Unusual traits of cis and trans-2,3-dibromo-1,1-dimethylindane on the way from 1,1-dimethylindene to 2-bromo-, 3-bromo-, and 2,3-dibromo-1,1-dimethylindene

Article abstract of DOI:10.3762/bjoc.12.113

Do not rely on the widely accepted rule that vicinal, sp³-positioned protons in cyclopentene moieties should always have more positive ³J NMR coupling constants for the cis than for the trans arrangement: Unrecognized exceptions might misguide one to wrong stereochemical assignments and thence to erroneous mechanistic conclusions. We show here that two structurally innocent-looking 2,3-dibromo-1,1-dimethylindanes violate the rule by means of their values of ³J(cis) = 6.1 Hz and ³J(trans) = 8.4 Hz. The stereoselective formation of the trans diastereomer from 1,1-dimethylindene was improved with the tribromide anion (Br^3-) as the brominating agent in place of elemental bromine; the ensuing, regiospecific HBr elimination afforded 3-bromo-1,1-dimethylindene. The addition of elemental bromine to the latter compound, followed by thermal HBr elimination, furnished 2,3-dibromo-1,1-dimethylindene, whose Br/Li interchange reaction, precipitation, and subsequent protolysis yielded only 2-bromo-1,1-dimethylindene.

Full text of DOI:10.3762/bjoc.12.113

Unusual traits of cis and trans-2,3-dibromo-1,1-dimethyl-
indane on the way from 1,1-dimethylindene to 2-bromo-,
3-bromo-, and 2,3-dibromo-1,1-dimethylindene
Rudolf Knorr*, David S. Stephenson, Ernst Lattke, Petra Böhrer and Jakob Ruhdorfer
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2016, 12, 1178–1184.
Department Chemie, Ludwig-Maximilians-Universität München,
Butenandtstrasse 5–13 (Haus F), 81377 München, Germany
doi:10.3762/bjoc.12.113
Received: 08 February 2016
Accepted: 20 May 2016
Published: 10 June 2016
Email:
Rudolf Knorr* - rhk@cup.uni-muenchen.de
* Corresponding author
Associate Editor: J. N. Johnston
Keywords:
© 2016 Knorr et al; licensee Beilstein-Institut.
License and terms: see end of document.
base-free dehydrobromination; cis/trans stereochemistry;
five-membered ring conformation; indenes; NMR couplings
Abstract
Do not rely on the widely accepted rule that vicinal, sp3-positioned protons in cyclopentene moieties should always have more posi-
tive 3J NMR coupling constants for the cis than for the trans arrangement: Unrecognized exceptions might misguide one to wrong
stereochemical assignments and thence to erroneous mechanistic conclusions. We show here that two structurally innocent-looking
2,3-dibromo-1,1-dimethylindanes violate the rule by means of their values of 3J(cis) = 6.1 Hz and 3J(trans) = 8.4 Hz. The stereo-
selective formation of the trans diastereomer from 1,1-dimethylindene was improved with the tribromide anion (Br3−) as the bromi-
nating agent in place of elemental bromine; the ensuing, regiospecific HBr elimination afforded 3-bromo-1,1-dimethylindene. The
addition of elemental bromine to the latter compound, followed by thermal HBr elimination, furnished 2,3-dibromo-1,1-dimethyl-
indene, whose Br/Li interchange reaction, precipitation, and subsequent protolysis yielded only 2-bromo-1,1-dimethylindene.
Introduction
The basic mechanistic features of competing suprafacial and mixture. For the cis/trans assignments, common wisdom [5]
antarafacial additions of elemental bromine to an olefin are commends the simple criterion that three-bond NMR coupling
reasonably well established [1-3]. With indene as a cyclic constants (3JH,H) should be more positive for a cis than for a
olefin, the major product trans-1,2-dibromoindane was formed trans relationship of the vicinal, sp3-positioned protons in five-
through antarafacial addition; the accompanying cis diastereo- membered rings. Indeed, cis-1,2-dibromoindane displayed
mer resulted through the suprafacial bromine addition and 3J(1-H,2-H) = 5.0 Hz, whereas the trans diastereomer exhib-
rarely [4] exceeded 30% of the diastereomeric trans/cis product ited 3J(1-H,2-H) = 1.3 Hz [6]. However, we report here on the
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closely related trans diastereomer of 2,3-dibromo-1,1-dimethyl- (2ax-H,3eq-H) cis interproton relationships. Such distances may
indane (trans-1) whose grossly deviating value of 3J(2-H,3-H) be estimated through nuclear magnetic Overhauser enhance-
= 8.4 Hz violates the above 3JH,H rule.
ments (NOE). As expected if trans-1 populates predominantly
the 2ax-H,3ax-H conformation shown in Scheme 1, our one-
dimensional NOE difference experiments revealed an approxi-
Results and Discussion
The addition of elemental bromine to 1,1-dimethylindene (2, mately eight-fold stronger enhancement of the 3-H doublet
see Supporting Information File 1) in CCl4 as the solvent signal of cis-1 than of trans-1 on irradiation of the almost coin-
afforded a 7:3 mixture of trans-1 and cis-1 (Scheme 1). A more cident two 2-H NMR doublets of the two diastereomers; this
useful 9:1 mixture was obtained through the slow titration of a established our assignments. In addition, a two-dimensional
well-stirred chloroform solution of equimolar amounts of 2 and NOESY experiment displayed a cross-peak between 3-H and
tetraethylammonium bromide with elemental bromine in one of the two 1-CH3 signals of trans-1. The necessary short
chloroform. Such a higher trans selectivity is typical of the very distance of the involved protons can be traced to a 1,3-pseudo-
rapidly [1] formed tribromide anion (Br3−) as the reactive diaxial arrangement of 3-H and one of the methyl groups in the
species.
2ax-H,3ax-H conformation. Thus, a close to 160° torsional rela-
tionship between the C(2)–H and C(3)–H bonds gives rise to the
What kind of evidence supports our stereochemical assign- surprisingly high value of 3J(2-H,3-H) = 8.4 Hz [7,8]. The
ments of trans-1 and cis-1? Although the three-bond NMR cou- hyperconjugative interaction of this pseudoaxial C(3)–H bond
pling constant 3J(2-H,3-H) = 6.1 Hz of cis-1 is close to normal, with the aromatic π system causes a long-range (hence weak)
trans-1 exhibits the abnormally high value of 8.4 Hz (compare magnetic coupling (J = 0.7 Hz) between 3-H and (presumably)
that with 1.3 Hz for trans-1,2-dibromoindane [6]), violating the 4-H in trans-1 (but not found in cis-1). The different conforma-
commonly accepted 3JH,H rule that was mentioned in the Intro- tional preference of trans-1 as compared with the methyl-free
duction. A more reliable criterion may be visualized from the trans-1,2-dibromoindene (3J = 1.3 Hz [6]) may obviously be
envelope shape (expected puckering ca. 22–33°) of the ascribed to the two 1-Me groups [9]. In accord with the
cyclopentene parts of 1 (lines 2 and 3 of Scheme 1): the dis- pseudoaxial C(3)–H bond, HMBC (hetero multiple bond corre-
tance between two vicinal, sp3-positioned protons in indanes lation) cross peaks of 3-H in trans-1 were absent with both C-1
clearly must be substantially longer for the pseudodiaxial and C-7a. On the other hand, the corresponding cross peaks
(2ax-H,3ax-H) trans than for the pseudoaxial/pseudoequatorial were strong in cis-1 between 3eq-H and both C-1 and C-7a,
Scheme 1: Bromine adducts (trans-1 and cis-1) of 1,1-dimethylindene (2) and their envelope conformations: ax = pseudoaxial, eq = pseudo-
equatorial; Me = methyl.
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which indicated a significant 3JC,H NMR coupling via the inter-
vening single bonds in their roughly coplanar arrangement
shown in Scheme 1. It may also be noticed that the small
C(2)–H/C(3)–H torsional angles in either one of the two cis-1
conformations are of similar sizes and do not permit a confor-
mational differentiation. On the other hand, the close to 90°
torsional angle between 3-H and 2-H in the 2eq-H,3eq-H con-
formation of trans-1 would imply an almost vanishing 3JH,H
value, in contrast with the observed value of 8.4 Hz that is ex-
plained by the predominant 2ax-H,3ax-H conformation.
Distillation of the trans/cis product mixture led to some enrich-
ment of the thermally more stable diastereomer trans-1 due to
the “base-free” HBr elimination from cis-1 with formation of
2-bromo-1,1-dimethylindene (4 in Scheme 2) [10]. We ob-
served a less distinct kinetic preference in the corresponding
base-induced processes: In di(2-methoxyethyl) ether (diglyme)
as the solvent, a substoichiometric amount of KOt-Bu (potas-
sium tert-butoxide) reacted faster with cis-1 than with trans-1
by a factor of roughly 9 at room temperature (rt). With an
excess (>2 equiv) of KOt-Bu, both of these weakly exothermic
HBr elimination reactions were completed within less than
30 min. With KOt-Bu (at rt) or KOEt (at 50 °C) but not with
NEt3 (no reaction at rt), the exclusive formation of 3-bromo-
1,1-dimethylindene (3) from trans-1 and of 4 from cis-1 be-
came evident through the similarity of the emerging 3/4 ratios
as compared with the trans-1/cis-1 ratios in the employed mix-
tures [11]. This regiospecificity is readily understandable since
trans-1 has no anti relationship of vicinal Br and H available
(Scheme 1), whereas each cis-1 conformer holds a pseudo-
diaxial, vicinal Br/H anti relationship and hence is (presumably)
able to react somewhat faster.
Scheme 2: The ways to 2-bromo- (4), 3-bromo- (3), and 2,3-dibromo-
1,1-dimethylindene (7); SuIm = succinimide, NBS = N-bromosuccin-
imide, Me = methyl.
We abstained from separating trans-1 and cis-1 since the avail-
ability of two different mixtures facilitated the NMR assign-
ments and because any cis-1/trans-1 mixture or the ensuing 3/4 Information File 1), which decomposed already on distillation
mixtures may be used for preparing 2,3-dibromo-1,1-dimethyl- to yield 1,1-dimethylindene (2). With two equivalents of NBS,
indene (7). Both 3 and 4 can add elemental bromine and the however, 9 afforded a mixture of 3 and 7 through the following
adducts (5 or 6, respectively) eliminated HBr either spontane- sequence in the bottom part of Scheme 2: 9 → 8 → 3 → 5 → 7.
ously (5) or in the presence of KOt-Bu or NEt3 (6) at rt to Under these conditions, the spontaneous HBr elimination from
furnish the same product 7. We found through NOESY and 8 had produced 3, which added Br2 to generate the thermola-
HMBC analyses that the thermally more stable tribromide 6 bile tribromide 5, whose HBr elimination gave 7; the required
populates the conformation which has a pseudoaxial 3-H (and Br2 was visible in the weakly brownish gas phase and had been
hence a pseudoequatorial 3-Br) orientation (like trans-1). provided through the well-known reaction of HBr with the
Therefore, the unusually high thermolability of 5 seemed to be accompanying NBS. Consequently, three equivalents of NBS
due to the unavoidable presence of one pseudoaxial C(3)–Br would be necessary for obtaining 7 in a maximum yield. This
bond [12]. If so, the hitherto unknown 3,3-dibromo-1,1-di- encouraged us to reflux 9 in CCl4 with NBS (4 equiv), which
methylindane (8) might also be prone to such thermal HBr elim- furnished mainly 7 along with succinimide (3.6 equiv) and
ination. For comparison, treatment of 1,1-dimethylindane (9) remnant NBS (0.4 equiv). As a side-reaction, the slower ther-
with one equivalent of N-bromosuccinimide (NBS) furnished mal HBr elimination from the intermediate 3-bromo-1,1-di-
the expected 3-bromo-1,1-dimethylindane (see Supporting methylindane (see Supporting Information File 1) generated
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1,1-dimethylindene (2), whose in situ bromination furnished 1 Conclusion
(ca. 1%) in a trans/cis ratio of ca. 3:2. Since both dibromides Cis/trans differentiation in the saturated part of cyclopentene
trans-1 and cis-1 were stable under the reaction conditions and moieties should be based on 1H nuclear magnetic Overhauser
would distil together with 7, they were destroyed through HBr enhancements rather than on the magnitudes of vicinal cis and
elimination by KOt-Bu (or KOH in EtOH) to produce the trans 3JH,H NMR coupling constants which are not always reli-
monobromides 3 and 4. It may be noticed that 4 (from cis-1) able. The deceivingly high value of 8.4 Hz in trans-2,3-
cannot have been an intermediate in the initial step of the above dibromo-1,1-dimethylindane (trans-1) is explained in this work
“base-free” conversion of 9 to 7, since 4 would generate the by a preferentially populated envelope conformation with
thermally stable tribromide 6 that was not detected in the initial pseudoequatorial 2-Br and hence pseudodiaxial 2-H and 3-H.
product mixture of 1 and 7.
The alternative (incorrect) stereoassignment (“cis-19” in refer-
ence [8] and “cis-33” in reference [7] for the presently analyzed
For practical purposes, 7 may be useful as an alternative starting trans-1) would have misguided us to claim erroneously that we
material in place of 2,3-diiodo-1,1-dimethylindene that had discovered a most unusual, highly cis selective olefin bromina-
been employed [13,14] in cross-coupling studies. We actually tion.
used crude 7 as follows for a first specific route to 2-bromo-1,1-
dimethylindene (4). The rapid Br/Li interchange reaction of 7 in What else may appear unusual with 1 and its congeners?
hexane as the solvent with n-butyllithium (n-BuLi) ocurred pre- Trans-1 and cis-1 undergo regiospecific HBr eliminations even
dominantly at the 3-position of 7 with formation of 2-bromo-3- in the absence of bases, cis-1 does so more rapidly than trans-1.
lithio-1,1-dimethylindene (10, Scheme 3). In the absence of The products 3 and 4, respectively, can serve as precursors for
cycloalkanes or benzene from the hydrocarbon solvent, rather the same product 2,3-dibromo-1,1-dimethylindene (7).
concentrated mixtures of 7 and n-BuLi slowly deposited unsol- Exploiting the unusually high inclination of 3,3-di- (8) and
vated 10, which opened the possibility of purifying 10 through 2,3,3-tribromo-1,1-dimethylindane (5) toward “base-free” HBr
simple washings with dry pentane under inert gas cover. Like elimination at close to rt [12], we were able to convert 1,1-di-
the related 3-chloro-2-lithio-1,1-dimethylindene [15], 10 did not methylindane (9) with NBS directly to 7. The preparation of
eliminate LiHal at rt, so that its final hydrolytic work-up provi- clean 2-bromo-1,1-dimethylindene (4) became possible through
ded clean 4 even from moderately contaminated 7. Due to a purification and hydrolysis of crystalline 2-bromo-3-lithio-1,1-
well-known mixing problem [16,17], this final protolysis will dimethylindene (10).
be successful only in the absence (or at least after an adequate
washing-out) of residual n-BuLi: Since protonation of n-BuLi Experimental
and 10 is comparably rapid, a local depletion of the added General remark. 1H and 13C NMR chemical shifts δ (ppm)
proton source will leave the generated portion of 4 together with were referenced to internal tetramethylsilane.
remnant n-BuLi, so that a very rapid Br/Li interchange reaction
of 4 with n-BuLi will produce 1,1-dimethyl-2-lithioindene, 2,3-Dibromo-1,1-dimethylindane (1). a) Trans-1: Tetraethyl-
whose protolysis forms 1,1-dimethylindene (2).
ammonium bromide (18.32 g, 87.2 mmol) was dissolved with
magnetic stirring in a minimum volume of chloroform
(120 mL), treated with 1,1-dimethylindene (2, 12.55 g,
87.1 mmol, see Supporting Information File 1), and then cooled
in an ice-bath. Elemental bromine (4.44 mL, 13.9 g, 87.1 mmol)
in chloroform (40 mL) was added dropwise at such a rate that
each drop was quickly decolorized (65 min). After warm-up to
rt within the next hour, the mixture was immediately shaken
with aqueous Na2CO3 (2 M) until alkaline, washed with
distilled water until neutral, dried over Na2SO4, and concen-
trated. The crude material (23.1 g, 87%) was a colorless, liquid
mixture of trans-1 and cis-1 (9:1) with bp 145–149 °C/11 Torr
(no data given in reference [7]).
1H NMR (CDCl3, 400 MHz) δ 1.22 (s, 3H, pseudoaxial 1-CH3),
1.42 (s, 3H, pseudoequatorial 1-CH3), 4.35 (d, 3J = 8.4 Hz, 1H,
2-H), 5.40 (dd, 3J = 8.4 Hz, 4J = 0.7 Hz, 1H, 3-H), 7.17 (m, 1H,
7-H), 7.28 (m, 1H, 5-H), 7.31 (m, 1H, 6-H), 7.41 (m, 1H, 4-H)
Scheme 3: Unsolvated 2-bromo-3-lithio-1,1-dimethylindene (10) pre-
cipitated from the reaction mixture of 7 with n-BuLi in hexane; after
purification, 10 provided 4 only; Me = methyl.
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Beilstein J. Org. Chem. 2016, 12, 1178–1184.
ppm, assigned through HSQC, HMBC (see below), and the extracted with Et2O (4 × 100 mL). The combined Et2O extracts
following NOESY correlations: 2-H ↔ pseudoequatorial 1-CH3 were washed with distilled water until neutral, dried over
↔ 7-H ↔ pseudoaxial 1-CH3 ↔ 2-H (very weak), 4-H ↔ CaCl2, concentrated, and distilled to yield a pure 92:8 mixture
pseudoaxial 3-H ↔ pseudoaxial 1-CH3 (strong); 1H NMR (11.19 g, ≥67%) of 3- and 2-bromo-1,1-dimethylindene (3 and
(D3C–C≡N, 200 MHz) δ 1.21 and 1.43 (2 s, 2 × 3H, 2 × 4) with bp 115–117 °C/12 Torr.
1-CH3), 4.45 and 5.58 (AB system, 3J = 8.4 Hz, 2 × 1H, 2-H
and 3-H), ca. 7.2 (m, 7-H) ppm; 13C NMR (CDCl3, 100.6 MHz) 1H NMR of 3 (CDCl3, 400 MHz) δ 1.32 (s, 6H, 2 × 1-CH3),
δ 25.77 (pseudoequatorial 1-CH3), 26.98 (pseudoaxial 1-CH3), 6.46 (s, 1H, 2-H), 7.25 (tm, 3J = 7 Hz, 1H, 6-H), 7.28 (m, 1H,
46.95 (C-1), 56.61 (C-3), 68.31 (C-2), 122.16 (C-7), 125.85 7-H), 7.30 (m, 1H, 5-H), 7.33 (dm, 3J = 7.5 Hz, 1H, 4-H) ppm,
(C-4), 127.94 (C-5), 129.43 (C-6), 138.70 (C-3a), 147.68 (C-7a) assigned through HSQC and 1H/13C HMBC (see below);
ppm, assigned through HSQC and the following 1H/13C HMBC 13C NMR (CDCl3, 100.6 MHz) δ 24.17 (2 × 1-CH3), 49.97
3J and 2J interactions. 3J: 2-H → both 1-CH3, pseudoaxial 3-H (C-1), 118.19 (C-3), 120.48 (C-4), 120.81 (C-7), 126.41 (C-6),
→ neither C-7a nor C-1, 4-H → C-6, 7-H → C-5, both 1-CH3 126.87 (C-5), 140.84 (C-3a), 145.13 (C-2), 151.74 (C-7a) ppm,
→ C-2 and C-7a, C-3a → 5-H and 7-H, C-4 → 6-H, C-7 → assigned through HSQC and the following 1H/13C HMBC 3J
5-H, C-7a → 4-H and 6-H, pseudoaxial 1-CH3 → pseudo- interactions. 1-CH3 → C-2 and C-7a, 2-H → C-3a and C-7a,
equatorial 1-CH3, pseudoequatorial 1-CH3 → pseudoaxial C-3 → 4-H → C-6, C-3a → 7-H → C-5, C-4 → 6-H, C-7 →
1-CH3; 2J: 2-H → C-3, 3-H → C-2 and C-3a, both 1-CH3 → 5-H, C-7a → 2-/4-/6-H; Anal. calcd for C11H11Br (223.13): C,
C-1. Anal. calcd for C11H12Br2 (304.02): C, 43.46; H, 3.98; 59.22; H, 4.97; found [18]: C, 58.79,; H, 4.91. The alternative
found: C, 44.06; H, 3.92.
HBr elimination with KOt-Bu was rapid and exothermic in
diglyme as the solvent.
b) Cis-1: This was analyzed in the 3:7 mixture with trans-1 as
obtained from 1,1-dimethylindene (2) through titration with 2-Bromo-1,1-dimethylindene (4). A sample of contaminated
elemental bromine (not Br3−). 1H NMR (CDCl3, 400 MHz) δ 2,3-dibromo-1,1-dimethylindene (7, 8.43 g, 27.7 mmol) in
1.33 and 1.42 (2 s, 2 × 3H, 2 × 1-CH3), 4.34 (d, 3J = 6.1 Hz, pentane (5.0 mL) was treated with n-BuLi (ca. 40 mmol) in
1H, 2-H), 5.55 (d, 3J = 6.1 Hz, 1H, 3-H), 7.20 (m, 1H, 7-H), hexane (35 mL) at −70 °C under argon gas cover. Since this
7.27 (m, 5-H), 7.34 (m, 6-H), 7.42 (m, 4-H) ppm, assigned reaction was run in an acyclic, saturated hydrocarbon as the sol-
through HSQC, HMBC (see below), and the following NOESY vent (no cyclopentane, no benzene), a voluminous precipitate
correlations: 2-H ↔ both 1-CH3 ↔ 7-H, but pseudoequatorial began to emerge slowly at rt within ca. one hour. When this
3-H ↔ 4-H only (not 1-CH3); 1H NMR (D3C–C≡N, 200 MHz) colorless powder of 2-bromo-3-lithio-1,1-dimethylindene (10)
δ 4.54 and 5.76 (AB system, 3J = 6.0 Hz, 2 × 1H, 2-H and 3-H) had settled after 20 hours at rt, the supernatant was withdrawn
ppm; 13C NMR (CDCl3, 100.6 MHz) δ 26.07 and 26.58 (2 × by syringe, and the residue was washed with dry pentane
1-CH3), 47.23 (C-1), 55.70 (C-3), 62.07 (C-2), 123.00 (C-7), (3 × 15 mL). This purified, solid material was suspended in
125.56 (C-4), 127.83 (C-5), 130.00 (C-6), 139.30 (C-3a), pentane at −70 °C under argon gas and quenched with metha-
148.67 (C-7a) ppm, assigned through HSQC and the following nol (2.0 mL). After dilution with water and Et2O, the aqueous
1H/13C HMBC 3J and 2J interactions. 3J: 2-H → both 1-CH3, layer was extracted with Et2O (2×). The combined Et2O phases
pseudoequatorial 3-H → C-1 (strong) and C-7a (strong), both were washed with water until neutral and dried over Na2SO4.
1-CH3 → C-2 and C-7a, C-3a → 5-H and 7-H, C-4 → 6-H, C-5 The crude material contained 4 and 1,1-dimethylindene (2,
→ 7-H, C-6 → 4-H, C-7 → 5-H, C-7a → 4-H and 6-H, uncer- 77:23) without any other indene derivative. Pure 4 (2.10 g,
tain pseudoaxial 1-CH3 → pseudoequatorial 1-CH3, uncertain 34%) distilled at 101–103 °C/12 Torr. 1H NMR (CDCl3,
pseudoequatorial 1-CH3 → pseudoaxial 1-CH3; 2J: 3-H → C-3a 400 MHz) δ 1.25 (s, 6H, 2 × 1-CH3), 6.75 (s, 1H, 3-H), 7.15
but not C-2, both 1-CH3 → C-1; MS (EI) m/z (%): 225.008 (52, (tm, 3J = 7.5 Hz, 1H, 6-H), 7.18 (tm, 3J = 7.5 Hz, 1H, 5-H),
C11H1281Br+, M – Br−), 223.006 (62, C11H1279Br+, M – Br−); 7.23 (dm, 3J = 7.5 Hz, 1H, 4-H), 7.27 (dm, 3J = ca. 7 Hz, 1H,
HRMS (EI) m/z: 223.0164 (C11H1279Br+, M – Br−, calcd 7-H) ppm, assigned through comparisons with 3 and 7, HSQC
223.0117), no M+ peak.
and 1H/13C HMBC (see below), and the NOESY correlation
1-CH3 ↔ 7-H; 1H NMR (D3C–C≡N, 200 MHz) δ 1.25 (s, 6H,
3-Bromo-1,1-dimethylindene (3). A crude sample of the 9:1 2 × 1-CH3), 6.89 (s, 1H, 3-H) ppm; 13C NMR (CDCl3,
mixture of trans-1 and cis-1 (23.0 g, max. 75 mmol) was added 100.6 MHz) δ 23.94 (2 × 1-CH3), 52.05 (C-1), 120.48 (C-4),
to a saturated solution of solid KOH (30.0 g, 833 mmol) in 121.51 (C-7), 125.11 (C-6), 126.70 (C-5), 128.99 (C-3), 139.86
ethanol (190 mL) and heated to 50 °C for 4 hours. After (C-2), 141.07 (C-3a), 151.66 (C-7a) ppm, assigned through
cautious removal of some ethanol (ca. 130 mL) in vacuo, the HSQC, comparison with 7, and the following 1H/13C HMBC 3J
residue was poured into distilled water (ca. 400 mL) and and 2J interactions. 3J: 1-CH3 → 1-CH3, 1-CH3 → C-2 and
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Beilstein J. Org. Chem. 2016, 12, 1178–1184.
C-7a, 3-H → C-1 and C-7a, 7-H → C-3a and C-5, C-6 → 4-H; end. After 2 hours at rt, the solution contained some product 7
2J: 1-CH3 → C-1, 3-H → C-3a; MS (EI, 70 eV, 80 °C) m/z (%) and mainly 2,3,3-tribromo-1,1-dimethylindane (5). Upon CCl4
224 and 222 (2 × 11, M+), 143 (100, M – Br−), 128 (56, M+ − evaporation in vacuo up to 80 °C (darkening), the primary prod-
CH3Br); HRMS (EI) m/z 224.0026 (C11H1181Br+, M+), uct 5 became thermally converted into 7 during distillation that
222.0045 (C11H1179Br+, M+); Anal. calcd for C11H11Br yielded 7 (4.42 g, 80%) as a colorless, slightly light-sensitive
(223.13): C, 59.22; H, 4.97; found: C, 60.55 H, 4.97.
liquid; analytically pure 7 had bp 144–146 °C/13 Torr. 1H NMR
(CDCl3, 400 MHz) δ 1.31 (s, 6H, 2 × 1-CH3), 7.26 (m, 3J =
2,3,3-Tribromo-1,1-dimethylindane (5): This thermolabile 7.5 Hz, 1H, 6-H), 7.30 (m, 1H, 5-H), 7.31 (m, 1H, 7-H), 7.36
adduct of 3-bromo-1,1-dimethylindene (3) and elemental (dm, 3J = 7.5 Hz, 1H, 4-H) ppm, assigned through HSQC, com-
bromine (see 7) was not purified but recognized through its parison with 3, and the NOESY correlation 1-CH3 ↔ 7-H;
1H NMR chemical shifts and its thermolysis product 7. 13C NMR (CDCl3, 100.6 MHz) δ 24.2 (2 × 1-CH3), 52.6 (C-1),
1H NMR (CDCl3, 200 MHz) δ 1.36 (s, 3H, 1-CH3), 1.39 (s, 3H, 120.0 (C-3), 120.3 (C-4), 121.3 (C-7), 126.4 (C-6), 127.2 (C-5),
1-CH3), 4.78 (s, 1H, 2-H) ppm; 1H NMR (CCl4, 200 MHz) δ 138.9 (C-2), 139.9 (C-3a), 150.0 (C-7a) ppm, assigned through
1.34 (s, 3H, 1-CH3), 1.37 (s, 3H, 1-CH3), 4.69 (s, 1H, 2-H) HSQC, comparison with 3, and the following 3J and 2J HMBC
ppm.
cross peaks. 3J: 1-CH3 → C-2 and C-7a, 4-H → C-3 and C-6
and C-7a, 7-H → C-3a and C-5, C-4 → 6-H, C-7 → 5-H; 2J:
2,2,3-Tribromo-1,1-dimethylindane (6): A crude sample of 1-CH3 → C-1; HRMS (EI) m/z (%) 303.9135 (14,
2-bromo-1,1-dimethylindene (4, ca. 3 mmol) in CCl4 (4 mL) C11H1081Br2+, calcd 303.9103, M+), 301.9119 (25,
was overtitrated with elemental bromine in CCl4 solution at rt. C11H1079Br81Br+, calcd 301.9123, M+), 299.9146 (14,
After 3 hours, the excess of bromine was swept off in a stream C11H1079Br2+, calcd 299.9144, M+), 222.9936 (83,
of N2 gas or destroyed with aqueous sodium sulfite. Almost C11H1081Br+, M – Br−), 220.9974 (77, C11H1079Br+, M – Br−);
pure 6 distilled at 157–161 °C (bath temp.)/3 mbar as a nearly Anal. calcd for C11H10Br2 (302.0): C, 43.75; H, 3.34; Br, 52.92;
colorless, viscos liquid (528 mg, 1.38 mmol). 1H NMR (CDCl3, found: C, 44.06; H, 3.42; Br, 52.00.
400 MHz) δ 1.48 (s, 3H, pseudoaxial 1-CH3), 1.72 (s, 3H,
pseudoequatorial 1-CH3), 5.94 (s, 1H, 3-H), 7.18 (dm, 3J = 7.4 b) From 2-bromo-1,1-dimethylindene (4) via 2,2,3-tribromo-
Hz, 1H, 7-H), 7.31 (td, 3J = 7.4 Hz, 4J = 1.3 Hz, 1H, 5-H), 7.35 1,1-dimethylindane (6): A small sample (44 mg, 0.11 mmol) of
(td, 3J = 7.2 Hz, 1H, 6-H), 7.42 (dm, 3J = 7 Hz, 1H, 4-H) ppm, distilled tribromide 6 (obtained as above from 4 and containing
assigned through HMBC (see below) and the NOESY correla- no trace of 7) in CCl4 was placed in an NMR tube (5 mm) and
tions 4-H ↔ pseudoaxial 3-H ↔ pseudoaxial 1-CH3 ↔ 7-H ↔ treated with an excess of solid KOt-Bu, which consumed 6
pseudoequatorial 1-CH3; 13C NMR (CDCl3, 100.6 MHz) δ within less than 2 hours at rt. Aqueous work-up with Et2O
27.49 (slighly broadened pseudoequatorial 1-CH3), 27.84 afforded the dibromide 7 (29 mg, 87%) as the only product
(pseudoaxial 1-CH3), 55.18 (C-1), 63.97 (C-3), 84.42 (C-2), (hence, no SN2 reaction by KOt-Bu). NEt3 as the base in place
122.45 (C-7), 125.64 (C-4), 128.03 (C-5), 129.77 (C-6), 137.56 of KOt-Bu required 12 days at rt.
(C-3a), 146.18 (C-7a) ppm, assigned through HSQC and the
following 3J and 2J HMBC cross peaks. 3J: both 1-CH3 → C-2 c) From 1,1-dimethylindane (9): A mixture of N-bromosuccin-
and C-7a, 3-H → C-4 and C-7a (but not C-1 since 3-H is imide (NBS, 7.13 g, 40 mmol), 1,1-dimethylindane (9, 1.46 g,
pseudoaxial), 4-H → C-6 and C-7a, 7-H → C-3a and C-5, C-4 10 mmol, see Supporting Information File 1), and CCl4 (50 mL)
→ 6-H, C-3a → 5-H; 2J: both 1-CH3 → C-1, 3-H → C-3a; was treated with azobis(isobutyronitrile) (40 mg) and warmed
HRMS and MS (EI) m/z (%) 385.8143 (0.1, C11H1181Br3+, slowly up to 85 °C. After 30 min of vived refluxing, the dark
M+), 383.8302 (0.4, C11H1179Br81Br2+, M+), 381.8358 (0.5, red suspension showed traces of elemental bromine in the gas
C11H1179Br281Br+, M+), 379.8274 (0.3, C11H1179Br3+, M+), phase and was cooled in an ice bath (15 min). A 1H NMR spec-
304.98 (12, C11H1181Br2+, M – Br−), 302.98 (26, trum of the solution revealed that the starting material 9 was
C11H1179Br81Br+, M – Br−), 300.98 (13, C11H1179Br2+, M – completely consumed and that a mixture containing three gem-
Br−).
dimethyl compounds had been generated: 2,3-dibromo-1,1-di-
methylindene (7, 76%), 1 (1%, trans/cis ca. 3:2), and an
2,3-Dibromo-1,1-dimethylindene (7): a) From 3-bromo-1,1- unknown side-product (20%). The suspension was filtered, and
dimethylindene (3): A solution of 3 (4.08 g, 18.3 mmol) in CCl4 the undissolved portion was washed with CCl4 (2 × 5 mL),
(10 mL) was cooled and stirred in an ice-bath and titrated with affording a colorless, powdery mixture of NBS and succin-
elemental bromine (2.92 g, 18.3 mmol) in CCl4. The initially in- imide (4:36 by 1H NMR). The dark red CCl4 filtrate became
stantaneous decolorization of bromine became progressively colorless on shaking with an aqueous solution of sodium sulfite
slower with a half-reaction time of roughly 2 min toward the (at least 0.6 g) and was washed with distilled water (10 mL),
1183

Beilstein J. Org. Chem. 2016, 12, 1178–1184.
10.Kong, J.; Galabov, B.; Koleva, G.; Zou, J.-J.; Schaefer, H. F., III;
von Ragué Schleyer, P. Angew. Chem., Int. Ed. 2011, 50, 6809–6813.
doi:10.1002/anie.201101852
then dried through stirring with granulated CaCl2 (30 min).
After removal of CaCl2, the colorless solution became violet on
stirring with a sufficient amount of solid KOt-Bu (2.6 g) for
30 min, which destroyed the two dibromides 1 and other small
contaminations. The CCl4 solution was shaken with H2O
(10 mL), aqueous HCl (2 M, 10 mL), and H2O until neutral,
then dried as above with CaCl2 (35 min). Evaporation of CCl4
and subsequent distillation in vacuo furnished the colorless
liquid 7 (1.35 g, 45%).
See this for more recent evidence concerning well-known thermal
(“base-free”) HBr eliminations from -CHBr-CHBr-moieties.
11.Reference [7] mentioned that the alleged “cis” isomer (compound 33
therein) formed crude 3 (compound 37 on p 362 therein) on treatment
with KOt-Bu, which behavior equals that of our trans-1.
12.Tutar, A.; Cakmak, O.; Balci, M. Tetrahedron 2001, 57, 9759–9763.
doi:10.1016/S0040-4020(01)00978-4
See this for a report of methyl-free 1,1,3,3-tetrabromo-and
1,1,2,3,3-pentabromoindenes undergoing thermal HBr eliminations at
or above 120 °C.
Supporting Information
13.Zhu, H.-T.; Ji, K.-G.; Yang, F.; Wang, L.-J.; Zhao, S.-C.; Ali, S.;
Liu, X.-Y.; Liang, Y.-M. Org. Lett. 2011, 13, 684–687.
doi:10.1021/ol1029194
Supporting Information File 1
Alternative synthetic routes to 1,1-dimethylindene (2) and
congeners; experimental procedures for 2,
14.Zhou, C.; Chen, X.; Lu, P.; Wang, Y. Tetrahedron 2012, 68,
2844–2850. doi:10.1016/j.tet.2012.01.093
15.Wittig, G.; Heyn, H. Chem. Ber. 1964, 97, 1609–1618.
doi:10.1002/cber.19640970613
1,1-dimehylindane (9), 3-methyl-1-phenylbutan-2-ol,
N-(1,1-dimethylindan-3-ylidene)hydrazine, and
N,N´-bis(1,1-dimethylindan-3-ylidene)hydrazine.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-12-113-S1.pdf]
16.Beak, P.; Musick, T. J.; Chen, C.-W. J. Am. Chem. Soc. 1988, 110,
3538–3542. doi:10.1021/ja00219a031
17.Beak, P.; Chen, C.-W. Tetrahedron Lett. 1985, 26, 4979–4980.
doi:10.1016/S0040-4039(01)80830-3
18.Reference [8] reported MS, IR, and UV data of 3 as listed for 3- (not
“2-”!) bromo-1,1-dimethylindene (compound 11i on p 990 therein) that
had been prepared through brominative deoxygenation of
1,1-dimethyl-3-indanone.
Acknowledgements
This article is dedicated to Professor Manfred Heuschmann on
the occasion of his retirement. Technical support of this
research by the Organic Chemistry Division of the Department
Chemie is gratefully acknowledged.
License and Terms
This is an Open Access article under the terms of the
Creative Commons Attribution License
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1184