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

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 procedures^1,2. 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 conditions^4,5. 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. ....

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) D....

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 co.......

Discussion

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

Eq. 1:          

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

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.