The effect of reaction time on the yield of 5C2P
Fig. 1 shows the variation in chemical signal intensity of 5C2P with increasing reaction time by 1H NMR spectra. Other structural information of 5C2P is characterized by 1H NMR (1H δ = 3.58, 2.59, 2.1 and 1.91 ppm) and 13C NMR (13C δ = 29.92, 207.52, 40.18, 26.67 and 45.01 ppm) (Fig. S1 and Fig. S2). It is seen that the yield of 5C2P increased to 97.93% within 2 h and remained constant basically (Fig. 2). Further prolongation of the reaction time led to a slight decrease in the yield. Even if the reaction time was prolonged to 3.5 h, the yield had hardly changed much. Therefore, the appropriate reaction time was an important factor to obtain the high yield of 5C2P.
The effect of reaction temperature on the yield of 5C2P
Fig. 3 shows the influence of reaction temperature on the conversion from acetyl-n-propanol to 5C2P. The yields achieved 33.24% or 88.91% at 60 °C or 70 °C respectively within reaction time approached approximately 2 h. It is clearly that the yield increased gradually and reached the maximum (97.93%) at 80 °C. Obviously, it indicated that raising the reaction temperature efficiently improved the rate of chlorination reaction. The high temperature accelerated the decomposition of BTC into phosgene and increased the concentration of free Cl- in the system. In short, suitable reaction temperature has an important synergic effect in maintaining the high yield of 5C2P.
The effect of substrate molar ratio on the yield of 5C2P
To investigate the influence of substrate molar ratio, several different molar ratios were tested under the optimized reaction conditions (Fig. 4). The results indicated that the yield of 5C2P obtained 94.27% while the substrate molar ratio was 1:0.3. However, high substrate molar ratio led to the decrease of yield because the unnecessary BTC resulted in the presence of intermediate product (1H δ = 5.7 ppm) (Fig. S3). According to previous studies, 1 mol BTC can be decomposed to produce 3 mol phosgene[24]. However, because the chlorination reaction was carried out under normal atmospheric reflux, some of the phosgene escaped before it participated the chlorination reaction.
The effect of solvent on the yield of 5C2P
To explore the effect of solvents on the yield of 5C2P, several common solvents were employed and the corresponding yields were shown in Fig. 5. It was clearly that the reaction was carried out in solvent with weak polarity, such as DCE, 5C2P was obtained in up to 97.93% yield. But in some polar solvents, such as Diox, CHCl3, EA, the yields significantly dropped. Besides, in other solvents, such as THF and PhMe, the yields of 5C2P were moderate. Therefore, it found that the polarity of the solvent was one of the main reasons for the discrepancy in yields of 5C2P.
The effect of initiator on the yield of 5C2P
Since the reaction rate was slow when BTC was directly involved as a chlorine source, amines were often added to accelerate the reaction due to its initiation[25]. As shown in Fig. 6, different initiators were introduced into the chlorination reaction and the comparison was shown in Fig. 6. The results indicated that strong nucleophilic amines, such as DMAC and DMF, showed preferable catalytic performance and yields of 5C2P achieved up to 97.93% or 95.71% respectively. However, amine with weak nucleophilicity, such as NMP, showed moderate catalytic performance and resulted in the decline of yield dramatically. Through the observation of experimental phenomena and analysis of experimental results, the discrepancy may be related to the steric hindrance of the amines.
Study on the reaction mechanism
The optimal reaction conditions were taken as an example to explore the chlorination reaction mechanism strategically. BTC and DMAC were mixed in CHCl3 at 60 °C for 1 h, and acetyl-n-propanol was added subsequently. The experiment process was detected by diverse NMR techniques. Based on the experimental data and previous work, a possible mechanism was proposed in Fig. 7. DMAC, the initiator, synergistically promoted the reaction from two aspects[26, 27]. Firstly, DMAC reacted with phosgene decomposed by BTC to generate Vilsmeier-Haack salt, which improved the positive charge of the carbonyl carbon and facilitated Cl- to attack the intermediate product, and released DMAC simultaneously[28]. Secondly, DMAC absorbed the by-product HCl to form DMAC hydrochloride because of its basicity, which was favorable for the reaction to proceed in the direction of generating 5C2P.
Considerable progress has been achieved in the mixture sample analysis of the biomass catalytic conversion by NMR[29, 30]. In particular, the Sel-TOCSY experiment is a highly sensitive NMR experiment widely used for the fast and effective identification and assignment of complete proton spin systems under routine conditions, even in the case of overcrowded proton regions or in complex mixture samples[31]. Single and pure spectrum can be obtained by Sel-TOCSY, so it has a broad application on qualitative and quantitative analysis due to its high selectivity[32-34]. In this work, the Sel-TOCSY experiment was performed, setting the excitation peaks at 3.06 ppm. The excitation frequency was labeled with a red lightning(Fig. 8). Comparing to standard 1H NMR spectrum, the intermediate product of 1-(dimethylamino)ethyl carbonochloridate was illustrated. The signal peaks of intermediate product were also observed clearly in the 1H-13C HSQC NMR spectrum (Fig. 9). The chemical structure information of C atoms of intermediate product was characterized by 13C NMR (δ = 156.18, 96.55, 43.54 and 13.54 ppm) (Fig. S4). Thus, through the identification of spectra, the signal peaks of the intermediate product were analyzed and confirmed.