Selective apical bromination of diamantane and conversion to the dihydroxy and dicarboxylic acid derivatives

Article abstract of DOI:10.1080/00397910600943428

New conditions have been found that provide for the selective bromination of diamantane at the 4,9-positions. Subsequent hydrolysis and Koch-Haaf reaction gave the 4,9-dihydroxy- and 4,9-dicarboxylic acid derivatives, respectively. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910600943428

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Selective Apical Bromination of Diamantane
and Conversion to the Dihydroxy and
Dicarboxylic Acid Derivatives
a
b
Matthew C. Davis & Shenggao Liu
a
Chemistry and Materials Division, Michelson Laboratory, Laboratory, Naval
Air Warfare Center, China Lake, California, USA
b
MolecularDiamond Technologies, Chevron Technology Ventures LLC,
Richmond, California, USA
Published online: 24 Nov 2006.
To cite this article: Matthew C. Davis & Shenggao Liu (2006) Selective Apical Bromination of Diamantane
and Conversion to the Dihydroxy and Dicarboxylic Acid Derivatives, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 36:23, 3509-3514, DOI:
10.1080/00397910600943428
To link to this article: http://dx.doi.org/10.1080/00397910600943428
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Synthetic Communications , 36: 3509–3514, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600943428
Selective Apical Bromination of Diamantane
and Conversion to the Dihydroxy
and Dicarboxylic Acid Derivatives
Matthew C. Davis
Chemistry and Materials Division, Michelson Laboratory, Naval Air
Warfare Center, China Lake, California, USA
Shenggao Liu
MolecularDiamond Technologies, Chevron Technology Ventures LLC,
Richmond, California, USA
Abstract: New conditions have been found that provide for the selective bromination
of diamantane at the 4,9-positions. Subsequent hydrolysis and Koch–Haaf reaction
gave the 4,9-dihydroxy- and 4,9-dicarboxylic acid derivatives, respectively.
Keywords: Bromination, diamantane, dibromide, dicarboxylic acid, dihydroxy, iron,
Koch–Haaf
A program to make thermally stable polymers from diamondoids required
selective difunctionalization of diamantane at the 4,9-positions (apical)
(Scheme 1). The most convenient starting point is bromination, because
many functional group transformations can be performed on tertiary alkylbro-
mides. It has been shown that bromination of diamantane in the presence of
Lewis acids, traditionally aluminum tribromide, gives a mixture of
[
1,2]
bromides, one of which is 4,9-dibromodiamantane (1).
reaction is not selective, the yield of 1 is moderate, and purification requires
Because the
[3]
chromatography and/or repeated crystallizations. A selective synthesis of
[
4]
the 4,9-dichlorodiamantane was reported by Blaney et al. However, this
Received in the USA May 9, 2006
Address correspondence to Matthew C. Davis, Chemistry and Materials Division
(Code 498220D), Michelson Laboratory, Naval Air Warfare Center, China Lake,
CA 93555, USA. E-mail: matthew.davis@navy.mil
3
509

3
510
M. C. Davis and S. Liu
Scheme 1. Reagent and conditions: a) Br , Freon 113, Fe, rt, 62%; b) DMF, H O,
2
2
HCl, reflux, 70%; c) Ag
2
SO
4
, H
2
SO
4
, formic acid, 100%; and d) SOCl
2
, reflux, 100%.
[5]
method requires tetrahydro-Binor-S as the starting material. At the time of
writing, we learned of a patent from Tokuyama Corporation whereby 4,9-
dichlorodiamantane was selectively prepared from diamantane by reaction
[6]
with chlorosulfonic acid in sulfuric acid.
[7]
In recent studies with adamantane, the conditions of Rahkimov et al.
[8]
were used for selective bromination of the 1,3-positions. The key features of
the method were freon-113 as solvent with stoichiometric bromine and iron
catalysis. When diamantane was reacted under similar conditions, the major
product was found to be the apical dibromide 1. The yield was good (62%),
and the product precipitated during the reaction. The product was more than
9
5% pure after a single reslurry with hexanes.
[3,4,9,10]
A useful derivative was the previously reported
mantane, 2, made by hydrolysis of 1. Studies began with the previous
4,9-dihydroxydia-
[
9]
[3]
conditions of Vodi cˇ ka et al. and later Archibald et al. that employed
hot nitric acid. The reaction was capricious; the resulting product 2 always
contained an unidentified, nonpolar impurity that was not removed by recrys-
tallization. In addition, prolonged reaction time resulted in a mixture of 2 and
[
11]
its isomer, 1,6-dihydroxydiamantane.
[
Therefore, a switch was made to the
(hot dimethylformamide/aqueous hydro-
10]
conditions of Courtney et al.
chloric acid), which gave 2 in good yield without isomerization or impurities.
The dicarboxylic acid 3 is also useful to make polymers. It has been pre-
[
11]
[3,4,9]
viously prepared by a Koch–Haaf reaction on 1
procedure eliminates the need for silver salts. For a direct approach, reaction
or 2.
Using the latter
[12]
with 1 was chosen under conditions similar to those of Chern and Wang.
It
was found that using a slightly dilute grade of formic acid minimized foaming
of the reaction. In workup, the product invariably co-precipitated with the
AgBr by-product. Therefore, the collected solids were extracted with
aqueous base, and the silver salts were removed by filtration. In this way, 3
was obtained in quantitative yield but a suitable solvent for recrystallization
[13,14]
could not be found. The corresponding dicarboxylic acid dichloride 4

Diamantane Bromination
3511
was also prepared in quantitative yield by simply refluxing in thionyl chloride.
The product crystallized directly from the reaction mixture in high purity.
In conclusion, new conditions for the selective bromination of diaman-
tane at the 4,9-positions are reported. The corresponding dihydroxy and dicar-
boxylic acid derivatives were also made in good yield.
EXPERIMENTAL
Melting points were collected on an electrothermal capillary melting-point
apparatus and are not corrected. NMR spectra were obtained on a Bruker
1
13
AC-200 spectrometer ( H at 200 MHz, C at 50 MHz) and are referenced
to solvent or tetramethylsilane. Iron powder (325 mesh) was purchased
w
from Alfa Products (Andover, MA). MolecularDiamond diamantane
(99%) was provided by MolecularDiamond Technologies, a subsidiary of
Chevron Technology Ventures, LLC (Richmond, CA). Freon-113 (1,1,2-
trichloro-1,2,2-trifluoroethane), reagent-grade bromine, 95–97% formic
acid, and AgNO3 were obtained from Sigma-Aldrich (Milwaukee). All
other reagents and solvents were obtained commercially and used as
received. The reaction vessel (part 1932-02, 1944-01, and 141-02) was
purchased from ChemGlass, Inc. (Vineland, NJ).
4
,9-Dibromodiamantane (1)
A 3 L, two-piece, spherical glass reaction vessel with a three-neck lid
including an adapter for thermometer) was charged with 200 g of freshly pul-
(
verized diamantane (1.06 mol), 10.68 g of Fe powder (0.19 mol, 0.18 equiv),
and 1 L of Freon-113. The mixture was stirred by a magnetic stirbar at such a
rate that the Fe powder was suspended. The diamantane did not dissolve and
made an evenly dispersed suspension. A 200 mL addition funnel (with
pressure-equalizing arm) was attached to center neck of the lid, and in the
w
other two necks adapters for tubing were placed. With Tygon tubing, a
nitrogen line was connected to the top of the addition funnel, and the
adapters on the lid were connected to a double-stage gas scrubber (each
stage containing 1 L of 1 M NaOH, connected in series). In this way, a
steady stream of nitrogen passes through the reactor, sweeping away and neu-
tralizing the by-product HBr formed. The addition funnel was charged with
1
37 mL of Br (2.68 mol, 2.5 equiv), which was added dropwise over 1.5 h.
2
The temperature of the reaction peaked at 308C, then gradually returned to
rt. The reaction was monitored by thin-layer chromatography (hexanes/
EtOAc), and after 4 h the reaction was complete. A solid had precipitated
during the reaction, and the supernatant liquid was clear and red-brown in
color. The reaction mixture was filtered through a medium porosity glass
frit to obtain a red-brown solid and a red-orange filtrate. The filtrate was

3
512
M. C. Davis and S. Liu
rotary evaporated to recover the Freon-113. The filter cake and evaporated
residue were combined and dissolved in 1.5 L of CHCl . After stirring
3
30 min, the remaining Fe powder was removed by the magnetic stirbar in
three iterations. The organic phase was extracted with 1 L of H O for 1 h,
w
and the phases were split. The organic layer was treated with 25 g Darco
2
of G-60 charcoal for 30 min. The mixture was filtered, through diatomaceous
earth on a medium glass frit. The light orange filtrate was dried over anhydrous
MgSO , filtered, and rotary evaporated. The remaining brown solid was
4
slurried with 500 mL of hexanes and filtered through a medium-porosity
glass frit. The filter cake was washed with a total of 200 mL of hexanes and
air-dried on the frit. The 225.4 g of off-white powder was more than 95%
1
4,9-dibromodiamantane by H NMR. The yield of the reaction was 62%.
The crude product was recrystallized from toluene to give the title
[1]
compound as colorless crystals. Mp 320–3238C (lit. 324–3268C). dH
(
CDCl ): 2.34 (s, 12H), 1.99 (s, 6H); d (CDCl ): 63.29, 48.57, 39.74.
3
C
3
4,9-Dihydroxydiamantane (2)
A 2 L, round-bottomed flask equipped with magnetic stirbar and heating mantle
was charged with 300 mL of DMF, 35.2 g of 4,9-dibromodiamantane (0.1 mol),
and 300 mL of 1 M HCl. A condenser was attached, and the mixture was stirred
at reflux for 36 h. The reaction remains a suspension throughout this time. The
reaction was cooled to rt, and 500 mL of H O was added. The white precipitate
2
was filtered using a medium-porosity glass frit. The filter cake was washed three
times on the frit with 250 mL portions of H O and air dried on the frit for 1 h,
2
whereby the solid becomes free flowing. The beige granular solid was recrystal-
lized from MeOH, and residual solvent was removed (608C, 10 torr) to give
[
10]
1
5.4 g of the title compound as white crystals (70%). Mp 290–2948C (lit.
90–2928C). d (DMSO, 758C): 3.96 (s, 2H), 1.79 (s, 6H), 1.61 (2, 12H); d
2
H
C
(
DMSO, 758C): 64.60, 44.41, 38.21.
Silver(I) Sulfate (Ag SO )
2
4
A 500 mL, Erlenmeyer flask was charged with 100 mL of H O and stirbar.
2
AgNO (50 g, 0.29 mol) was added, and the mixture stirred until all the
3
solids dissolved. A mild endotherm resulted as the salt dissolved, cooling
the mixture to 158C. After the solution warmed to rt, 8.06 mL of conc.
H SO (0.145 mol, 0.5 equiv) was added in a gentle stream over 10 min.
2
4
Immediately a white precipitate formed, and the temperature rose to 388C.
After stirring at rt for 1 h, the solids were filtered on a medium glass frit,
washed with 100 mL of H O, and air-dried on the frit. The mass of product
2
was 38.2 g (85%), and it was stored in an amber-glass bottle. No further
purification was performed.

Diamantane Bromination
,9-Diamantanedicarboxylic Acid (3)
3513
4
Warning! This reaction generates extremely toxic carbon monoxide and must
be performed in a well-ventilated hood. The reaction foams and should be run
in a vessel at least three times the total volume of the reagents.
A 2 L, single-neck, round-bottomed flask equipped with a magnetic
stirbar was charged with 300 mL of conc. H SO and 25.9 g of Ag SO
4
2
4
2
(
0.083 mol, 1.1 equiv) and placed in an ice bath to stir. In one portion,
6.1 g of 1 (0.075 mol) was added to the reaction mixture. A 250 mL
2
pressure-equalizing addition funnel equipped with a gas outlet adapter was
attached to the flask. Tubing was attached to the gas outlet adapter to
exhaust the apparatus to the back of the hood. The funnel was charged with
1
00 mL of 95–97% formic acid, and the addition was made over 1 h. The
cooling bath was removed, and the mixture stirred at rt 18 h. The mixture
was filtered through a medium-porosity glass fritted funnel. The solid on
the filter was washed with H O into a 1 L beaker. H O (500 mL) was added
2
2
to the beaker, and 50% aqueous NaOH was added portionwise to basify the
mixture (pH 10). The mixture was filtered through a medium-porosity glass
frit to remove the insoluble silver salts. The colorless filtrate was stirred and
made acidic with conc HCl. The white precipitate was filtered on a medium
glass frit and washed three times with 200 mL portions of H O. The solid
2
was placed in a vacuum oven to remove residual H O (608C, 10 torr, 18 h),
2
yielding 18.8 g of the title compound. The initial filtrate from the reaction
can be diluted with H O to give, after drying, an additional 1.9 g of
product. The total yield was 20.7 g (100%). The compound precipitates as a
2
[4]
white amorphous powder from DMSO. Mp . 4008C (lit. 4568C]. dH
DMSO): 12.00 (bs, 2H), 1.76 (s, 18H).
(
4
,9-Diamantanedicarbonyl Dichloride (4)
A 250 mL, round-bottomed flask equipped with stirbar was charged with 8 g of
(0.03 mol) and 100 mL of SOCl . A condenser and N bubbler were
3
2
2
attached, and the mixture was refluxed for 12 h. The suspended solid is seen
to change over time from a white powder to colorless crystals. The reaction
was cooled to rt and filtered on a medium-porosity glass frit. Removal of
residual SOCl2 (rt, 10 torr) gave 9 g of the title compound as small
[
14]
colorless crystals (100%). Mp 230–2358C (dec; lit.
234–2368C). dH
C D ): 1.53 (s, 12H), 1.09 (s, 6H); d (C D ): 170.77, 49.6, 39.24, 35.90.
(
6
6
C
6 6
ACKNOWLEDGMENTS
The authors thank the Office of Naval Research for generous support of
this project. The authors also thank Andrew P. Chafin (NAWCWD) and Dr.

3
514
M. C. Davis and S. Liu
Robert M. Carlson (Chevron, Richmond, CA) for comments and suggestions
regarding this manuscript.
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