Continuous Flow Plug Flow and CSTR Reactors

Under GL-PTC conditions, a gaseous stream of reagent and DMC flows over a catalytic bed usually composed of a porous inorganic material (usually corundum in the form of a spherical extrudate of 1-3 mm of diameter), which acts as a support for both an inorganic base (an alkaline carbonate) and a phase-transfer (PT) agent such as phosphonium salts,13 crown ethers,14 and polyethylene glycols (PEGs). These latter in particular, although less efficient than other PT agents, are desirable because they are thermally stable, nontoxic, and inexpensive.15

In a typical configuration, the CF methylation reaction with DMC takes place in a plug-flow reactor made by a bed of K2CO3 coated with PEG 6000 (0.5-5% mol. eq.), and heated to 160-180°C.5,16 A mixture of DMC and substrate (YH) is fed into the reactor where the base generates the reactive nucleophilic anion (Y_) from the substrate. The role of the PT agent is to complex the alkaline metal cation, thereby increasing the basic strength of the solid carbonate. As shown in the Scheme of Figure 4.1, the immobilized PT agent is in the liquid phase throughout the reaction, and allows the continuous transfer of the products and reactants between the gas and liquid phases. The methylated product is then condensed and collected at the other end.

Flowing gas phase

Reagents

Products

Reagents

Products

Liquid phase

Anion exchange (K2C03)

Figure 4.1 General picture of gas liquid phase transfer catalysis (GL-PTC).

Anion exchange (K2C03)

Figure 4.1 General picture of gas liquid phase transfer catalysis (GL-PTC).

TABLE 4.3 Reactions of DMC with Different Nucleophiles Under GL-PTC Conditions

Entry Reagent Product, Yield %

TABLE 4.3 Reactions of DMC with Different Nucleophiles Under GL-PTC Conditions

Entry Reagent Product, Yield %

1

ArOH

ArOMe, 100

2

ArSH

ArSMe, 100

3

ROH

ROCO2Me + (RO)2CO

4

PhCH2CN

PhCH(Me)CN, 98

J

5

AXr

^CN J^Xj CN'95

Ibuprofen precursor

Conditions: GL-PTC, plug-flow reactor, catalyst: K2CO3 coated with 0.5-5mol % of PEG 6000, T = 160-180°C.

Conditions: GL-PTC, plug-flow reactor, catalyst: K2CO3 coated with 0.5-5mol % of PEG 6000, T = 160-180°C.

Quantitative conversions are obtained from all the substrates listed in Table 4.3.4,16,17 Moreover, in the case of CH2-active compounds, the reaction proceeds with a mono-methyl selectivity >99% (entries 4 and 5). An example reaction, shown in Figure 4.2, is the methylation of phenol under GL-PTC conditions.

In a typical experimental procedure, when a mixture of phenol (94 g, 1 mol) and DMC (2.0 mol) is made to flow over a 100-g catalytic bed composed of 95 wt % K2CO3 g and 5 wt % PEG 6000 at 180°C, pure anisole is recovered with a 100% yield in 1 h (residence time ~10 s).17a'17b Pyrocatecol and hydroquinone can also be selectively mono- or di-alkylated under CF conditions in a pilot plant scale.10

In Table 4.3, it should be noted, however, that hard alkoxide anions (RO_) react with DMC via a BAc2 mechanism to yield exclusively transesterification products (ROCO2Me) with no trace of methyl ethers (entry 3). Such a peculiar selectivity is currently under investigation.

An alternative CF methodology for DMC methylations was developed as well, by using a CSTR (Figure 4.3).18 In this configuration, the catalyst fills the reactor in the form of a liquid slurry of the PT agent (usually PEG 1000) and K2CO3, and it is kept under vigorous stirring at the desired temperature (160-200°C). The mixture of DMC and the reagent is vaporized when it comes into contact with the

Cstr Apparatus
Figure 4.2 CF methylation of phenol in a plug-flow reactor under GL-PTC conditions. R: reagent's reservoir; P: metering pump; T: thermostat; C: condenser; P': product store.

Liquid reagents: ArOH + DMC

Vapor phase

PEG 1000 and K2C03

160-200°C

Figure 4.3 Schematic chart of a CSTR reactor for the O-methylation of phenols with DMC. Liquid reagents are vaporized by contact with the hot slurry (mechanically stirred) and bubbled through it. Reaction takes place instantaneously and anisoles are picked up from the vapor phase.

catalytic bed. When a suitable feeding rate is chosen, the apparatus works under gradientless conditions: the composition of the mixture collected at the outlet is equal to that present inside the reactor, and the reaction takes place instantaneously as far as reagents bubble through the bed. At atmospheric pressure, different phenols are transformed quantitatively into the corresponding anisoles with a weight hourly space velocity (WHSV) up to 9.5 x 10_2h_1.10 The reaction could run without interruption for at least two weeks. Some results are listed in Table 4.4.

TABLE 4.4 The O-Methylation of Different Phenols (ArOH) with DMC in a CSTRa

Substrate

Flow Rate

Time of

Converted

Product,

WHSV x

100,

ArOH, Ar

T (°C)

(mL/h)

Flowing (h)

(g)

ArOMe (%)

gprod/gbed

(h)

Ph

200

80

2.5

97.5

97

8.4

p-MeC6H4

160

80

4

128.0

98

9.5

"Reactions carried out over a catalytic bed of PEG 1000 (300 g) and K2CO3 (6 g). Molar ratios ArOH:DMC were 1:1.05 and 1:1.5 for PhOH and p-MeC6H4OH, respectively. WHSV: grams of ArOMe obtained hourly per gram of catalyst.

"Reactions carried out over a catalytic bed of PEG 1000 (300 g) and K2CO3 (6 g). Molar ratios ArOH:DMC were 1:1.05 and 1:1.5 for PhOH and p-MeC6H4OH, respectively. WHSV: grams of ArOMe obtained hourly per gram of catalyst.

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Responses

  • melissa
    Do it yourself continuous reactor?
    2 months ago

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