ARTICLE IN PRESS
JID: CCLET
[m5G;June 4, 2021;10:52]
J. Li, M. Zhang, L. Yang et al.
Chinese Chemical Letters xxx (xxxx) xxx
Scheme 1. Synthesis of various new carbo-rhodamines (10, 16a, 16b, Sulfo-16a, Sulfo-16b).
steric protection toward nucleophilic attack. Having the two alkyl
groups replaced by two bulkier phenyl groups does not address
this difficulty either because the two phenyl rings are rotatable and
they tend to adopt a geometry, in which the two peripheral hydro-
gen atoms are also twisted away from the central methine carbon
and not provide much steric protection over the central methine
carbon. We envisage that the steric protection of the two phenyl
group could be greatly enhanced if they are tethered together. This
way, the two hydrogen atoms of the phenyl rings, highlighted in
orange colour, are forced to point down toward the central me-
thine carbon (Fig. 2). Following this line of research, our first at-
tempt is a rhodamine with a benzophenone bridge. They exhibit
the desired high chemical stability, and however is still difficult for
further functionalization due to its electron deficient nature.
In this work, it is our goal to design and synthesize new carbo-
rhodamine analogs, which not only exhibit high resistance toward
aggregation or nucleophilic attack, but also allow convenient fur-
ther modification. Herein, we report the design, synthesis, spec-
tral studies and proof-of-concept applications of fluoreno-xanthene
(10) and xantheno-xanthene (16a and 16b), i.e. xanthene dyes with
a “fluorene” or a “xanthene” bridging group, which fulfils the re-
quirements discussed previously (Scheme 1).
2-(4-diethylaminobenzyl)phenyl)diphenylmethanol, which was re-
fluxed with MeSO3H in CH2Cl2 for 2 h and then oxidized to
3,6-bis(diethylamino)-10,10-diphenylanthracen-9(10H)-one (6) by
KMnO4 in an overall 48% yield. Compound 6 reacted with Grig-
nard reagent (7, 2 equiv.) at 45 °C for 5 h to produce 8
in 65% yield. Dye 10 was synthesized similarly with fluo-
a
renone (9) instead of benzophenone (5) in an overall 37% yield.
Surprisingly, the preparation of 16a and 16b from xanthenone
was not successful. So, we proposed an alternative synthesis
ꢀ
starting from 4,4 -methylenebis(3-bromo-N,N-diethylaniline) (11),
whose synthesis was reported during the first synthesis of sil-
icon rhodamine by Xiao and Qian et al. [28,29]. Compound 11
was treated with nBuLi (2.4 equiv.) at −78 °C for 15 min to
prepare the corresponding lithium reagent in situ via halogen-
lithium exchange before methyl 2-phenoxybenzoate 13 (1.0 equiv.)
was added to furnish 2,7-bis(diethylamino)-9-(2-phenoxyphenyl)-
9,10-dihydroanthr-acen-9-ol, which was oxidized by KMnO4 be-
fore refluxing with MeSO3H in CH2Cl2 for 2 h to produce the
ꢀ
desired 2,7-bis(diethylamino)-10H-spiro[anthracene-9,9 -xanthen]-
10-one (14) in a 63% yield. Compound 14 was further treated with
Grignard reagent (15a and 15b, 2 equiv.) at 45 °C for 5 h to pro-
duce 16a and 16b in good yields. The single-crystal structure of
16b was obtained (Fig. S1 in Supporting information). The upper
diphenyl ether plane is perpendicular to the fluorochromic xan-
thene structure.
We devised a new synthesis for carbo-rhodamine dyes, and
the feasibility was first exemplified by synthezing a bis-phenyl
substituted carbo-rhodamine (8). 3-Bromo-N,N-diethylaniline (1)
was prepared via alkylation of 3-bromoaniline with EtI in
We tested the feasibility of 16a and 16b for functionalization,
i.e., sulfonation, which is a valued substitution for dyes because
it improves water solubility, photo/chemo stability, and resistance
toward aggregation simultaneously. Compound 10 was dissolved
in concentrated H2SO4 in an ice bath and stirred for 24 h, and
no desired sulfonated derivatives were observed. Presumably, the
biphenyl moiety is not sufficiently electron-rich. We then tested
a
nearly quantitative yield. Acid-catalysed condensation of
1
with (4-(diethylamino)phenyl)methanol (2) at 80 °C for
3
in
a 96% yield. Compound 3 was treated with nBuLi (1.2 equiv.)
at −78 °C for 15 min to prepare the corresponding lithium
reagent in situ via halogen-lithium exchange before benzophe-
none 5 (1.0 equiv. in THF) was added to furnish (5-diethylamino-
2