3. DESIGN, DEVELOPMENT AND INVESTIGATION OF
3.1. Perfuorocyclopentene-based switches (C5F)
3.1.1. Furan derivatives
Abovementioned specific features of furan derivatives provide restrictions on the synthetic pathways to difurylethenes. Another important detail is the necessity of modifiable substituents in the switching unit for further construction of desired photochromic objects. The "ideal" starting fragment must look like
Design, Development and Investigation of Thiophene-Free Diarylethenes
O (1)CH3
H3C(2)
R
(3)
with its methyl group (1) (small enough not to enhance cycloreversion) to avoid the dehydrogenization followed by aromatization to the inactive furobenzofuran derivative; methyl group (2) for steric hindrance caused by its repulsion with cycloalkene fragments (to avoid the by-product formation (for details see 1.1.4.C); substituent R for further modification (if absent, the reactive -hydrogen atom on its place will be attacked, for example, by BuLi required for later steps, or by electrophile in case of Friedel-Crafts approach), and a vacant position (3) either for bromination with subsequent metallation and coupling with perfluorocyclopentene, or for acylation/alkylation in case of the "McMurry"
synthetic route.
O H O H
O H O H
R R R R
UV
VIS -H2
O O
R R
Scheme 27
Irreversible oxidative transformation of diarylethene lacking substituents at the reactive carbon atoms.
One promising starting compound was 2,4-dimethylfuran, which should be further transformed according to Scheme 28 using the different activity of two bromine atoms towards substitution.
O Br O
Br
O O
R R
CF2
F2 F2C C Br2
Scheme 28
Unfortunately, all attempts to brominate the 2,4-dimethylfuran ended up with spontaneous polymerization of the reactant, most likely caused by protonation of the furan ring and ring-opening to dicarbonyl compound. A significant role in rejecting this compound played also its poor availability (the practically useful procedure in ref. [102] unfortunately did not allow upscaling from milligramm to gramm quantities).
Design, Development and Investigation of Thiophene-Free Diarylethenes
2-Methylfuran was also brominated under various conditions but either aforementioned polymerization to black tar or polybromination occured. In other words, furans with donor substituents appeared unsuitable for bromination.That is why the commercially available 2-formyl-5-methylfuran (1) was chosen as starting material. Indeed, the electron-withdrawing formyl group stabilizes the furan ring against addition reactions and orientates the bromination to the 4-position with monobromoderivative 2 as the sole product. Also, the formyl group is rather reactive and can be transformed to various derivatives, which is significant for further molecular switch design. After successful bromination, direct metallation was impossible in presence of an aldehyde group:
O O
Metal-halogen exchange suppressed by presence of an active formyl group
Aldehyde 2 was transformed to the diacetal 3a according to Gorzynski103; ethylene glycol was used as the alcohol component. Subsequent metallation with n-butyllithium and reaction with octafluorocyclopentene at -78°C resulted in the formation of 1,2-bis[5-(1,3-dioxolan-2-yl)-2-methylfuran-3-yl]perfluorocyclopentene (4a) (Scheme 30).
O
Design, Development and Investigation of Thiophene-Free Diarylethenes
After recrystallization from hexanes and sublimation, single crystals of 4a were grown by slow diffusion of n-hexane into a saturated solution of diethyl ether. The compound crystallizes in the monoclinic system in the centrosymmetric space group C2/c with half a molecule in the asymmetric unit with the carbon atom C7 located on a two-fold rotation axis. In the crystalline state, the molecule adopts the antiparallel conformation with both furan rings pointing away from the central hexafluorocyclopentene. With a value of 11.46° the torsion angle (C4-C5-C4i-C5i) between the furan rings is much larger than the corresponding angle in the two other structurally related furan derivatives known so far (7.21 for C5F-Ph and 6.95° for C5F-Me). However, in the crystal a distance of 3.59 Å between the reactive carbon atoms C8 and C8i in 4 (Figure 1) is in surprisingly good accordance with the data from reference104 have been retrieved from the Cambridge Structural Database. Identifier:
CESWED for C5F-Ph and CESWON for C5F-Me (3.54 for C5F-Ph and 3.74 Å for C5F-Me), for which a value of 4.2 Å is given as a condition sufficient for photochromic ring closure in the crystal105.
Figure 3
X-ray crystal structure of the protected aldehyde 4a. Thermal ellipsoids are drawn at the 50% probability level.
Main occupancy is shown for disordered fluorine atoms; hydrogen atoms are omitted for clarity.
Attempts to improve the reaction conditions resulted in:
1) 2,2-dimethylpropan-1,3-diol instead of ethylene glycol as aldehydeprotecting group.
Protected bromo derivative 3b was crystalline (easier to handle compared to oily 3a) and diacetal formation was irreversible, positively affecting the reaction yield.
2) n-BuLi and t-BuLi were tested as metallating agents and reaction temperature was altered.
With both lithium organyls the unavoidable formation of several by-products was observed (some of
Design, Development and Investigation of Thiophene-Free Diarylethenes
them were isolated in deprotected (aldehyde) form), but immediate addition of t-BuLi (2.2 equivalents) in one portion to the solution of 3 at -90°C, stirring for 5 min, addition of octafluorocyclopentene also in one portion and leaving the reaction mixture without external cooling overnight resulted, despite slightly lower overall reaction yield, in clean formation of diarylethene 4 without significant amounts of alternative products 5-9.O O
By- and semi-products in the diarylethene formation reaction
Deprotection by adding HCl solution to the THF/acetone/water solution of diacetals gave the desired starting switch 11, whose reactive aldehyde groups offer a wide range of possibilities for further modifications (extending the π-system, prolonging an aliphatic side-chain to increase solubility, connecting with chelating ligands with further metal coordination etc.). Traces of monoprotected acetal 10 were isolated from the reaction mixture, but its controlled formation for further unsymmetric derivatization was not achieved in acceptable yields because of fast parallel formation of fully deprotected 11.
Design, Development and Investigation of Thiophene-Free Diarylethenes
Figure 4
X-ray crystal structure of the deprotected aldehyde (1,2-bis(2-methyl-5-formylfuran-3-yl)perfluorocyclopentene 11). Thermal ellipsoids are drawn at the 50% probability level; hydrogen atoms are omitted for clarity.
Aldehyde groups of 11 were smoothly oxidized and reduced to the dicarboxylic acid 12 and dialcohol 13, correspondingly, both valuable building blocks for designed diarylethene derivatizations (Scheme 33).
56%
O O
O
CF2 F2 F2C C
O
11
O O
HO
CF2 F2 F2C C
OH
13
O O
O
CF2 F2 F2C C
O
OH 12 OH
AgNO3/NaOH LiAlH4
Et2O 61%
Scheme 33
Reductive and oxidative transformation of the aldehyde group in 11.
Availability of 13 led to design and synthesis of the molecular switch 15 with sulphur-containing anchoring thiol groups (protected by acetyl groups to prevent oxidative polymerization by storage) separated from the switching core with methylene fragments for use in MCBJ, realizing the
Design, Development and Investigation of Thiophene-Free Diarylethenes
idea of investigating of a "pure" (not conjugated with additional -systems) sulphur-free switching fragment of difurylethene isolated from electrode contacts with "non-conducting" CH2-joints (Scheme 34).Synthesis of diarylethene 15 with flexibly attached protected thiol anchoring groups
As it can be seen from UV/Vis data, the elongation of the diarylethene-system by introducing
-conjugated substituents induces a bathochromic shift of absorption bands of the closed isomer; it also has influence on the conversion ratio of open and closed forms. Due to the (partial) overlap of short-wavelength bands of open and closed forms, irradiation with UV light induces not only cyclization to the closed form, but at the same time the reverse ring-opening. Indeed, at the photostationary state (when, despite further irradiation, no changes in UV/Vis spectrum are observed and the equilibrium state is achieved) both open and closed form of diarylethene are present (in some cases the ratio can be determined by NMR spectroscopy). Introducing conjugated substituents elongates the -system over the whole molecule in closed form thus separating the short-wavelength bands of both forms via batochromic shift of the closed form absorption band. It results in the possibility of selective irradiation at the wavelength corresponding to the absorption of only the open form and leads to the full conversion to the closed form of diarylethene. Interpretation of obtained (photo)chemical and physical data when applying the switchable material in physical experiments is distinctly simplified in such case.
O O
Derivatization of diarylethene with conjugatively attached thioamide anchoring groups
Design, Development and Investigation of Thiophene-Free Diarylethenes
The following synthesis of thiosemicarbazide derivatives 16 and 17 supported the concept mentioned above; both molecular switches exhibited full conversion to closed form by irradiation with light at 366 nm and were successfully used in physical experiments (Scheme 35).105
11
Synthesis of functionalised molecular switches based on either the formation of an azomethine (16, 17), a Knoevenagel-approach (18, 19, 20) or a Wittig-reaction (21). Reagents and conditions: a) thiosemicarbazide, MeOH, r.t., 24h; b) methylthiosemicar-bazide, MeOH, r.t., 24h; c) rhodanine, dichloromethane, piperidine, r.t.,
12h; d); (4-(methylthio)benzyl)triphenylphosphonium bromide, MeOH, MeONa, r.t., 36 h; e) 2-(pyridin-4-yl)acetonitrile hydrochloride, K2CO3, MeOH, r.t, 48h; f) malodinitrile, cat. piperidine, benzene, r.t., 4h.
Four other photoswitchable difluorocyclopentenes 18-21 (Scheme 36) for physical application carrying vinylogous terminal -systems attached to the furan rings were successfully synthesized. All
Design, Development and Investigation of Thiophene-Free Diarylethenes
the N and S atom containing endgroups bear the affinity to bind to gold, thereby providing suitable anchoring of the switches between two gold contacts.Interestingly, the unavoidable formation of by-product 4c (diacetal similar in its properties to 4a and 4b) was observed by obtaining 20 applying Knoevenagel-like conditions for the condensation between 11 and pyridine-4-acetonitrile hydrochloride. Changing the solvent from methanol to ethanol or to isopropanol resulted in lower reaction yields but no diacetal was formed and thereby the work-up procedure was simplified.
pure20and pyridine oligomerization products 36-45%
+
Scheme 37
Diacetal by-product formation