Dediazoniative functionalization of chromen-4-one and chromen-2-one diazonium-BF4 salts in BMIM-ILs. direct access to the [sbnd]F, [sbnd]I, [sbnd]OSO(CF3)[dbnd]NTf, and [sbnd]N(Tf)2 derivatives, and facile synthesis of chromenone azo-dyes by coupling to a

Article abstract of DOI:10.1016/j.tetlet.2020.152179

Chromenone-diazonium-BF₄ salts were isolated as stable powders by diazotization of the 7-amino-derivatives with NaNO₂/HBF₄. The 7-Fluoro-derivatives were synthesized by fluorodediazoniation in [BMIM][PF₆], while

Full text of DOI:10.1016/j.tetlet.2020.152179

Journal Pre-proofs
Dediazoniative Functionalization of Chromen-4-one and Chromen-2-one Di‐
azonium-BF4 Salts in BMIM-ILs. Direct Access to the -F, -I, -
OSO(CF3)=NTf, and -N(Tf)2 Derivatives, and Facile Synthesis of Chrome‐
none Azo-Dyes by Coupling to Activated Arenes
Luisa F. Gutierrez, Yuki Agemura, Kenneth K. Laali
PII:
S0040-4039(20)30639-0
DOI:
Reference:
https://doi.org/10.1016/j.tetlet.2020.152179
TETL 152179
To appear in:
Tetrahedron Letters
Received Date:
Accepted Date:
10 June 2020
25 June 2020
Please cite this article as: Gutierrez, L.F., Agemura, Y., Laali, K.K., Dediazoniative Functionalization of
Chromen-4-one and Chromen-2-one Diazonium-BF4 Salts in BMIM-ILs. Direct Access to the -F, -I, -
OSO(CF3)=NTf, and -N(Tf)2 Derivatives, and Facile Synthesis of Chromenone Azo-Dyes by Coupling to
Activated Arenes, Tetrahedron Letters (2020), doi: https://doi.org/10.1016/j.tetlet.2020.152179
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover
page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version
will undergo additional copyediting, typesetting and review before it is published in its final form, but we are
providing this version to give early visibility of the article. Please note that, during the production process, errors
may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
© 2020 Published by Elsevier Ltd.

1
Dediazoniative Functionalization of Chromen-4-one and Chromen-2-one
Diazonium-BF4 Salts in BMIM-ILs. Direct Access to the -F, -I, -
OSO(CF3)=NTf, and -N(Tf)2 Derivatives, and Facile Synthesis of
Chromenone Azo-Dyes by Coupling to Activated Arenes
Luisa F. Gutierrez, Yuki Agemura, Kenneth K. Laali*
Department of Chemistry, University of North Florida, 1, UNF Drive, Jacksonville, Florida
32224, USA; Corresponding author e-mail: Kenneth.Laali@UNF.edu (K.K. Laali). Tel.: +1
904 620 1503; fax: +1 904 620 3535.
Graphical Abstract
O
[BMIM][PF6]
F
O
R
Monowave
O
O
100 °C, 1 1/2 h
O
O
I
O
O
NIS (1.1 eq.)
TMSI
I
R
[BMIM][PF6]
100 °C, 2h
I
R
N
R
[BMIM][PF6]
Monowave
75 °C, 1 h
N
O
O
BF4
N(SO2CF3)2
O
R
+
R
[BMIM][NTf2]
O
S
F3C
N
O
O
O
O
Me2N
Me2N
F3C
S
O
O
N
R
N
CH3
O
[BMIM][PF6]
Monowave
F
O
100 °C, 1 1/2 h
CH3
O
CH3
TMSI
[BMIM][PF6]
Monowave
75 °C, 1 h
N
N
BF4
O
I
O
O
O
CH3
N(SO2CF3)2
O
O
[BMIM][NTf2]
+
O
O
CH3
F3C
N
S
O
F3C
S
O
O
Abstract
Chromenone-diazonium-BF4 salts were isolated as stable powders by diazotization of
the 7-amino-derivatives with NaNO2/HBF4. The 7-Fluoro-derivatives were synthesized by
fluorodediazoniation in [BMIM][PF6], while the 7-iodo-derivatives were obtained by
iododediazoniation with TMSI/[BMIM][PF6]. Further iodination with NIS furnished the 2,7-
di-iodo derivative. Dediazoniation in [BMIM][Tf2N] gave the corresponding chromenone-
OSO(CF3)=NTf compounds as major products, along with chromenone-N(Tf)2 and the 7-
fluoro-derivatives. Chromenone-diazonium salts undergo facile diazo-coupling with isomeric

2
trimethoxybenzenes and dimethylaniline at r.t in aqueous EtOH or in [BMIM][PF6] to give
azo-dyes.
Keywords
Chromenone diazonium salts; fluorodediazoniation; iododediazoniation; chromenone-
OSO(CF3)=NTf and chromenone-NTf2; diazo-coupling
Highlights
Synthesis of stable chromenone diazonium salts
IL-mediated halo-functionalization of chromenones
Direct access to iodo- and fluoro-chromenones
Synthesis of chromenone azo-dyes
Chromen-4-one and its 2-phenyl-derivative (flavone), and chromen-2-one (coumarin)
constitute highly significant structural motifs that are present in a broad range of natural
products with diverse biological activities.1,2 As privileged building blocks with antitumor,
antioxidant, anti-inflammatory, and antimicrobial activity, they are widely employed in
medicinal chemistry and drug development.3-6 In addition, the coumarin moiety has been
adopted in the design of small-molecule fluorescent chemosensors.7
Developing iodo-functionalization approaches for chromenones is important since
these compounds can then be further functionalized by metal-mediated coupling
methodologies. Interest in fluoro-functionalization stems from possible application of the
fluorinated derivatives in drug development. The 3-iodo-chromones have been synthesized by
cyclization of 2-methoxyarylalkynones and suitably functionalized chalcones,8,9 and by a
number of other methods that involve multistep operations and those that suffer from poor
regioselectivity.9 Synthesis of difluorinated chromenones were reported by
cyclization/fluorination of ortho-hydroxyaryl-enaminone using Selectfluor,10 and synthesis of
some hydroxyl-fluoro-amino-chromenones was realized by a multicomponent reaction that
employed NFSI.11
In connection to our previous studies on dediazoniative functionalization of arenes in
BMIM-ILs,12-16 we report here facile methods for halo-functionalization of substituted

3
chromenones via dediazoniative functionalization of their diazonium-BF4 salts in BMIM-ILs,
and for the synthesis of their azo-dyes by coupling to activated arenes.
Chromenone diazonium salts 1a-3a were synthesized by diazotization of their
commercially available 7-amino-precursors with NaNO2/HBF4 and isolated as stable salts in
85% to 74% yields after purification (Figure 1).
O
O
O
O
50% HBF4
NaNO2, H2O, 0°C
H2N
R
N
R
N
BF4
1a
2a
R = Me;
R = Ph;
1
2
R = Me;
R = Ph;
CH3
CH3
50% HBF4
NaNO2, H2O, 0°C
H2N
O
3
O
N
O
O
N
BF4
3a
Figure 1. Stable chromenone-diazonium-BF4 salts
The 7-fluoro-chromenones 1b-3b were synthesized by fluorodediazoniation in
[BMIM][PF6] (Figure 2) in yields ranging from 50% to 40% by heating in a Monowave
reactor17 or in a conventional oil bath.
O
O
[BMIM][PF6]
F
O
R
N
O
R
Monowave
100 °C, 1 1/2 h
N
1b
2b
BF4
R = Me;
R = Ph;
1a
2a
R = Me;
R = Ph;
CH3
CH3
[BMIM][PF6]
Monowave
100 °C, 1 1/2 h
F
O
O
N
O
O
N
BF4
3b
3a
Figure 2. Facile access to the 7-Fluoro-derivatives

4
Focusing on iodo-functionalization, the 7-iodo-chromenones 1c-3c (Figure 3) were
obtained by reaction with TMSI in [BMIM][PF6], in isolated yields ranging from 75% to 57%
after purification. Subsequently, the 3,7-diiodo-derivative 1d was successfully obtained by
further iodination of 1c with NIS in [BMIM][PF6].18 Attempted direct di-iodination with NIS
in BMIM-IL starting with the diazonium salts 1a-2a gave mixtures from which the di-iodo
compounds 1d-2d could not be isolated cleanly.
O
O
O
O
TMSI
[BMIM][PF6]
Monowave
75 °C, 1 h
N
R
I
R
N
BF4
1c
R = Me;
R = Ph;
1a
2a
R = Me;
R = Ph;
2c
CH3
CH3
O
TMSI
[BMIM][PF6]
Monowave
75 °C, 1 h
N
O
O
I
O
I
N
3c
BF4
3a
O
O
NIS (1.1 eq.)
[BMIM][PF6]
100 °C, 2h
I
O
CH3
I
O
CH3
1d
1c
O
O
I
NIS (2.1 eq.)
[BMIM][PF6]
Monowave
100 °C, 1h
I
O
R
N
O
R
N
BF4
1d
2d
R = Me;
R = Ph;
1a
2a
R = Me;
R = Ph;
(obtained as mixture with other by-product)
Figure 3. Synthesis of the iodo-chromenones
We have previously shown that substituted benzenediazonium-BF4 salts undergo
metathesis in [BMIM][NTf2] and upon thermal or photolytic dediazoniation produce the N-
(trifluoromethylsulfonyl)aryloxytrifluoromethylsulfoximines as major products, along with
Ar-N(Tf)2 and Ar-F.14,15 This method provides direct access to trifluoromethylated derivatives
whose syntheses are otherwise quite challenging. Since the efficacy of this protocol for
fluorofunctionalization of heterocyclic diazonium salts was an open question, we explored
this method in the present study to introduce these fluoro-substituents into chromenones. Thus
thermal dediazoniation of 1a-3a in [BMIM][NTf2] produced the novel chromenone-

5
sulfoximines 1e-3e, in a mixture with the 7-fluoro-derivatives 1b-3b, along with minor
amounts of the N-triflamides 1f-3f (Figure 4). Product ratios, as determined by 19F NMR,
demonstrate that despite the “non-nucleophilic” nature of [NTf2] it can compete effectively
with fluoride anion to capture the heteroaryl cations derived from chromenone-diazonium
salts, but its relative effectiveness decreases in going from 1a to 3a, and this in turn could
provide an additional route for harvesting more of the corresponding 7-F derivatives (1b-3b).
O
O
O
O
N(SO2CF3)2
H3C
O
O
[BMIM][NTf2]
[BMIM][NTf2]
+
+
CH3
F
O
O
S
CH3
N
O
CH3
F3C
N
N
1b (15%)
1f (5%)
BF4
O
1a
1e (80%)
O
F3C
S
O
O
O
O
N(SO2CF3)2
Ph
O
O
O
O
+
+
F
Ph
O
S
O
Ph
F3C
N
N
Ph
N
2b (40%)
2f (4%)
O
BF4
2e (54%)
F3C
O
2a
S
O
CH3
CH3
CH3
N(SO2CF3)2
O
O
[BMIM][NTf2]
+
O
S
O
O
+
F
O
O
N
O
O
F3C
N
N
CH3
BF4
O
3b (58%)
3a
3e (39%)
3f (3%)
F3C
S
O
O
Figure 4. Dediazoniation products in [BMIM][NTf2]
Coumarin-containing azo-dyes have attracted attention for their favorable
photophysical properties. These compounds are typically synthesized by using coumarin or a
+
coumarin-bearing moiety as nucleophile which is coupled to an activated PhN2 salt.19
Examples in which the coumarin moiety is the electrophilic partner reacting with activated
nucleophiles to form azo-dye appear to be quite rare.20
In the present study, chromenone-diazonium salts 1a and 2a reacted with isomeric
trimethoxybenzenes (TMB) and dimethylaniline (DMA) in EtOH solvent at r.t. to give the
corresponding azo-dyes (Figure 5). Isolated yields for coupling to TMB were in 79% to 60%
range. Lower yields were obtained in coupling with DMA due to isolation difficulties and
solubility issues. Azo-coupling of 1a and 2a with 1,3,5-TMB was also performed in BMIM-
IL as solvent, but extraction/isolation issues were more challenging. The color of

6
chromenone-bearing azo-dyes range from dark red to orange, depending on the coupling
component. Considering the ongoing interest in the optical properties of coumarin-dyes,18-19
the presently described simple method could help increase the diversity of chromenone-based
azo-dyes for photophysical studies.
O
OMe
1g
2g
R = Me;
R = Ph;
1,3,5-TMB
N
O
R
N
95% EtOH
r.t.
MeO
OMe
OR
O
O
[BMIM][PF6]
O
O
1h
2h
R = Me;
R = Ph;
N
R
1,2,4-TMB
MeO
MeO
N
N
R
N
BF4
1a
2a
R = Me;
R = Ph;
95% EtOH
r.t.
OMe
O
O
DMA
N
1i
2i
R = Me;
R = Ph;
R
N
95% EtOH
r.t.
Me2N
In summary, the efficacy of IL-mediated halo-dediazoniation protocols for direct
access to iodinated and fluorinated chromenones is demonstrated. Coupling of chromenone-
diazonium salts to activated arenes provides a straightforward method to access new
chromenone-bearing azo-dyes.

7
References
1.
2.
3.
Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem. Rev. 2003, 103, 893−930
Pratap, R; Ram, V. J. Chem. Rev. 2014, 114, 10476−10526.
Dahlen, K.; Wallen, E. A. A.; Grøtli, M.; Luthman, K. J. Org. Chem. 2006, 71,
6863-6871.
4.
5.
6.
7.
8.
9.
Wallen, E. A. A.; Dahlen, K.; Grøtli, M.; Luthman, K. Org. Lett. 2007, 9, 389-
391.
Dyrager, C.; Mollers , L. N.; Kjall, L. K.; Alao, J. P.; Diner, P.; Wallner, F. K.;
Per Sunnerhagen, P.; Grøtli, M. J. Med. Chem. 2011, 54, 7427–7431.
Zhao, W.; Wang, B.; Liu, Y.; Fu, L.; Sheng, L.; Zhao, H.; Lu, Y.; Zhang, D.
Eur. J. Med. Chem. 2020, 189, 112075.
Cao, D.; Liu, Z.; Verwilst, P.; Koo, S.; Jangjili, P.; Kim, J. S.; Lin, W. Chem.
Rev. 2019, 119, 10403−10519.
Zhou, C.; Dubrovsky, A. V., Larock, R. C. J. Org. Chem. 2006, 71, 1626-
1632.
Patil, A. M.; Kamble, D. A.; Lokhande, P. D. Synth.Commun. 2018, 48, 1299-
1307 and references cited therein.
10.
Zhao, Q.; Xiang, H.; Xiao, J.-A.; Xia P.-J.; Wang, J.-J.; Chen, X.; Yang, H. J.
Org. Chem. 2017, 82, 9837-9843.
11.
Reddy, N. S.; Swaroop, D. K.; Kumar, N. R.; Sreenivas, A.; BandaNarsaiah
ChemistrySelect 2019, 4, 13768– 13771.
12.
13.
14.
15.
Laali, K. K.; Gettwert, V. J. J. Fluorine.Chem. 2001, 107, 31-34.
Hubbard, A,; Okazaki, T.; Laali, K. K. J. Org. Chem. 2008, 73, 316-319.
Laali, K. K.; Okazaki, T.; Bunge, S. D. J. Org. Chem. 2007, 72, 6758-6762.
Okazaki, T.; Laali, K. K.; Bunge, S. D.; Adas, S. K. Eur. J. Org. Chem. 2014,
1630–1644.
16.
Laali, K. K. ARKIVOC 2016 (i) 150-171
17. Obermayer, D.; Znidar, D.; Glotz, G; Stadler, A.; Dallinger, A.; Kappe; C. O.
J. Org. Chem. 2016, 81, 11788-11801.
18.
Yadav, J. S.; Reddy, B. V. S.; Reddy, P. S. R.; Basak, A. K.; Narsaiah, A. V.
Adv. Synth. Catal. 2004, 346, 77-82.
19.
Ayare, N. N.; Ramugade, S. H.; Sekar, N. Dyes and Pigments 2019, 163, 692-
699; Tathe, A. B.; Sekar, N. J. Fluoresc 2016, 26, 1279-1293; Ayare, N. N.;

8
Sharma, S.; Sonigara, K. K.; Prasad, J.; Soni, S. S.; Sekar, N. J. Photochem
Photobiol-A 2020, 394, 112466.
20.
Djeukoua, K. S. D.; Fondjo, E. S.; Tamokou, J.; Tsemeugne, J.; Simon, P. F.
W.; Tsopmo, A.; Tchieno, F. M. M.; Ekom, S. E.; Pecheu, C. N.; Tonle, I. K.;
Kuiate, J.-R. Arkivoc, 2019 (vi), 416-430.
Supporting Information
Experimental procedures and analytical data for this article are gathered in the supplemental
information file along with NMR spectra.
Declaration of interest: None
Acknowledgements
K.L. thanks University of North Florida for the Outstanding Faculty Scholarship and
Presidential Professorship awards, Faculty scholarship and UNF Foundation Board grants,
and the Dean’s Leadership Council award.
Declaration of Interest Statement
☒ The authors declare that they have no known competing financial interests or personal
relationships that could have appeared to influence the work reported in this paper.
☐The authors declare the following financial interests/personal relationships which may be
considered as potential competing interests:
Highlights
Synthesis of stable chromenone diazonium salts.
IL-mediated halo-functionalization of chromenones.
Direct access to iodo- and fluoro-chromenones.
Synthesis of chromenone azo dyes.

9
Graphical Abstract
O
O
[BMIM][PF6]
F
R
Monowave
O
O
100 °C, 1 1/2 h
O
O
I
O
NIS (1.1 eq.)
TMSI
I
R
[BMIM][PF6]
100 °C, 2h
I
R
N
O
R
[BMIM][PF6]
Monowave
75 °C, 1 h
N
O
O
BF4
N(SO2CF3)2
O
R
+
R
[BMIM][NTf2]
O
S
F3C
N
O
O
O
O
Me2N
Me2N
F3C
S
O
O
N
R
N
CH3
O
[BMIM][PF6]
Monowave
F
O
100 °C, 1 1/2 h
CH3
O
CH3
TMSI
[BMIM][PF6]
Monowave
75 °C, 1 h
N
N
BF4
O
I
O
O
O
CH3
N(SO2CF3)2
O
O
[BMIM][NTf2]
+
O
O
CH3
F3C
N
S
O
F3C
S
O
O