View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Journal of Saudi Chemical Society (2016) 20, S382–S386 King Saud University Journal of Saudi Chemical Society www.ksu.edu.sa www.sciencedirect.com Cross-Aldol condensation of isobutyraldehyde and formaldehyde using phase transfer catalyst Azhar Hashmi * Saudi Basic Industries Corporation (SABIC), P.O. Box 42503, Riyadh 11551, Saudi Arabia Received 8 July 2012; accepted 22 December 2012 Available online 11 January 2013 KEYWORDS Abstract The hydroxypivaldehyde (HPA) precursor intermediate for the synthesis of neopentyl Hydroxypivaldehyde; glycol (NPG) is prepared by novel cross Aldol condensation of isobutyraldehyde and formaldehyde Neopentyl glycol; at 20 °C using benzyltrimethylammonium hydroxide, a basic phase transfer catalyst. A feed mole Benzyltrimethylammonium ratio of 1.1:1.0:0.04 (isobutyraldehyde:formaldehyde:benzyltrimethylammonium hydroxide) affor- hydroxide ded hydroxypivaldehyde as white solid in almost quantitative yield with 100% selectivity. ª 2013 Production and hosting by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 1. Introduction such as polymers, petrochemicals, pharmaceuticals, agrochem- icals, and other commodity, specialty and fine organic chemi- Phase Transfer Catalysis (PTC) technology (Starks and Liotta, cals (Goldberg, 1992; Dozeman et al., 1997; McKillop et al., 1994; Makosza and Wawrzyniewicz, 1969; Makosza, 1975; 1974; Maurin, 1983; Kantam et al., 1990). The advantages of Brandstrom, 1982; Weber and Gokel, 1977) is presently used a PTC process over classical non-PTC process have been re- in the manufacture of an extremely wide variety of chemicals ported for many reaction categories (Sato et al., 1997; Grace and Wood, 1994; Duke et al., 1964; Tummes et al., 1970; Jac- obson et al., 1968; Stark, 1971). * Tel.: +966 1 499 9727; fax: +966 1 499 9101. However, to our surprise very little work has been reported E-mail address: [email protected]. using PTC on Aldol condensation of aliphatic aldehydes, an Peer review under responsibility of King Saud University. industrially important reaction. Traditionally aliphatic alde- hydes are condensed using alkali hydroxides, alkali carbon- ates, and alkaline earth metal hydroxide as a base catalyst Production and hosting by Elsevier (Hausen et al., 1978; Yoneoka et al., 1995; Cull et al., 1967; http://dx.doi.org/10.1016/j.jscs.2012.12.012 1319-6103 ª 2013 Production and hosting by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Cross-Aldol condensation of isobutyraldehyde and formaldehyde using phase transfer catalyst S383 Figure 1 Consecutive process in a liq–liq reaction. Figure 2 Mechanism of hydroxypivaldehyde formation. Morris et al., 1989; Merger et al., 1968). Other catalyst systems include Zn or Mg containing zeolites (Merger et al., 1974), ter- obtained as an aqueous solution and anhydrous forms of tiary amines (Salek et al., 1992) and basic ion exchange resins formaldehyde, such as paraformaldehyde and trioxane. (Erkki et al., 1998). There are a few relevant references in the Figure 2 shows the mechanism of the cross-Aldol condensa- literature on phase-transfer catalyzed Aldol condensation with tion of isobutyraldehyde and formaldehyde catalyzed by phase aromatic aldehydes but none reported with aliphatic aldehydes transfer catalyst. The problem at hand in this reaction is the (Cortese and Gastrock, 1985; Cardillo et al., 1975). To the best following. Reaction between two substances located in differ- of our knowledge only one report mentioned the use of PTC ent phases of a mixture is often inhibited because of the inabil- (quaternary ammonium halide) as co-catalyst surfactant in ity of reagents to come together. Isobutyraldehyde is a liquid the Aldol condensation carried out using alkali hydroxides material that makes the water insoluble organic phase. On as catalyst (Deem and Stueben, 1976). the other hand, formaldehyde solution makes the aqueous Herein, we report in this paper for the first time, an example phase because it comes as 37–40% aqueous solution. In the Al- of the cross-Aldol condensation reactions of aliphatic alde- dol condensation process, these two reacting components cre- hydes (Deem and Stueben, 1976). Figure 1 shows the cross-Al- ate a non-homogeneous two phase reaction medium. dol condensation of isobutyraldehyde and formaldehyde Therefore, interaction of the two reacting components is not performed using basic-PTC (quaternary ammonium hydrox- sufficient enough for smooth cross- Aldol condensation lead- ide) as sole catalyst and Table 1 shows the benefits achieved ing to the product hydroxypivaldehyde. Thus, the equilibrium in terms of high productivity, better quality, smaller catalyst in the first step of the reaction mechanism tries to be more to charge, control exothermicity, improved safety, enhanced envi- the backward (i.e., to the starting isobutyraldehyde). ronmental performance, etc. over the conventional method One way to solve this problem is to make the reaction mix- from the industrial viewpoint. This reaction represents cross- ture homogeneous by using a solvent such as methanol or eth- Aldol condensation between two different aldehydes, namely anol. However, by doing this we will decrease the isobutyraldehyde having a-hydrogen atom and formaldehyde concentration of the reacting components, thereby decreasing having no a-hydrogen atom, for the synthesis of aldehyde- the reaction rate. The other but a better way to solve this prob- alcohol, namely hydroxypivaldehyde (HPA). The expression lem, according to the present invention, is to make use of an ‘‘formaldehyde’’ comprises both conventional formaldehyde appropriate basic phase-transfer catalyst (PTC). Reaction is Table 1 Comparison of catalyst performance in Aldol condensation reaction of isobutyraldehyde and formaldehyde. Process Non-PTC PTC Catalyst type Tertiary amineb Ion exchange resinc Alkali hydroxidea Quaternary ammonium hydroxided Physical state Liquid Solid Solid Liquid Conversion 98% 95% 85% 100% Selectivity 96% 98% <70% 100% Reaction time 2 h >7 h 4 h 1h Reaction temperature 90 °C60°C70°C20°C Pressure 1 Atm. 1 Atm. 1 Atm. 1 Atm. Exothermicity Moderate Moderate High Moderate Catalyst amount 5–6% (mol equiv.) 25–60% (by wt.) 4% (mol equiv.) 4% (mol equiv.) Catalyst separation Distillation Filtration Electrolytic Extraction a Ref. Merger et al. (1968) b Ref. Merger et al. (1974) c Ref. Morris et al. (1989) d Ref. Starks and Liotta (1994) S384 A. Hashmi Table 2 Temperature profile for the Aldol condensation reaction of isobutyraldehyde and formaldehyde at 20 °C. Entry no Reaction Reaction mixture Cooling bath time (min) temp. (°C) temp. (°C)b 1 0.0a 15 c 2 0.5 26 8.0 3 1.0 25 8.0 4 1.5 25 8.0 5 2.0 24 7.6 6 2.5 22 7.5 Figure 3 Benzyltrimethylammonium hydroxide (BTAH). 7 3.0 21 7.3 8 3.5 20 7.2 9 4.0 18 7.0 10 4.5 17 7.5 11 5.0 16 8.6 brought about by the use of small quantities of an agent, which 12 5.5 15 9.3 transfers one reactant across the interface into the other phase, 13 6.0 15 9.6 so that reaction can proceed. Thus, phase transfer catalysts are 14 6.5 14 9.8 defined as compounds whose addition to a two-phase organic- 15 7.0 14 9.9 water system helps transfer a water soluble reactant across the 16 8.0 14 9.9 interface to the organic phase where a homogeneous reaction 17 9.0 13 12.2 can occur. This can also help transfer a water insoluble reac- 18 10.0 14 14.3 tant across the interface to the aqueous phase where a homo- 19 11.0 15 16.4 geneous reaction can occur. 20 12.0 17 18.4 21 13.0 18 19.6 The phase-transfer agent is not consumed but performs the 22 14.0 20 19.8 transport function repeatedly. Organic-soluble quaternary 23 16.0 21 19.9 ammonium or phosphonium cations have been found to be 24 18.0 21 19.9 excellent agents for the transport of anions from the aqueous 25 20.0 20 20.0 phase to an organic phase. We have used a specific phase- a Before catalyst addition. transfer catalyst, namely benzyltrimethyl or benzyltriethyl b Fluid temperature. ammonium hydroxide which is also known as Triton B c No water circulation. (methyl version) (Fluka Catalog, #13991). This comes as a 40% solution in water. Its chemical formula is shown in Fig- ure 3. The hydroxide counter anion acts as a base entity to de-protonate a-hydrogen of the isobutyraldehyde molecule, ing process, and also handling of these polymeric materials to whereas the quaternary ammonium cation part assists in the the precise molar ratio is difficult. The use of triethylamine re- phase-transfer mechanism. quires elevated temperatures and also longer reaction times are usually required. However, to the best of our knowledge only 2. Results and discussion one report describes the Aldol condensation of aldehydes and ketone with the phase-transfer catalyst benzyltriethylammo- The hydroxypivaldehyde (HPA) precursor intermediate for the nium chloride. Herein we report for the first time a cross Aldol synthesis of neopentyl glycol (NPG) is prepared traditionally condensation reaction between a first aldehyde selected from by cross Aldol condensation of isobutyraldehyde and formal- the aldehydes containing at least one a-hydrogen atom, and dehyde using triethylamine or alkali metal hydroxides or car- a second different aldehyde selected from aldehydes having bonates or alkaline earth metal hydroxides (hydrated) or by the formula R2CHO, wherein R2 is selected from H, alkyl hav- ion exchange resins as base catalyst.