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Sustainability Improvements through Catalyst Recycling in a Liquidliquid Batch and Continuous Phase Transfer Catalysed Process Soo Khean Teoh, Qiao Yan Toh, Mohammad Salih Noorulameen, and Paul N. Sharratt Org. Process Res. Dev., Just Accepted Manuscript • DOI: 10.1021/acs.oprd.6b00337 • Publication Date (Web): 02 Mar 2017 Downloaded from http://pubs.acs.org on March 15, 2017
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Organic Process Research & Development
SUSTAINABILITY IMPROVEMENTS THROUGH CATALYST RECYCLING IN A LIQUID-LIQUID BATCH AND CONTINUOUS PHASE TRANSFER CATALYSED PROCESS Soo Khean Teoh†, Qiao Yan Toh*†, Mohammad Salih Noorulameen†, and Paul N. Sharratt*† †
INCOME team, Process Science and Modeling group, Institute of Chemical and Engineering Sciences (ICES), 1 Pesek Road, Jurong Island, Singapore 627833 AUTHOR INFORMATION Corresponding Authors *Email:
[email protected],
[email protected] Page 1 of 20
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TABLE OF CONTENTS GRAPHIC
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ABSTRACT Phase transfer catalysis (PTC) is a potentially useful approach to processing but often uses environmentally problematic substances that typically end up in waste streams. The sustainability benefits of catalyst recovery from a third liquid layer in a PTC system were investigated for the Oalkylation of 3-phenyl-1-propanol. The system was operated in both the batch and continuous modes. Formation of a third liquid phase and using it to recover catalyst reduces equipment footprint, product loss through the waste, VOC emissions and improves energy efficiency compared to the equivalent process designed without the third liquid layer, but at the expense of higher costs, E factor and lower volume efficiency. Overall, continuous phase transfer catalyst recycling is better than the equivalent batch process in volume efficiency, in-process inventory, mass efficiency, E factor, VOC emission, equipment footprint and operating cost. However, batch process with batch catalyst recycling is still more cost effective in capital investment. Keywords: catalyst recycling; sustainability; phase transfer catalysis; continuous process INTRODUCTION Three of the major environmental problems in the pharmaceutical industry are solvent-laden waste, catalyst-containing waste and waste produced from side reactions. While phase transfer catalysis can improve reaction selectivity and reduce use of more problematic solvents, it does produce wastes that have their own environmental issues. Phase transfer (PT) catalysts such as quaternary salts and crown ethers are particularly toxic to aquatic organisms1 2 3. Due to its small quantity, PT catalyst is commonly disposed in the commercial processes. Of all the methods used to separate and recycle the catalyst, extraction is the most commonly used commercial approach, especially for catalysts which are soluble in water. Other methods include distillation, adsorption and binding to an insoluble support4. Formation of a third liquid layer to retain catalyst between aqueous and organic phases has been reported to be one of the simpler, 3-5 convenient and economical extraction methods . Catalyst may form a third layer during PTC reaction with high salt concentration and nonpolar organic solvents. The factors affecting third layer formation include polarity of organic solvent, degree of saturation of the aqueous phase with salt or alkaline, type and quantity of catalyst used, nature of the substrate and reaction temperature3, 5. Third liquid layer has been observed for catalysts such as PEGs, quaternary-onium salts and crowns 4 , for instance Mason et al. reported the formation of third liquid layer in the reactions consisting of TBAB, aqueous NaOH and toluene6. The etherification process of a wide range of polyhydric alcohols with allyl chloride in the presence of (Bu)4NHSO4 was also reported to take place in the 3 third liquid layer system . Third liquid layer PT catalysis has been claimed to offer much higher reaction rate, better selectivity 7 5 and repeated use of catalyst compared to a liquid-liquid system without middle layer formation , . It 8 there is no holistic work is of considerable scientific and commercial interest . However, so far reported, from the economics and environmental perspectives, the benefits of catalyst recycling and reuse. In this paper, we extend the work from our past paper 9 to investigate different PT catalyst recycling approaches and its potential sustainability benefits in both batch and continuous liquidliquid PT catalysed processes. In this work, we evaluated two approaches to PT catalyst recovery and reuse for the O-alkylation of 3-phenyl-1-propanol in liquid-liquid mode, namely: (1) Allow the formation of middle layer at the right ionic strength to capture most of the catalyst. The middle layer consisting of catalyst, product and reactants could be reused directly. (2) Extract the catalyst from the crude product directly with water, followed by removing the catalyst from the wash water into organic reagents at the right ionic strength. The catalystladen organic reagents could be reused directly. The PT catalyst used in this study is tetra-n-butylammonium bromide (TBAB). TBAB is a potentially damaging environmental contaminant and it is toxic to marine life. The understanding on catalyst recycling was gathered through a series of small scale batch experiments, and the data gathered was used to model the various process schemes on a projected 100 ton/year production, with a product specification of at least 97% purity and a maximum of 0.1wt% PTC. Page 3 of 20
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EXPERIMENTAL DETAILS - Method of analysis Analysis for TBAB and TBA was achieved using the Agilent HPLC LC-1100 series coupled with a ELSD detector (Alltech 2000ES) for the aqueous samples. A mixed mode SIELC column (Primesep D) was used for the HPLC analysis. The analysis for TBA+ is run under isocratic conditions of 80% H2O, 20% ACN and 0.15% TFA. The amount of starting material and product in the middle layer was determined by GC-FID (Agilent 7890A) using a HP-FFAP column. Concentrations of Na+ and Brions in the aqueous phase were determined by ion chromatography (IC) and OH- was determined by acid titration. - Catalyst recycling studies Small scale experiments were conducted for the catalyst recycling studies. To 50% aq. NaOH (69 ml, 6 eq.) in a 250ml, 2-necked flask was added a solution of 3-phenyl-1-propanol (30 g, 1.0 eq.), allyl bromide (28 g, 1.05 eq.) and TBAB (2 g, 0.028 eq.). The reaction mixture was stirred at room temperature and sampled at regular intervals. Water was added to the samples collected and an aliquot of the organic phase was dissolved in CDCl3. Reaction conversion was measured by 1H NMR. At the end of the reaction, the reaction was left to phase separate and the aq. NaOH layer was removed, followed by three times water extraction in a separating funnel. Middle layer was observed in the first water extraction. The middle layer was isolated, and analysed for 3-phenyl-1propanol, product, TBAB and tributylamine (TBA). - Understanding of middle layer formation Two different experiments were performed. Experiment 1: At the end of the reaction, without removing the aq. NaOH layer, known aliquots of water was added and shaken till the first appearance of middle layer. A sample of the aqueous layer was taken. Aliquots of water were further added till the middle layer disappears and a second sample of the aqueous layer was taken. The samples were analysed for Na+, TBA+, Br-, OHconcentrations, so as to determine the ionic strength of the aqueous layer. Experiment 2: To the crude product (9.12 g) isolated from a previous run was added TBAB (0.512 g, 0.031 eq.). The crude mixture was extracted with deionised water (0.093 g). A sample was taken from the aqueous layer and analysed for TBAB. Subsequently, predetermined amounts of NaCl were added to the same aqueous layer to increase its ionic strength. After each extraction, a sample would be taken and analysed for TBAB. The corresponding ionic strength of the aqueous layer was determined from the amount of NaCl added. Calculation of partition coefficient was achieved by assuming that the remaining TBAB resides in the organic layer, where K = [TBAB]org/[TBAB]aq). TBAB in middle layer is considered as TBAB in organic phase as well. - Determination of partition coefficients from small scale experiments Partition coefficients were determined from small scale experiments (30 g scale) in which extraction was carried out by the shake-flask method. TBAB in the aqueous layer was determined by HPLC and the remaining TBAB amount assumed to be in the organic layer. The organic layer is washed until the TBAB amount in the aqueous wash is negligible. Therefore the amount of TBAB in organic phase is determined through calculations backwards from the final extraction, i.e. amount of TBAB in the organic layer of 2nd extraction is assumed to be the same amount of TBAB in the aqueous layer rd of 3 extraction. In that case, partition coefficient for second extraction, K2, will be: K2 =
( / ) ( / )
And partition coefficient for first extraction, K1, will be: K1 =
( / ) ( / )
- Continuous run on counter-current LLE The reaction is conducted in a 5 L liquid-liquid extractor. An organic reaction mixture containing allyl bromide (1.05 mol equiv.), 3-phenyl-1-propanol (1 mol equiv.) and TBAB (0.028 mol equiv.) is Page 4 of 20
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prepared in a fume cupboard and transferred to a carboy. An aqueous solution of 50 wt% NaOH in a carboy is pumped into the LLE using a peristaltic pump through the top inlet at a rate of 50 ml/min. The mechanical agitator in LLE is turned on to improve the mixing. After the column is filled until the sight glass from top of LLE (approx. 85%), the organic mixture that has been prepared is pumped into the LLE at 21.5 mL/min using a peristaltic pump through the bottom inlet. Liquid interface height is controlled using a lute. Organic samples are taken from top outlet at specified intervals and reaction conversion and TBAB amount are monitored using H-NMR and HPLC. - Calculations of sustainability metrics Sustainability metrics were calculated based on 100 tonnes per year of product. Experiments conducted at lab scale were used to size the equipment at plant scale for batch process without recycling and provide the batch operation time. Based on the equipment size, utilities for the process were calculated such as chilled water, steam, electricity requirement. CAPEX for the equipment was calculated based on equipment size while OPEX was calculated as a combination of costs for raw material, waste treatment and energy. A separate process scheme was designed for middle layer recycling in batch process and its CAPEX and OPEX were similarly calculated. For the continuous processes, reaction conditions optimised at lab scale and the data gathered from the pilot LLE run were used to size the equipment at plant scale at steady state conditions with catalyst recycling. Three different continuous processes were designed (C1, C2 & C3) where the catalyst was either recycled in the form of a middle layer or through aqueous extractions using different technology. All sustainability metrics are derived from equipment size, operation time, CAPEX, OPEX and product produced per year. RESULTS AND DISCUSSION -
Recovery of catalyst via middle layer 9
In our previous work on O-alkylation , the organic phase consisting of 3-phenyl-1-propanol and allyl bromide was run neat with 6 mol equivalents of 50 w/w% NaOH(aq.) at ambient temperature to give an equivalently good conversion as a conventional batch process at a shorter reaction duration. At this reaction condition, the reaction mixture appeared to be in two phases. Only after the NaOH-rich aqueous layer was removed and the wash water was added into the organic phase, a third liquid layer or middle layer appeared in between the aqueous and organic phase (Figure 1). This middle layer had about 58-76 mol% of the TBAB input in the initial reaction (Table 1). The recycling of the catalyst is expected to be easier via the reuse of middle layer and the corresponding top up of the catalyst in the next reaction.
Organic layer
Middle layer Aqueous layer
Figure 1: Middle layer formation
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Table 1: Amount of TBAB in middle layer over time Time to recycling (day) Mol% TBAB recovered in middle layer Initial reaction 2
72 47 (Some middle layer was accidently removed due to indistinct interface) 76 70 65 58
6 14 45 120
The middle layer was kept in the lab at room temperature and tested for its degree of degradation and performance for an extended period of time. No degradation product (eg. tributylamine) from TBAB was observed in the analysis of the middle layer and crude product. The isolated middle layer was recycled into the next reaction, with top-up of fresh TBAB to the required stoichiometry (0.028 mol eq.). The reaction performance of the recycled TBAB-rich middle layer with corresponding top up of fresh catalyst was as good as the initial reaction after recycling for 6 times over a 7-month span (Figure 2).
ML recycling in L-L System T= 25 oC, 6 mol eq. 50w/w% NaOH, 1.05 mol eq AB, 0.028 mol eq. TBAB, without Toluene
100 95 90
% SM converted (NMR)
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13 Sep 2013 - another initial reaction
85
Initial reaction - 0 day 1st ML recycle - 2 days
80
2nd ML recycle - 6 days 75
3rd ML recycle - 14 days 4th ML recycle - 45 days
70
5th ML recycle - 120 days
65
6th ML recycle - 212 days 60 0
100
200
300
400
500
Time (min)
Figure 2: Performance of recycled middle layer -
Understanding of the middle layer formation
A simple experiment was conducted to determine the threshold for formation and dissolution of middle layer by adding aliquots of water to the biphasic reaction mixture at the end of reaction. Without removal of the NaOH layer, the reaction mixture existed with an indistinct interface between the two phases at the end of the reaction. The results showed that the indistinct interface becomes a stable third liquid phase below the ionic strength of 3.71 mol/kg and that the middle layer dissolves into the two liquid phases when the ionic strength is further decreased beyond 0.98 mol / kg (Figure 3).
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Disappearance of middle layer at 0.98 mol/kg
First appearance of middle layer at 3.71 mol/kg
Example of indistinct interface
Figure 3: Effect of ionic strength on the formation of middle layer TBAB is known to prefer alcoholic solvents (partition coefficient, K = 69 in butanol/water) to ethereal 10 solvents (K =
