Nitrile ylide dimerization: Investigation of the carbene reactivity of nitrile ylides

Article abstract of DOI:10.1021/jo049748g

A series of novel hexaaryl diazatrienes 5 ("nitrile ylide dimers") were synthesized directly from the corresponding diaryl ketimines 12 and dichlorotoluenes 13 in a facile one-pot synthesis. The carbene character of the nitrile ylides was investigated by varying the substituents on the aromatic ring adjacent to the carbene center. The isolation of the corresponding carbene dimers as stable crystalline materials with absorption maxima (λ_max) from 363 to 422 nm was shown to be promoted by the absence of strongly electron-withdrawing substituents. The crystal structures indicate that the E-isomers were isolated when phenyl, 3-methylphenyl, and 3-chlorophenyl substituents are present at the carbene carbon; the Z-isomer was isolated when the more sterically hindered 2,4,6-trimethylphenyl substituent (Mes) is present. The ¹H NMR spectra of the E-isomers demonstrate the nonequivalence of the aromatic rings, in which two of the aromatic rings of the imine moiety are pseudoaxial and the remaining aromatic rings are pseudoequatorial. The reactions proceed via the intermediate nitrile ylides 1 generated by the base-promoted 1,1-elimination of HCl from the intermediate chloroimine 14. The nitrile ylide was also generated by 1,3-elimination of HCl from the imidoyl chloride 18, confirming common pathways via the nitrile ylide as the dimer products obtained from these different routes were identical. The strongly electron-withdrawing 4-nitrophenyl substituent promotes the linear carbanion character of the 1,3-dipole and no dimer is formed.

Full text of DOI:10.1021/jo049748g

Nitr ile Ylid e Dim er iza tion : In vestiga tion of th e Ca r ben e
Rea ctivity of Nitr ile Ylid es
Suzanne Fergus, Stephen J . Eustace, and Anthony F. Hegarty*
Chemistry Department, University College Dublin, Dublin 4, Ireland
f.hegarty@ucd.ie
Received February 12, 2004
A series of novel hexaaryl diazatrienes 5 (“nitrile ylide dimers”) were synthesized directly from the
corresponding diaryl ketimines 12 and dichlorotoluenes 13 in a facile one-pot synthesis. The carbene
character of the nitrile ylides was investigated by varying the substituents on the aromatic ring
adjacent to the carbene center. The isolation of the corresponding carbene dimers as stable
crystalline materials with absorption maxima (λmax) from 363 to 422 nm was shown to be promoted
by the absence of strongly electron-withdrawing substituents. The crystal structures indicate that
the E-isomers were isolated when phenyl, 3-methylphenyl, and 3-chlorophenyl substituents are
present at the carbene carbon; the Z-isomer was isolated when the more sterically hindered 2,4,6-
1
trimethylphenyl substituent (Mes) is present. The H NMR spectra of the E-isomers demonstrate
the nonequivalence of the aromatic rings, in which two of the aromatic rings of the imine moiety
are pseudoaxial and the remaining aromatic rings are pseudoequatorial. The reactions proceed via
the intermediate nitrile ylides 1 generated by the base-promoted 1,1-elimination of HCl from the
intermediate chloroimine 14. The nitrile ylide was also generated by 1,3-elimination of HCl from
the imidoyl chloride 18, confirming common pathways via the nitrile ylide as the dimer products
obtained from these different routes were identical. The strongly electron-withdrawing 4-nitrophenyl
substituent promotes the linear carbanion character of the 1,3-dipole and no dimer is formed.
SCHEME 1. Electr on ic Ar r a n gem en ts of Nitr ile
Ylid e
In tr od u ction
Nitrile ylides 1 are 1,3-dipolar species that were first
predicted and prepared by Rolf Huisgen in the 1960s
when he was investigating and studying 1,3-dipoles and
their cycloaddition reactions.1,2 They are classified as
“nitrile ylides” due to the presence of the -CtN- moiety
at the cationic center and are described by a C-N-C
framework containing six electrons in n and π orbitals,
and three ligands linked with the carbon atoms. The
nitrile ylides can be described by using six electronic
arrangements with either a bent or linear framework
(Scheme 1), illustrating two possible octet forms 1a and
1b, one carbene-like sextet structure 1c, two zwitterionic
sextet forms 1d and 1e, and a diradical structure 1f.
In 1961, Huisgen generated the first nitrile ylide
(Scheme 2), via the base-promoted 1,3-elimination of
hydrogen chloride from the imidoyl chloride N-(4-ni-
trobenzyl)benzoic acid imidoyl chloride 2, using triethyl-
amine at 0-20 °C;1a triethylammonium chloride was
separated and a deep purple solution of the nitrile ylide
benzonitrile-4-nitrobenzylide 3 resulted. The nitrile ylide
3 was not isolated from the reaction mixture but could
be trapped with dipolarophiles, e.g. in the presence of
acrylonitrile two diastereoisomeric ∆1-pyrrolines 4 were
obtained.
We have previously reported3 the formation of kineti-
cally stable trifluoromethyl-substituted nitrile ylides in
acetonitrile and aqueous dioxane solutions using this
method. Highly colored solutions typified by long-
wavelength absorbances were observed when the nitrile
ylides contained a 4-nitrophenyl substituent. Trapping
reactions using dipolarophiles such as acrylonitrile and
methyl acrylate confirmed the presence of these 1,3-
dipoles.
(1) (a) Huisgen, R.; Stangl, H.; Sturm, H. J .; Wagenhofer, H. Angew.
Chem., Int. Ed. Engl. 1962, 1, 50. (b) Huisgen, R. Angew. Chem., Int.
Ed. Engl. 1963, 2, 565. (c) Huisgen, R. Angew. Chem., Int. Ed. Engl.
1963, 2, 633. (d) Huisgen, R.; Grashey, R.; Sauer, J . In The Chemistry
of Alkenes; Patai, S., Ed.; Interscience: New York, 1964; pp 806-878.
(e) Huisgen, R. J . Org. Chem. 1968, 33, 2291. (f) Huisgen, R. J . Org.
Chem. 1976, 41, 403.
Nitrile ylides may also be generated by a number of
methods including thermolysis of ∆3-oxazolinones4 and
(2) Nitrile ylide review: Hansen, H. J .; Heimgartner, H. 1,3-Dipolar
Cycloaddition Chemistry; Padwa, A., Ed.; Wiley: New York, 1984; p
177.
(3) Hegarty, A. F.; Eustace, S. J .; Tynan, N. M.; Pham-Tran, N. N.;
Nguyen, M. T. J . Chem. Soc., Perkin Trans. 2 2001, 1239.
10.1021/jo049748g CCC: $27.50 © 2004 American Chemical Society
Published on Web 06/08/2004
J . Org. Chem. 2004, 69, 4663-4669
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Fergus et al.
SCHEME 2. Hu isgen ’s Gen er a tion of Nitr ile Ylid e
There are limited reports on the behavior of these
nitrile ylides as imine-stabilized carbenes. The carbene-
like reactivity of nitrile ylides is supported by their
observed dimerization in the absence of trapping reagents
to form diazahexatrienes 5. Padwa was the first to isolate
such structures 5a and 5b, from the photolysis of 2H-
azirines;8e-g,11 Heimgartner and Schmid have reported
on the dimerization of nitrile ylides produced photo-
chemically from 2H-azirines,12 and similarly, Taniguchi13
isolated an aryl-substituted diazahexatriene 5c, which
was also formed via the azirine.
oxazaphospholes,5 the reactions of carbenes with nitriles6
and isonitriles with triphenylborane,7 and the photolysis
of 2H-azirines.8 Recently it was reported that the pho-
tolysis of 3-pyridylcarbene and 3-pyridylnitrene results
in ring opening to nitrile ylides.9 Presently, the most
efficient and convenient pathways for the generation of
nitrile ylides are the photolysis of 2H-azirines together
with Huisgen’s method employing imidoyl chlorides.
Huisgen originally suggested that the bent form of a
nitrile ylide would be less stable than the linear form,
since allyl resonance would be at a maximum with the
linear arrangement.1c However, ab initio LCAO-MO-SCF
and MINDO calculations carried out by Houk and Cara-
mella show that the parent nitrile ylide is bent with an
HCN angle of 114-116°.10 The stabilization over the
optimized linear form was calculated to be 11.1 kcal/mol
(4-31G).
(4) Steglich, W.; Gruber, P.; Ulrich, H. H.; Kneidl, F. Chem. Ber.
1971, 104, 3816.
(5) (a) Burger, K.; Fehn, J .; Moll, E. Chem. Ber. 1971, 104, 1826.
(b) Burger, K.; Fehn, J . Chem. Ber. 1972, 105, 3814. (c) Wentrup, C.;
Fischer, S.; Berstermann, H.-M.; Kuzaj, M.; Lu¨erssen, H.; Burger K.
Angew. Chem., Int. Ed. Engl. 1986, 25, 85.
(6) (a) Turro, N. J .; Cha, Y.; Gould, I. R.; Padwa, A.; Gasdaska, J .
R.; Thomas, M. J . Org. Chem. 1985, 50, 4415. (b) Padwa, A.; Gasdaska,
J . R.; Thomas, M.; Turro, N. J .; Cha, Y.; Gould, I. R. J . Am. Chem.
Soc. 1986, 108, 6739. (c) Turro, N. J .; Cha, Y.; Gould, I. R. J . Am. Chem.
Soc. 1987, 109, 2101.
The diazahexatriene 5d is postulated as an intermedi-
ate in the formation of dimer 7 from the thermolysis or
photolysis of 4,5-dihydro-1,3,2λ5-dioxaphosphole 6 with
the cycloelimination of phosphoric acid ester (Scheme 3).14
There is one further example of such a diazahexatriene
5e, which was probably also generated via the ylide,
although these results were not explained.15
(7) (a) Hesse, G.; Witte, H.; Bittner, G. Liebigs Ann. Chem. 1965,
687, 9. (b) Bittner, G.; Witte, H.; Hesse, G. Liebigs Ann. Chem. 1968,
713, 1.
(8) (a) Padwa, A.; Dharan, M.; Smolanoff, J .; Wetmore, S. I., J r. Pure
Appl. Chem. 1973, 33, 269. (b) Padwa, A. Acc. Chem. Res. 1976, 9,
371. (c) Padwa, A.; Smolanoff, J . J . Am. Chem. Soc. 1971, 93, 548. (d)
Padwa, A.; Dharan, M.; Smolanoff, J .; Wetmore, S. I., J r. J . Am. Chem.
Soc. 1973, 95, 1945. (e) Padwa, A.; Dharan, M.; Smolanoff, J .; Wetmore,
S. I., J r. J . Am. Chem. Soc. 1973, 95, 1954. (f) Padwa, A.; Wetmore, S.
I., J r. J . Org. Chem. 1973, 38, 1333. (g) Padwa, A.; Wetmore, S. I., J r.
J . Org. Chem. 1974, 39, 1396. (h) Padwa, A.; Wetmore, S. I., J r. J .
Am. Chem. Soc. 1974, 96, 2414. (i) Gilgen, P.; Heimgartner, H.; Schmid,
H. Heterocycles 1977, 6, 143. (j) Gakis, N.; Ma¨rky, M.; Hansen, H. J .;
Schmid, H. Helv. Chim. Acta 1972, 55, 748. (k) Hansen, H. J .; Schmid,
H. Helv. Chim. Acta 1972, 55, 745. (l) Claus, P.; Doppler, T.; Gakis,
N.; Gerorgarakis, M.; Giezendanner, H.; Gilgen, P.; Heimgartner, H.;
J ackson, B.; Ma¨rky, M.; Narasimhan, N. S.; Rosenkranz, H. J .;
Wunderli, A.; Hansen, H. J .; Schmid, H. Pure Appl. Chem. 1973, 33,
339.
We wish to report a study on the factors which promote
(or suppress) the “carbene-like” character of the 1,3-
dipoles. These imine nitrogen stabilized structures 1c are
(11) (a) Padwa, A.; Clough, S.; Dharan, M.; Smolanoff, J .; Wetmore,
S. I. J . Am. Chem. Soc. 1972, 94, 1395. (b) Padwa, A.; Wetmore, S. I.
J . Chem. Soc., Chem. Commun. 1972, 1116. See also the following for
a review of carbenes in heterocyclic chemistry: Wentrup, C. Adv.
Heterocycl. Chem. 1981, 28, 231-361.
(12) (a) Orahovats, A.; Heimgartner, H.; Schmid, H.; Heinzelmann,
W. Helv. Chim. Acta 1977, 58, 2662. (b) Gakis, N.; Ma¨rky, M.; Hansen,
H.-J .; H.; Schmid, H. Helv. Chim. Acta 1972, 55, 748. (c) See also:
George, M. V.; Mitra, A.; Sukumuran, K. B. Angew. Chem., Int. Ed.
Engl. 1980, 19, 973.
(13) (a) Kitamura T.; Kobayashi, S.; Taniguchi, H. Tetrahedron Lett.
1979, 18, 1619. (b) Kitamura, T.; Kobayashi, S.; Taniguchi, H. J . Org.
Chem. 1984, 49, 4755.
(14) Burger, K.; Einhellig, K.; Su¨ss, G.; Gieren, A. Angew. Chem.,
Int. Ed. Engl. 1973, 12, 156.
(9) (a) Bednarek, P.; Wentrup, C. J . Am. Chem. Soc. 2003, 125, 9083.
(b) Maltsev, A.; Bally, T.; Tsao, M.-L.; Platz, M. S.; Kuhn, A.;
Vosswinkel, M.; Wentrup, C. J . Am. Chem. Soc. 2004, 126, 237.
(10) (a) Caramella, P.; Houk, K. N. J . Am. Chem. Soc. 1976, 98, 6397.
(b) Caramella, P.; Gandour, R. W.; Hall, J . A.; Deville, C. G.; Houk, K.
N. J . Am. Chem. Soc., 1977, 99, 385.
(15) Weidner, R.; Wu¨rthwein, E. U. Chem. Ber. 1989, 122, 1095.
4664 J . Org. Chem., Vol. 69, No. 14, 2004

Carbene Reactivity of Nitrile Ylides
SCHEME 3. Th er m olysis or P h otolysis of
SCHEME 4. F or m a tion of Nitr ile Ylid e Dim er s
4,5-Dih yd r o-1,3,2λ5-d ioxa p h osp h ole
related to the Arduengo bisamino-stabilized carbenes 8,16
and the recently reported aminoarylcarbenes 9,17 where
substituents can be varied on an aromatic ring directly
attached to the carbene center.
TABLE 1. Yield s (%) of Dim er s 5
5
X
Y
yield
The intermediates 1 were formed by the 1,1-elimina-
tion of HCl upon condensation of diaryl ketimines 12 with
a variety of R,R-dichlorotoluenes 13 (Scheme 4) and in
certain cases by the 1,3-elimination from the correspond-
ing imidoyl halides.
f
H
H
H
H
H
H
H
H
27
11
25
13
11
4
2.4
6
6
g
h
i
j
k
l
m
n
o
2-CH3
3-CH3
4-CH3
4-OCH3
3-Cl
2,4,6-(CH3)3
2,4,6-(CH3)3
H
Resu lts a n d Discu ssion
2,4,6-(CH3)3
4-CH3
4-CH3
1,1-Elim in a tion . Under suitable alkylation conditions,
diaryl ketimines undergo reaction to form N-substituted
imines; benzophenone imine 12i reacts with R-chloroben-
zylmethyl ether and dichlorodiphenylmethane to form the
N-substituted imines,N-(diphenylmethylene)-R-methoxy-
benzylamine (10)15 and diphenylketiminodiphenylmethyl
chloride (11),18 respectively. However, when the conden-
4-CH3
7
chloride product 14 could not be isolated (Scheme 4). No
reaction occurred when triethylamine in benzene was
employed as the base, or on changing the solvent from
benzene to the more polar acetonitrile.
Elemental analysis, in conjunction with mass spec-
trometry, indicated loss of a second mole of HCl followed
by dimerization had occurred. The structure and stereo-
chemistry of this dimer, which was isolated only as the
E-isomer 5f, was determined by X-ray crystallography
(see Figure S1 in the Supporting Information).
This reaction was successfully repeated for a number
of substituted analogues 5f-o (Table 1) with either
electron-donating substituents (3-methyl [σm -0.06],
4-methyl [σp -0.14], 4-methoxy [σp -0.27]) or the electron-
withdrawing 3-chlorophenyl (σm 0.37) substituent present
at the C1 carbon atom of the nitrile ylide.
sation is carried out with benzophenone imine 12i and
R,R-dichlorotoluene 13 under a wide variety of experi-
mental conditions, we have found that the expected
(16) Arduengo, A. J ., III Acc. Chem. Res. 1999, 32, 913.
(17) (a) Sole´, S.; Pradel, C.; Gornitzka, H.; Schoeller, W. W.;
Bourissou, D.; Bertrand, G. Science 2001, 292, 1901. (b) Cattoe¨n, X.;
Sole´, S.; Pradel, C.; Gornitzka, H.; Miqueu, K.; Bourissou, D.; Bertrand,
G. J . Org. Chem. 2003, 68, 911.
(18) (a) Samuel, B.; Wade, K. J . Chem. Soc., Chem. Commun. 1968,
1081. (b) Samuel, B.; Wade, K. J . Chem. Soc. (A) 1969, 1742.
In contrast, however, no dimerization was observed
when the strongly electron-withdrawing 4-NO2-phenyl
substituent (σp 0.78) was present. In this case the alkene
(E)-R,R′-dichloro-4,4′-dinitrostilbene 16 was isolated from
the reaction mixture. A reaction pathway (Scheme 5)
J . Org. Chem, Vol. 69, No. 14, 2004 4665

Fergus et al.
TABLE 2. P r od u ct Distr ibu tion (%) of Im id oyl Ch lor id e
18 F or m a tion
SCHEME 5. Rea ction P a th w a y F or m a tion of 16
imidoyl
compd
chloride
von Braun
18a
18b
88
95
12
5
1,3-Elim in a tion . The generation of nitrile ylides by
the 1,3-elimination of hydrogen chloride from imidoyl
chlorides was also examined. The imidoyl chlorides 18
were prepared by reacting phosphorus pentachloride
(PCl5) and the corresponding amide 17 in dry benzene.
Once synthesized, the imidoyl chlorides were stored
under nitrogen at 0 °C as they are highly susceptible to
hydrolysis. They were used in all cases either im-
mediately or within 1-2 days.
A competing pathway, known as von Braun degrada-
tion,22 proved problematic during their synthesis. This
reaction resulted in the formation of the chloride 20 and
the nitrile 21 (which were observed spectroscopically),
via the nitrilium ion 19 (Scheme 6).
It was found that the extent of von Braun degradation
is minimized by avoiding heat when removing the reac-
tion solvent during the workup of the imidoyl chlorides.
After solvent removal, the product is placed on a vacuum
pump immediately to remove any traces of POCl3, which
is an ionizing solvent, thus helping to promote von Braun
degradation. The optimized product distribution during
the formation of the imidoyl chlorides 18 is shown in
Table 2.
Huisgen’s method to generate nitrile ylides from imi-
doyl chlorides using the base triethylamine proved
unsuccessful in the 1,3-elimination pathway. The N-
butyl-substituted imine 22 was formed when n-butyl-
lithium was employed as base.
However, the more sterically hindered and less nu-
cleophilic base LDA successfully generated the nitrile
ylide from the corresponding imidoyl chloride and in the
absence of a dipolarophile the hexaaryl diazatrienes 5
(“nitrile ylide dimers”) were again formed.
observed by Chan19 accounts for the formation of 16,
indicating that the reaction of base with the aryl halide
forms radicals, which subsequently dimerize followed by
elimination of HCl to give 16.
In an attempt to optimize the yield of dimer, the base
(its nature and the number of equivalents), the time of
reaction, and the temperature were varied. It is con-
cluded from these reactions that the main difficulty
encountered in the reaction sequence was the removal
of the imine hydrogen (benzophenone imine 12i has a
reported pKa of 31).20
Initially the base n-butyllithium was used but the yield
of the dimer 5f was low (33.4%) as determined from
HPLC product analysis. Other bases that were examined
include LDA, tert-butyllithium, and a 1:1 mixture of
n-butyllithium and potassium tert-butoxide, referred to
as a “superbase”.21 Also investigated were the effects of
temperature variation and the addition of a second
equivalent of base when the R,R-dichlorotoluene 13 was
added at -78 °C. It was concluded that using 1 equiv of
tert-butyllithium affords the maximum formation of
dimer although product analysis showed that some
unreacted starting material remained in the reaction
mixture under these conditions.
SCHEME 6. Von Br a u n Degr a d a tion of Im id oyl Ch lor id es
4666 J . Org. Chem., Vol. 69, No. 14, 2004

Carbene Reactivity of Nitrile Ylides
SCHEME 7. Hyd r olysis of Dia za tr ien es
The addition of LDA to the imidoyl chloride N-benzhy-
dryl-4-nitrobenzimidoyl chloride 18b resulted in the
initial formation of a purple solution. As indicated above,
a purple color is characteristic of nitrile ylides containing
a 4-nitrophenyl substituent. The reaction mixture turned
a dark orange/brown color after being warmed to ambient
temperature and stirred overnight. Unlike the case with
N-benzhydrylbenzimidoyl chloride 18a (where a phenyl
substituent is present at the carbene carbon of the nitrile
ylide), no evidence for the 4-nitrophenyl dimer in the
mass spectrum of the crude product was present.
Ca r ben e Ch a r a cter of Nitr ile Ylid e. The hexaaryl-
trienes 5 were isolated as the E-isomers in the cases of
5f, 5h , and 5k when a phenyl, 3-methylphenyl, and
3-chlorophenyl substituent are present respectively ad-
jacent to the carbene center.
SCHEME 8. Deloca liza tion by Nitr o Gr ou p on
Nitr ile Ylid e
However, in the case of 5l (Figure S25 in the Support-
ing Information) the sterically hindered Mes substituent
adopts the Z-configuration. The Schekal program was
used to display the crystal structures allowing rotation
of the molecule, but it was not possible to rotate 180°
about the double bond in 5l illustrating that the E-isomer
is destabilized by the presence of the Mes substituents.
Recrystallization of the products by using the mixed
solvent system chloroform/acetonitrile afforded the dimers
as highly colored compounds with absorption maxima
(λmax) from 363 to 422 nm. The dimers do not appear to
be stable on silica; further decomposition of the dimers
appeared on thin-layer chromatography (TLC) after
separation. Previous reports by Padwa8b on the behavior
of similar structures indicate that during separation via
column chromatography protonation followed by hydroly-
sis occurs resulting in the decomposition of the phenyl
dimer 5f to produce benzophenone 23 and 2-amino-1,2-
diphenylethanone 24 as shown in Scheme 7.
tion, e.g., CF3 and C6H5-4-NO2, and a H substituent
promote 1,3-dipolar cycloadditions with linear geometry
of the nitrile ylide.
From our results on intermolecular reactions of nitrile
ylides, it appears that the primary control of carbene
behavior of the nitrile ylides is through electronic effects
at C1. The use of strongly electron-withdrawing substit-
uents diminishes the carbene-like reactivity of the nitrile
ylides and promotes its linear and carbanion character
resulting in a lower yield of isolated dimer. This is also
evident in comparing the yields of isolated phenyl dimer
5f and 3-chloro dimer 5k . The steric effects offered by
the electron-donating 2-methylphenyl and Mes substit-
uents result in lower yields of their isolated dimers,
presumably due to steric shielding of the reactive site at
the carbene center C1, which reduces the yield of dimer.
The presence of the strongly electron-withdrawing
4-nitrophenyl substituent on the nitrile ylide (generated
via 1,3-elimination of HCl from the N-benzhydryl-4-
nitrobenzimidoyl chloride 18b or via the 1,1-elimination
pathway) suppresses the formation of the resulting dimer
product. The presence of the nitro group on the phenyl
ring allows the negative charge formed to be delocalized
throughout the molecule, resulting in the linear nitrile
ylide as shown in Scheme 8.
Padwa23 has reported on the role of substituents in
controlling intramolecular cycloaddition reactions of ni-
trile ylides. He has demonstrated that electron-donating
substituents, e.g., CH3 on carbon C3 of the nitrile ylide,
favor the carbene character resulting in 1,1-cycloaddi-
tions where the nitrile ylide has a bent geometry,
whereas electron-withdrawing substituents at this posi-
Mech a n ism . Steenken24 has shown that nitrile ylides
generated on the photochemical ring opening of 2H-
azirines 25 react rapidly in the presence of proton donors
(such as alcohols) to form the aza-allenium cations 26 as
intermediates ultimately yielding the alkoxyimines 27.
This occurs in preference to protonation on the other
(19) Chan, K. C.; Goh, S. H.; Teoh, S. E.; Wong, W. H. Aust. J . Chem.
1974, 27, 421.
(20) Bordwell, F. G.; J i, G.-Z. J . Am. Chem. Soc. 1991, 113, 8398.
(21) (a) Marsch, M.; Harms, K.; Lochmann, L.; Boche, G. Angew.
Chem., Int. Ed. Engl. 1990, 29, 308. (b) Schlosser, M.; Strunk, S.
Tetrahedron Lett. 1984, 25, 741.
(22) Bonnett, R. The Chemistry of the Carbon-Nitrogen Double
Bond; Patai, S., Ed.; Chichester Interscience: New York, 1970; p 653.
(23) Padwa, A.; Carlsen, P. H. J .; Ku, A. J . Am. Chem. Soc. 1978,
100, 3494.
(24) Albrecht, E.; Mattay, J .; Steenken, S. J . Am. Chem. Soc. 1997,
119, 11605. See also ref 2, pp 206-214.
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Fergus et al.
SCHEME 9. P r oton a tion of Nitr ile Ylid es
SCHEME 10. Ca r ben e Dim er F or m a tion
Str u ctu r e of Dim er s a n d NMR Sp ectr a . The crystal
structures of the hexaaryl diazatrienes 5h and 5k
isolated as the E-dimer do not deviate or illustrate
unusual properties relative to the unsubstituted phenyl
dimer 5f. The Z-isomer 5l is not equiplanar about the
CdC, with an angle of 5° between both planes. There is
a distance of 2.66 Å between H21 of the Mes substituent
and C8 of the adjacent Mes substituent.
The NMR spectra of these dimeric structures were
assigned by using (1H-1H) COSY and (1H-1H) NOESY.
The 1H spectra of the dimers clearly illustrate the
consistency of the doublets corresponding to the ortho
protons in the aromatic rings of the imine moiety, which
occur at 6.6-6.7 ppm for the pseudoequatorial rings, and
at 7.5-7.6 ppm for the pseudoaxial rings.
Two of the aromatic rings of the imine moiety are
pseudoaxial whereas the remaining aromatic rings are
pseudoequatorial. This nonequivalence in each of the
aromatic rings may be explained in terms of slow
interconversion of the imine functionalities, which gener-
ally occurs via nitrogen inversion. There is no evidence
for π-stacking of the equatorial aromatic rings from their
crystal structures.
carbon (C3), which would give the nitrilium cation 28,
yielding the amides 29 upon reaction with water (Scheme
9).25 However, an amide of type 29 is formed with an
electronegatively substituted nitrile ylide [(CF3)2 at C3]
and hence a linear carbanion nitrile ylide.5c
Condensation of diaryl ketimines 12 with a variety of
R,R-dichlorotoluenes 13 most likely proceeds via the
chloroimine 14, which then ionizes to the aza-allenium
ion 15 followed by loss of a proton in the presence of a
strong base. Evidence to support this mechanism (Scheme
4) comes from the isolation of the intermediate imine in
cases when ionization to the cation is unfavorable due
to the lack of a suitable leaving group (for example, in
compounds 10 and 11).
The dimerization of singlet carbenes normally involves
the attack of the occupied in-plane σ lone pair of one
carbene center on the out-of-plane vacant pπ orbital of a
second carbene.26 Alder27 has observed 13C NMR and
X-ray evidence for the interaction between stable di-
aminocarbenes and imidazol-2-ylidene with lithium,
sodium, and potassium species in toluene and THF
solutions. The question of alkali metal coordination is
important with regard to the generation of carbenes by
deprotonation, using bases with alkali metal counterions
(e.g. n-BuLi, NaH, LDA) as the carbene may be com-
plexed with a metal or held in a solvent cage with a salt.
Recently Bertrand has reported a new synthetic route
to form stable metal-free diaminocarbenes and transient
monoaminocarbenes.28
Con clu sion
A series of novel hexaaryl diazatrienes 5 (“nitrile ylide
dimers”) were formed via the nitrile ylide 1 generated
by the base-promoted 1,1-elimination of HCl from the
intermediate chloroimine 14. These dimers were isolated
as stable crystalline materials in both the E and Z
configurations depending on the substituents present on
the aromatic ring adjacent to the carbene center. A
second route, using 1,3-elimination of HCl from the
imidoyl chloride 18, was also successfully used to syn-
thesize the dimer product 5, confirming that the two
pathways proceed via the same nitrile ylide intermediate.
It was found that the 1,1-elimination of HCl from the
intermediate chloroimines 14 was generally a less prob-
lematic and more facile route to the nitrile ylides than
the 1,3-elimination of HCl from the corresponding imidoyl
chlorides 18.
It is concluded that the reaction most likely proceeds
via the chloroimine 14, which then ionizes to the aza-
allenium ion 15 followed by loss of a proton.
The behavior of nitrile ylides is controlled by the
substituent groups present, with the bent carbene form
1c favored with electron-donating substituents or a
3-chlorophenyl substituent; however, the strong electron-
withdrawing substituents (i.e., 4-NO2-C6H4) suppress the
carbene-like reactivity of the nitrile ylides.
It must be stated that when formal carbene dimers are
isolated, a mechanism of nucleophilic attack of one
carbene upon its conjugate acid followed by proton
elimination may also explain their formation (Scheme
10), as suggested by Chen and J ordan.29 However, the
basic conditions used in the present study make this
unlikely.
Exp er im en ta l Section
(25) (a) Ugi, I.; Beck, F.; Fetzer, U. Chem. Ber. 1962, 95, 126. (b)
Hegarty, A. F.; Cronin, J . D.; Scott, F. L. J . Chem. Soc., Perkin Trans.
2 1975, 429.
(26) (a) Carter, E. A.; Goddard, W. A. J . Phys. Chem. 1986, 90, 998.
(b) Malrieu, J . P.; Trinquier, G. J . Am. Chem. Soc. 1989, 111, 5916.
(27) Alder, R. W.; Blake, M. E.; Bortolotti, C.; Bufali, S.; Butts, C.
P.; Linehan, E.; Oliva, J . M.; Orpen, G.; Quale, M. J . J . Chem. Soc.,
Chem. Commun. 1999, 241.
Dim er Syn th esis: 1,1,3,4,6,6-Hexa k isp h en yl-2,5-d ia za -
1,3,5-h exa tr ien e (5f). A solution of 11i (0.5 mL, 3.0 mmol)
in dry THF (5 cm3) was cooled to -78 °C. Dropwise addition
(28) Otto, M.; Conejero, S.; Canac, Y.; Romanenko, V. D.; Rudzevitch,
V.; Bertrand, G. J . Am. Chem. Soc. 2004, 126, 1016.
(29) Chen, Y. T.; J ordan, F. J . Org. Chem. 1991, 56, 5029.
4668 J . Org. Chem., Vol. 69, No. 14, 2004

Carbene Reactivity of Nitrile Ylides
of tert-butyllithium (1.7 M, 1.76 mL, 8.56 mmol) resulted in a
bright red solution, which was stirred for 1 h at -78 °C and
30 min at ambient temperature. The addition of R,R-dichlo-
rotoluene (0.38 mL, 3.0 mmol) in dry THF (3 mL) was
subsequently carried out at -78 °C. The cooling bath was
removed and the red solution was left to stir overnight at
ambient temperature. The following day, the solvent was
removed and the residue dissolved in toluene before filtration
to remove insoluble inorganic materials. The solvent was
removed in vacuo to give 5f (0.22 g 27%) as an orange/red
material, which was recrystallized from chloroform/acetoni-
trile. Mp 213-214 °C. UV (CH3CN, nm) 249 (ꢀ 35 022), 411 nm
(ꢀ 5830). IR (KBr, cm-1) 1615 (CdN), 1595 (CdC, aromatic).
1H NMR (500 MHz, CDCl3) δ 6.64 (4H, d, J ) 7.44 Hz, H10,
H14), 6.98-7.06 (6H, m, H5-H7), 7.11-7.15 (8H, m, H4, H8,
H11, H13), 7.23 (2H, m, H12), 7.29 (4H, m, H17, H19), 7.36
(2H, m, H18), 7.58 (4H, d, J ) 7.52 Hz, H16, H20). 13C NMR
(126 MHz, CDCl3) δ 126.0, 127.3, 127.4, 127.5, 128.0, 128.1,
128.2, 128.4, 129.1, 129.2, 130.2, 132.9, 137.9, 139.7, 139.8,
168.7. Anal. Calcd for C40H30N2: C, 89.30; H, 5.62; N, 5.21.
Found: C, 88.90; H, 5.70; N, 5.15. MS 538 (M+, 19%), 269 (M+/
2, 23%), 165 (100%).
was washed with bicarbonate solution, dried over MgSO4, and
filtered, and solvent was removed in vacuo to give a clear oil.
Vacuum distillation was carried out to purify the product 13g
(4.85 g, 80%). Bp 54 °C (0.2 mbar Hg) [lit. bp32 225 °C]. IR (liq
1
film, cm-1) 1604 (CdC, aromatic), 727 (C-Cl). H NMR (300
MHz, CDCl3) δ 2.43 (3H, s), 6.91 (1H, s), 7.12-7.77 (4H, m).
13C NMR (75 MHz, CDC13) δ 19.0, 69.9, 127.0, 127.2, 130.1,
131.0, 134.4, 138.4.
N-Ben zh yd r ylben za m id e (17a ). A solution of freshly
distilled triethylamine (8.08 mL, 0.058 mol) and aminodiphen-
ylmethane (10.0 mL, 0.058 mol) in dry CH2Cl2 (50 mL) was
added dropwise over 30 min to a vigorously stirred solution
(large magnetic bob) of benzoyl chloride (6.73 mL, 0.058 mol)
in dry CH2Cl2 (50 mL). Upon complete addition, the reaction
mixture was refluxed for 3 h. After cooling, deionized water
was added and the organic layer was washed with deionized
water, 1 M HCl, followed by sat. NaCl solution. The organic
layers were dried over MgSO4 and filtered and solvent removed
in vacuo to give a pale yellow crystalline solid. Recrystalliza-
tion with absolute alcohol yielded 17a (14.88 g, 89.3%) as white
crystals. Mp 169-172 °C (lit. mp33 174 °C). UV (CH3CN, nm)
221 nm (ꢀ 16 475). IR (KBr, cm-1) 3310 (N-H), 3054 (νas CH),
3028 (νs CH), 1638 (CdO), 1601 (CdC, aromatic). 1H NMR (300
MHz, CDCl3) δ 6.45 (d, 1H, J ) 7.615 Hz), 6.75 (d br, 1H, J )
7.029 Hz), 7.25-7.53 (m, 13H), 7.82 (m, 2H). 13C NMR (75
MHz, CDCl3) δ 57.3, 127.3, 127.8, 127.8, 128.9, 129.0, 131.9,
134.6, 141.8, 167.8. Anal. Calcd for C20H17NO: C, 83.95; H,
5.96; N, 4.87. Found: C, 83.59; H, 5.95; N, 4.91. MS 287 (M+,
46%), 210 (8%), 182 (23%), 165 (21%), 105 (100%).
N-Ben zh yd r ylben zim id oyl Ch lor id e (18a ). A solution of
PCl5 (1.07 g, 5.14 mmol) in dry benzene (45 mL) was added
via cannula to a suspension of 17a (1.44 g, 5.01 mmol) in dry
benzene (50 mL) at 0 °C. The reaction was left to stir overnight
at ambient temperature. The following day, the benzene was
removed in vacuo and traces of POCl3 were removed im-
mediately, using the vacuum pump to yield 18a (1.51 g). IR
(liq film, cm-1) 2967 (νas CH), 2928 (νs CH), 1660 (CdN), 1601
(CdC, aromatic), 672 (C-Cl). 1H NMR (300 MHz, CDCl3) δ
6.25 (s, 1H), 7.21-7.51 (13H, m), 8.11 (2H, dd, J ) 8.347 Hz,
J ) 1.464 Hz). 13C NMR (75 MHz, CDCl3) δ 71.3, 127.5, 127.9,
128.0, 128.3, 128.5, 128.6, 128.8, 129.5, 131.7, 136.2, 140.9,
142.96.
Syn th esis of Im in es. The imines were prepared by a
procedure reported by Pickard and Tolbert.30 The process
involves a Grignard reaction with an aryl nitrile and subse-
quent decomposition of the complex with anhydrous methanol.
2,4,6,2′,4′,6′-Hexam eth ylben zoph en on eim in e (12ii). Bro-
momesitylene 30 (5.0 g, 0.025mol) was added dropwise to
magnesium turnings (0.75 g, 0.3mol) in 20 mL of dry THF
under an atmosphere of nitrogen. A crystal of iodine was
necessary to initiate the Grignard reaction. The reaction was
refluxed for 2 h. Then the THF was distilled from the reaction
mixture and a solution of 2,4,6-trimethylbenzonitrile 32 (2.78
g, 0.019mol) in dry toluene (30 mL) was added slowly. The
reaction mixture was refluxed for 12 h. After cooling, dry
methanol (15 mL) was added slowly, the gummy mixture was
filtered ,and the filtered solid was washed ether. The solvent
was removed in vacuo and recrystallization of the brown solid
was carried out with absolute alcohol to give 12ii (2.61 g, 52%)
as pale brown crystals. Mp 128-130 °C (lit.31 mp 130 °C). IR
(KBr, cm-1) 3253 (N-H), 2961 (νas CH3), 2916 (νs CH3), 1608
1
(CdN), 1598 (CdC, aromatic). H NMR (300 MHz, CDCl3) δ
2.14 (s, 12H), 2.27 (s, 6H), 6.84 (s, 4H). 13C NMR (75 MHz,
CDCl3) δ 21.2, 21.2, 129.9, 136.3, 138.4, 178.6. Anal. Calcd for
Ack n ow led gm en t. We thank Ms. Geraldine Fitz-
patrick and Dr. Ken Glass for their support and as-
sistance with NMR, Dr. Helge Mueller-Bunz and Dr.
Patrick McArdle for their work on the X-ray crystal
structures, and Ms. Ann Connolly in the Microanalytical
Laboratory, University College Dublin. S. Fergus thanks
Enterprise Ireland for postgraduate funding.
C
19H23N: C, 85.99; H, 8.74; N, 5.28. Found: C, 85.79; H, 8.75;
N, 5.53. MS 265 (M+, 1%), 250 (M+ - NH, 100%), 235 (22%),
219 (3%), 144 (12%), 118 (12%).
Syn th esis of r,r-Dich lor otolu en es. The R,R-dichlorotolu-
enes were used immediately due to their high reactivity, which
also made microanalyses difficult to obtain.
1-Dich lor om eth yl-2-m eth ylben zen e (13g). A solution of
o-tolualdehyde (4.00 mL, 0.035 mol) in dry toluene (30 mL)
was added dropwise via cannula to a suspension of PCl5 (7.20
g, 0.035 mol) in dry toluene (40 mL). The reaction was
maintained under an atmosphere of nitrogen and stirred
overnight at ambient temperature.
Su p p or tin g In for m a tion Ava ila ble: General experimen-
tal information, characterization data for 5g-o, 13h -m , 16,
17b, and 18b, supplementary IR data for 5f and 13g, synthesis
of 5f by the 1,3-elimination pathway, synthesis of 12i and 30-
32, 1H NMR for 5f-o, 17a , and 17b, 13C NMR for 5f-k ,m -o,
COSY NMR for 5f-k , NOESY NMR for 5g-k , X-ray crystal
structures for 5f,h ,k ,l, and X-ray crystal structure data for
5f,h ,k ,l. This material is available free of charge via the
Internet at http://pubs.acs.org.
The pale pink solution was poured onto ice, the organic layer
(30) Pickard, P. L.; Tolbert, T. L. J . Org. Chem. 1961, 26, 4886.
(31) Hauser, C. R.; Hoffenberg, D. S. J . Am. Chem. Soc. 1955, 77,
4885.
(32) Rayman, B. Bull. Soc. Chim. Fr. 1876, 26, 532.
(33) MacPherson, E. J .; Smith, J . G. Can. J . Chem. 1970, 48, 1915.
J O049748G
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