Electrochemical oxidation of Δ9-tetrahydrocannabinol: a simple strategy for marijuana detection

Article abstract of DOI:10.1021/acs.orglett.0c01241

Recently, it has been estimated that nearly 200 million people use marijuana with growing usage being attributed to the legalization and decriminalization of the drug around the world. A concerning implication of increased marijuana use is the alarming number of individuals who report driving under the influence of the drug, which has prompted the development of detection technologies. An electrochemical-based detection technology, akin to how the alcohol breathalyzer functions, would provide an attractive solution to this growing societal problem. The first step toward this goal is to develop a reaction that converts Δ⁹-tetrahydrocannabinol (Δ⁹-THC), the primary psychoactive substance in marijuana, to a derivative with diagnostic spectroscopic changes. We report the development of a mild electrochemical method for the oxidation of Δ⁹-THC to its corresponding p-quinone isomer. The photophysical and electrochemical properties of the resultant quinone show a dramatic shift in comparison to Δ⁹-THC. This simple protocol provides the foundation for the development of an electrochemical-based marijuana breathalyzer.

Full text of DOI:10.1021/acs.orglett.0c01241

pubs.acs.org/OrgLett
Letter
Electrochemical Oxidation of Δ9‑Tetrahydrocannabinol: A Simple
Strategy for Marijuana Detection
Evan R. Darzi and Neil K. Garg*
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ABSTRACT: Recently, it has been estimated that nearly 200
million people use marijuana with growing usage being attributed
to the legalization and decriminalization of the drug around the
world. A concerning implication of increased marijuana use is the
alarming number of individuals who report driving under the
influence of the drug, which has prompted the development of
detection technologies. An electrochemical-based detection tech-
nology, akin to how the alcohol breathalyzer functions, would
provide an attractive solution to this growing societal problem. The
first step toward this goal is to develop a reaction that converts Δ9-
tetrahydrocannabinol (Δ9-THC), the primary psychoactive sub-
stance in marijuana, to a derivative with diagnostic spectroscopic
changes. We report the development of a mild electrochemical
method for the oxidation of Δ9-THC to its corresponding p-quinone isomer. The photophysical and electrochemical properties of
the resultant quinone show a dramatic shift in comparison to Δ9-THC. This simple protocol provides the foundation for the
development of an electrochemical-based marijuana breathalyzer.
arijuana has been used for many millennia with some
Mreports of marijuana usage dating back to 3000 BC. Its
historic usage has been attributed to heightened sensations of
euphoria in addition to increased relaxation, among other
effects.1 Nowadays, marijuana has become one of the most
commonly used drugs. It was recently estimated that nearly
200 million people use the drug worldwide, which represents a
60% increase over the span of just one decade.2,3 Although
marijuana and other cannabinoid products have historically
been considered illicit substances in many countries, there have
been efforts to legalize these drugs. For example, the
recreational use of marijuana is legal or undergoing
decriminalization in more than 30 countries, including Canada,
Spain, Chile, The Netherlands, and Australia (Figure 1a). In
the United States, recreational marijuana usage has been
legalized in 11 states as well as in the District of Columbia.
With the relaxation of laws and enforcement concerning
marijuana, there has been a growing interest in safety,
especially when it comes to driving motorized vehicles, akin
to long-standing concerns about driving under the influence of
alcohol. Recent studies involving the United States show that
4.6% of the population (nearly 12 million individuals) reported
driving under the influence of marijuana during the prior year.
This is particularly striking given the well-known negative
impact marijuana has on spatial and temporal judgment.4−7
It is known that more than 100 different cannabinoids are
present in marijuana;8 however, the primary psychoactive
component responsible for driving impairment is Δ9-
tetrahydrocannabinol (Δ9-THC, 1). Δ9-THC (1) can
constitute between 5−30 wt% of a marijuana source9 and
has been identified as an ideal compound to detect when
assessing potential marijuana usage.10−15 Current roadside
tests for Δ9-THC (1) impairment are time-consuming and
require special training, such as blood/saliva tests, or are based
on behavioral signs and the officer’s discretion. New chemical-
based technologies can offer practical solutions for the growing
problem of marijuana detection. Not surprisingly, many new
inventions have been put forth in recent years with the aim of
developing technologies reminiscent of alcohol breathalyzers,
which are used widely due to their simplicity and reliability. It
has been demonstrated that Δ9-THC (1) levels in the breath
correlate reliably with time of marijuana consumption for 4 h
and with blood concentration levels. As such, breath-based
methods offer an attractive means for roadside detection
technologies.13,16
The current state-of-the-art Δ9-THC breathalyzers require
specialized mass spectrometry (Figure 1b),10−12 covalent
modification for optical sensing (Figure 1c),14,15 and
Received: April 7, 2020
https://dx.doi.org/10.1021/acs.orglett.0c01241
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Figure 2. Predicted absorption spectra and oxidation of 1 to 2.
density functional theory (TD-DFT) calculations to predict
the absorption spectra for 1 and 2. Although key diagnostic
UV peaks have been reported for Δ8-THCQ, compound 2 was
not known.21 Calculations predicted a shift in absorbance from
the UV range, in the case of 1, into the visible range for 2.
Additionally, the oxidation of 1 to 2 would result in a lowering
of the LUMO to a range that could be measured electro-
chemically. We therefore pursued the key electrochemical
transformation of Δ9-THC (1) to Δ9-THCQ (2) exper-
imentally with the expectation that the oxidation event would
be accompanied by a measurable change in electrochemical
and photochemical properties. Such changes, as well as a
diagnostic change in mass, could plausibly be used
independently or in combination with current detection
methods described above.
Before pursuing an electrochemical conversion, we examined
a more traditional chemical approach to access quinone 2, as
the conversion of THC (1) to 2 had not been reported (Figure
2b). Interestingly, oxidation of marijuana extracts dates back to
1911 when Beam first observed an ethanolic potassium
hydroxide solution would turn purple upon exposure to
hashish extracts.22 Mechoulam later determined that this test
was ineffective for Δ9-THC and Δ8-THC and instead
developed alternative oxidations strategies for accessing
quinones.21 Nowadays, many conditions are available for the
oxidation of phenols to p-quinone, and we were drawn to the
hypervalent iodine reagent bis(trifluoroacetoxy)iodobenzene
(PIFA), which has been used as a phenol oxidant for many
decades.23 PIFA has also been used to make cannabinoids in
the context of medicinal chemistry, although using the alkene
isomer Δ8-THC instead of Δ9-THC (1).24−26 We were
delighted to find that treatment of Δ9-THC (1) with PIFA in
aqueous media and under ambient conditions gave Δ9-THCQ
(2) in moderate yield. Consistent with our computational
predictions, the oxidized Δ9-THCQ (2) showed strong
absorbance peaks in the UV region at 204 and 266 nm, as
well as a diagnostic peak in the visible spectrum at 402 nm.
To understand the differences in UV absorption spectra for
1 and 2, we calculated the orbital contributions to the key
Figure 1. Overview of marijuana usage, Δ9-tetrahydrocannabinol (1),
and state-of-the-art chemical-based detection methods.
chemiresistors based on carbon nanotube (CNT) adsorption
(Figure 1d).13,16 Each method focuses on a single detection
mode (mass spectrometry, photochemical, or electrochemical)
to determine Δ9-THC (1) levels. Moreover, each bears
limitations, including specialized equipment in the case of
mass detection, toxic reagents used for covalent modification,
and batch-to-batch variability in CNT sensing. An electro-
chemical-based detection technology would provide an
attractive alternative, as such technology could ultimately
avoid the use of reagents or costly equipment, be rendered
portable, and take advantage of highly developed alcohol
breathalyzer technology. Although attempts to use direct
electrochemical methods have been used to detect simple
synthetic cannabinoids,17 efforts to use electrochemical
methods for the direct detection of Δ9-THC have remained
unrealized and typically resulted in polymerization18 or
required additional chemical mediators19,20 to alter the
properties of Δ9-THC for detection.
We sought to develop a mild electrochemical transformation
that would convert Δ9-THC directly into a stable and
structurally defined intermediate. Toward this end, we first
attempted to uncover a simple transformation of Δ9-THC (1)
that would provide a derivative with diagnostic spectroscopic
changes. As shown in Figure 2a, we hypothesized that a simple
oxidation would transform 1 into the corresponding p-
quinone, Δ9-THCQ (2). We performed time-dependent
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electronic transitions, as well as the orbital distributions and
energies, using DFT and TD-DFT calculations. The lowest
energy transition for 1 had an experimental peak at 282 nm,
primarily comprised of the HOMO−LUMO transition with
orbital densities located on the electron rich aromatic system
(Figure 3). The red-shifted visible absorbance for 2 was found
Figure 4. Cyclic voltammograms of Δ9-THC (1) and Δ9-THCQ (2).
Dry MeCN was used with NBu4BF4 (0.1 M) as the support
electrolyte (scan rate of 100 mV/s). Each spectrum was collected
using a glassy carbon working electrode, platinum counter electrode,
and a Ag/Ag+ reference electrode.
Figure 3. DFT calculated (B3LYP/6-31G(d)) HOMO and LUMO
energy levels and orbital distributions for 1 and 2.
to be comprised of a combination of the HOMO−LUMO and
HOMO−1−LUMO transition. In this case, the HOMO and
HOMO−1 are distributed over the electron rich alkene, while
the LUMO is localized on the electron poor quinone. This
π−π* transition is reminiscent of a donor−acceptor inter-
action. The electronegative carbonyl groups lead to a net
lowering of the LUMO energy, a narrowing of the HOMO−
LUMO transition energy, and ultimately a red-shift into the
visible spectrum for 2 relative to 1.
Having assessed key photophysical and redox properties, we
sought to achieve the electrochemical conversion of 1 to 2. As
suggested earlier, this approach could offer a simple oxidation
protocol akin to the fundamental technology used in alcohol
breathalyzers. Although chemical-based approaches for the
oxidation of phenols to quinones is well-known, the
corresponding transformation using electrochemistry31 is not
well-developed.32,33 One procedure is available,32 which had
resulted from a failed attempt to perform an oxidative
dimerization of a 2,5-dialkylphenol using electrochemistry.
We applied these known conditions to model substrate 2,5-
dimethylphenol (3) using an ElectraSyn plate (Figure 5).31a,34
Phenol 3 was exposed to 1.5 V using a carbon cathode and a
platinum anode at ambient temperature using LiClO4 as the
electrolyte. Although these conditions had previously been
reported on a related system, they failed to deliver the desired
With the aim of performing the oxidation of 1 electro-
chemically (toward a reagentless detection device), we sought
to understand the redox properties of both Δ9-THC (1) and
Δ9-THCQ (2). Thus, 1 and 2 were assessed using cyclic
voltammetry. The oxidation potential for 1 was measured,
which showed an irreversible oxidation event at a peak
potential of 1.02 V in line with reported values for 1 (Figure
4a).27,28 The measured oxidation potentials for 2 showed an
irreversible oxidation event at 1.71 V, along with a broad peak
at 1.92 V. The HOMO of 2 is thought to be lower in energy
compared to the HOMO of 1, thus rendering the removal of
an electron from 1 (i.e., oxidation) more favorable (Figure 3).
Next, the reduction potentials for 1 and 2 were compared
(Figure 4b). For 1, a negative scan from 0.0 to −2.5 V showed
no measurable reduction events, indicative of an inaccessible
LUMO energy. Reduction of 2 showed two reversible
(1)
(2)
reduction events at E1/2 = −1.02 V and E1/2 = −1.75 V.
The reduction events for 2 are thought to arise from a single-
electron reduction to the semiquinone and a second single
electron reduction to arrive at the hydroquinone. These values
are in line with previously reported reduction potentials for
both benzoquinones29 and synthetic cannabinoid analogues.30
The stark differences observed in redox (and photophysical
properties) between 1 and 2 bode well for the use of
electrochemical technologies for THC detection.
Figure 5. Electrochemical oxidation of phenol 3.
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quinone derivative of 4 and instead resulted in insoluble
polymer build-up at the electrode surface. We therefore carried
out optimization studies that involved varying the electrode
combinations, electrolyte, current, concentration, solvent to
water ratio, and the effect of additives. Ultimately, this led to
the use of carbon electrodes, NBu4BF4 as an electrolyte, with a
constant current of 26 mA. Using these conditions, quinone 4
was isolated in 57% yield.
prompts further efforts. More specifically, the present study
stimulates the need for many future endeavors, such as
assessments of the substrate specificity of the oxidation
reaction, studies regarding limits of detection and interaction
of metabolites, evaluation of false positives, and device
optimization using electrochemistry, colorimetric assays, or
combinations thereof. Nonetheless, the ability to oxidize Δ9-
THC (1) to a product displaying different photophysical and
redox properties using simple electrochemistry lays a
foundation for a marijuana breathalyzer that could be used
independently or in combination with existing technologies to
address a growing societal problem.36
We next applied these conditions to Δ9-THC (1). Of note,
the electrochemical oxidation of 1 or any complex phenols to
yield quinones selectively had not been reported. Many
experiments were ultimately performed (see Supporting
Information), with select examples using tetrabutylammonium
tetrafluoroborate as electrolyte shown in Table 1. Unfortu-
ASSOCIATED CONTENT
■
sı
* Supporting Information
a
Table 1. Electrochemical Conversion of 1 to 2
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c01241.
Experimental details and compound characterization
data (PDF)
AUTHOR INFORMATION
■
Corresponding Author
Neil K. Garg − Department of Chemistry and Biochemistry,
University of California, Los Angeles, California 90095-1569,
United States; orcid.org/0000-0002-7793-2629;
Email: neilgarg@chem.ucla.edu
Author
Evan R. Darzi − Department of Chemistry and Biochemistry,
University of California, Los Angeles, California 90095-1569,
United States; orcid.org/0000-0002-6900-2229
a
Conditions: Δ9-THC (1) (1.00 equiv, 22.3 μM), 6.60 mM (0.100 M
NBu4BF4 in MeCN), MeCN:H2O (8:1), 23 °C, 1 h, polarity
alternation every 60 s.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c01241
nately, our attempts to apply the successful model system
conditions to 1 were unsuccessful. Modulating current in an
attempt to control the oxidation led to decomposition and
insoluble buildup without formation of p-quinone 2 (entries 1
and 2) even when polarity alternation was included. However,
changing the cathode and anode to platinum (entry 3) and
including polarity alternation every 60 seconds led to full
consumption of phenol 1 and a 30% isolated yield of p-
quinone 2. Switching the cathode to glassy carbon (entry 4)
gave a comparable isolated yield of 2. Next, we tested the use
of a graphite electrode in place of glassy carbon or platinum as
an inexpensive alternative (entry 5). We were delighted to
observe a substantial boost in isolated yield to 67%.35
Interestingly, we exclusively observe the formation of 2
under the present electrochemical conditions, in contrast to
the chemical oxidation used in Figure 2b, where several side-
products were observed. Thus, the conversion of 1 to 2 can be
achieved using inexpensive electrodes and simple electro-
chemical oxidation conditions.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors are grateful to the University of California, Los
Angeles and the Trueblood family for financial support. These
studies were also supported by shared instrumentation grants
from the NSF (CHE-1048804) and the National Center for
Research Resources (S10RR025631).
REFERENCES
■
(1) Booth, M. Cannabis: A History; Thomas Dunne Books: New
York, 2015, pp 1−448.
(2) United Nations Office on Drugs and Crime. World Drug Report
2019; UN, New York, NY, 2019.
(3) Substance Abuse and Mental Health Services Administration.
Results from the 2018 Survey on Drug Use and Health: Detailed tables;
Center for Behavioral Health Statistics and Quality, Substance Abuse,
and Mental Health Services Administration: Rockville, MD, 2019.
Retrieved from https://www.samhsa.gov/data/, accessed 2020/04/
04.
(4) Hartman, R. L.; Huestis, M. A. Cannabis effect on driving skills.
Clin. Chem. 2013, 59, 478−492.
(5) Hartman, R. L.; Brown, T. L.; Milavetz, G.; Spurgin, A.; Pierce,
R. S.; Gorelick, D. A.; Gaffney, G.; Huestis, M. A. Cannabis effects on
driving lateral control with and without alcohol. Drug Alcohol Depend.
2015, 154, 25−37.
Our studies have shown that Δ9-THC (1) undergoes facile
oxidation to its p-quinone counterpart, Δ9-THCQ (2). In turn,
2 displays dramatic differences in photophysical and redox
properties. Moreover, we have found both chemical and
electrochemical transformations can be employed for the
oxidation, with the latter performing more efficiently and
providing an exceptionally simple means to manipulate 1.
Although this transformation validates our strategy, it also
D
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Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
́
(6) Lenne, M. G.; Dietze, P. M.; Triggs, T. J.; Walmsley, S.; Murphy,
(25) Mechoulam, R.; Kogan, N. M.; Rabinowitz, R.; Schlesinger, M.
Compositions including quinoid derivatives of cannabinoids for
therapeutic use. US Patent No. US 8,497,299 B2.
(26) Mechoulam, R.; Kogan, N. M.; Rabinowitz, R.; Schlesinger, M.
Therapeutic use of quinoid derivatives of cannabinoids. International
Patent No. WO 2005067917 A1.
B.; Redman, J. R. The effect of cannabis and alcohol on stimulated
arterial driving: Influences of driving experience and task demand.
Accid. Anal. Prev. 2010, 42, 859−866.
(7) Compton, R. Marijuana-Impaired Driving - A Report to Congress,
DOT HS 812 440; National Highway Traffic Safety Administration,
Washington, DC, 2017.
́
(27) Balbino, M. A.; Teles de Menezes, M. M.; Eleoterio, I. C.;
Saczk, A. A.; Okumura, L. L.; Tristao, H. M.; de Oliveira, M. F.
̃
̌
(8) Hanus, L. O.; Meyer, S. M.; Munoz, M.; Taglialatela-Scafati, O.;
̃
Voltammetric determination of Δ9-THC in glassy carbon electrode:
An important contribution to forensic electroanalysis. Forensic Sci. Int.
2012, 221, 29−32.
Appendino, G. Phytocannabinoids: a unified critical inventory. Nat.
Prod. Rep. 2016, 33, 1357−1448.
(9) Ashton, C. H. Adverse effects of cannabis and cannabinoids. Br.
J. Anaesth. 1999, 83, 637−649.
́
(28) Balbino, M. A.; Oiye, E. N.; Ribeiro, M. F. M.; Junior, J. W. C.;
́
́
Eleoterio, I. C.; Ipolito, A. J.; de Oliveira, M. F. Use of screen-printed
electrodes for quantification of cocaine and Δ9-THC: adaptions to
portable systems for forensic purposes. J. Solid State Electrochem.
2016, 20, 2435−2443.
(10) Attariwala, R.; Malhi, K.; Yost, R.; Boock, J.; Costanzo, M. T.
Device and method for the detection of cannabis and other controlled
substances using FAIMS. International Patent No. WO 2017/147687
A2.
(29) Khan, F. A.; Choudhury, S. Synthesis and electrochemical
properties of substituted para-benzoquinone derivatives. Tetrahedron
Lett. 2010, 51, 2541−2544.
(11) Costanzo, M. T.; Boock, J. J.; Kemperman, R. H. J.; Wei, M. S.;
Beekman, C. R.; Yost, R. A. Portable FAIMS: Applications and future
perspectives. Int. J. Mass Spectrom. 2017, 422, 188−196.
(12) Lai, H.; Corbin, I.; Almirall, J. R. Headspace sampling and
detection of cocaine, MDMA, and marijuana via volatile markers in
the presence of potential interferences by solid phase microextraction-
ion mobility spectrometry (SPME-IMS). Anal. Bioanal. Chem. 2008,
392, 105−113.
(13) Lynch, K. L.; Luo, Y. R.; Hooshfar, S.; Yun, C. Correlation of
breath and blood Δ9-tetrahydrocannabinol concentrations and release
kinetics following controlled administration of smoked cannabis. Clin.
Chem. 2019, 65, 1171−1179.
(14) Lynn, M. S.; Tang, H. R.; Bechtel, K. L.; Holst, P. A.
Compositions and methods for detection of target constituent in
exhaled breath. US Patent No. US 9,921,234 B1.
(15) Hwang, S. I.; Franconi, N. G.; Rothfuss, M. A.; Bocan, K. N.;
Bian, L.; White, D. L.; Burkert, S. C.; Euler, R. W.; Sopher, B. J.;
Vinay, M. L.; Sejdic, E.; Star, A. Tetrahydrocannabinol detection
using semiconductor-enriched single-walled carbon nanotube chem-
iresistors. ACS Sens. 2019, 4, 2084−2093.
(16) (a) Himes, S. K.; Scheidweiler, K. B.; Beck, O.; Gorelick, D. A.;
Desrosiers, N. A.; Huestis, M. A. Cannabinoids in exhaled breath
following controlled administration of smoked cannabis. Clin. Chem.
2013, 59, 1780−1789. (b) Manolis, A.; McBurney, L. J.; Bobbie, B. A.
The detection of Δ9-tetrahydrocannabinol in the breath of human
subjects. Clin. Biochem. 1983, 16, 229−233.
(17) Dronova, M.; Smolianitski, E.; Lev, O. Electrooxidation of new
synthetic cannabinoids: Voltammetric determination of drugs in
seized street samples and artificial saliva. Anal. Chem. 2016, 88, 4487−
4493.
(18) Nissim, R.; Compton, R. G. Absorptive stripping voltammetry
for cannabis detection. Chem. Cent. J. 2015, 9, 1−7.
(19) Wanklyn, C.; Burton, D.; Enston, E.; Bartlett, C.-A.; Taylor, S.;
Raniczkowska, A.; Black, M.; Murphy, L. Disposable screen printed
sensor for the electrochemical detection of delta-9-tetrahydrocanna-
binol in undiluted saliva. Chem. Cent. J. 2016, 10, 1−11.
(20) Renaud-Young, M.; Mayall, R. M.; Salehi, V.; Goledzinowski,
M.; Comeau, F. J. E.; MacCallum, J. L.; Birss, V. I. Development of an
ultra-sensitive electrochemical sensor for Δ9-tetrahydrocannabinol
(THC) and its metabolites using carbon paper electrodes. Electrochim.
Acta 2019, 307, 351−359.
́
́
̃
iga, M. C.; Olea-
(30) Morales, P.; Vara, D.; Gomez-Can
̃
as, M.; Zun
́
Azar, C.; Goya, P.; Fernandez-Ruiz, J.; Díaz-Laviada, I.; Jagerovic, N.
Synthetic cannabinoid quinones: Preparation, in vitro antiproliferative
effects and in vivo prostate antitumor activity. Eur. J. Med. Chem.
2013, 70, 111−119.
(31) For reviews regarding electrochemical oxidation in synthetic
chemistry, see: (a) Kingston, C.; Palkowitz, M. D.; Takahira, Y.;
Vantourout, J. C.; Peters, B. K.; Kawamata, Y.; Baran, P. S. A survival
guide for the “electro-curious”. Acc. Chem. Res. 2020, 53, 72−83.
̈
̈
(b) Karkas, M. D. Electrochemical strategies for C−H functionaliza-
tion and C−N bond formation. Chem. Soc. Rev. 2018, 47, 5786−5865.
(c) Yan, M.; Kawamata, Y.; Baran, P. S. Synthetic organic
electrochemical methods since 2000: on the verge of a renaissance.
Chem. Rev. 2017, 117, 13230−13319. (d) Moeller, K. D. Synthetic
applications of anodic electrochemistry. Tetrahedron 2000, 56, 9527−
9554.
́
(32) Quideau, S.; Pouysegu, L.; Deffieux, D.; Ozanne, A.;
Gagnepain, J.; Fabre, I.; Oxoby, M. Iodane-mediated and electro-
chemical oxidative transformation of 2-methoxy- and 2-methylphe-
nols. Arkivoc 2003, 6, 106−119.
(33) Enache, T. A.; Oliveira-Brett, A. M. Phenol and para-
substituted phenols electrochemical oxidation pathways. J. Electroanal.
Chem. 2011, 655, 9−16.
(34) For product description of the Electrasyn 2.0, see: https://
www.ika.com/en/Products-Lab-Eq/Electrochemistry-Kit-csp-516/,
accessed 2020/04/04.
(35) Applying the literature electrochemical oxidation procedure
(see ref 32) to 1 using C−/Pt+ electrodes, 1.5 V, and LiClO4 gave 2
in ∼20% yield as part of a complex mixture of products.
(36) Darzi, E. R.; Garg, N. K. Toward an optical and electrochemical
method for marijuana detection: A simple electrochemical oxidation
of Δ9-THC. ChemRxiv March 12, 2019.
(21) Mechoulam, R.; Ben-Zvi, Z.; Gaoni, Y. Hashish III On the
nature of the beam test. Tetrahedron 1968, 24, 5615−5624.
(22) Beam, W. Fourth Report Wellcome Tropical Research Lab.
Chem. Sect., Khartoum 1911, B25.
(23) Tamura, Y.; Yakura, T.; Tohma, H.; Ki-kuchi, K.; Kita, Y.
Hypervalent iodine oxidation of p-alkoxy- and related phenols: A
facile and efficient synthesis of p-quinones. Synthesis 1989, 126−127.
(24) Kogan, N. M.; Rabinowitz, R.; Levi, P.; Gibson, D.; Sandor, P.;
Schlesinger, M.; Mechoulam, R. Synthesis and antitumor activity of
quinoid derivatives of cannabinoids. J. Med. Chem. 2004, 47, 3800−
3806.
E
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