Intramolecular electrophilic rearrangements in saturated acyclic systems. C→N migrations of acetyl group

Article abstract of DOI:10.1023/A:1013158208411

Reactions between isocyanates and carbanions with an acetyl group at the carbanion center occur via rearrangement of the intermediate N-anions into isomeric C-anions by C→N-migration of the MeC(O) group. The acetyl group undergoes migration easier than the ethoxycarbonyl group. The P-zwitterionic rearrangement products were subjected to X-ray diffraction analysis.

Full text of DOI:10.1023/A:1013158208411

Russian Journal of Organic Chemistry, Vol. 37, No. 8, 2001, pp. 1061 1067. Translated from Zhurnal Organicheskoi Khimii, Vol. 37, No. 8, 2001,
pp. 1119 1125.
Original Russian Text Copyright
,
2001 by Gololobov, Galkina, Dovgan , Krasnova, Petrovskii, Schmutzler, Karasar, Freitag, Jones.
Intramolecular Electrophilic Rearrangements in Saturated
Acyclic Systems. C N Migrations of Acetyl Group*
Yu. G. Gololobov1, M. A. Galkina1, O. V. Dovgan,1,
I. Yu. Krasnova1, P. V. Petrovskii1, R. Schmutzler2,
A. Karasar2, M. Freitag2, P. G. Jones2
1Nesmeyanov Institute of Organoelemental Compounds, Russian Academy of Sciences, Moscow, 117813 Russia
2Institut fur Anorganische und Analytische Chemie der Technischen Universitat, Braunschweig, Germany
Received December 30, 1999
Abstract Reactions between isocyanates and carbanions with an acetyl group at the carbanion center occur
via rearrangement of the intermediate N-anions into isomeric C-anions by C N-migration of the MeC(O)
group. The acetyl group undergoes migration easier than the ethoxycarbonyl group. The P-zwitterionic
rearrangement products were subjected to X-ray diffraction analysis.
In the preceding communications of this series
[1 10] reactions were described of iso(thio)cyanates
with carbanions I and II, derivatives of CH-acids
with a single labile hydrogen at the carbanion center.
The reactions occurred in an unusual way with migra-
tion of COOAlk group from carbon atom to the
negatively charged nitrogen. Thus the reaction results
in an insertion of iso(thio)cyanates into a C C bond:
this process was not known before with iso(thio)-
cyanates (Schemes 1 and 2).
with sodium hydride in anhydrous THF readily reacts
with phenyl isocyanate; the acidification of the reac-
tion mixture yields amide VI containing the acetyl
group not at the carbon but at the nitrogen of the
phenylisocyanate group inserted in the C C bond
(Scheme 3).
Scheme 2.
In extension of the studies on intramolecular
N migration of electron-deficient groups we
C
investigated the isocyanates reactions with carbanions
V and XII containing an acetyl group at the carbanion
center.
Ketone IV (56.4% of enol form) being trans-
formed into the corresponding anion V by treatment
Scheme 1.
X = O, S; R = Alk , Ar.
Scheme 3.
*
The study was carried out under financial support of the Rus-
sian Foundation for Basic Research (grant no. 98-03-33117a)
and DFG (Aktenreichen 436 RUS 17/44/99).
1070-4280/01/3708-1061$25.00 2001 MAIK Nauka/Interperiodica

1062
GOLOLOBOV et al.
Scheme 4.
Scheme 5.
The first stage of carbanion V reaction with phenyl
belonging to a methine proton [7]. The methine
proton resulting from the C N migration of the
acetyl group should likely appear in the similar region
isocyanate apparently affords N-anion (A); intra-
molecular contact of the latter with the keto group
carbon induces the cleavage of the C C bond and a
migration of the acetyl group from carbon to nitrogen.
It is essentially a nucleophilic substitution at the
carbon atom where the carbanion plays the role of a
leaving group. Such processes were considered by
Hesse when treating the cycle expansion reactions
with isocyanates [11]. Obviously like in the case of
such migrations of alkoxycarbonyl group the driving
force of the C N shift of the acyl group is the
energy gain at transformation of the N-anion (A) into
an isomeric C-anion (B) [8].
1
(Scheme 3, compound VI). Actually, the H NMR
spectrum of compound VI contains a singlet at
6.06 ppm. In the 13C NMR spectrum appear the
signals of C=O group carbon (167.4 and 172.6 ppm)
(Table 1). In the same table are given the results of
calculation of the chemical shifts in the 1H and
13C NMR spectra of compound VI performed accord-
ing to additive scheme.
Likewise occurs the C N-rearrangement in reac-
tion between carbanion V and 1,4-phenylene diiso-
cyanate (Scheme 4).
The products of COOEt group C N migration
(Scheme 1) are characterized by an appearance of a
We carried out a comparison of C N-migration
ability of ethoxycarbonyl and acetyl groups by per-
1
singlet in 6 ppm region of the H NMR spectrum
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 8 2001

INTRAMOLECULAR ELECTROPHILIC REARRANGEMENTS
1063
1
Table 1. H and 13C NMR spectra of reaction products obtained in keeping with Schemes 4 and 5 and the corresponding
spectra calculated along the additive procedure
Compd.
no.
13C NMR spectrum, C, ppm (JCH, Hz)
1H NMR spectrum, , ppm (J, Hz)
CH_C(O)N< > N _C(O)CH3 > N _COOC2H5 _COOC2H5 _COCH3
VI
2.06 s (3H, CH3), 6.06 s (1H, CHCN), 7.2
7.43 m (10H, 2Ph)
167.4
160.60
168.7
172.6
VIa 2.47 s (3H, CH3), 5.06 s (1H, CHCN), 7.33
167.13
170.72
7.76 m (10H, 2Ph)
1.18 t (3H, C_H3CH2, JHH 7.2), 2.08 s (3H,
X
172.56
CH3CO), 3.26 d.d (1H, C_H H CH, JH
JHH 6.4), 3.37 d.d (1H, CH _H CH, JH
14,
14,
(2J 3.43) (2J 6.34)
(2J 4.22)
H
H
JHH 8.4), 4.12 q (2H, C_H2CH3, JHH 7.2),
4.53 d.d (1H, CH_ CH2, JHH 6.4, JHH 8.4),
7.53 d(2H, C6H4NO2, J 8.4), 7.13 7.65 m (5H,
C6H4), 8.17 d (2H, C6H4NO2, J 8.4)
XIa 1.23 t (3H, C_H3CH2), 2.23 s (3H, CH3CO),
2.92 q(1H, C_H H CH), 3.65 q(1H, CH H CH),
3.91 q (2H, CH_ 2CH3), 3.87 d.d (1H, CHCH2),
7.33 d (2H, C6H4NO2), 6.85 7.34 m (5H, C6H5),
8.28 d (2H, C6H4NO2)
170.54
151.89
206.15
a
Spectrum calculated by additive procedure.
forming reaction of phenyl isocyanate with carbanion
IX containing both these groups at the carbanion
center (Scheme 5).
cyanates and phosphorus-containing carbanion XII
with the use of 31P NMR spectroscopy. The previous-
ly unknown P-zwitterion XII was prepared along
procedure from [12] where the analogous carbanions
were obtained by reaction with trimethyl-, dimethyl-
phenyl-, or diethylphenylphosphine with 3-benzyl-
idenepentane-2,4-dione. We reacted with the latter
triisopropylphosphine and tributylphosphine. Note
that in contrast to tributylphosphine the triisopropyl-
phosphine even at large excess and in minimum
amount of solvent reacts with 3-benzylidene-2,4-
dione very slowly and not selectively. We failed to
obtain therewith the corresponding P-zwitterion.
Apparently in the triisobutylphosphine the phos-
phorus atom is considerably sterically hindered. At
the same time the tributylphosphine relatively fast and
selectively reacted with 3-benzylidene-2,4-dione to
yield P-zwitterion XII (Scheme 6).
1
In the H NMR spectrum of the reaction product
obtained along Scheme 5 are observed signals char-
acteristic of CH2CH moiety (Table 1). However this
group should be present both in carbamate XI and
1
amide X, and therefore the H NMR spectrum is not
sufficient for assignment of the product structure.
Therewith the 13C NMR spectrum indicated with
certainty that the reaction afforded exclusively amide
X and not carbamate XI or their mixture. Table 1
contains the data on 13C NMR spectrum of compound
X and the calculation results performed by additive
scheme for isomer XI. In the 13C NMR spectrum of
compound X are present characteristic signals of
C=O carbons (172.58, 170.72, and 168.83 ppm)
belonging apparently to carbonyls of amide
[Me(CO)N and CHC(O)N respectively] and ester
groups; no carbon signal from the keto group of
isomer XI is observed. In the calculated
carbamate XI spectrum the signal from the keto group
carbon is located at 206.15 ppm. Therefore in keep-
ing with Scheme 5 migration from carbon to nitrogen
occurs only with acyl group.
P-Zwitterion XII formed in dichloromethane on
removing the solvent slowly crystallizes at room
Scheme 6.
The rearrangements under consideration are
conveniently followed on reaction between iso-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 8 2001

1064
GOLOLOBOV et al.
Scheme 7.
Scheme 8.
R = cyclo-C6H11 (XIV), Ph (XV), 3,4-Cl2C6H3 (XVI).
Fig. 1. Structure of compound XII in a crystal.
moiety that appear in the 1H NMR spectrum as
typical doublets of doublets.
temperature. Note that apparently due to high hydro-
phobicity zwitterion XII is well soluble in ethyl ether
and even in pentane. Since such zwitterions are
known to rearrange into isomeric ylides through self-
Zwitterion XII readily reacts in dichloromethane
solution at room temperature with cyclohexyl,
phenyl, or 3,4-dichlorophenyl isocyanates to furnish
amides XIV XVI with the acyl attached to the nitro-
gen of the amide group (Scheme 8).
protonation due to the presence of
a labile
-hydrogen we have established the structure of
zwitterion XII by X-ray diffraction analysis. In the
crystalline state the compound XII molecule exists as
a zwitterion with a tetrahedral phosphorus atom and
a planar carbanion center around which the sum of
angles amounts to 360 .
The structure of reaction products was established
1
from H, 13C, and 31P NMR and IR spectra, and from
X-ray diffraction study. It is interesting that com-
pound XV crystallized with one water molecule that
in the hydrate is linked by a hydrogen bond to the
amide group conjugated with the anion charge
(Fig. 2). The zwitterionic structure of compound XV
is determined by the presence of a phosphonium
group and of carbanion center located in -position
to the phosphorus atom. The X-ray data show that
both carbanion center and amide nitrogen have planar
structure. The sum of angles at the carbanion center is
359.9 , at the amide nitrogen 359.8 .
As show IR and X-ray data the anion charge in the
zwitterion XII is strongly delocalized in the pentade
O1 C3 C2 C4 O2 (Fig. 1). For instance, whereas the
absorption band of the carbonyl group in the IR
spectrum of compound XIII appears in the region
1
1750 cm , in the spectrum of zwitterion XII the
frequency of the absorption of the carbonyl group
conjugated with the anion charge is shifted to
1
1480 cm .
In the reaction products obtained along Scheme 8
the negative charge is significantly delocalized in the
pentade O1 C3 C2 C5 O2 as show IR spectra and
X-ray analysis data. In the IR spectra of compounds
XIV and XVI the absorption bands of carbonyl
groups are observed in the region 1470 1490 (con-
jugated keto group), 1528 1574 (conjugated CO from
It is known that the bond lengths of C=O (in
ketones) and C C (in paraffins) are 1.23 and 1.54
respectively, whereas in compound XII obviously
because of conjugation the bond lengths C3 = O 1 ,
C4 = O 2 and C2 C3 , C2 C4 are equal respectively
to 1.2499, 1.2710, and 1.4062, 1.4313
.
1
the amide group), and 1623 1667 cm (noncon-
The protonation of zwitterion XII (Scheme 7)
gives rise to a crystalline phosphonium salt XIII; its
structure follows from the NMR data. The most
informative are the resonances from P CH CH
jugated CO from the amide group). The noncon-
jugated amide C=O groups in compounds VI and
VII have the respective absorption bands in 1693
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 8 2001

INTRAMOLECULAR ELECTROPHILIC REARRANGEMENTS
1728 cm region. The length of the C C bond
1065
1
in ketones is 1.516 [13] whereas in compound XV
the C2 C3 bond is considerably shorter, 1.411 . At
the same time the length of the C3 O1 bond of keto
group (1.257 ) is more than the standard C=O
length value in ketones (1.215 ). Likewise is
shortened the C2 C5 bond (1.41 ) and extended the
C5 O2 bond (1.23 ) in the amide fragment of the
molecule as compared with the similar bond in
acetamide (1.21 ).
Analogous trends appear in compounds XIV and
XVI (Figs. 3, 4).
Characteristic bond lengths in compound XIV are
as follows : N C6 1.3624 (19), N C5 1.4494(18),
O3 C6 1.2278(18), O1 C3 1.2602(17), O2 C5
1.2420(16), C2 C5 1.412(2), C2 C3 1.4204(19).
Characteristic angles, deg: C6NC5 122.05(12),
C6NC8 118.23(12), C5NC8 118.41(12), O1C3C2
119.24(13), O1C3C4 115.62(12), C2C3C4 125.14
(14), O2C5C2 124.42(13), O2C5N 116.06(13),
C2C5N 119.52(12).
Fig. 2. Structure of compound XV in a crystal.
Characteristic angles, deg: C6NC8 123.74(13),
C6NC5 118.91(12), C8NC5 116.64(12), O1C3C2
119.97(14), O1C3C4 118.15(13), C2C3C4 121.88 (14),
O2C5C2 129.62(14), O2C5N 115.19(13), C2C5N
115.18(12).
Characteristic bond lengths in compound XVI are
as follows
: N C6 1.381(2), N C5 1.5049(18),
O1 C3 1.2509(18), O2 C5 1.2321(18), O3 C6
1.2210(19), C2 C5 1.406(2), C2 C3 1.425(2).
Thus the migration of electron-deficient group
from a carbon to a negatively charged nitrogen in the
Fig. 3. Structure of compound XIV in a crystal.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 8 2001

1066
GOLOLOBOV et al.
Table 2. Yields, melting points, and elemental analyses of compounds obtained
Compd.
no.
Found, %
Calculated, %
Yield, %
mp,
C
Formula
C
H
C
H
VI
VII
X
XII
XIII
XIV
XV
XVI
37
20
78
67
71
85
32
32
77 79
102 103
72.85
69.64
62.15
73.22
55.24
72.42
70.29
64.26
5.08
5.02
5.42
10.04
7.49
9.79
8.71
7.39
C17H14N2O2
C28H22N4O4
C20H20N2O6
C24H39O2P
C25H40F3O5PS
C31H50O3NP
C31H44O3NP
C31H42Cl2O3NP
73.37
70.28
62.54
73.85
55.55
71.23
70.58
64.36
5.07
4.63
5.21
10.00
7.96
10.3
8.72
7.26
70
116 117
136 137
99 100
119
series of acyclic saturated compounds occurs not only
with alkoxycarbonyl but also with acyl groups.
Phenylcyanoacetic acid (N-acetyl-N-phenyl)-
amide (VI). To a solution of 0.8 g (5 mmol) of
1-phenyl-1-cyanopropan-2-one in 80 ml of THF was
added at stirring 0.2 g (5.25 mmol) of sodium
hydride. In 2 h was added dropwise 0.6 g (5 mmol)
of phenyl isocyanate in 20 ml of THF, and the
mixture was stirred for 2 h at 20 C. Then to the
stirred reaction mixture at 4 C was added a mixture
of 5.0 mmol of trifluoroacetic acid and 20 ml of
hexane. The precipitated sodium trifluoroacetate was
filtered off, the solvent was removed in a vacuum,
and to the residue was added ether. The ether solution
was evaporated in a vacuum, and the solid residue
EXPERIMENTAL
NMR spectra were recorded on spectrometer
1
Bruker AMX-400, H (400.26 MHz), 13C (100.68
MHz) and 31P (162.02 MHz), ( , ppm relative to
TMS, CDCl3, and 80% H3PO4 for 1H, 13C, 31P
respectively). IR spectra were registered on Specord
M-82 instrument. The reactions were carried out
under dry nitrogen atmosphere. The solvents used
were preliminary thoroughly purified and dried.
Sodium hydride contained 90% of the main substance.
The elemental analyses, yields, and melting points of
compounds are listed in Table 2.
1
was recrystallized from hexane. H NMR spectrum
( , ppm): 2.064 s (3H, CH3), 6.06 s (1H, CHCN),
1
7.2 7.43 m (10H, 2Ph). IR spectrum, , cm : 2976
(H CCN), 2251 (CN), 1728 [C(O)CH3], 1700
[C(O)N ].
Bis[N-acetyl-N-(cyanophenylacetyl)]phenylene-
1,4-diamine (VII). To a solution of 1 g (6.24 mmol)
of 1-phenyl-1-cyanopropan-2-one in 40 ml of THF
was added at stirring and cooling to 4 C 0.25 g
(6.24 mmol) of sodium hydride. In 1 h was added
dropwise a solution of 0.5 g (3.12 mmol) of 1,4-
phenylene diisocyanate in 20 ml of THF, and the
mixture was stirred for 3 h at 4 C. The reaction
mixture was left standing overnight. Then to the
stirred reaction mixture at 4 C was added a mixture
of 0.71 g (6.24 mmol) of trifluoroacetic acid and
20 ml of anhydrous hexane. The sodium trifluoro-
acetate was filtered off, the solvent was removed in a
vacuum, and to the residue was added ethyl ether. At
cooling from the ether extract precipitated colorless
crystals of compound VII. 1H NMR spectrum
( , ppm): 2.14 s (3H, CH3), 6.01 s (2H, CHCN),
7.32 7.45 m (14H, H arom).
Fig. 4. Structure of compound XVI in a crystal.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 8 2001

INTRAMOLECULAR ELECTROPHILIC REARRANGEMENTS
1067
Reaction of P-zwitterion XII with isocyanates.
An equimolar mixture of P-zwitterion XII and an
appropriate aryl isocyanate (2 mmol each) in 2 ml of
CH2Cl2 was maintained in dry nitrogen atmosphere at
room temperature for 24 h. The solvent was removed,
and the residue was crystallized from pentane ether
mixture. At the use of cyclohexyl isocyanate the latter
was taken in 3-fold excess, and the reaction mixture
was kept at 20 C for a week. Afterwards the solvent
was removed, and the residue was crystallized from
acetone.
2. Krylova, T.O., Shishkin, O.V., Struchkov, Yu.T.,
Kolomnikova, G.D., and Gololobov, Yu.G., Zh. Org.
Khim., 1995, vol. 65, no. 8, pp. 1393 1397.
3. Gololobov, Yu.G., Kolomnikova, G.D., Krylo-
va, T.O., Izv. Akad. Nauk, Ser. Khim., 1995, no. 1,
pp. 186 187.
4. Gololobov, Yu G., Pinchuk, V A., Thonnessen, H.,
Jones, P.G., and Schmutzler, R., Phosphorus, Sulfur
and Silicon, 1996, vol. 115, no. 1, pp. 19 37.
5. Gololobov, Yu.G. and Petrovskii, P.V., Izv. Akad.
Nauk, Ser. Khim., 1996, no. 9, pp. 2377 2378.
6. Gololobov, Yu.G., Kardanov, N.A., Khrousta-
lyov, V.N., and Petrovskii, P.V., Tetrahedron Lett.,
1997, vol. 38, no. 42, pp. 7437 7440.
1
Compound XIV. H NMR spectrum ( , ppm):
0.92 t (9H, CH3, J 7.3 Hz), 1.23 2.22 m (24H,
CH2, CH3COC , CH3CON), 5.09 br. signal (1H,
CHPh), 7.28 7.35 m (5H, Ph).
7. Gololobov, Yu.G., Galkina, M.A., Kuz,mintse-
va, I.Yu., and Petrovskii P.V., Izv. Akad. Nauk, Ser.
Khim., 1998, no. 9, pp. 1878 1879.
1
Compound XV . H NMR spectrum ( , ppm):
0. 85 t (9H, C H3, J 7. 3 Hz), 0. 93 1. 9 m
(18H, CH2), 2.04 s (3C, CH3COC ), 2.52 s (3C,
CH3CON), 4.18 br. signal (1H, CHPh), 7.15
7.34 m (10H, 2Ph).
8. Galkin, V.I., Bakhtiyarova, Yu.V., Gololobov, Yu.G.,
Polezhaeva, N.A., and Cherkasov, R.A., Heteroatom.
Chem., 1998, vol. 9, no. 7, pp. 665 668.
9. Gololobov, Yu.G., Kardanov, N.A., Kuzminse-
va, I.Yu., and Petrovskii, P.V., Phosphorus, Sulfur
and Silicon, 1999, vols. 144 146, no. 1, pp. 355 358.
10. Gololobov, Yu.G., Kuzminseva, I.Yu., Khrousta-
lyov, V.N., Petrovskii, P.V., and Griffiths, V.,
Heteroatom. Chem., 1999, vol. 10, no. 7,
pp. 664 670.
11. Ognyanov, V.J. and Hesse, M., Helv. Chim. Acta,
1989, vol. 72, no. 7, pp. 1522 1526.
12. Ramirez, F., Pilot, J.F., and Smith, C.P., Tetra-
hedron, 1968, vol. 24, no. 9, pp. 3735 3745.
13. Gordon, A.J. and Ford, R.A., The Chemist,s
Companion, New York: Wiley Interscience, 1972.
1
Compound XVI. H NMR spectrum ( , ppm):
0. 84 t (9H, CH3, J 7. 1 Hz), 0. 96 1. 89 m
(18H, CH2), 1.85 s (3C, CH3COC ), 2.36 s (3C,
CH3CON), 5.08 br. signal (1H, CHPh), 7.06
7.70 m (10H, 2Ph).
REFERENCES
1. Gololobov, Yu.G., Galkina, M.A., Dovgan,, O.V.,
Guseva, T.I., Kuz,mintseva, I.Yu., Senchenya, N.G.,
and Petrovskii, P.V., Izv. Akad. Nauk, Ser. Khim.,
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 8 2001