A cyclic merocyanine UV-A absorber: Mechanism of formation and crystal structure

Article abstract of DOI:10.1016/j.tetlet.2014.01.113

The product of the reaction of 3-(3-methoxypropylamino)cyclohex-2-en-1-one and diethylsulfate has been crystallized and its structure has been determined by X-ray crystallography. The study allowed insight into the formation mechanism of cyclic merocyanine UV absorbers. X-ray diffraction analysis of the merocyanine product made it possible to define the E/Z-stereoconfiguration.

Full text of DOI:10.1016/j.tetlet.2014.01.113

Tetrahedron Letters 55 (2014) 1749–1751
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A cyclic merocyanine UV-A absorber: mechanism of formation
and crystal structure
b,
a
b
Barbara Winkler a, , Hans Wolfgang Hoeffken , Kai Eichin , Wolfgang Houy
⇑
⇑
a BASF Schweiz AG, GMV/ST–R1059, 4002 Basel, Switzerland
b BASF SE, GVM/C–A030, 67056 Ludwigshafen, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
The product of the reaction of 3-(3-methoxypropylamino)cyclohex-2-en-1-one and diethylsulfate has
been crystallized and its structure has been determined by X-ray crystallography. The study allowed
insight into the formation mechanism of cyclic merocyanine UV absorbers. X-ray diffraction analysis of
the merocyanine product made it possible to define the E/Z-stereoconfiguration.
Ó 2014 Elsevier Ltd. All rights reserved.
Received 25 November 2013
Revised 21 January 2014
Accepted 24 January 2014
Available online 4 February 2014
Keywords:
Reactive intermediate
Structure elucidation
X-ray diffraction
Merocyanines
UV absorbers
Cyclic merocyanine structures of the general formula of 1 have
recently gained interest as particularly efficient UV-AI absorbers.
The UV-AI (360–400 nm) range is the longwave part of the UV-A
(320–400 nm) radiation. Those compounds are industrially inter-
esting as protectants for organic materials such as plastics, photo-
graphic materials,1 organic photovoltaic materials,2 dyes,3,4
perfumes,3,4 agrochemicals,5 consumer products like liquid deter-
gents4 and for human skin and hair.6 UV-AI absorbers complement
UV absorbers which protect the UV-B (290–320 nm) or UV-AII
(320–360 nm) range thus allowing complete UV protection of sub-
strates.7 The cyclic merocyanine compound 1a exhibits an absorp-
react with DMS (dimethylsulfate) at 100 °C for 40 min and
subsequently with methylene active compounds like malonates
in the presence of TEA (triethylamine) as a base at 110 °C for
40 min. On addition of water the product precipitates which can
be recrystallized from a suitable solvent. We were particularly
interested in the mode of action of the alkylating reagent DMS.
Oehlschlaeger et al.1 described a quaternarization without indicat-
ing the reaction site. Conventional wisdom implies quaternariza-
tion of the nitrogen atom resulting in the formation of
a
quaternary ammonium salt. However, this intermediate would
not form the desired final merocyanine structure (Fig. 1).
tion maximum at 385 nm with an absorption coefficient
e
of 63
We used an analogous synthesis protocol as described by
Oehlschlaeger et al.1 DES (diethylsulfate) was used as the
alkylating reagent. The reaction sequence was performed in
toluene as solvent. We were interested in the reaction mechanism
of this synthesis and the nature of the intermediate formed by
the reaction of enaminone 2 with the sulfate. The reaction product
of the enaminone 2 with diethylsulfate was stored at 4 °C until
052 (investigated in ethanol at 0.02 mM of 1a) leading to a full cov-
erage of the UV-AI region. We herein describe the synthesis and
crystal structure of merocyanine 1a. The X-ray diffraction analysis
of an intermediate allowed insight into the mechanism of forma-
tion of cyclic merocyanines.
The synthesis of cyclic merocyanines of general formula 1 was
first described by Oehlschlaeger et al.1 The synthesis starts from
1-aminocyclohexan-3-one derivatives which are easily available
through the condensation of 1,3-cyclohexandiones with amines
under azeotropic removal of water. For the production of merocy-
anines the 1-aminocyclohexan-3-one derivatives are allowed to
O
O
R
N
X
H
N
O
O
R
X
N
⇑
Corresponding authors. Tel.: +41 61 6368716; fax: +41 61 6362332 (B.W.); tel.:
1a
1
+49 621 60 49418; fax: +49 621 60 6649418 (H.W.H.).
E-mail addresses: Barbara.winkler@basf.com (B. Winkler), wolfgang.hoeffken@
basf.com (H.W. Hoeffken).
R = H, alkyl; X = COOR, COR, CN;
Figure 1. Chemical structure of cyclic merocyanine UV-AI absorbers.
http://dx.doi.org/10.1016/j.tetlet.2014.01.113
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

1750
B. Winkler et al. / Tetrahedron Letters 55 (2014) 1749–1751
Figure 3. X-ray crystal structure of 1a.
Figure 2. X-ray crystal structure of 3.
from cyanoacetate 4 in the presence of the base TEA. The TEA
assists the fast elimination of EtOH yielding subsequently
merocyanine 1a (Scheme 2).
Single crystals of merocyanine 1a were produced by crystalliza-
tion from heptane/ethyl acetate (2:1). A yellow single-crystal with
dimension 0.02 Â 0.10 Â 0.16 mm3 was selected for data collec-
tion. The X-ray analysis on those crystals showed the formation
of only Z-isomers as depicted in Scheme 1 and presented in
Figure 3.
crystallization occurred. A yellow single-crystal with dimension
0.04 Â 0.15 Â 0.20 mm3 was selected for data collection. As shown
in Figure 2, single X-ray analysis unambiguously confirmed the for-
mation of enolether 3 showing that alkylation occurs at the oxygen
rather than at the nitrogen.
We propose that in the formation of merocyanine 1a a nucleo-
philic attack of a cyanoacetate anion 5 toward the vinylogous imin-
ium cation 3 is involved leading to adduct 6. Anion 5 is formed
O
H
H
N+
H5C2
O
S
O
C2H5
O
N
O
O
O
O
S
O
–O
O
C2H5
O
2
3
O
O
O
O
O
H
N
O
4
N
O
S
O
HO
–O
Et3NH+
O
C2H5
+
+
N
+ TEA
O
1a
Scheme 1. Conversion of 3-(3-methoxypropylamino)-cyclohex-2-en-1-one to the corresponding merocyanine 1a by using DES.
H
H
N
O
O+
CH3
E
O
S
O
N+
E
O
CH3
H3C
H3C
–O
OC2H5
O
3
O
H3C
O
CH–
N
CH3
O
O
O
+
N
O
5
H
N
1a
O
O
CH3
H3C
-EtOH
6
Scheme 2. Proposed mechanism of merocyanine formation.

B. Winkler et al. / Tetrahedron Letters 55 (2014) 1749–1751
2. Mustonen, T.; Chebotareva, N. WO Patent 2012,095,796 A1, Jul 19, 2012.
1751
Supplementary material
3. (a) Espel, A.; Blohm, A.; Schaefer, J.; Fey, S.; Ruppert, S. WO patent application
2009,124,630 A2, Oct 15, 2009.; (b) Espel, A.; Blohm, A.; Schaefer, J.; Fey, S.;
Ruppert, S. WO patent application 2009,124,633 A2, Oct 15, 2009.
4. (a) Wagner, B.; Reich, O. WO Patent 2007,014,848 A2, Feb 08, 2007.; (b) Wagner,
B.; Reich, O.; Mantler, A.; Schork, M. WO 2009,027,258 A2, Mar 05, 2009.
5. Ehrhardt, T.; Grossmann, K.; Hutzler, J.; Simon, A.; Haremza, S.; Ishaque, M.;
Newton, T.W.; Reinhard, R.; Bowe, S.; Keller, K. et al. WO patent application
2011,161,105 A2, Nov 29, 2011.
6. (a) Wagner, B.; Ehlis, T.; Eichin, K. WO Patent 2004,006,878 A1, Jan 22, 2004.; (b)
Wagner, B. WO patent application 2008,080,645 A1, Jul 10, 2008.; (c) Richard,
H.; Muller, B. FR Patent 2,957,250 A1, Sep 16, 2011.; (d) Richard, H.; Muller, B.
WO patent application 2011,113,718 A1, Sep 22, 2011.
Crystallographic data for the structures of 1a and 3 have been
deposited with the Cambridge Crystal Data Center as supplemen-
tary publication nos. (CCDC 973065 contains the supplementary
crystallographic data for the compound 1a. CCDC 973066 contains
the supplementary crystallographic data for the compound 3.)
Copies of the data can be obtained, free of charge via http://
www.ccdc.cam.ac.uk/conts/retrieving.html, or on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK, (fax: +44 (0)1223
336033 or e-mail: deposit@ccdc.cam.ac.Uk).
7. (a) Osterwalder, U.; Herzog, B. Basic Clin. Dermatol. 2009, 43, 11–38; (b)
Shirinian, V. Z.; Shimkin, A. A. Top. Heterocycl. Chem. 2008, 14, 75–105; (c)
Poronik, Y. M. et al Chem. Eur. J. 2012, 18, 9258–9266.
References and notes
1. Oehlschlaeger, H.; Langen, H.; Sobel, J. DE Patent 3,531,383 A1, Sep 03, 1985.