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JoVE Journal Chemistry

Chemistry

Achieving Moderate Pressures in Sealed Vessels Using Dry Ice As a Solid CO2 Source

Published: August 17, 2018 doi: 10.3791/58281
Automatic Translation
1,2, *1,2, *1,2, 1,2
1Department of Chemistry and Biochemistry, University of Toledo, 2School of Green Chemistry and Engineering, University of Toledo
* These authors contributed equally

Summary

Here we present a protocol for performing reactions in simple reaction vessels under low-to-moderate pressures of CO2. The reactions can be performed in a variety of vessels simply by administering the carbon dioxide in the form of dry ice, without the need for costly or elaborate equipment or set-ups.

Abstract

Herein is presented a general strategy to perform reactions under mild to moderate CO2 pressures with dry ice. This technique obviates the need for specialized equipment to achieve modest pressures, and can even be used to achieve higher pressures in more specialized equipment and sturdier reaction vessels. At the end of the reaction, the vials can be easily depressurized by opening at room temperature. In the present example CO2 serves as both a putative directing group as well as a way to passivate amine substrates, thereby preventing oxidation during the organometallic reaction. In addition to being easily added, the directing group is also removed under vacuum, obviating the need for extensive purification to remove the directing group. This strategy allows the facile γ-C(sp3)-H arylation of aliphatic amines and has the potential to be applied to a variety of other amine-based reactions.

Introduction

The use of gaseous compounds in chemical reactions typically requires specialized equipment and procedures1,2. At bench scale, some gases can be added directly from a tank using a high pressure regulator3. An alternative method is to condense the gas under cryogenic conditions4,5. Although useful, these strategies require the use of specialized pressure reactors with valves, which can be cost prohibitive for running numerous reactions in parallel. This can therefore greatly slow the rate at which reaction screening can proceed. As a result, chemists have found it desirable to introduce these compounds using alternative methods. Ammonia can be added to reactions using different ammonium carboxylate salts, taking advantage of the weak equilibrium between these salts and free ammonia6. Transfer hydrogenation is an important strategy for reduction reactions of olefins, carbonyl, and nitro groups that circumvents the use of flammable hydrogen gas with compounds such as ammonium formate or hydrazine as carriers of H27. Another gas of interest in this area is carbon monoxide8 – CO can be generated in situ by liberation from metal carbonyl complexes9,10, or alternatively it can be generated by decarbonylation from sources such as formates and formamides11,12,13 or chloroform14,15.

One gas which has not enjoyed significant development in this respect is carbon dioxide16. One reason for this is that many transformations that involve CO2 also require high temperatures and pressures, and thus are automatically relegated to specialized reactors17,18. Recent efforts to develop more reactive catalysts, however, have facilitated running many of these reactions under atmospheric pressures of CO219,20,21,22. We recently discovered a reaction in which carbon dioxide could be used to mediate the γ-C(sp3)–H arylation of aliphatic amines23. This strategy was expected to combine the benefits of a static directing group approach including amide24,25,26,27,28, sulfonamide29,30,31,32, thiocarbonyl33,34, or hydrazone35-based directing groups (chemical robusticity), with the ease of a transient directing group (decreased step economy)36,37,38,39.

Although the reaction could occur under atmospheric pressure of CO2, the need for a Schlenk set-up to screen reactions proved prohibitively slow. Furthermore, increasing the pressure slightly led to improved reaction yields, but could not be easily achieved using a Schlenk line. We therefore sought an alternative strategy, and subsequently identified that dry ice could be easily used as a solid source of CO2 that could be added to a variety of reaction vessels to introduce the necessary amount of carbon dioxide to achieve moderate pressures (Figure 1). Though underutilized in synthesis, a similar strategy is fairly common as a method to generate liquid CO2 for chromatography and extraction applications40,41,42,43,44. Utilizing this strategy allowed our group to rapidly screen large numbers of reactions in parallel, while the ability to access moderate CO2 pressures of between 2-20 atmospheres were critical to improving the yields of the reactions. Under these conditions, both primary (1°) and secondary (2°) amines can be arylated with electron rich and electron poor aryl halides.

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Protocol

CAUTION: 1) The following protocols have been deemed safe through repeated trials. However, caution should be exercised when sealing vials, throughout the reaction, and especially when opening the reactions, as inhomogeneity in the reaction vials may lead to equipment failure. Vials should be inspected for physical defects prior to use. Vials should be placed behind some form of blast shield or hood sash immediately after sealing to prevent incidents should the vials fail. 2) Although there is little chance for asphyxiation due to the small quantities of CO2 used, reactions should be set-up as well as opened in a well-ventilated area or in a fume hood. 3) Dry ice is a cryogen and can cause serious tissue damage. Care should therefore be exercised while manipulating it to avoid frostbite, such as limiting direct contact or using cryogenic gloves. 4) Dry ice will condense water vapor, meaning that prior to use, the dry ice should be mechanically exfoliated to ensure the mass is of CO2(s) only. This can be achieved by simply rubbing the dry ice between one’s fingers, or more safely, rubbing it between one’s fingers with a protective layer such as a glove or towel.

1. Reaction in a 7.5 mL Vial (Air Not Excluded)

  1. Add a stir bar to a dry 7.5 mL vial.
  2. Add palladium acetate (6.7 mg, 0.03 mmol) to the vial.
  3. Add silver trifluoroacetate (99.9 mg, 0.45 mmol) to the vial.
  4. Add phenyl iodide (92.3 mg, 0.45 mmol) to the vial.
  5. Add tert-amyl amine (26.3 mg, 0.30 mmol) to the vial.
  6. Add acetic acid (1.0 mL) to the vial.
    Note: The ratio of solution volume to vial size is important, as the immediate sublimation of CO2 upon addition of dry ice can mechanically displace solvent if too much is used relative to the size of the reaction vessel.
  7. Add deionized water (21.7 μL, 12.1 mmol) to the vial.
  8. Weigh dry ice (26.3 mg, 0.60 mmol), and immediately add the dry ice to the vial, while ensuring to also immediately seal the vial with a PTFE-lined cap.
    Note: The whole operation should be performed within approximately 5 seconds to prevent sublimation and escape of the small amount of CO2 added (this is slowed by the formation of frozen acetic acid around the dry ice). The amount of CO2 added will be an approximate value, and in our hands a deviation of a few mg is permissible.
  9. Stir the sealed reaction vial for 15 minutes at room temperature.
  10. Transfer the reaction vessel to a pre-heated plate at 110 °C and stir for 14 hours before allowing to cool.
  11. Upon cooling, carefully open the vial to vent CO2.
  12. Remove all of the volatiles in vacuo.
    Note: This operation can be performed in the vial, or the solution can be transferred to a larger round bottom flask.
  13. Add 1.2 M HCl(aq) (6 mL) to the reaction mixture and stir open to air for 15 minutes.
  14. Transfer the aqueous fraction to a separatory funnel, washing with additional 1.2 M HCl (4 mL), and extract with a 1:1 diethyl ether/hexanes mixture (3 x 8 mL).
    Note: This organic wash contains excess phenyl iodide and other neutral by-products, and can be disposed of.
  15. Neutralize and make basic the aqueous solution by addition of saturated NH4OH(aq) (10 mL is a good starting point).
  16. Extract the aqueous layer with dichloromethane (2 x 10 mL).
  17. Dry the combined organic fractions over Na2SO4, then filter into a tared sample vial.
  18. Evaporate the solvent in vacuo, giving the product (2-Methyl-4-phenyl-butanamine) as a yellow oil.

2. Reaction in a 7.5 mL Vial (Purging Conditions – Air Excluded)

  1. Add a stir bar to a dry 7.5 mL vial.
  2. Add palladium acetate (6.7 mg, 0.03 mmol) to the vial.
  3. Add silver trifluoroacetate (99.9 mg, 0.45 mmol) to the vial.
  4. Add phenyl iodide (92.3 mg, 0.45 mmol) to the vial.
  5. Add tert-amyl amine (26.3 mg, 0.30 mmol) to the vial.
  6. Add acetic acid (1.0 mL) to the vial.
    Note: The ratio of solution volume to vial size is important, as the immediate sublimation of CO2 upon addition of dry ice can mechanically displace solvent if too much is used relative to the size of the reaction vessel.
  7. Add deionized water (21.7 μL, 12.1 mmol) to the vial.
  8. Tare the vial on a balance, add approximately 98 mg of dry ice, and then allow the CO2 to sublimate off until a final mass of approximately 26 mg is achieved, followed by immediately sealing the vial with a PTFE-lined cap.
    Note: If desirable, this step can be performed with a greater mass of dry ice to further exclude air from the vial. It is noteworthy that this may introduce water, and thus may not be the most effective strategy for water sensitive reactions.
  9. Stir the sealed reaction vial for 15 minutes at room temperature.
  10. Transfer the reaction vessel to a pre-heated plate at 110 °C and stir for 14 hours before allowing to cool.
  11. Upon cooling, carefully open the vial to vent CO2.
  12. Remove all of the volatiles in vacuo.
    Note: This operation can be performed in the vial, or the solution can be transferred to a larger round bottom flask.
  13. Add 1.2 M HCl(aq) (6 mL) to the reaction mixture, and stir open to air for 15 minutes.
  14. Transfer the aqueous fraction to a separatory funnel, washing with additional 1.2 M HCl (4 mL), and extract with a 1:1 diethyl ether/hexanes mixture (3 x 8 mL).
    Note: This organic wash contains excess phenyl iodide and other neutral by-products, and can be disposed of.
  15. Neutralize and make basic the aqueous solution by addition of saturated NH4OH(aq) (10 mL is a good starting point).
  16. Extract the aqueous layer with dichloromethane (2 x 10 mL).
  17. Dry the combined organic fractions over Na2SO4, then filter into a tared sample vial.
  18. Evaporate the solvent in vacuo, giving the product (2-Methyl-4-phenyl-butanamine) as a yellow oil.

3. Reaction in a 40 mL Vial (Air Not Excluded)

  1. Add a stir bar to a dry 40 mL vial.
  2. Add palladium acetate (33.5 mg, 0.15 mmol) to the vial.
  3. Add silver trifluoroacetate (499.5 mg, 2.25 mmol) to the vial.
  4. Add phenyl iodide (461.5 mg, 2.25 mmol) to the vial.
  5. Add tert-amyl amine (131.5 mg, 1.5 mmol) to the vial.
  6. Add acetic acid (5.0 mL) to the vial.
    Note: The ratio of solution volume to vial size is important, as the immediate sublimation of CO2 upon addition of dry ice can mechanically displace solvent if too much is used relative to the size of the reaction vessel.
  7. Add deionized water (108.5 μL, 6.02 mmol) to the vial.
  8. Weigh dry ice (131.5 mg, 3.0 mmol), and immediately add the dry ice to the vial, while ensuring to also immediately seal the vial with a PTFE-lined cap.
    Note: The whole operation should be performed within approximately 5 seconds to prevent sublimation and escape of the small amount of CO2 added (this is slowed by the formation of frozen acetic acid around the dry ice). The amount of CO2 added will be an approximate value, and in our hands a deviation of a few mg is permissible.
  9. Stir the sealed reaction vial for 15 minutes at room temperature.
  10. Transfer the reaction vessel to a pre-heated plate at 110 °C and stir for 14 hours before allowing to cool.
  11. Upon cooling, carefully open the vial to vent CO2.
  12. Remove all of the volatiles in vacuo.
    Note: This operation can be performed in the vial, or the solution can be transferred to a larger round bottom flask.
  13. Add 1.2 M HCl(aq) (30 mL) to the reaction mixture and stir open to air for 15 minutes.
  14. Transfer the aqueous fraction to a separatory funnel, washing with additional 1.2 M HCl (20 mL), and extract with a 1:1 diethyl ether/hexanes mixture (3 x 8 mL).
    Note: This organic wash contains excess phenyl iodide and other neutral by-products, and can be disposed of.
  15. Neutralize and make basic the aqueous solution by addition of saturated NH4OH(aq) (10 mL is a good starting point).
  16. Extract the aqueous layer with dichloromethane (2 x 20 mL).
  17. Dry the combined organic fractions over Na2SO4, then filter into a tared sample vial.
  18. Evaporate the solvent in vacuo, giving the product (2-Methyl-4-phenyl-butanamine) as a yellow oil.

4. Reaction in a 35 mL Pressure Tube (Air not excluded)

  1. Add a stir bar to a dry 35 mL pressure tube.
  2. Add palladium acetate (6.7 mg, 0.03 mmol) to the pressure tube.
  3. Add silver trifluoroacetate (132.5 mg, 0.6 mmol) to the pressure tube.
  4. Add phenyl iodide (183.6 mg, 0.9 mmol) to the pressure tube.
  5. Add 2-methyl-N-(3-methylbenzyl)butan-2-amine (57.4 mg, 0.3 mmol) to the pressure tube.
  6. Add acetic acid (1.0 mL) to the vial, followed by 1,1,1,3,3,3,-hexafluoroisopropanol (1.0 mL).
    Note: The ratio of solution volume to vial size is important, as the immediate sublimation of CO2 upon addition of dry ice can mechanically displace solvent if too much is used relative to the size of the reaction vessel.
  7. Add deionized water (21.7 μL, 1.2 mmol) to the pressure tube.
  8. Weigh dry ice (1.32 g, 30 mmol), and immediately add the dry ice to the pressure tube, while ensuring to also immediately seal the pressure tube with the appropriate Teflon screw cap.
    Note: The whole operation should be performed within approximately 5 seconds to prevent sublimation and escape of the small amount of CO2 added (this is slowed by the formation of frozen acetic acid around the dry ice). The amount of CO2 added will be an approximate value, and in our hands a deviation of a few mg is permissible.
  9. Stir the sealed reaction vessel for 15 minutes at room temperature.
  10. Transfer the reaction vessel to a pre-heated plate at 90 °C and stir for 24 hours before allowing to cool.
  11. Upon cooling, put a towel or padded glove over the cap, and carefully open the pressure tube to vent CO2.
  12. Remove all of the volatiles in vacuo.
    Note: This operation can be performed in the pressure tube with an appropriate adaptor, or the solution can be transferred to a larger round bottom flask.
  13. Add 1.2 M HCl(aq) (12 mL) to the reaction mixture and stir open to air for 15 minutes.
  14. Transfer the aqueous fraction to a separatory funnel, washing with additional 1.2 M HCl (8 mL), and extract with a 1:1 diethyl ether/hexanes mixture (3 x 8 mL).
    Note: This organic wash contains excess phenyl iodide and other neutral by-products and can be disposed of.
  15. Neutralize and make basic the aqueous solution by addition of saturated NH4OH(aq) (10 mL is a good starting point).
  16. Extract the aqueous layer with dichloromethane (2 x 10 mL).
  17. Dry the combined organic fractions over Na2SO4, then filter into a tared sample vial.
  18. Evaporate the solvent in vacuo, giving the product (2-Methyl-N-(3-methylbenzyl)-4-phenylbutan-2-amine) as a yellow oil.

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Representative Results

Following these protocols, it is possible to charge a reaction vial with an appropriate amount of carbon dioxide to achieve chemical reactions that require CO2 atmospheres. The pressure achieved in Step 1 is calculated to be approximately 3 atmospheres (see discussion for determination of this value), although due to partial solvation, the observed pressure is in the vicinity of 2 atmospheres at room temperature, and should be approximately 2.6 atmospheres under the reaction conditions. Therefore, under the conditions in Step 1, 2-Methyl-4-phenyl-butanamine can be obtained in 69% yield (Figure 2). By first purging the flask of air through displacement by sublimating CO2 (Step 2), the yield can be increased slightly to 72%. To distinguish between these results at ~2.6 atmospheres of pressure, performing the reaction under 1 atmosphere of CO2 using a standard Schlenk set-up furnishes the desired product in only 49% isolated yield. If no CO2 is used, or the vial is not properly sealed and thus a stable CO2 atmosphere is not maintained, then <5% yield of the desired product is detected by 1H NMR (using 1,1,2,2-tetrachloroethane as reference standard). Meanwhile, scaling the reaction up by a factor of 5 while simultaneously using a larger reaction vial (Step 3) can still give product, albeit in a slightly decreased yield of 42%. The reactions can also be performed in pressure reaction tubes (Figure 1), in this case allowing the synthesis of 2-Methyl-N-(3-methylbenzyl)-4-phenylbutan-2-amine in 40% yield (Figure 3).

Figure 1
Figure 1. Reaction Vessels Used in this Study. From left to right: 2 dram Vial, 10 Dram Vial, 35 mL Pressure Tube). Please click here to view a larger version of this figure.

Figure 2
Figure 2. 1H NMR of 2-Methyl-4-phenyl-butanamine. 400 MHz, CDCl3, 298 K. Please click here to view a larger version of this figure.

Figure 3
Figure 3. 1H NMR of 2-Methyl-N-(3-methylbenzyl)-4-phenylbutan-2-amine. 400 MHz, CDCl3, 298 K. Please click here to view a larger version of this figure.

Carbon Dioxide Loading in Empty Vials
100 mg 125 mg 150 mg 175 mg 200 mg 225 mg 250 mg 275 mg 300 mg Legend
25ºC √ √ √ √ √ √ √ √ √ √ =  Stable Under Conditions
60ºC √ √ √ √ √ √ √ √ √ x =  Unstable Under Conditions
70ºC √ √ √ √ √ √ √ √ √
80ºC √ √ √ √ √ √ √ √ √
90ºC √ √ √ √ √ √ √ √ √
Temperature 100ºC √ √ √ √ √ √ √ √ √
110ºC √ √ √ √ √ √ √ √ √
120ºC √ √ √ √ √ √ √ √ √
130ºC √ √ √ √ √ √ √ √ √
140ºC √ √ √ √ √ √ √ √ √
150ºC √ √ √ √ √ √ √ √ √
160ºC √ √ √ √ √ √ √ √ √

Table 1. Relative Stability of 7.5 mL Vials Based on CO2 Loading and Temperature. Vials were loaded with the requisite amount of dry ice, followed by immediately sealing with a PTFE-lined cap. The vials were immediately placed into Pie-blocks behind a blast shield in a fumehood, followed by heating to 60 °C, followed by raising 10 °C every hour to a peak of 160 °C. The vials were then cooled, and opened carefully to confirm no loss of CO2 pressure had occurred.

Carbon Dioxide Loading in Empty Vials
300 mg 325 mg 350 mg 375 mg 400 mg 425 mg 450 mg 475 mg 500 mg 525 mg Legend
25ºC √ √ √ √ √ √ √ √ √ x √ =  Stable Under Conditions
60ºC √ √ √ √ √ √ √ √ √ x x =  Unstable Under Conditions
70ºC √ √ √ √ √ √ √ √ √ x
80ºC √ √ √ √ √ √ √ √ √ x
90ºC √ √ √ √ √ √ √ √ √ x
Temperature 100ºC √ √ √ √ √ √ √ √ √ x
110ºC √ √ √ √ √ √ √ √ √ x
120ºC √ √ √ √ √ √ √ √ √ x
130ºC √ √ √ √ √ √ √ √ √ x
140ºC √ √ √ √ √ √ √ √ √ x
150ºC √ √ √ √ √ √ √ √ √ x
160ºC √ √ √ √ √ √ √ √ √ x

Table 2. Relative Stability of 40 mL Vials Based on CO2 Loading and Temperature. Vials were loaded with the requisite amount of dry ice, followed by immediately sealing with a PTFE-lined cap. The vials were immediately placed into Pie-blocks behind a blast shield in a fumehood, followed by heating to 60 °C, followed by raising 10 °C every hour to a peak of 160 °C. The vials were then cooled, and opened carefully to confirm no loss of CO2 pressure had occurred.

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Discussion

Using the van der Waals Equation of State, the approximate pressure of these systems can be calculated45

Eq. 1:          Equation

Under the conditions in Protocol 1, we can assume 26.3 mg of CO2 gives n =5.98 x 10-4 mols

Equation 1b

As a rough estimate, this suggests that in Protocol 1 the reactions were performed under approximately 2.8 atmospheres of CO2. Assuming negligible displacement of the native atmosphere in the vessel (as noted above, a patina of frozen acetic acid will slow the initial sublimation of the dry ice, facilitating better accuracy in the measurement of added dry ice), however, the total pressure would then be expected to be modeled better by Dalton's law:

Eq. 2:          Equation 2

Equation 2b

This model does not take into account that some of the gases will be dissolved in the solvent. In that case, it was necessary to attach a pressure gauge to adequately assess the pressure. By attaching a septum to the vial and inserting a pressure gauge, it was possible to measure the pressure at room temperature. The observed pressures over multiple reactions were only 15 ± 3 psi above atmospheric pressure (≈ 1 ± 0.2 atmospheres), or around 2 atmospheres total. Although the Henry constant of CO2 in neat acetic acid was not readily available for comparison, it is known that addition of acetic acid to water improves the solubility of carbon dioxide46. The estimated pressure at room temperature could be calculated using the previous approach:

Equation 5

Equation 6

The expected pressure would therefore be a slightly lower 3.3 atmospheres at room temperature in the absence of gas dissolving in the solvent. The difference between the observed and calculated pressures imply that CO2 has relatively high solubility in the organic solvent. Assuming negligible difference in the amount of dissolved CO2 over the temperature range, an increase in temperature from 298 K to the reaction temperature of 383 K would increase the pressure within the 2 dram vial to ~2.6 atmospheres.

To adequately assess the practical operating conditions, 2 dram vials were set-up with varying amounts of CO2, followed by screening these at different temperatures. To ensure operator safety, the vials were only heated after being placed behind a blast shield to contain any vial failures. If the vials blew up, the conditions were considered too harsh for the vials. Through these experiments it was determined that CO2 loading of up to 200 mg was tolerated at 110 °C for the 2 dram (7.5 mL) vials through consistent trials. This corresponds to approximately 20.7 atmospheres of pressure based on the previous approach, not withstanding the amount of gas dissolved, which may decrease the total pressure by a few atmospheres. Beyond 200 mg loading, however, the reaction vials would generally explode before reaching the target temperature of 110 °C. Caution should be exercised when modifying the conditions, however: In one scenario a related reaction was attempted at 160 °C with only 150 mg of CO2, but the vial failed before it had reached the target temperature. The greatest danger for modifying the reaction conditions would be from increasing the loading of CO2, as this can cause the vials to fail before safe engineering controls, such as blast shields, can be implemented.

A potential limitation to this strategy is the lack of data about the stability of the vials under different conditions. Therefore, it was necessary to screen the vials for their ability to withstand different pressures under a range of different temperatures. This was initiated with the 7.5 mL vials (Table 1). Each vial was charged with a pre-determined quantity of dry ice, followed by immediate sealing with a PTFE-lined screw cap. These vials were observed to be tolerant of these conditions, and none failed at room temperature. The temperature was then raised for all of the vials, and no explosions occurred during the experiment. Upon cooling, each vial was opened to confirm they had maintained pressurization with CO2. This suggests that the vials can tolerate upwards of 26.5 atmospheres of pressure, which is in contrast to the reaction conditions in which ~20.7 atmospheres of pressure was the consistent limit. It is therefore encouraged that solvent identity and volume be carefully considered in deviation from the disclosed method.

A similar screen for maximum tolerance was performed using 40 mL reaction vials (Table 2). In this case, an upper limit for the CO2 loading of empty vials was determined to be 500 mg. Above this the vials quickly failed at room temperature. Surprisingly, the calculated pressure of the samples that began to fail at room temperature was approximately 7 atmospheres and above. This is in contrast to the vial containing 500 mg of CO2, which was stable at 160 °C, which would correspond to a calculated pressure of just under 10.5 atmospheres. These results were reproducible across different vials, but there is no clear explanation for this phenomenon at this time. Under the conditions described under Protocol 3, only approximately 300 mg loadings of CO2 were tolerated. However, this is actually in line with the previous experiments, as under the conditions the pressure, uncorrected for potential absorption of carbon dioxide by the solvent, would be approximately 10 atmospheres. The decreased stability of the larger vials to pressure is expected, and suggests that these procedures are better performed in vessels that have smaller diameters and thicker walls47.

In summary, this protocol for using dry ice as a solid CO2 source in readily available glassware is expected to open new directions in the field of synthetic chemistry. By generating low to moderate pressures inside of sealed vials or pressure tubes, carbon dioxide fixation processes such as carboxylation48,49,50, as well as CO2 reduction51,52,53, can be achieved without the use of expensive specialized equipment. This newly adopted strategy will facilitate advances in the area of valorization of CO2 by incorporation into useful chemical feedstocks such as cyclic carbonates, poly carbonates, and carbamates54. Furthermore, the strategy of introducing CO2 as a solid may also be beneficial where mixtures of gases are desired, such as CO2 and CO, or CO2 and H2, as this facilitates the addition of both reagents in a non-gaseous form. Although use of dry ice to introduce liquid CO2 has been used for extractions and chromatography40,41,42,43,44, this protocol for introducing CO2 as a solid may also be useful for in situ generation of CO2(L) for use as a reaction solvent55,56,57, Future work exploring other uses for this approach, especially the combination of CO2 with other gas-precursors, are currently underway in our group.

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Disclosures

The use of CO2 as a directing group for C-H activation of Lewis basic substrates is currently the focus of United States Provisional Patent #62/608,074.

Acknowledgments

The authors wish to acknowledge start-up funding from The University of Toledo, as well as funds from the American Chemical Society's Herman Frasch Foundation in partial support of this work. Mr. Thomas Kina is acknowledged for his assistance with developing a suitable pressure gauge for measuring the reaction pressures. Mr. Steve Modar is thanked for useful discussions.

Materials

Name Company Catalog Number Comments
7.5 mL Sample Vial with Screw Cap (Thermoset) Qorpak GLC-00984 Can be reused.
40 mL Sample Vial with Screw Cap (Thermoset) Qorpak GLC-01039 Can be reused.
Pressure Tube, #15 Thread, 7" Long, 25.4 mm O.D. Ace Glass 8648-06 Can be reused.
Pie-Block for 2 Dram Vials ChemGlass CG-1991-P14 Can be reused.
Pie-Block for 10 Dram Vials ChemGlass CG-1991-P12 Can be reused.
3.2 mm PTFE Disposable Stir Bars Fisher 14-513-93 Can be reused.
C-MAG HS 7 Control Hotplate IKA 20002695
Analytical Weighing Balance Sartorius QUINTIX2241S
Double-Ended Micro-Tapered Spatula Fisher Scientific 21-401-10
Hei-VAP Advantage - Hand Lift Model with G5 Dry Ice Condenser Rotary Evaporator Heidolph 561-01500-00
Bump Trap 14/20 Joint ChemGlass CG-1322-01
tert-Amyl amine Alfa Aesar B24639-14 Used as received.
2-Methyl-N-(3-methylbenzyl)butan-2-amine N/A N/A Prepared from reductive amination of tert-amyl amine and 3-tolualdehyde in the presence of sodium borohydride in methanol.
Palladium Acetate Chem-Impex International, Inc. 4898 Used as received.
Silver Trifluoroacetate Oakwood Chemicals 007271 Used as received.
Phenyl Iodide Oakwood Chemicals 003461 Used as received.
Acetic Acid Fisher Chemical A38 Used as received.
1,1,1,3,3,3-Hexafluoroisopropanol Oakwood Chemicals 003409 Used as received.
Deionized Water Obtained from in-house deionized water system.
Dry Ice Carbonic Enterprises Dry Ice Inc. Non-food grade dry ice.
Concentrated Hydrochloric Acid Fisher Chemical A144SI Diluted to a 1.2 M solution prior to use.
Diethyl Ether, Certified Fisher Chemical E138 Used as received.
Hexanes, Certified ACS Fisher Chemical H292 Used as received.
Saturated Ammonium Hydroxide Fisher Chemical A669 Used as received.
Dichloromethane Fisher Chemical D37 Used as received.
Sodium Sulfate, Anhydrous Oakwood Chemicals 044702 Used as received.
250 mL Separatory Funnel Prepared in-house by staff glassblower.
100 mL Round Bottom Flask Prepared in-house by staff glassblower.
Scientific Disposable Funnel Caplugs 2085136030
Borosilicate Glass Scintillation Vials, 20 mL Fisher Scientific 03-337-15
5 mm O.D. Thin Walled Precision NMR Tubes Wilmad 666000575
Chloroform-d Cambridge Isotope Laboratories, Inc. DLM-7 Used as received.

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References

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Achieving Moderate Pressures in Sealed Vessels Using Dry Ice As a Solid CO<sub>2</sub> Source
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Kapoor, M., Chand-Thakuri, P.,… More

Kapoor, M., Chand-Thakuri, P., Maxwell, J. M., Young, M. C. Achieving Moderate Pressures in Sealed Vessels Using Dry Ice As a Solid CO2 Source. J. Vis. Exp. (138), e58281, doi:10.3791/58281 (2018).

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