Deuterated Liquid Crystals - design and synthesis of deuterium labelled 4,4ʺ-dialkyl-2′,3′-difluoro-[1,1′:4′,1ʺ]terphenyls using batch and continuous flow systems

ABSTRACT The high interest of isotopically labelled compounds is induced by two important factors: (i) improvement of highly sensitive and precise analytical methods for isotope identification and (ii) development of new synthetic approaches for isotopically labelled compounds. However, there is still a lack of efficient and cheap methods for the design of deuterium labelled liquid crystalline materials. Herein, the continuous flow system was adapted for the synthesis of deuterated Liquid Crystals using the H-Cube Pro reactor, where deuterium gas was generated in situ from heavy water. We designed and developed the synthesis of homologous series of 4,4ʺ-dialkyl-2′,3′-difluoro-[1,1′:4′,1ʺ]terphenyls where deuterium atoms are placed at carbon α and carbon β positions or only at carbon α positions of alkyl terminal chains. The synthetic strategy involves mainly selective deuteration reactions of C≡C bonds as well as reduction of carbonyl groups C=O using batch or continuous flow conditions. Theoretical calculation and experimental study show that deuterium labelled Liquid Crystals exhibit increased photochemical stability compared to protonated ones. Moreover, the comparison of physicochemical properties between deuterium labelled and non-labelled 4,4ʺ-dialkyl-2′,3′-difluoro-[1,1′:4′,1ʺ]terphenyls is presented. This work provides efficient methods to obtain deuterated liquid crystalline materials with much better photochemical stability compared to their fully protonated isotopologues. GRAPHICAL ABSTRACT


Introduction
Isotopically labelled compounds are widely used mainly as tracers of chemical, biological, and biochemical processes [1][2][3]. They are used to explain reaction mechanisms, including stereochemistry reactions [4][5][6]. Isotopically labelled compounds are used for determination of metabolic pathways in organisms, the metabolic activity of living organisms, the relationship between substrates and enzymes, radioisotope imaging, and as drugs in cancer therapies or as internal standards [7][8][9][10][11]. Deuterium ( 2 H, D) is one of the most studied isotope, which is used in the synthesis of labelled molecules [12]. Deuterated compounds are widely used, ranging from nuclear energy, chemistry, and pharmacy to biology and materials science [13]. Substitution of a hydrogen atom by deuterium has a beneficial impact on drug stabilisation and inhibiting of unfavourable processes (e.g. racemization) [14,15]. Furthermore, isotopically labelled molecules are used as chiral auxiliaries in the synthesis of chiral compounds [16,17]. Due to the access to new highly sensitive and precise analytical methods and development of new synthetic tools, the interest in isotopically labelled compounds is constantly growing [18][19][20][21][22][23]. Despite their high utility in so many different areas of life, it is safe to say that the potential of deuterated compounds has not yet been fully discovered and applied. Among deuterated compounds, such as drugs or internal standards, we can find deuterated Liquid Crystals (LCs). Deuterated LCs have been intensively studied in relation to the significant impact on the phase behaviour for nematic twist-bend phase (N TB ) [24][25][26], columnar phases for coronenes [27] and liquid crystal dendrimers [28,29], macromolecular LC materials [30][31][32][33] as well as for the nematic phase [34,35], reentrant ferroelectric SmC* [36] and ferroelectric SmC* phases [37], smectic E phase [38]. One of the flag LC is 4-pentyl-4′-cyano- [1,1′]biphenyl, well known as 5CB. Its perdeuterated version (5CB-d 19 ) can be synthesised according to three different strategies, first published in 1978 by G.W. Gray and A. Mosley [39], followed in 2002 by the S.T. Wu group [40], and the last one in 2014 by the P. Kula group [41]. However, a synthesis of a wide range of labelled intermediates was described by H. Zimmermann in ref [42]. Isotopologues of 5CB have been intensively studied in many works [43][44][45].
LCs play an important role in many non-display devices [46][47][48][49][50][51][52][53][54][55][56]. The parameter that determines the development of liquid crystalline materials for photonic and display applications is birefringence (∆n). This parameter is related to the maximum light modulation that can be obtained after the light ray passes through an appropriately oriented layer of LC material in a specific geometry. One of the most important parameters that LC-based devices should show is a fast response time, which can be achieved by using thinner cells, increased temperature, using a special construction of devices and voltage regulators, or by using LCs characterised by a higher Figure-of-Merit (FoM) [57,58]. This parameter combines most of the relevant variables simultaneously: elasticity constant (K), ∆n and rotational viscosity (ɣ) and is defined as K(∆n) 2 /ɣ. For most LC applications, high optical anisotropy, a wide mesophase temperature range and low viscosity are desirable. To achieve this, LC mixture components are structurally modified. However, despite achieving of high FoM, the basic material problem is still the lifetime of the optical medium itself, which comes down to the chemical structure of each individual LC included in a given multicomponent LC mixture [59]. A long, undisturbed working time is required for LC devices as well as for other devices. LC devices working in the long-wave ranges (like IR, THz and GHz regions) are not highly exposed to photodegradation processes, because radiation from such a spectral range possesses low-energy. On the other hand, exposure to electromagnetic radiation from a higher energy range, such as the UV range (especially the UVA range, λ = 315-400 nm; molar photon energy E = 299-380 kJ/mol) and the lower visible light range (violet, blue and cyan, 400-500 nm; E = 240-300 kJ/mol), excites delocalised electrons and transfers them to higher energy levels.
Considering that the energy in this wavelength range is comparable to the energy of chemical bonds, photodegradation processes could be initiated. As a result, photoaging of LC molecules occurs, which in turn causes disturbances in the operation of LC devices [60][61][62]. In addition, alignment layers also contribute to the LC device lifetime [63,64]. The research conducted so far has focused on the elimination of the weakest components of LC mixtures. It was indicated which classes of compounds showed better photostability and on this basis, LC mixtures were optimised and prepared [65][66][67][68][69][70][71]. In this article, we present a completely different, constructive approach to solving the problem.
Our preliminary research on deuterated 4-alkyl-4ʺisothiocyanato-[1,1′:4′,1ʺ]terphenyls has shown increased photostability of such materials [72]. These compounds appear to be helpful in particularly sensitive and demanding areas such as holography and photolithography in the field of blue lasers, including spatial light modulators (SLMs) operating in the range of 300-400 nm. An additional advantage of such solutions is the possibility of producing isotopological LC mixtures, which may only slightly differ in terms of physicochemical and electrooptical properties from standard non-deuterated mixtures, which will significantly facilitate the implementation of such materials for applications in LC devices. Our idea is based on the strengthening of the weakest bonds in the molecule by replacing selected aliphatic C-H bonds with C-D bonds [72]. In the case of dialkylterphenyl compounds, these are the α and β positions or only α positions of the terminal alkyl chains. Recent articles have shown that deuterated molecules such as OLEDs [73][74][75][76][77], photovoltaic materials [78], optical fibres [79], ligands [80], and others [10,12,[81][82][83] indicate extended lifetime and better performance parameters and appear to be promising for future applications.

Model compounds
The aim of the work is to obtain new liquid crystalline materials that show increased photochemical stability. Therefore, the research began with the design of model molecules with a simplified structure resembling the structure of liquid crystalline dialkylterphenyls. We decided to select for the initial research single benzene ring compounds, substituted with alkyl chains at 1 and 4 positions, in which selected hydrogen atoms were replaced with deuterium.
For a non-deuterated compound M1, the dissociation energy of the C α -C β (D 0 H ) bond is 339.1 kJ/mol, while for the C β -C γ bond it shows a slightly higher value (385.9 kJ/mol). For compounds with deuterium atoms (M2-M6), the dissociation energies of the considered bonds are higher than for a protonated compound M1. For compound M3, with 4 deuterium atoms in its structure (at C α -C β ), the difference in bond dissociation energy (ΔD 0 = D 0 H -D 0 M2-7 ) is 8.1 kJ/mol and it is a value more than 6 times greater than ΔD 0 for compound M2 (1.3 kJ/mol), which has only 2 deuterium atoms in its structure at C α . On the other hand, the introduction of subsequent deuterium atoms into the whole alkyl chain or chains (compounds M4-M6) does not or only slightly affects the increase of ΔD 0 . Substitution of the carbon atom at the β and γ positions of the propyl chain with deuterium atoms (M7) also increases the D 0 value by 3 kJ/mol relative to the C β -C γ bond of the non-deuterated compound, but the bond is generally much less prone to breakage. Next we have gone through the same computational analysis but for the LC structures M8-M10 that we selected for research and then planned to synthesise. Results presented in Figure 1 confirm the effect of deuteration on increasing the bond strength C α -C β .
Quantum-chemical calculations indicate the correctness of the proposed approach of strengthening the α and β positions or only the α position in the aliphatic part with deuterium atoms for single benzene ring model molecules as well as for three-ring liquid crystalline structures. From among the considered group of model molecules, three representatives (compounds M1, M3 and M5 differing in the number of deuterium atoms in their structure by 4 and by 8) were selected for further stability research. Molecules were obtained according to the Figures S2-S4 presented in the Supporting Information. The obtained compounds were used to conduct further experiments, which also helped to confirm the presented approach.

Mass spectra analysis and fragmentation
Compounds M1, M3 and M5 were ionised with an electron beam (EI) of 70 eV in an ionisation chamber and analysed using a mass spectrometer. Corresponding mass spectra were obtained. Based on the typical fragmentation processes for compounds in the 1,4-alkylbenzene family, possible fragmentation pathways for M1 have been proposed ( Figure 2).
For the protonated radical cation M +• (m/z = 176), there are two possible fragmentation pathways that involve breaking the C-C bonds between C α -C β of the alkyl chain. Carbocations formed in this way with the ratios m/z = 147 and m/z = 133 are characterised by high intensity in the mass spectrum. Analogous interpretations for compounds M3 and M5 are listed in the Supporting Information in Figures S42 and S43. As the length of the alkyl chain increases, the intensity of the corresponding 4-alkylbenzyl cation decreases because fragmentation yield for longer aliphatic chains is higher. Therefore, ions with a propyl chain (m/z = 133; 137; 139) have a higher intensity in the mass spectra than ions with a butyl chain (m/z = 147; 149; 153). The ions obtained in this way undergo further fragmentation, which breaks the second C-C bond between C α -C β with respect to the aromatic ring, which leads to the formation of the ion m/z = 105 for the compound M1 and the deuterium ions at m/z = 107 and 109 for the compounds M3 and M5. If the C-C bond between the Csp 2 of the aromatic ring and the Csp 3 of the alkyl chain is broken, a benzyl cation with m/z = 91 is formed for the compound M1. For the remaining compounds, benzyl cations have deuterium atoms in their structure, therefore they differ in the value of m/z (m/z = 93; 94).

Influence of the collision chamber energy on ion intensities
For selected 1,4-dialkylbenzenes, the influence of the collision chamber energy on the ionisation of molecular ions and daughter ions was investigated using an Agilent Technologies GC-MS/MS gas chromatograph equipped with an Agilent Technologies 7000D GC-MS Triple Quad tandem mass spectrometer MS/MS(EI) operating in MRM (Multiple Reaction Monitoring) mode. The measurements were performed for equimolar samples in a manner analogous to the measurements in our earlier article [72]. The obtained results are presented in the diagrams below ( Figure 3).
For the molecular ion with m/z = 176 (compound M1), the maximum ionisation is observed at 5 eV (Figure 3(a)). With the increase in the energy of the electrons in the collision cell, the disappearance of the molecular ion in favour of the daughter ions is observed. For 10 eV, the maximum ionisation was obtained for the 4-alkylbenzyl ion, and the detector response for the 4-propylbenzyl ion (m/z = 133) is higher than for the ion with a longer alkyl chain (4-butylbenzyl ion, m/z = 147). Additionally, by further increasing the collision energy, an increase in the signal intensity is observed for ions 105 and 91, for which the maximum ionisation falls at 18 and 24 eV, respectively. For compounds M3 and M5, the obtained relationships are similar to those discussed above. For all molecular ions of the tested compounds (m/z = 176; 180; 184) the maximum signal intensity was obtained with the collision chamber energy equal to 5 eV (Figure 3(b)). As the energy of the collision chamber increases, the differences in the signal intensities between these ions decrease. The molecular ion with 8 deuterium atoms (m/z = 184), formed from compound M5, is more stable than the protonated ion (m/z = 176). The exception is the ion with 4 deuterium atoms (m/z = 180), which has a slightly higher affinity for ionisation than ion 176. Considering the formation of 4-alkylbenzyl ions (Figure 3(c,d)), we observe much lower signal intensities of deuterated 4-butylbenzyl ions (m/z = 149; 153) than of the protonated ion (m/ z = 147). On the other hand, considering the fragmentation of the aliphatic part that takes place on the side of the longer alkyl chain, it can be seen that the 4-propylbenzyl ion formed from a compound deuterated in only one aliphatic chain at m/z = 137 has even a slightly higher affinity for ionisation than the ion (m/z = 133), formed from the protonated molecule M1. The ion m/ z = 139, formed as a result of the fragmentation of compound M5 (deuterated in both alkyl chains), shows a much lower ability to ionise. For ions with m/z = 105; 107; 109, a proportional decrease in the intensity of the signals is observed with an increasing number of deuterium atoms. In turn, for ions with m/z = 93; 94 there is an approximately twofold decrease in signal intensity in relation to signal intensity for the benzyl cation m/z = 91, which has only carbon and hydrogen in its structure.
The different intensities of the signals from the molecular ions and the daughter ions of the studied molecules are due to the presence of the Kinetic Isotope Effect (KIE). The obtained results are consistent with the computational results concerning the dissociation energy of the bond presented in the previous section. Both the molecular ion and the daughter ions resulting from the fragmentation of the compound M5 (deuterated in two alkyl chains), are the least willing to ionise. This indicates that fragmentation-prone elements of the molecule (C α -C β bonds of the alkyl chains) have been broadened by replacing hydrogen atoms at these positions with deuterium atoms.

Voltage holding ratio parameter
One of the most important parameters that determine the suitability of LCs for use in various types of electrooptical devices is a complex parameter called the Voltage Holding Ratio (VHR) [85]. It determines the ratio of the voltage in the capacitor plates after the time (t) to the initial voltage applied to the plates (Figure 4). The idea of its measurement comes from the determination of the typical behaviour of the LC material under real active control conditions. The capacitor that is to maintain the voltage for the duration of the time slot (duration of the given optical modulation) is a measuring cell filled with LC material. Ideal LC materials should have high specific resistivity and have a VHR >98%. VHR is a common electrical parameter, however it is hardly related with the chemical structure of organic material, but with its high sensitivity and responsibility is the main validation tool used by display companies. Ideally, the capacitor exhibits a constant voltage on the plates as a function of time, resulting from the infinite specific resistance of the dielectric between the plates. However, the LC material has finite resistance and exhibits a so-called 'parasitic current' which causes the voltage to drop over time. The presence of various types of impurities, including ionic impurities and trace amounts of water, additionally adversely affects the VHR value. It should be mentioned that this is a complex parameter, being a superposition of the filled material and the liquid crystal cell, in which the properties of the ordering layers are important.
For selected model molecules M1 and M3, the VHR parameter was measured as a function of exposure time to UV radiation ( Figure 4). These compounds were placed in liquid crystal cells connected to a measuring device. To eliminate errors, the measurement series included the measurement of 16 voltage-time characteristics. An OmniCure UV (Hg) lamp was used to irradiate the samples (the entire spectral range 290-900 nm, 750 mW/cm 2 ). Equipment and software for measuring the VHR have been developed in the Department of Chemistry of the Military University of Technology. LC cells were covered with a layer of indium tin oxide (ITO), without SiO 2 and an alignment layer, the thickness of the measuring cavity was 5 μm. For both tested compounds, a decrease in the VHR value was observed with the extension of the irradiation time of the LC cell. For the deuterated compound M3, a drop of only 3% was observed, while for the non-deuterated compound M1 a decrease of more than 10% was observed. The preliminary results of both theoretical and experimental studies for the model dialkylbenzenes confirmed the higher stability of compounds containing deuterium atoms in the α β positions of the alkyl chains. Therefore, further research was focused on the synthesis of deuterated Liquid Crystals and their photochemical stability.

Synthesis
One of the most convenient laboratory equipment to carry out many hydrogenation experiments is the H-Cube Pro continuous flow reactor. This tool improves new synthetic pathways and can be adapted to the preparation of deuterated compounds. When we change water (H 2 O) to heavy water (D 2 O) in the liquid reservoir, deuterium gas (D 2 ) is generated by the electrolysis process [87,88]. The H-Cube Pro system enables easy control of parameters such as pressure, temperature and flow velocity. Additionally, the short contact time of the reagent with the catalyst surface may lead to greater selectivity of the reaction. On the other hand, batch systems are also used to carry out hydrogenation and deuteration reactions. Batch reactors are especially recommended in the multigram synthesis of small building blocks in multistep synthetic pathways, where a shorter reaction time can be achieved. This system is characterised by a relatively high yield and a maximum conversion. In the synthesis of deuterium labelled LCs we observed the superiority of the batch system for small components and precursors with C=O groups, while the continuous flow system gave higher purity for larger molecules (rod-like precursors with C≡C bridges) and was more recommended as the last step in the synthetic protocol. In this work, the deuterium atoms are placed at the carbon α and carbon β positions of the alkyl terminal chains or only at the carbon α positions. In large part, we used ethynyl units C≡C and carbonyl groups C=O as precursors of -C 2 D 4and -CD 2groups.

Synthesis of dialkylterphenyls deuterated at α and β positions of the alkyl chain
For most of the molecules we used nATAn precursors with the ethynyl groups C≡C ( Figure 5, Route II), the synthesis of which was described in the previous work [89]. For deuterated terphenyls having an (1,1,2,2,2-2 H 5 )ethyl chain on one side of the molecule, we decided to use 4'-ethynyl-2,3-difluoro-[1,1'] biphenyl 1 ( Figure 5, Route I) to speed up the multistep process. Then, acidic acetylene hydrogen atom was exchanged with deuterium and in the next step deuteration of the -C≡CD group was performed in an autoclave batch reactor. During this reaction, we noticed that the 'acidic proton' in the aromatic ring (from the ortho position to the fluorine atom) was replaced with a deuterium atom (compound 4). Albeit such a mixture of two isotopologues could not be separated by conventional purification methods, this was no problem in the subsequent synthesis. The next step was ortho-functionalization with the use of an organolithium base and iodine. Such reactions lead to high yields, reaching 95-99% (6→7). In the case of a given two isotopologues (mixture in a ratio of 7:3) even the use of a 20% excess of n-BuLi was found to be insufficient to completely form the aryllithium derivative. When iodine was introduced into such a reaction, it turned out that the starting compound was also present in the post-reaction mixture. Mass spectra analysis indicated that the unreacted substrate was only deuterated compound 4 (m/z = 224). This demonstrates the presence of a strong primary KIE. KIE was not the subject of research here, but it has been observed many times during syntheses. The synthetic path discussed above was used to obtain two LCs with one C≡C ethynyl unit in their structure (compounds 2TA3-d 5 and 2TA4-d 5 ). The last stage was the deuteration reaction of nATAn and 2TAn-d 5 under a continuous flow system. The deuteration reactions of such large molecules in the H-Cube Pro reactor proceeded without the formation of impurities. For comparison, we performed the same reactions in a pressure batch reactor (D 2 , Pd/C, THF) for some selected nATAn compounds. Although we obtained deuterated target molecules, we also found trace amounts of impurities in the reaction mixture.

Synthesis of dialkylterphenyls deuterated at the α positions of the alkyl chain
Keto-carbonyl groups C=O attached directly to the aromatic ring were used as precursors to α-deuterated LCs. This strategy required the protection of certain functional groups present in the molecule (see cyclic acetals 74-77). C=O groups were reduced to a dideuteromethylene groups -CD 2 -by reduction with deuterium gas (D 2 ) and Pd catalyst ( Figure 6).
For the reduction of the C=O group in the biphenyl molecules 42-45 we chose the continuous flow reactor H-Cube Pro. The next step was ortho-directed metalation with n-BuLi and the introduction of iodine into the molecule. The final stage in the synthesis of precursors of deuterated compounds with one carbonyl group was the Suzuki-Miyaura coupling that led to the formation of compounds 54-63 (nCD 2 TC=On). These compounds are only precursors of tetradeuterated dialkylterphenyls, but they already exhibit liquid crystalline properties (see Supporting Information, Table S2). In the next step, we reduced carbonyl group in nCD 2 TC=On compounds. For these structures it was necessary to replace the H-Cube Pro continuous flow reactor with a batch pressure reactor.

Physicochemical properties
The temperatures and enthalpies of phase transformations of compounds 18-26, 35-37 (nTn-d 8/9 ) and 64-73 (nTn-d 4 ) are summarised in Table S3 and  Table S4. The obtained compounds show a wide temperature range of nematic phase. Within one series, the typical zig-zag behaviour of the clearing temperature can be seen (e.g. for nTn-d 8/9 see the hexyl series nT6-d 8/9 or the pentyl series nT5-d 8/9 , for nTn-d 4 see the pentyl series nT5-d 4 and the butyl series nT4-d 4 ). These results are consistent with the results presented in the previous work, where we showed a homologous series of analogues nondeuterated terphenyls (nTn H) [90]. The values of the enthalpy of phase transitions of deuterated compounds are comparable with their non-deuterated counterparts however, no relationship can be indicated here. The phase transition temperatures of Cr-N are in most cases slightly lower for deuterated compounds (nTn-d 8/9 ) than for non-deuterated molecules. The situation is similar to the clearing points (N-Iso), which are also lower for compounds in the nTn-d 8/9 series. Considering the nTn-d 4 series, for some compounds, we can also notice slight deviations in their phase transition temperatures in relation to the nTn-d 8/9 and nTn H series, but generalising the following relationship can be observed: with an increasing number of deuterium atoms in the alkyl chains of dialkylterphenyls, a slight decrease in phase transition temperatures is observed as follows: nTn H > nTn-d 4 > nTn-d 8/9 .
For terphenyls with deuterium atoms located at α and β positions of alkyl chains (18-26 and 35-37) we achieved excellent isotopic purity (91-96% of the deuterium content). For terphenyls deuterated only at α position (64-73) the deuterium content is slightly lower. The average isotopic purity at C α for most nTn-d 4 compounds is approximately 80% deuterium.
Changes in the 1 H NMR and 13 C NMR spectra caused by the introduction of deuterium atoms in the area of signals from protons from alkyl groups were presented on the example of isotopologues from the 2T3 family (see Figures S5 and S6). The deuterium content expressed in % was determined from the 1 H NMR spectra and the values are placed in parentheses next to the respective equivalent deuterium atoms. In most cases, deuterium was introduced into molecules with isotopic purity above 90% D.   2.3.2.1. DSC measurements. Three representatives from the 2T3 series were selected for the study of photochemical stability (non-deuterated molecule 2T3 H, deuterated molecules 2T3-d 4 72 and 2T3-d 9 35, Figure 7). We carried out a photodegradation process as described in the Analytical Instrumentation in the Supporting Information and then the changes in the phase transition temperatures were recorded using DSC.

Photochemical stability
Changes in phase transition temperatures (ΔT), both melting and clearing for a molecule containing 9 deuterium atoms in its structure (at the α and β positions of the alkyl chain, 2T3-d 9 ) were the lowest of all tested compounds. Bigger changes were observed for the tetradeuterated compound (α-deuterated positions of the alkyl chain, 2T3-d 4 ). The greatest changes in temperature were recorded for the protonated compound 2T3 H. After one-hour exposure to UV radiation, the melting point (Cr-N) decreased by 1.8 ºC for 2T3-d 9 , 2.5 ºC for 2T3-d 4 and 3.1 ºC for 2T3 H. The same sequence applies to the clearing point (N-Iso): decrease by 2.1 ºC, 2.7 ºC and 4.4 ºC for 2T3-d 9 , 2T3-d 4 and 2T3 H. In summary, it can be concluded that deuteration at the α and β positions of the alkyl chain best stabilises the phase transition temperatures of the tested terphenyls exposed to UV radiation. The changes in phase transition temperatures are caused by the formation of trace amounts of photodegradation products however, no new signals were observed in the 1 H NMR spectra of the samples (deuterated and non-deuterated). Nevertheless, we decided to perform the MS spectra (GC-MS analysis) for possible photodegradation products for symmetric non-deuterated (6T6 H, Figure 8(a)) and deuterated (6T6-d 8 -24, Figure 8(b)) molecules and stronger UV radiation was used. The details of the experiment are described in the Analytical Instrumentation section and are listed in the Supporting Information.
The places where C-C bonds were broken are most often the α and β positions of the alkyl chains, as evidenced by the presence of methyl, ethyl, isopropyl, hexyl chains with a double bond located directly next to the benzylic position and with a methyl group in the αposition of the alkyl chain and the absence of one of the terminal chains. Similar photodegradation products can be identified for the deuterated compound. The proposed chemical structures of the photodegradation process suggest a radical mechanism of this process, which is the most common in the case of the interaction of ultraviolet radiation and visible light with other materials. As a result of the energy quantum's absorption by the molecule, chemical bonds can be broken and free radicals are formed. These, in turn, undergo secondary chemical reactions to form new compounds.

Influence of the collision chamber energy on ion intensities.
To compare the stability of the obtained structures and their hydrogen analogues, a mass spectrometer and a collision chamber were used, in which it is possible to determine the energy of collisions and link their values with the breaking of appropriate chemical bonds in the molecule. For this study, we selected deuterated 2T3-d 9 and non-deuterated 2T3 H compounds (Figure 9). In this experiment, as for the model single benzene ring molecules, we used the MRM mode and the selected precursor ion was the appropriate molecular ion. Figure 9(a) shows the juxtaposition of a molecular ion (blue line, m/z = 336) with two daughter ions (yellow line m/z = 307; pink line m/z = 292) resulting from ionisation and fragmentation in the collision chamber of a non-deuterated molecule 2T3 H. The intensity of the non-deuterated precursor ion (m/z = 336) is twice that of the deuterated precursor ion (m/z = 345) (Figure 9(b)). On the other hand, in the case of the daughter ions, the intensities of non-deuterated ions (m/z = 307 and m/z = 292) are more than twice as high as their deuterated counterparts (m/z = 314 and m/z = 296) (Figure 9(c,d)). For each pair of precursor and daughter ions the maximum ionisation value is the same. The maximum ionisation of 5 eV is for the precursor ions m/z = 336 and m/z = 345, 15 eV for the daughter ions m/z = 307 and m/z = 314 and 32 eV for the daughter ions m/z = 292 and m/z = 296. Comparing the signal intensity expressed in arbitrary units [a.u.] for molecular ions of the two terphenyl structures 2T3 H and 2T3-d 9 and their fragmentation ions it can be concluded that the intensity of the ions formed (at a given value of the ionisation energy in the ionisation chamber) is lower for the deuterated structure than for the non-deuterated analogues. The kinetic isotope effect is clearly noticeable here. The greater stability of the C-C bonds, at which hydrogen atoms were replaced with deuterium atoms, was indicated. The structures containing a such C-D system are less labile and more difficult to decompose in the electron beam.

Conclusion
In this work, we synthesised isotopically labelled Liquid Crystals with deuterium atoms located at the α and β positions (nTn-d 8/9 ) as well as deuterated at the α position (nTn-d 4 ) of the terminal alkyl chains. The article focuses mainly on the problems of the synthesis of organic materials, on the other hand, it shows their increased photostability. Deuterated 4,4ʺ-dialkyl-2′,3′-difluoro-[1,1′:4′,1ʺ]terphenyls were designed along two different synthetic pathways. For α,β-deuterated molecules primarily used selective deuteration of C≡C bonds, which took place in the last step of the synthesis. A flow reactor was used here as an easy and quick tool. However, for shorter homologues, it was necessary to obtain deuterated intermediates first. On the other hand, for αdeuterated 4,4ʺ-dialkyl-2′,3′-difluoro-[1,1′:4′,1ʺ]terphenyls we developed deuteration of C=O groups. In this case, it was necessary to use a batch reactor. Obtained deuterated Liquid Crystals show excellent isotopic purity (91-96% D for α,β-deuterated terphenyls 18-26, 35-37 and 80% D for α-deuterated terphenyls 64-73). The experimental work carried out on the photochemical stability of deuterated terphenyls indicates an increased stability of deuterated compounds. Compounds deuterated at the α position of the alkyl chain show increased photostability compared to non-deuterated analogues. The addition of additional deuterium atoms (at the β position) improves photostability even more. The photostability was confirmed by monitoring the phase transition temperatures after UV irradiation and by measuring the ionisation efficiency of precursor and daughter ions. Additionally, the analysis of photodegradation products (chromatographic + mass spectral analysis) indicates that the benzylic position of dialkylterphenyls is the weakest place where the C-C bonds break and photodegradation processes begin. The idea of strengthening the weakest bonds in the molecule by replacing selected C-H bonds with C-D bonds proved to be the right approach. The increased photostability of the deuterated compounds is a direct result of the Kinetic Isotope Effect and is sufficiently noticeable by the research techniques used in the work. The presented new LC materials seem to be attractive for modern LC applications, for which a crucial factor is the undisturbed working time of the device. It comes down to the lifetime of the optical medium, which depends on the chemical structure of each individual Liquid Crystal in the LC mixture.