, 1H), 4.05 (t, 2H, J ) 10.0 Hz), 3.56 (t, 2H, J )
10.2 Hz), 3.09 (hept, 2H, J ) 6.9 Hz), 1.19 (dd, 12H, J ) 11.9
Hz, J ) 6.9 Hz); 13C NMR (CDCl3, 62.5 MHz) δ 156.1, 148.3,
134.2, 128.5, 124.1, 55.1, 51.5, 28.4, 24.8, 24.0; IR (KBr) 2962,
2926, 2866, 1678, 1598, 1585, 1456, 1203 cm-1. Anal. Calcd for
C15H22N2: C, 78.21; H, 9.63; N, 12.16. Found: C, 78.10; H, 9.63;
N, 12.16.
N-Adamantylethylenediamine (8d).41 Starting from 7d (5.00
g, 21.3 mmol) and LiAlH4 (3.24 g, 85.36 mmol) in 125 mL of
THF, 8d was obtained (3.02 g, 15.56 mmol, 73%) as a pale yellow
oil: 1H NMR (CDCl3, 250 MHz) δ 2.65-2.60 (m, 2H), 2.51-
1-((1′R)-1′-Phenylethyl)-4,5-dihydro-1H-imidazole (9c).18 Start-
ing from 8c (2.00 g. 12.2 mmol) and (CH3)2NCH(OCH3)2 (1.46 g,
1.63 mL, 12.2 mmol) in 10 mL of cyclohexane, 9c was obtained
(2.10 g, 12.0 mmol, 99%) as a light yellow oil: 1H NMR (CDCl3,
250 MHz) δ 7.38-7.24 (m, 5H), 7.01 (s, 1H), 4.32 (q, 1H, J )
6.9 Hz), 3.77 (dt, 2H, J ) 9.8 Hz, J ) 1.7 Hz), 3.10 (t, 2H, J )
9.8 Hz), 1.56 (d, 3H, J ) 6.9 Hz); 13C NMR (CDCl3, 62.5 MHz)
δ 155.3, 141.9, 128.5, 127.3, 126.4, 56.4, 54.3, 46.5, 20.7; [R]546
) +48.7 (c 3.1, CH2Cl2); IR (KBr) 3287, 2972, 2872, 2829, 1657,
1568, 1492, 1450, 761, 700 cm-1. Anal. Calcd for C11H14N2: C,
75.82; H, 8.10; N, 16.08. Found: C, 75.63; H, 8.15; N, 16.21.
1-Adamantyl-4,5-dihydro-1H-imidazole (9d). Starting from 8d
(3.00 g, 15.4 mmol) and (CH3)2NCH(OCH3)2 (1.84 g, 2.06 mL,
15.4 mmol) in 15 mL of cyclohexane, 9d was obtained (3.08 g,
15.1 mmol, 98%) as a light brown solid: mp 40-41 °C; 1H NMR
(CDCl3, 250 MHz) δ 6.94 (t, 1H, J ) 1.6 Hz), 3.6 (t, 2H, J ) 9.5
Hz), 3.14 (t, 2H, J ) 9.6 Hz), 1.98 (s, 3), 1.72-1.65 (m, 6H),
1.62-1.45 (m, 6H); 13C NMR (CDCl3, 62.5 MHz) δ 153.0, 53.5,
51.9, 42.4, 41.4, 35.9, 28.9; IR (KBr) 2904, 2849, 1591 cm-1. Anal.
Calcd for C13H20N2: C, 76.42; H, 9.87; N, 13.71. Found: C, 76.34;
H, 9.73; N, 13.68.
2.46 (m, 2H), 1.92 (s, 3H), 1.55-1.43 (m, 12H), 1.06 (s, 3H); 13
C
NMR (CDCl3, 62.5 MHz) δ 49.8, 42.9, 42.7, 42.6, 36.5, 29.3; IR
(KBr) 2900, 2845 cm-1. Anal. Calcd for C12H22N2: C, 74.17; H,
11.41; N, 14.42. Found: C, 74.05; H, 11.55; N, 14.25.
N-((2′R)-3′,3′-Dimethylbut-2′-yl)ethylenediamine (8e). Starting
from 7e (5.00 g, 27.13 mmol) and LiAlH4 (4.12 g, 108 mmol) in
125 mL of diethyl ether, 8e was obtained (3.05 g, 21.2 mmol, 78%)
as a colorless oil: 1H NMR (CDCl3, 250 MHz) δ 2.85-2.66 (m,
3H), 2.57-2.45 (m, 1H), 2.18 (q, 1H, J ) 6.5 Hz), 1.28 (s, 3H),
0.97 (d, 3H, J ) 6.5 Hz), 0.88 (s, 9H); 13C NMR (CDCl3, 62.5
MHz) δ 61.75, 51.05, 41.81, 34.10, 26.17, 14.70; [R]546 ) -66.5
(c 5.5, CH2Cl2); IR (KBr) 2955, 2868, 2827, 1487, 1120 cm-1
.
Anal. Calcd for C8H20N2: C, 66.61; H, 13.97; N, 19.42. Found:
C, 66.54; H, 13.76; N, 19.29.
N-Mesitylpropylenediamine (8f).42 Starting from 7f (5.00 g,
21.5 mmol) and LiAlH4 (3.27 g, 86.1 mmol) in 125 mL of THF,
8f was obtained (2.77 g, 14.4 mmol, 67%) as a pale yellow oil:
1H NMR (CDCl3, 250 MHz) δ 6.83 (s, 2H), 3.00 (t, 2H, J ) 6.7
Hz), 2.85 (t, 2H, J ) 6.8 Hz), 2.27 (s, 6H), 2.24 (s, 3H), 1.9 (br s,
3H), 1.74 (quint., 2H, J ) 6.7 Hz); 13C NMR (CDCl3, 62.5 MHz)
δ 143.5, 130.9, 129.4, 129.2, 46.7, 40.3, 34.5, 20.3, 18.1; IR (KBr)
3360, 2942, 2860, 2839, 1483, 1230, 852 cm-1. Anal. Calcd for
C12H20N2: C, 74.95; H, 10.48; N, 14.57. Found: C, 74.88; H, 10.52;
N, 14.33.
1-((2′R)-3′,3′-Dimethylbut-2′-yl)-4,5-dihydro-1H-imidazole (9e).
Starting from 8e (2.00 g, 13.9 mmol) and (CH3)2NCH(OCH3)2 (1.66
g, 1.86 mL, 13.9 mmol) in 10 mL of cyclohexane, 9e was obtained
(2.09 g, 13.58 mmol, 98%) as a pale yellow oil: 1H NMR (CDCl3,
250 MHz) δ 6.73 (s, 1H), 3.75-3.66 (m, 2H), 3.35-3.17 (m, 2H),
3.02 (q, 1H J ) 7.1 Hz), 1.07 (d, 3H, J ) 7.1 Hz), 0.86 (s,9H);
13C NMR (CDCl3, 62.5 MHz) δ 157.2, 60.7, 54.0, 47.0, 35.6, 26.9,
13.2; [R]546 ) -38.6 (c 2.5, CH2Cl2); IR (KBr) 2955, 2869, 2832,
1658, 1599, 1192 cm-1. Anal. Calcd for C9H18N2: C, 70.08; H,
11.76; N, 18.16. Found: C, 70.04; H, 11.73; N, 18.21.
(39) Perillo, I.; Caterina, M. C.; Lopez, J.; Salerno, A. Synthesis 2004,
851-856.
(40) Potapov, V. M.; Gracheva, R. A.; Savina, S. A. J. Org. Chem. USSR
(Engl. Transl.) 1987, 23, 1902-1904.
(41) Arya, V. P.; Fernandes, F.; Ghate, S. P.; Costa-Pereira, F. X. R.;
Wasaiwalla, Y. H. Indian J. Chem. 1972, 10, 686-690.
(42) Bisceglia, J. A.; Garcia, M. B.; Massa, R.; Magri, M. L.; Zani, M.;
Gutkind, G. O.; Orelli, L. R. J. Heterocycl. Chem. 2004, 41, 85-90.
3-Mesityl-3,4,5,6-tetrahydropyrimidine (9f).39 Starting from 8f
(3.00 g, 15.6 mmol) and 30 mL of trimethyl orthoformate, 9f was
obtained (2.05 g, 10.1 mmol, 65% yield) as a white solid: mp 80-
5978 J. Org. Chem., Vol. 71, No. 16, 2006

Modular Synthesis of Heterocyclic Carbene Precursors
1
80.5 °C; H NMR (CDCl3, 250 MHz) δ 6.86 (s, 3H), 3.40 (t, 2H,
(m, 1H), 6.93-6.75 (m, 2H), 6.69 (dd, 1H, J ) 15.8 Hz, J ) 1
Hz), 6.20 (dq, 1H, J ) 15.8 Hz, J ) 6.6 Hz), 3.93 (t, 2H, J ) 6.0
Hz), 3.23 (t, 2H, J ) 6.7 Hz), 2.06-1.80 (m, 7H); Z: 7.26 (dd,
1H, J ) 7.4 Hz, J ) 1.5 Hz), 7.20-7.08 (m, 1H), 6.93-6.75 (m,
2H), 6.53 (dd, 1H, J ) 11.4 Hz, J ) 1.6 Hz), 5.80 (dq, 1H, J )
11.4 Hz, J ) 7.1 Hz), 3.93 (t, 2H, J ) 6.0 Hz), 3.21 (dt, 2H, J )
6.3 Hz, J ) 4.4 Hz), 2.06-1.80 (m, 7H); 13C NMR (CDCl3, 62.5
MHz) δ 156.1, 155.2, 129.9, 127.7, 127.5, 126.9, 126.4, 126.3,
126.2, 126.1, 125.4, 125.0, 120.6, 119.9, 111.6, 111.3, 66.8, 66.7,
30.2, 30.1, 29.9, 18.9, 14.6, 6.57; IR (KBr) 3030, 2937, 2871, 1596,
1488, 1448, 1237, 747 cm-1. Anal. Calcd for C13H17IO: C, 49.38;
H, 5.42. Found: C, 49.43; H, 5.41.
J ) 5.1 Hz), 3.28 (t, 2H, J ) 6.0 Hz), 2.23 (s, 3H), 2.18 (s, 6H),
1.96 (quint., 2H, J ) 5.7 Hz); 13C NMR (CDCl3, 62.5 MHz) δ
149.0, 139.6, 137.0, 136.3, 129.0, 45.2, 42.9, 21.2, 20.7, 17.5; IR
(KBr) 3230, 2955, 2922, 2851, 2730, 2102, 1627, 1483, 1289, 1029
cm-1. Anal. Calcd for C13H18N2: C, 77.18; H, 8.97; N, 13.85.
Found: C, 77.03; H, 8.75; N, 13.57.
2-(6′-Chlorohexyloxy)benzaldehyde (10d). The mixture of
salicylic aldehyde (1.22 g, 1.05 mL, 10 mmol), 1-bromo-6-
chlorohexane (1.99 g, 1.49 mL, 10 mmol), and potassium carbonate
(2.76 g, 20 mmol) was stirred in 50 mL of DMF at ambient
temperature until completion. The K2CO3 was filtered off, and after
evaporation of the DMF under reduced pressure, the product was
purified by column chromatography using hexane/ethyl acetate
mixtures as eluent. Compound 10d (2.03 g, 8.4 mmol, 84%) was
obtained as a colorless oil: 1H NMR (CDCl3, 250 MHz) δ 10.49
(d, 1H, J ) 0.8 Hz), 7.81 (dd, 1H, J ) 6.2 Hz, J ) 1.8 Hz), 7.55
(ddd, 1H, J ) 8.4 Hz, J ) 7.5 Hz, J ) 1.9 Hz), 7.02-6.94 (m,
2H), 4.06 (t, 2H, J ) 6.3 Hz), 3.54 (t, 2H, J ) 6.6 Hz), 1.91-1.74
(m, 4H), 1.59-1.46 (m, 4H); 13C NMR (CDCl3, 250 MHz) δ 189.6,
161.3, 135.8, 128.1, 124.8, 120.5, 112.4, 68.2, 44.8, 32.3, 28.9,
26.5, 25.3; IR (KBr) 2939, 2860, 1686, 1598, 1457, 1387, 1285,
1241, 757 cm-1. Anal. Calcd for C13H17ClO2: C, 64.86; H, 7.12.
Found: C, 64.85; H, 7.20.
General Procedure for the Preparation of the Alkylating
Agents 11a-d. To the suspension of ethyltriphenylphosphonium
iodide in freshly distilled THF was added n-BuLi at room
temperature under Ar atmosphere. After completion of the addition,
the reaction mixture turned into a homogeneous red solution. Further
stirring for 1 h was followed by the addition of the appropriate
aldehyde. The reaction was monitored by GC and TLC. After the
starting materials had disappeared, the reaction mixture was poured
onto aq NH4Cl solution, which was followed by extraction with
diethyl ether. The combined organic extracts were dried over
MgSO4 and then concentrated in vacuo. The crude products were
further purified by column chromatography using hexane as eluent.
Due to partial exchange of the pendant halogens, all products were
converted to their iodo derivatives using NaI in acetone.
O-(3′-Iodopropyl)-2-propenylphenol (11a). Starting from 10a
(3.00 g, 15.1 mmol), ethyltriphenylphosphonium iodide (6.31 g,
15.1 mmol), and 10.4 mL of n-BuLi (1.6 M in hexane, 16.6 mmol)
in 50 mL of THF, 11a (2.55 g, 11.0 mmol, 73%) was obtained as
a yellow oil: 60:40 mixture of Z and E isomers; 1H NMR (CDCl3,
250 MHz) E: δ 7.39 (dd, 1H, J ) 7.5 Hz, J ) 1.5 Hz), 7.22-7.10
(m, 1H), 6.95-6.80 (m, 2H), 6.68 (dd, 1H, J ) 15.9 Hz, J ) 1,7
Hz), 6.20 (dq, 1H, J ) 15.9 Hz, J ) 6.6 Hz), 4.00 (t, 2H, J ) 5.7
Hz), 3.35 (t, 2H, J ) 6.8 Hz), 2.32-2.19 (m, 2H), 1.89 (dd, 3H, J
) 6.6 Hz, J ) 1,7 Hz); Z: 7.26 (dd, 1H, J ) 7.4 Hz, J ) 1.5 Hz),
7.22-7.10 (m, 1H), 6.95-6.80 (m, 2H), 6.52 (dd, 1H, J ) 11.5
Hz, J ) 1,6 Hz), 5.80 (dq, 1H, J ) 11.5 Hz, J ) 7.1 Hz), 3.99 (t,
2H, J ) 5.7 Hz), 3.33 (t, 2H, J ) 6.8 Hz), 2.32-2.19 (m, 2H),
1.82 (dd, 3H, J ) 7.1 Hz, J ) 1,9 Hz); 13C NMR (CDCl3, 62.5
MHz) δ 155.9, 155.0, 130.1, 127.8, 127.6, 127.1, 126.6, 126.4,
126.3, 125.3, 124.9, 120.8, 120.2, 111.9, 111.6, 67.5, 67.4, 32.9,
18.9, 14.6, 2.7, 2.6; IR (KBr) 3030, 2934, 2878, 1597, 1488, 1448,
1238, 748 cm-1. Anal. Calcd for C12H15IO: C, 47.70; H, 5.00.
Found: C, 47.84; H, 5.01.
O-(5′-Iodopentyl)-2-propenylphenol (11c). Starting from 10c
(5 g, 18.4 mmol), ethyltriphenylphosphonium iodide (7.68 g, 18.4
mmol), and 12.6 mL of n-BuLi (1.6 M in hexane, 20.2 mmol) in
50 mL of THF, 11c (4.74 g, 14.35 mmol, 78%) was obtained as a
1
yellow oil: 60:40 mixture of Z and E isomers; H NMR (CDCl3,
250 MHz) E: δ 7.38 (dd, 1H, J ) 7.8 Hz, J ) 1.7 Hz), 7.21-7.09
(m, 1H), 6.93-6.78 (m, 2H), 6.72 (dd, 1H, J ) 15.9 Hz, J ) 1,7
Hz), 6.22 (dq, 1H, J ) 15.9 Hz, J ) 6.6 Hz), 3.94 (t, 2H, J ) 6.2
Hz), 3.19 (t, 2H, J ) 6.9 Hz), 1.94-1.73 (m, 7H), 1.64-1.49 (m,
2H); Z: 7.27 (dd, 1H, J ) 7.4 Hz, J ) 1.5 Hz), 7.21-7.09 (m,
1H), 6.93-6.78 (m, 2H), 6.55 (dd, 1H, J ) 11.6 Hz, J ) 1,9 Hz),
5.81 (dq, 1H, J ) 11.7 Hz, J ) 7 Hz), 3.94 (t, 2H, J ) 6.2 Hz),
3.18 (t, 2H, J ) 6.9 Hz), 1.94-1.73 (m, 7H), 1.64-1.49 (m, 2H);
13C NMR (CDCl3, 62.5 MHz) δ 156.3, 155.4, 130.0, 127.7, 127.5,
126.9, 126.4, 126.3, 126.2, 126.1, 125.5, 125.1, 120.5, 119.8, 111.7,
111.4, 67.7, 67.6, 33.1, 33.0, 28.2, 28.1, 27.2, 27.1, 18.9, 14.7, 6.8,
6.7; IR (KBr) 3029, 2938, 2866, 1688, 1597, 1449, 1239, 748 cm-1
.
Anal. Calcd for C14H19IO: C, 50.92; H, 5.80. Found: C, 50.84; H,
5.71.
O-(6′-Iodohexyl)-2-propenylphenol (11d). Starting from 10d
(1.50 g, 6.2 mmol), ethyltriphenylphosphonium iodide (2.6 g, 6.2
mmol), and 4.3 mL of n-BuLi (1.6 M in hexane, 6.9 mmol) in 25
mL of THF, 11a (1.72 g, 5.1 mmol, 82%) was obtained as a yellow
oil: 60:40 mixture of E and Z isomers; 1H NMR (CDCl3, 250 MHz)
E: δ 7.39 (dd, 1H, J ) 7.6 Hz, J ) 1.8 Hz), 7.23-7.11 (m, 1H),
6.94-6.80 (m, 2H), 6.71 (dd, 1H, J ) 15.8 Hz, J ) 1,5 Hz), 6.23
(dq, 1H, J ) 15.8 Hz, J ) 6.7 Hz), 3.96 (t, 2H, J ) 6.2 Hz), 3.20
(t, 2H, J ) 7.1 Hz), 1.92-1.75 (m, 7H), 1.51-1.46 (m, 4H); Z:
7.28 (dd, 1H, J ) 7.4 Hz, J ) 1.5 Hz), 7.23-7.11 (m, 1H), 6.94-
6.80 (m, 2H), 6.55 (dd, 1H, J ) 11.6 Hz, J ) 1,7 Hz), 5.81 (dq,
1H, J ) 11.6 Hz, J ) 7.1 Hz), 3.96 (t, 2H, J ) 6.4 Hz), 3.19 (t,
2H, J ) 7.0 Hz), 1.92-1.75 (m, 7H), 1.51-1.46 (m, 4H); 13C NMR
(CDCl3, 62.5 MHz) δ 156.4, 155.5, 130.0, 127.8, 127.6, 127.0,
126.5, 126.4, 126.3, 126.2, 125.6, 125.2, 120.5, 119.8, 111.8, 111.5,
68.0, 67.9, 33.3, 30.2, 29.1, 29.0, 25.1, 25.0, 19.0, 14.7, 7.0, 6.9;
IR (KBr) 3031, 2860, 1599, 1490, 1451, 1241, 751 cm-1. Anal.
Calcd for C15H21IO: C, 52.34; H, 6.15. Found: C, 52.42; H, 6.01.
Acknowledgment. The help of Dr. Korne´l Torkos with the
analytical measurements as well as the financial support of the
Hungarian Scientific Research Fund (OTKA F047125) and
NKTH (GVOP-3.2.1.-0358/04) is gratefully acknowledged.
A.C.B. is grateful for the Istva´n Sze´chenyi Fellowship of the
Hungarian Ministry of Education.
O-(4′-Iodobutyl)-2-propenylphenol (11b). Starting from 10b
(10 g, 38.9 mmol), ethyltriphenylphosphonium iodide (16.26 g, 38.9
mmol), and 29 mL of n-BuLi (1.6 M in hexane, 46.4 mmol) in
100 mL of THF, 11c (8.6 g, 27.22 mmol, 70%) was obtained as a
Supporting Information Available: Crystal data, structure
refinement data, and crystal packing of 6o; NMR spectra of the
products. This material is available free of charge via the Internet
at http://pubs.acs.org.
1
yellow oil: 60:40 mixture of Z and E isomers; H NMR (CDCl3,
250 MHz) E: δ 7.37 (dd, 1H, J ) 7.5 Hz, J ) 1.5 Hz), 7.20-7.08
JO060594+
J. Org. Chem, Vol. 71, No. 16, 2006 5979