Thermography of cannabis extract vaporization cartridge heating coils in temperature- and voltage-controlled systems during a simulated human puff.

Vaporized cannabis is believed to be safer than smoking, but when heated to excessive temperatures nearing combustion (>900 °C) harmful byproducts may form. While some cannabis extract vaporizers operate well below these high temperatures, heating coil temperatures obtained during actual use are frequently not reported and many operate at high temperatures. We report on two major objectives: 1) development of an infrared thermography method to measure heating coil temperatures in cannabis extract vaporizers during a simulated puff and 2) a comparison of temperature- to voltage- controlled cannabis extract vaporization systems during a puff. Infrared thermography was used to measure heating coil temperatures in one temperature-controlled and two voltage-controlled systems. The cartridges were modified for direct line-of-sight on the heating coils, the wick and coils were saturated with cannabis extract, and fixtures were developed to force two liters per minute air flow past the coils for the full duration of the puff allowed by the device. The voltage-controlled systems produced higher temperatures with greater variability than the temperature-controlled system. At the highest temperature setting (420 °C) the temperature-controlled system reached an average heating coil temperature of 420 ± 9.5 °C whereas the 4.0V setting on the variable voltage system reached an average temperature of 543 ± 95.9 °C and the single voltage (3.2V) system an average of 450 ± 60.8 °C. The average temperature at the lowest setting (270 °C) on the temperature-controlled system was 246 ± 5.1 °C and the variable voltage system (2.4V) was 443 ± 56.1 °C. Voltage alone was a poor indicator of coil temperature and only the temperature-controlled system consistently maintained temperatures less than 400 °C for the full puff duration. These lower temperatures could reduce the likelihood of harmful thermal degradation products and thus may reduce potential health risk to consumers when vaporizing cannabis extracts.

Rate and Computational Studies for Pd-NHC-Catalyzed Amination with Primary Alkylamines and Secondary Anilines: Rationalizing Selectivity for Monoarylation versus Diarylation with NHC Ligands.

The relative rates of arylation of primary alkylamines with different Pd-NHC catalysts have been measured, as have the relative rates of arylation of the secondary aniline product in an attempt to understand the key ligand design features necessary to have high selectivity for the monoarylated amine product. As the substituents on the N-aryl ring of the NHC increase in size, selectivity for monoarylation increases and this is further enhanced by chlorinating the back of the NHC ring. Computations have been performed on the catalytic cycle of this transformation in order to understand the selectivity obtained with the different catalysts.

Designing Pd-N-Heterocyclic Carbene Complexes for High Reactivity and Selectivity for Cross-Coupling Applications.

Over the past decade, the use of Pd-NHC complexes in cross-coupling applications has blossomed, and reactions that were either not previously possible or possible only under very forcing conditions (e.g., > 100 °C, strong base) are now feasible under mild conditions (e.g., room temperature, weak base). Access to tools such as computational chemistry has facilitated a much greater mechanistic understanding of catalytic cycles, which has enabled the design of new NHC ligands and accelerated advances in cross-coupling. With these elements of rational design, highly reactive Pd-NHC complexes have been invented to catalyze the selective formation of single products in a variety of transformations that have the potential to afford multiple compounds (e.g., isomers). Pd-NHC catalysts may be prepared as stable Pd(II) precatalysts that are readily reduced to the active Pd(0) species in the presence of an organometallic cross-coupling partner or nucleophile possessing ß-hydrogens. It has been found from computational and experimental results that Pd-NHC complexes bearing a single bulky NHC ligand are well-suited to tackle challenging cross-coupling reactions. N-Aryl-substituted imidazole-2-ylidenes with branched alkyl chains at the ortho positions of the aryl group are effective for the challenging couplings of hindered biaryls, secondary alkyl organozincs, electron-deficient anilines, α-amino esters, primary alkylamines, and ammonia. The bulk of the NHC has been tuned by increasing the size of the alkyl groups at the ortho positions and substituting the NHC core with chlorine substituents. All of the cross-coupling transformations studied benefit from the increased bulk when the ortho groups are changed from methyl to 2-propyl to 3-pentyl. However, there is a limit to the positive effect of steric bulk, as some reactions do not benefit from the increased size of the 4-heptyl group compared with 3-pentyl. Thus, there is an optimum size for the NHC ligand that depends upon whether reactivity (turnover frequency and turnover number), selectivity, or both are needed to obtain the desired reaction outcome. In the cases that we have studied, reactivity and selectivity increase together (i.e., the fastest catalyst is also the most selective), allowing cross-couplings to be carried out under mild conditions to obtain one product with high selectivity. This Account focuses on seminal literature reports that have disclosed new Pd-NHC complexes that have led to significant breakthroughs in efficacy for challenging couplings while demonstrating high selectivity for the desired target. These catalysts have been used widely in materials science, pharmaceutical, and agrochemical applications.

Practical catalytic method for synthesis of sterically hindered anilines.

A practical catalytic method for the synthesis of sterically hindered anilines is described. The amination of aryl and heteroaryl boronic esters is accomplished using a catalyst prepared in situ from commercially available and air-stable copper(i) triflate and diphosphine ligand. For the first time, the method can be applied to the synthesis of both secondary and tertiary anilines in the presence of a wide range of functional groups. Esters, aldehydes, alcohols, aryl halides, ketones, nitriles, and nitro arenes are all compatible with the reaction conditions. Finally, even the most sterically hindered anilines can be successfully prepared under mild reaction conditions. Overall, the new method addresses significant practical limitations of a transformation previously developed in our lab, and provides a valuable complement to the existing methods for the synthesis of anilines.

Selective Monoarylation of Primary Amines Using the Pd-PEPPSI-IPent(Cl) Precatalyst.

A single set of reaction conditions for the palladium-catalyzed amination of a wide variety of (hetero)aryl halides using primary alkyl amines has been developed. By combining the exceptionally high reactivity of the Pd-PEPPSI-IPent(Cl) catalyst (PEPPSI=pyridine enhanced precatalyst preparation, stabilization, and initiation) with the soluble and nonaggressive sodium salt of BHT (BHT=2,6-di-tert-butyl-hydroxytoluene), both six- and five-membered (hetero)aryl halides undergo efficient and selective amination.

Catalytic anti-Markovnikov hydrobromination of alkynes.

We have developed the first catalytic method for anti-Markovnikov hydrobromination of alkynes. The reaction affords terminal E-alkenyl bromides in high yield and with excellent regio- and diastereoselectivity. Both aryl- and alkyl-substituted terminal alkynes can be used as substrates. Furthermore, the reaction conditions are compatible with a wide range of functional groups, including esters, nitriles, epoxides, aryl boronic esters, terminal alkenes, silyl ethers, aryl halides, and alkyl halides. A preliminary study of the reaction mechanism suggests that the hydrobromination reaction involves hydrocupration of an alkyne, followed by the bromination of the alkenyl copper intermediate. This study also suggests that 2-tert-butyl potassium phenoxide functions as a mild catalyst turnover reagent and provides a better understanding of the unique effectiveness of (BrCl2C)2 among brominating reagents.

Synthesis of tertiary alkyl amines from terminal alkenes: copper-catalyzed amination of alkyl boranes.

A method for highly selective anti-Markovnikov hydroamination of terminal alkenes is reported. The one-pot procedure involves hydroboration of the alkene followed by a novel electrophilic amination of the alkyl borane catalyzed by an NHC-Cu complex. Terminal alkenes are successfully transformed into tertiary alkyl amines in the presence of a variety of functional groups in yields ranging from 80 to 97% with excellent regioselectivity. Results of a preliminary study of the reaction mechanism are also described.

Synthesis of hindered anilines: copper-catalyzed electrophilic amination of aryl boronic esters.

No longer a hindrance: copper-catalyzed electrophilic amination of aryl boronic esters is accomplished under mild reaction conditions using 2.5-5.0 mol % of a catalyst derived from copper tert-butoxide and Xantphos ligand. The reaction tolerates a wide range of functional groups and can be used to prepare some of the most hindered anilines made to date.

Catalytic SN2'-selective substitution of allylic chlorides with arylboronic esters.

A copper-catalyzed S(N)2'-selective arylation of allylic chlorides has been achieved using arylboronic esters as nucleophiles. Arylation products were obtained in high yield with a variety of allylic chlorides and arylboronic esters in the presence of a wide range of functional groups. A mechanism is proposed on the basis of the results of stoichiometric experiments and the isolation of the proposed intermediate.