Synthesis of a series of focally-substituted organothiol dendrons

Article abstract of DOI:10.1021/jo961527q

The synthesis of new organothiol-functionalized dendrons of generation 1-4 is described. Several modifications to the original method for preparation of dendrons are detailed that were found to improve the yield and aid in scale-up. A particularly advanta

Full text of DOI:10.1021/jo961527q

J . Org. Chem. 1996, 61, 9229-9235
9229
Syn th esis of a Ser ies of F oca lly-Su bstitu ted Or ga n oth iol Den d r on s
Kang-Yi Chen and Christopher B. Gorman*
Box 8204, Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695
Received August 6, 1996X
The synthesis of new organothiol-functionalized dendrons of generation 1-4 is described. Several
modifications to the original method for preparation of dendrons are detailed that were found to
improve the yield and aid in scale-up. A particularly advantageous method for preparation of an
aromatic thiol is reported and is employed in this reaction sequence. Several uses of these dendrons
are anticipated and briefly described.
I. In tr od u ction
The use of organothiols in the formation of monolayers19,20
on coinage metals and on gallium arsenide21,22 and the
use of organothiols in the preparation of quantum-size
restricted nanoparticles23-28 suggests several potential
uses for these new molecules.
Dendrons are structures that contain multiple branch
points as one traverses from the focal point to the
peripheral points of the molecular structure.1-3 Such
structures have found great utility in the preparation of
new molecular architectures, particularly, in the prepa-
ration of dendrimers in which several of the dendrons
are covalently linked to a core structure.3-18 One can
envision many other novel architectures that employ
dendrons as their building blocks. These might include
dendrons attached via their focal points to a surface and
the use of dendrons as highly branched ligands sur-
rounding a metallic or semiconducting nanoparticle. To
advance the preparation of such new structures, methods
for the synthesis of a dendron that contains a specific
functional group at its focal point and specific functional
groups at its periphery are required. In this paper, we
describe the synthesis of dendrons of generations (i.e.,
degrees of branching) 1-4 that are functionalized with
an aromatic thiol group at their focal point (Figure 1).
Several challenges were faced when the task of syn-
thesizing thiol-substituted dendrons was approached.
The organothiol group is sufficiently reactive that a
convenient method for its protection and subsequent
deprotection was necessary. Since this group was ulti-
mately to be found at the focal point of the dendron, any
convergent synthesis3,15 (which we deemed to be most
expedient to the formation of monodispersed dendrons)
would require installation of this function and its depro-
tection at the end of the synthesis. High yields in these
final steps would be the most critical for a high overall
yield. Lastly, in preparative materials chemistry, the
widespread employment of new molecules often hinges
on convenient preparation amenable to scale-up. The
synthetic methodology reported herein is convenient, can
proceed in a high yield, and is amenable to scale-up to
the 10-100 gram scale.
X Abstract published in Advance ACS Abstracts, December 1, 1996.
(1) Tomalia, D. A.; Durst, H. D. Top. Curr. Chem. 1993, 165, 192-
313.
(2) Newkome, G. R.; Moorefield, C. N.; Baker, G. R. Aldrichim. Acta
1992, 25, 31-38.
II. Resu lts a n d Discu ssion
(3) Hawker, C. J .; Fre´chet, J . M. J . J . Am. Chem. Soc. 1990, 112,
7638-7647.
A. Mod ified Syn th esis of th e F r e´ch et-Typ e Den -
d r on . The branched structure employed in our synthesis
has originally been reported by Fre´chet et al.15 It is based
on inexpensive starting materials. With the modifica-
tions reported here, it was found that this synthesis could
be scaled-up substantially. The sequence for the prepa-
ration of such dendrons is illustrated in Schemes 1 and
2. Scheme 1 includes the preparation of the repeat unit
(4) Bharathi, P.; Patel, U.; Kawaguchi, T.; Pesak, D. J .; Moore, J .
S. Macrmolecules 1994, 28, 5955-5963.
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113, 4583-4588.
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Baker, G. R. J . Org. Chem. 1992, 57, 358-362.
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K.; Escamillia, G. H.; Saunders, M. J . Angew. Chem., Int. Ed. Engl.
1992, 31, 917-919.
(19) Ulman, A. An Introduction to Ultrathin Organic Films; Aca-
demic Press: San Diego, CA, 1991.
(20) Whitesides, G. M.; Gorman, C. B. In Handbook of Surface
Imaging and Visualization; Hubbard, A. T., Ed.; CRC Press: Boca
Raton, FL, 1995; pp 713-733.
(21) Sheen, C. W.; Shi, J .-X.; Ma˚rtensson, J .; Parikh, A. N.; Allara,
D. L. J . Am. Chem. Soc. 1992, 114, 1514-1515.
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W.; Allara, D. L. Appl. Phys. Lett. 1993, 62, 476-478.
(23) Herron, N.; Wang, Y.; Eckert, H. J . Am. Chem. Soc. 1990, 112,
1322-1326.
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1993, 115, 8706-8715.
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J . Org. Chem. 1987, 52, 5305-5312.
(12) Tomalia, D. A.; Baker, H.; Dwald, J .; Hall, M.; Kallos, G.;
Martin, S.; Roeck, J .; Ryder, J .; Smith, P. Macromolecules 1986, 19,
2466-2468.
(13) Tomalia, D. A.; Berry, V.; Hall, M.; Hedstrand, D. M. Macro-
molecules 1987, 20, 1164-1167.
(14) Tomalia, D. A.; Hall, M.; Hedstrand, D. M. J . Am. Chem. Soc.
1987, 109, 1601-1603.
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Soc. 1991, 113, 4252-4261.
(25) Noglik, H.; Pietro, W. J . Chem. Mater. 1995, 7, 1333-1336.
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D.; Kortan, R.; Muller, A. J .; Thayer, A. M.; Duncan, T. M.; Douglass,
D. C.; Brus, L. E. J . Am. Chem. Soc. 1988, 110, 3046-3050.
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J . Am. Chem. Soc. 1993, 115, 1874-1880.
(16) Wooley, K. L.; Hawker, C. J .; Fre´chet, J . M. J . J . Am. Chem.
Soc. 1993, 115, 11496-11505.
(17) Xu, Z.; Moore, J . S. Angew. Chem., Int. Ed. Engl. 1993, 32, 246-
248.
(18) Xu, Z.; Kahr, M.; Walker, K. L.; Wilkins, C. L.; Moore, J . S. J .
Am. Chem. Soc. 1994, 116, 4537-4550.
(28) Weller, H. Angew. Chem., Int. Ed. Engl. 1993, 32, 41-53.
S0022-3263(96)01527-7 CCC: $12.00 © 1996 American Chemical Society

9230 J . Org. Chem., Vol. 61, No. 26, 1996
Chen and Gorman
F igu r e 1. Structures of the first through fourth generation dendrons synthesized.
Sch em e 1. Syn th esis of Rep ea t Un it 3 a n d F ir st Gen er a tion Alcoh ol ([G-1]-OH, 5)
(3) as well as the first generation focally-substituted with
required in this transformation. The resulting interme-
diate, 4, was not specifically reported in the original
paper.15 We found it convenient to isolate this interme-
diate (Scheme 1). It was readily and easily purified by
crystallization from ethyl acetate after workup. In the
presence of potassium carbonate/18-crown-6, we found
that benzyl chloride worked equally well in this reaction
and was the reagent employed in this synthesis. Both
of these modifications permit the synthesis of 3 and 5 in
30-50 g quantities.
a primary alcohol (5). The triol repeat unit 3 can be
prepared conveniently and in high yield from the origi-
nally reported methyl ester via direct lithium aluminum
hydride reduction. Previously, hexamethyl disilazide was
employed to protect the phenol alcohols in situ.15 We did
not find that the yield of this reaction suffered when this
step was omitted. The second step of this sequence was
the formation of the terminal unit, 5. In Fre´chet’s
original report, benzyl bromide was employed in the first
step, nominally to cap the phenol alcohols. We note that
benzyl bromide also reacts with the carboxylic acid
functionality of 1 to form the benzyl ester; thus, 3 equiv
(for optimal results, 3.3 equiv of benzyl halide) was
The original scheme15 for the activation of the [G-n ]-
OH dendrons (5, 10-12) and their coupling with 3 to
form the dendron of the next higher generation involved
two steps. The first step was conversion of these alcohols

Synthesis of Organothiol Dendrons
J . Org. Chem., Vol. 61, No. 26, 1996 9231
[G-1]-OH Ph P/DEAD/NHMeTS8 [G-1]-NMe(Ts) (3)
Sch em e 2. Con ver sion of F oca lly-Su bstitu ted
Alcoh ols to th e Mesyla te, Cou p lin g To F or m
High er Gen er a tion s, a n d Rea ction To F or m
F oca lly-Su bstitu ted Meth yla m in es
3
THF, r.t.
[G-1]-NMe(Ts) Na/naphthalene8 dec
(4)
THF, -78 98 0
B. Syn t h esis of a P r ot ect ed Ar om a t ic Th iol
Cou p lin g Un it. We sought a convenient route to a
protected aromatic thiol that could be used to couple to
the dendrons and subsequently deprotect in high yield.
It is particularly advantageous to optimize any transfor-
mations on the apex of the dendron unit since loss of
material at this stage is particularly unfortunate given
the lengthy, stepwise method for preparation of the
starting materials. Several possibilities were surveyed,
and the methodology described below was found to be
optimal in this case. Several routes for the protection/
deprotection of an aromatic thiol have been described in
the literature. These include the formation of thioethers,
thioacetals, and thioesters.33 Some protecting groups
(e.g., thioethers) are particularly robust. However, it is
not always easy to remove them in high yield.34 The
following procedure can be effected in three steps, none
of which require chromatographic purification (Scheme
3).
to focally-substituted bromides (e.g., [G-n ]-Br ) by treat-
ment with carbon tetrabromide/triphenyl phosphine (eq
1). The second step was a coupling of 2.2 equiv of this
Sch em e 3. Syn th esis of a P r otected Ar om a tic
Th iol Cou p lin g Un it
[G-n ]-OH CBr /Ph P8 [G-n ]-Br
(1)
4
3
K2CO3, 18-C-6
2[G-n ]-Br + 3
8 [G-(n + 1)]-OH (2)
acetone,reflux
focally-substituted bromide with the repeat unit 3 to form
the focally-substituted alcohol of the next higher genera-
tion (eq 2). Neither of these reactions proceeded in high
yield, particularly on a >5 g scale. Our best results gave
<80% yields for this first step in tetrahydrofuran, meth-
ylene chloride, and dimethylformamide. For these rea-
sons, we turned to a mesylate29 activating/leaving group
that, in our experience, is convenient and results in
higher yields for both steps (Scheme 2). In this manner,
[G-n ]-OMs (n ) 1-4, compounds 13-16) were prepared
in excellent yields (89-96%, 4-16 g scale) and coupled
with 3 to form [G-(n + 1)]-OH (n ) 1-3, compounds 10-
12) also in excellent yields (91-93%, 4-9 g scale).
The final step of this sequence was the preparation of
a focally-substituted dendron capable of reaction to form
a strong bond to a thiol-linking unit. Conversion of G-n -
OMs (n ) 1-4, compounds 13-16) to G-n -NHMe (n )
1-4, compounds 17-20) was effected by bubbling meth-
ylamine through a DMSO solution of the starting mate-
rial followed by reaction at 60-70 °C in a sealed tube.
Yields of these reactions were also high (g95%), and G-2-
NHMe (18) and G-4-NHMe (19) were analytically pure
after workup. Originally, to avoid the use of methyl-
amine gas, methyltosylamine was employed (eq 3). This
reaction gives a high yield of the tosylamine (e.g., [G-n ]-
NMe(Ts)) under Mitsonobu conditions (PPh3/DEAD/
TsNHMe, THF, room temperature).30,31 However, sub-
sequent deprotection (eq 4) failed.32
Methyl p-hydroxybenzoate (6) was converted to the
thiocarbamate with the addition of dimethylthiocarbam-
oyl chloride. The product, 7, can be isolated in the form
of large crystals. Rearrangement of 7 to 8 occurs at high
temperatures.35 However, in a sealed tube, little decom-
position was observed during this transformation. Fur-
thermore, this reaction could be conducted on a 5 g scale
in essentially quantitative yield. The final step in this
sequence involved conversion of the ester to the acid with
trimethylsilyl iodide.36 Use of milder Lewis acids (e.g.,
LiI) has been reported in similar deesterification reac-
tions.37 However, lower yields were obtained using
lithium iodide in this transformation. Satisfactory el-
emental analysis was obtained on 9 without chromato-
graphic purification.
(33) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 2nd Ed.; J ohn Wiley & Sons, Inc.: New York, 1991; Chapter
(29) Crossland, R. K.; Servis, K. L. J . Org. Chem. 1970, 35, 3195-
3196.
6.
(34) Hsung, R. P.; Babcock, J . R.; Sita, L. R. Tetrahedron Lett. 1995,
(30) Edwards, M. L.; Stemerick, D. M.; McCarthy, J . R. Tetrahedron
Lett. 1990, 31, 3417-3420.
(31) Henry, J . R.; Marcin, L. R.; McIntosh, M. C.; Scola, P. M.;
Harris, D.; Weinreb, S. M. Tetrahedron Lett. 1989, 30, 5709-5712.
(32) J i, S.; Gortler, L. B.; Waring, A.; Battisti, A.; Bank, S.; Closson,
W. D.; Wriede, P. J . Am. Chem. Soc. 1967, 89, 5311-5312.
36, 4525-4526.
(35) Newman, M. S.; Karnes, H. A. J . Org. Chem. 1966, 31, 3980-
3984.
(36) Ho, T.-L.; Olah, G. A. Angew. Chem., Int. Ed. Engl. 1976, 15,
774.
(37) Dean, P. D. G. J . Chem. Soc. 1965, 6655.

9232 J . Org. Chem., Vol. 61, No. 26, 1996
Chen and Gorman
1
95%; H NMR (CDCl3) δ 1.41 (s, 3 H), 2.01 (m, 2 H), 2.25 (m,
2 H), 3.48 (s, 3 H), 4.30-5.10 (br, 2 H), 6.61 (d, 4 H, J ) 9 Hz),
6.90 (d, 4 H, J ) 9 Hz); 13C NMR (CDCl3) 27.34, 29.86, 36.32,
Sch em e 4. Cou p lin g/Dep r otection of Ar om a tic
Th iol w ith Den d r on
44.01, 51.31, 114.45, 127.92, 139.88, 154.10, 175.07; IR (cm-1
3380, 3033, 1716, 1257.
)
4,4-Bis(4′-h yd r oxyp h en yl)p en ta n ol (3). To a stirred
suspension of lithium aluminum hydride (7.529 g , 198 mmol)
in dry tetrahydrofuran (200 mL) was added a solution of
methyl 4,4-bis(4′-hydroxyphenyl)valerate (2) (29.739 g, 98.98
mmol) in dry tetrahydrofuran (300 mL) dropwise at 0 °C under
nitrogen. After addition was completed, the reaction mixture
was warmed to room temperature and then heated at reflux
for 2 h. The reaction mixture was cooled to 0 °C, and 50 mL
of saturated ammonium chloride solution was added dropwise.
The mixture was filtered, and the filter cake was washed with
diethyl ether. The organic layer was washed with saturated
sodium chloride solution, dried with anhydrous magnesium
sulfate, and then filtered. The filtrates were evaporated to
dryness. The crude product was purified by flash chromatog-
raphy eluting with ethyl acetate to give the product: yield 91%;
1H NMR (CD3COCD3) δ 1.30-1.43 (m, 2 H), 1.59 (s, 3 H),
2.05-2.15 (m, 2 H), 2.93 (s, 1 H), 3.58 (t, 2 H, J ) 6 Hz), 6,75
(m, 4 H), 7.05 (m, 4 H), 8.14 (s, 2 H); 13C NMR (CD3COCD3)
28.18, 28.86, 38.82, 44.89, 62.92, 115.14, 128.77, 141.60,
155.43.
C. Cou p lin g of th e Den d r on to 9. An amide bond-
forming reaction was found to be ideal for the attachment
of the protected aromatic thiol to the dendron. This
reaction is tolerant of the thiol protecting group and also
1
forms a unit with a H NMR signal that is diagnostic for
its formation. Generation of the acid chloride of 9 in situ
followed by coupling to the dendritic methylamine (17-
20) resulted in formation of the amides in acceptable
yields (84-96%) (Scheme 4). Deprotection with base to
give the final product was straightforward and also
proceeded in acceptable yields (73-86%).
Ben zyl 4,4-Bis[4′-(ben zyloxy)p h en yl]va ler a te (4).
A
solution of 4,4-bis(4′-hydroxyphenyl)phenylvaleric acid (1) (50
g, 174 mmol), benzyl chloride (88.5 g, 698 mmol), 18-crown-6
(13.8 g, 52.4 mmol), and potassium carbonate (145 g, 1.047
mol) in 350 mL of acetone was heated to reflux under nitrogen
for 72 h (overhead stirrer). After it was cooled to room
temperature, the reaction mixture was quenched with water
(200 mL) and extracted with ethyl acetate (5 × 300 mL). The
organic layer was dried over anhydrous magnesium sulfate
and filtered. The product was precipitated as a white solid
by slowly evaporating the solvent: yield 90%; 1H NMR (CDCl3)
δ 1.59 (s, 3 H), 2.18 (m, 2 H), 2.46 (m, 2 H), 5.03 (s, 4 H), 5.08
(s, 2 H), 6.90 (d, 4 H, J ) 9 Hz), 7.13 (d, 4 H, J ) 9 Hz), 7.30-
7.50 (m, 15 H); 13C NMR (CDCl3) 27.72, 30.24, 36.42, 44.43,
66.18, 69.89, 114.19, 127.47, 127.70, 127.86, 128.18, 128.51,
129.41, 129.98, 135.87, 137.04, 141.14, 156.78, 173.71; IR
(cm-1) 3064, 3033, 1732, 1509, 1245, 1181, 1025. Anal. Calcd
for C38H36O4: C, 81.99; H, 6.52. Found: 81.90; H, 6.55.
III. Su m m a r y
Synthesis of organothiol dendrons (25-28) was ac-
complished in a straightforward reaction sequence. Dur-
ing the preparation of these compounds several alterna-
tives and improvements were discovered and are de-
scribed. A route to a protected aromatic thiol apex for
the dendron particularly suited to the preparation of such
compounds is described as is a facile deprotection route.
Several potential uses of these dendrons are envisioned,
including their use as encapsulating ligands in the
synthesis of hybrid organic-inorganic clusters and as
new architectures in the preparation of organic surfaces
via their attachment to gold. Experiments of these types
will be reported in future publications.
Red u ction of Ben zyl 4,4-Bis[4′-(ben zyloxy)p h en yl]va l-
er a te (5, [G-1]-OH). To a stirred suspension of lithium
aluminum hydride (2.74 g, 72 mmol) in dry tetrahydrofuran
(100 mL) was added a solution of benzyl 4,4-bis(4′-benzylphen-
yl ether)valerate (4) (20.02 g, 36 mmol) in dry tetrahydrofuran
(300 mL) dropwise at 0 °C under nitrogen. This mixture was
stirred for 4 h at 0 °C. Then 10 mL of ethyl acetate was added
rapidly, the mixture was stirred for 20 min at 0 °C, and then
20 mL of a saturated ammonium chloride solution was added.
After this mixture was warmed to room temperature, it was
filtered, and the filter cake was washed with diethyl ether.
The organic layer was washed with saturated sodium chloride
solution, dried over anhydrous magnesium sulfate, and then
filtered. The filtrates were evaporated to dryness. The crude
product was purified by flash chromatography eluting with
2:3 diethyl ether/petroleum ether to give the [G-1]-alcohol:
IV. Exp er im en ta l Section
Gen er a l Con sid er a tion s. All starting compounds were
purchased from Aldrich Chemical Co. and were used without
further purification unless otherwise noted. Acetone was dried
from molecular sieves. Methanol was distilled from magne-
sium methoxide. Chloroform and methylene chloride were
distilled from calcium hydride. Tetrahydrofuran was distilled
from sodium benzophenone ketyl. All reactions were run
under a nitrogen atmosphere. Flash chromatography was run
on 230-400 mesh silica gel (Merck). Nuclear magnetic
resonance characterization was performed at 300 MHz (1H)
or 75 MHz (13C) on a GE-NMR system. Elemental analysis
was performed by Atlantic microlaboratories. High-resolution
mass spectrometry was performed at the NC State mass
spectrometry facility.
1
yield 98%; H NMR (CDCl3) δ 1.30-1.40 (m, 2 H), 1.55 (s, 1
H), 1.57 (s, 3 H), 2.05-2.11 (m, 2 H), 3.57 (t, 2 H, J ) 6 Hz),
5.01 (s, 4 H), 6.87 (d, 4 H, J ) 9 Hz), 7.11 (d, 4 H, J ) 9 Hz),
7.26-7.45 (m, 10 H); 13C NMR (CDCl3) 27.85, 28.18, 37.93,
44.66, 63.43, 69.89, 114.06, 127.50, 127.86, 128.22, 128.51,
137.10, 142.08, 156.62; IR (cm-1) 3354, 3063, 3034, 1510, 1244,
1024.
O-4-Ca r bom eth oxyp h en yl Dim eth ylth ioca r ba m a te (7).
To a solution of methyl 4-hydroxybenzoate (6) (5.20 g, 34.2
mmol) in 60 mL of dimethylformamide were added 1,4-
diazabicyclo[2.2.2]octane (Dabco) (5.75 g, 51.3 mmol) and
dimethylthiocarbamoyl chloride (5.07 g, 41.0 mmol) in one
portion as solids. The mixture was heated at 50 °C for 5 h
and then was poured into 100 mL of water. The product was
taken into benzene/petroleum ether (4:1), and the organic
solution was washed with 1 N HCl (150 mL) and 10% NaOH
Meth yl 4,4-Bis(4′-h yd r oxyp h en yl)va ler a te (2). A solu-
tion of 4,4-bis(4′-hydroxyphenylvaleric acid (1) (30.0 g, 104.8
mmol) in 200 mL of methanol and 1.5 mL of concentrated H2-
SO4 was heated to reflux under nitrogen overnight. After it
was cooled to room temperature, the reaction mixture was
quenched with water (100 mL) and extracted with diethyl
ether (4 × 150 mL). The organic phase was dried over
anhydrous magnesium sulfate and then filtered. The filtrates
were evaporated to dryness to give the crude product: yield;

Synthesis of Organothiol Dendrons
J . Org. Chem., Vol. 61, No. 26, 1996 9233
(40 mL). Afterthe solution was dried over anhydrous magne-
sium sulfate, the solvents were removed and the residue was
recrystallized from methanol to yield white crystals: yield 90%;
1H NMR (CDCl3) δ 3.33 (d, 3 H, J ) 1.5 Hz), 3.43 (d, 3 H, J )
1.5 Hz), 3.89 (s, 3 H), 7.11 (d, 2 H, J ) 9 Hz), 8.06 (d, 2 H, J
) 9 Hz); 13C NMR (CDCl3) 37.84, 42.27, 51.15, 121.92, 126.73,
129.90, 156.46, 165.34, 185.93; IR (cm-1) 3099, 3065, 1714,
1600, 1538, 1399, 1275, 1208, 1110, 1094.
137.13, 141.01, 141.63, 142.01, 156.65, 156.81, 156.97; IR
(cm-1) 3034, 1607, 1509, 1245, 1180. Anal. Calcd for C176
-
H178O17S: C, 81.39; H, 6.91. Found: C, 81.27; H, 6.92.
1
[G-4]-OMs (16): yield 89% (4 g scale); H NMR (CDCl3) δ
1.60-1.85 (m, 75 H), 2.20-2.45 (m, 30 H), 2.99 (s, 3 H), 3.85-
4.40 (m, 30 H), 5.13 (s, 32 H), 6.90 (d, 24 H, J ) 9 Hz), 7.02 (d,
36 H, J ) 9 Hz), 7.18-7.32 (m, 60 H), 7.40-7.60 (m, 80 H);
13C NMR (CDCl3) 20.87, 22.88, 23.62, 24.17, 24.88, 27.85,
28.79, 30.24, 37.09, 37.58, 38.23, 44.46, 44.66, 52.18, 53.35,
64.82, 68.11, 69.79, 70.44, 113.64, 114.06, 127.41, 127.63,
127.80, 128.18, 128.44, 130.80, 137.04, 140.95, 141.53, 141.72,
141.92, 156.59, 156.75, 156.91; IR (cm-1) 3035, 1608, 1510,
1245, 1181. Anal. Calcd for C368H370O33S: C, 82.57; H, 6.97.
Found: 82.51; H, 6.99.
S-4-Ca r bom eth oxyp h en yl Dim eth ylth ioca r ba m a te (8).
O-4-carbomethoxyphenyl dimethylthiocarbamate (7) (2.04 g,
8.54 mmol) was put into a sealed tube and then heated
1
between 220 and 230 °C for 4 h. TLC and H NMR indicated
the crude product to be pure enough to be carried on to the
1
next step: crude yield g95%; H NMR (CDCl3) δ 3.02 (broad
Gen er a l P r oced u r e for th e Syn th esis of Den d r itic
Alcoh ols ([G-n ]-OH, 10-12). A mixture of the dendritic
mesylate 13-16 (2.1 equiv), 4,4-bis(4′-hydroxyphenyl)pentanol
(1.0 equiv), anhydrous potassium carbonate (3.0 equiv), and
18-crown-6 (0.2 equiv) in dry acetone (about 0.1 mmol alcohol/
mL acetone) was heated at reflux and stirred vigorously under
nitrogen for 60 h. The mixture was cooled, evaporated to
dryness under reduced pressure, and partitioned between
methylene chloride and water. The aqueous layer was ex-
tracted with methylene chloride (3 ×), and the combined
organic layers were dried and evaporated to dryness. The
crude product was purified by flash chromatography, eluting
with methylene chloride increasing to 1:5 ether/methylene
chloride to give the dendritic alcohol.
[G-2]-OH (10): yield 91% (9 g scale); 1H NMR (CDCl3) δ
1.20-1.40 (m, 2 H), 1.50-1.62 (m, 13 H), 2.02-2.10 (m, 2 H),
2.14-2.20 (m, 4 H), 3.55 (m, 2 H), 3.83 (t, 4 H, J ) 6 Hz), 5.00
(s, 8 H), 6.71 (d, 4 H, J ) 9 Hz), 6.85 (d, 8 H, J ) 8 Hz), 7.04
(d, 4 H, J ) 8 Hz), 7.10 (d, 8 H, J ) 9 Hz), 7.28-7.43 (m, 20
H).24.91, 27.89, 28.18, 37.93, 38.29, 44.59, 44.75, 63.43, 68.21,
69.92, 113.67, 114.09, 127.47, 127.86, 128.15, 128.25, 128.51,
137.10, 141.69, 141.98, 156.65, 156.78; IR (cm-1) 3362, 3064,
3031, 1507, 1236, 1183, 1017.
[G-3]-OH (11): yield 92% (8 g scale); 1H NMR (CDCl3) δ
1.25-1.40 (m, 2 H), 1.50-1.70 (m, 33 H), 2.00-2.25 (m, 14
H), 2.62 (s, 1 H), 3.55 (t, 2 H, J ) 7 Hz), 3.84 (t, 12 H, J ) 6
Hz), 5.01 (s, 16 H), 6.73 (d, 12 H, J ) 9 Hz), 6.87 (d, 16 H, J
) 9 Hz), 7.02-7.16 (m, 28 H), 7.26-7.45 (m, 40 H); 13C NMR
(CDCl3) 24.95, 27.89, 28.24, 37.97, 38.29, 44.59, 44.72, 63.43,
68.21, 69.89, 113.67, 114.10, 114.42, 127.47, 127.73, 127.86,
128.15, 128.25, 128.51, 128.80, 137.10, 141.59, 141.66, 141.98,
156.65, 156.78; IR (cm-1) 3539, 3034, 1511, 1245, 1182, 1025.
[G-4]-OH (12): yield 93% (4 g scale); 1H NMR (CDCl3) δ
1.25-1.70 (m, 75 H), 2.00-2.25 (m, 30 H), 3.54 (t, 2 H, J ) 6
Hz), 3.84 (m, 28 H), 5.01 (s, 32 H), 6.73 (d, 28 H, J ) 8 Hz),
6.86 (d, 32 H, J ) 8 Hz), 7.02-7.16 (m, 60 H), 7.26-7.46 (m,
80 H); 13C NMR (CDCl3) 24.98, 27.92, 38.32, 44.72, 44.79,
63.46, 68.28, 69.96, 113.71, 114.13, 127.50, 127.89, 128.28,
128.54, 137.17, 141.66, 142.01, 156.68, 156.84; IR (cm-1) 3578,
s, 3 H), 3.07 (broad s, 3 H), 3.90 (s, 3 H), 7.55 (d, 2 H, J ) 9
Hz), 8.01 (d, 2 H, J ) 9 Hz); 13C NMR (CDCl3) 36.90, 52.18,
129.77, 130.35, 134.61, 135.07, 165.67, 166.54; IR (cm-1) 3026,
1720, 1654, 1274, 1104.
4-[(Dim eth ylca r ba m oyl)th io]ben zoic Acid (9). A mix-
ture of S-4-carbomethoxyphenyl dimethylthiocarbamate (8)
(2.02 g, 8.45 mmol) and iodotrimethylsilane (2.4 mL, 16.9
mmol) was heated to 100 °C under nitrogen for 2 h. After the
reaction mixture was cooled to room temperature, it was
diluted with diethyl ether (200 mL) and washed with 10%
NaOH (3 × 100 mL). The alkaline solution was acidified with
6 N HCl and then extracted with chloroform (3 × 100 mL).
The organic layer was dried over anhydrous magnesium
sulfate and filtered, and the solvents were evaporated to obtain
the product: yield 80-90%; 1H NMR (CDCl3) δ 3.04 (broad s,
3 H), 3.09 (broad s, 3 H), 7.59 (d, 2 H, J ) 9 Hz), 8.06 (d, 2 H,
J ) 9 Hz); 13C NMR (CDCl3) 37.00, 129.67, 130.41, 135.23,
135.52, 165.83, 170.71; IR (cm-1) 3418 (b), 1662, 1292, 1084.
Anal. Calcd for C10H11NO3S: C, 53.32; H, 4.92. Found: 53.23;
H, 4.87.
Gen er a l P r oced u r e for Syn th esis of Den d r itic Mesy-
la tes ([G-n ]-OMs, 13-16). To a solution of the appropriate
alcohol 5 or 10-12 (1.0 equiv) in methylene chloride (0.5 mmol
alcohol/mL CH2Cl2) were added methanesulfonyl chloride (2.0
equiv), triethylamine (3.0 equiv), and 4-(dimethylamino)-
pyridine (0.02 equiv) with stirring at 0 °C. This mixture was
allowed to come to room temperature, and was further stirred
at room temperature under nitrogen for 12 h. Water was
added to quench the reaction, and the aqueous layer was
extracted with methylene chloride (3×). The combined organic
extracts were dried over anhydrous magnesium sulfate, fil-
tered, and evaporated to dryness. The crude product was
purified by flash chromatography, eluting with methylene
chloride.
[G-1]-OMs (13): yield 94% (16 g scale); 1H NMR (CDCl3) δ
1.50-1.65 (m, 2 H), 1.59 (s, 3 H), 2.15 (m, 2 H), 2.94 (s, 3 H),
4.15 (t, 2 H, J ) 6 Hz), 5.03 (s, 4 H), 6.89 (d, 4 H, J ) 9 Hz),
7.10 (d, 4 H, J ) 9 Hz), 7.30-7.45 (m, 10 H); 13C NMR (CDCl3)
24.82, 27.79, 37.22, 37.58, 44.56, 69.86, 70.47, 114.16, 127.47,
127.86, 128.12, 128.51, 137.00, 141.40, 156.75; IR (cm-1) 3074,
3034, 1501, 1352, 1241, 1175; HRMS calcd for C32H34O5S;
530.2127, found 530.2129.
3062, 3035, 1509, 1245, 1181, 1025. Anal. Calcd for C367H368
O31: C, 83.57; H, 7.03. Found: 83.63; H, 7.07.
-
Gen er a l P r oced u r e for th e Syn th esis of Den d r itic
Meth yla m in e ([G-n ]-NHMe, 17-20). Into a sealed tube
with a solution of the dendritic mesylate 13-16 (1 equiv) in
dimethyl sulfoxide (0.5 mmol/mL DMSO) was bubbled meth-
ylamine gas for 1 min at room temperature. Then the sealed
tube was weighed to make sure at least 10 equiv of methyl-
amine was added. The sealed tube was heated at 60-70 °C
for 3 h with stirring. After it was cooled and opened (CAU-
TION!), water was added, and the mixture was partitioned
between methylene chloride and water. The organic layer was
dried over anhydrous magnesium sulfate, filtered, and evapo-
rated to dryness. The crude product was pure enough to be
carried out to the next step.
[G-1]-NHMe (17): yield g95% (2.5 g scale); 1H NMR
(CDCl3) δ 1.20-1.35 (m, 2 H), 1.58 (s, 3 H), 2.02-2.08 (m, 2
H), 2.36 (s, 3 H), 2.52 (t, 2 H, J ) 7 Hz), 5.01 (s, 4 H), 6.86 (d,
4 H, J ) 9 Hz), 7.10 (d, 4 H, J ) 9 Hz), 7.26-7.43 (m, 10 H);
13C NMR (CDCl3) 25.24, 27.85, 36.48, 39.58, 44.82, 52.70,
69.92, 114.03, 127.50, 127.89, 128.25, 128.51, 137.13, 142.24,
156.59; IR (cm-1) 3421, 3058, 3034, 1500, 1243, 1181, 1024;
1
[G-2]-OMs (14): yield 92% (8 g scale); H NMR (CDCl3) δ
1.45-1.65 (m, 15 H), 2.10 (m, 2 H), 2.17 (m, 4 H), 2.92 (s 3 H),
3.84 (t, 4 H, J ) 6 Hz), 4.12 (t, 2 H, J ) 6 Hz), 5.01 (s, 8 H),
6.73 (d, 4 H, J ) 9 Hz), 6.86 (d, 8 H, J ) 9 Hz), 7.03 (d, 4 H,
J ) 9 Hz), 7.11 (d, 8 H, J ) 9 Hz), 7.26-7.44 (m, 20 H); 13C
NMR (CDCl3) 24.91, 27.89, 37.29, 37.61, 38.29, 44.53, 44.72,
68.28, 69.92, 70.57, 113.80, 114.10, 127.54, 127.89, 128.09,
128.25, 128.54, 137.10, 141.08, 141.98, 156.68, 156.97; IR
(cm-1) 3061, 1508, 1244, 1179; HRMS Calcd for C80H82O9S;
1218.5680, found 1218.5679. Anal. Calcd for C80H82O9S: C,
78.79; H, 6.78. Found: C, 78.71; H, 6.78.
1
[G-3]-OMs (15): yield 96% (7 g scale); H NMR (CDCl3) δ
1.45-1.65 (m, 35 H), 2.05-2.25 (m, 14 H), 2.92 (s, 3 H), 3.84
(t, 12 H, J ) 6 Hz), 4.12 (t, 2 H, J ) 6 Hz), 5.01 (s, 16 H), 6.73
(d, 12 H, J ) 9 Hz), 6.86 (d, 16 H, J ) 9 Hz), 7.00-7.16 (m, 28
H), 7.26-7.45 (m, 40 H); 13C NMR (CDCl3) 24.95, 27.92, 37.29,
37.68, 38.29, 44.56, 44.69, 44.75, 68.24, 69.92, 70.54, 113.71,
113.80, 114.09, 127.50, 127.89, 128.09, 128.18, 128.25, 128.51,

9234 J . Org. Chem., Vol. 61, No. 26, 1996
Chen and Gorman
HRMS calcd for C32H35NO2 (M + H) 466.2746, found 466.2748.
127.83, 128.05 (127.99), 128.18, 128.44, 130.19, 135.29, 137.04,
141.14 (141.53), 141.92, 156.59, 156.81, 166.09 (166.21), 171.03
(170.51); IR (cm-1) 3062, 3034, 1668, 1632, 1510, 1245, 1181,
1018; HRMS calcd for C90H92N2O8S (M + H) 1360.6574, found
1360.6568.
[G-2]-NHMe (18): yield g95% (>1 g scale); 1H NMR (CDCl3)
δ 1.25-1.40 (m, 2 H), 1.55-1.70 (m, 13 H), 2.05-2.15 (m, 2
H), 2.20-2.30 (m, 4 H), 2.41 (s, 3 H), 2.57 (t, 2 H, J ) 7 Hz),
3.90 (t, 4 H, J ) 6 Hz), 5.06 (s, 8 H), 6.81 (d, 4 H, J ) 9 Hz),
6.94 (d, 8 H, J ) 9 Hz), 7.14 (d, 4 H, J ) 9 Hz), 7.19 (d, 8 H,
J ) 9 Hz), 7.30-7.50 (m, 20 H); 13C NMR (CDCl3) 24.83, 24.95,
27.76, 36.19, 38.13, 39.39, 40.68, 44.56, 52.41, 68.02, 69.70,
113.48, 113.93, 127.31, 127.70, 127.99, 128.09, 128.34, 136.94,
141.66, 141.82, 156.49, 156.59; IR (cm-1) 3407, 3062, 3034,
1509, 1245, 1181, 1025; HRMS calcd for C80H83NO6; (M + H)
1154.6299, found 1154.6302.
[G-3]-Am id e (23): yield 84% (1.1 g scale); 1H NMR (CDCl3)
δ 1.35-1.85 (m, 35 H), 2.05-2.30 (m, 14 H), 2.74 (s, 1.5 H),
2.89 (s, 1.5 H), 3.02 (m, 6 H), 3.15 (m, 1 H), 3.48 (m, 1 H), 3.84
(t, 12 H, J ) 6 Hz), 5.01 (s, 16 H), 6.73 (d, 12 H, J ) 9 Hz),
6.86 (d, 16 H, J ) 9 Hz), 6.90-7.15 (m, 30 H), 7.25-7.55 (m,
42 H); 13C NMR (CDCl3) 24.59, 24.85, 25.20, 27.82, 32.41,
36.71, 36.97, 38.19, 38.61, 44.37, 44.62, 44.91, 60.20, 68.08,
69.76, 113.61, 113.87, 114.00, 126.96, 127.28, 127.34, 127.60,
127.73, 128.15, 128.38, 130.19, 135.23, 137.00, 137.13, 141.08,
141.50, 141.85, 156.55, 156.71, 156.78, 166.02, 170.90 (170.38);
IR (cm-1) 3061, 3034, 1666, 1632, 1245, 1181, 1081. Anal.
Calcd for C186H188N2O16S: C, 81.55; H, 6.92. Found: 81.55;
H, 7.00.
[G-3]-NHMe (19): yield g95% (2 g scale); 1H NMR (CDCl3)
δ 1.18-1.70 (m, 35 H), 1.95-2.25 (m, 14 H), 2.36 (s, 3 H), 2.37
(s, 1 H), 2.52 (m, 2 H), 3.84 (m, 12 H), 5.01 (s, 16 H), 6.73 (m,
12 H), 6.86 (m, 16 H), 7.00-7.20 (m, 28 H), 7.25-7.45 (m, 40
H); 13C NMR (CDCl3) 24.69, 24.95, 25.14, 27.92, 28.08, 35.90,
38.29, 39.45, 40.94, 44.62, 44.69, 44.75, 52.25, 68.24, 69.92,
113.67, 114.10, 127.50, 127.89, 128.18, 128.25, 128.54, 137.13,
141.63, 142.01, 156.65, 156.81; IR (cm-1) 3418, 3062, 3034,
1510, 1245, 1181, 1025. Anal. Calcd for C176H179NO14: C,
83.48; H, 7.12. Found: C, 83.23; H, 7.15.
[G-4]-NHMe (20): yield g95% (>1 g scale); 1H NMR (CDCl3)
δ 1.20-1.70 (m, 75 H), 2.00-2.40 (m, 36 H), 3.89 (m, 28 H),
5.04 (m, 32 H), 6.80 (d, 28 H, J ) 9 Hz), 6.92 (d, 32 H, J ) 9
Hz), 7.08-7.22 (m, 60 H), 7.28-7.50 (m, 80 H); 13C NMR
(CDCl3) 24.59, 24.65, 24.85, 25.11, 27.40, 27.66, 27.98, 38.19,
40.58, 41.00, 44.59, 44.66, 68.11, 69.25, 69.79, 70.34, 112.77,
113.13, 113.38, 113.74, 114.32, 114.52, 114.87, 114.97, 126.99,
127.81, 127.57, 127.83, 128.22, 128.44, 128.64, 137.04, 141.53,
141.88, 156.55, 156.71; IR (cm-1) 3090, 3035, 1504, 1244, 1181,
1025, 909. Anal. Calcd for C368H371NO30: C, 83.59; H, 7.07.
Found: C, 83.39; H, 7.02.
Gen er a l P r oced u r e for Syn th esis of Den d r itic Am id e
(21-24). To a solution of the 4-[(dimethylcarbamoyl)thio]-
benzoic acid (9) (3 equiv) in methylene chloride were added
0.01 equiv of dimethylformamide and oxalyl chloride (15 equiv)
via syringe at room temperature. The reaction mixture was
stirred for 3 h at room temperature. Then the mixture was
evaporated to dryness under reduced pressure and put on a
vacuum pump for 20 min. The solid acid chloride was
redissolved in methylene chloride and then transferred to a
solution of [G-n]-NHMe 17-20 (1 equiv) and anhydrous
triethylamine or pyridine (6 equiv, use of triethylamine
resulted in the best yields except for [G-4]-a m id e (24)) in
methylene chloride at 0 °C. The reaction mixture was gradu-
ally warmed to room temperature and stirred overnight at
room temperature. Water was added to quench the reaction,
and the mixture was partitioned between methylene chloride
and water. The organic layer was washed with 1 N HCl, 10%
NaOH solution, and saturated NaCl solution successively.
Then the organic layer was dried over anhydrous magnesium
sulfate and filtered, and the solvents were evaporated to
dryness. The crude product was purified by flash chromatog-
raphy eluting with 3% diethyl ether in methylene chloride.
[G-1]-Am id e (21): yield 96% (1.7 g scale); 1H NMR (CDCl3)
δ 1.25 (m, 2 H), 1.53 (s, 1.5 H), 1.61 (s, 1.5 H), 1.83 (m, 1 H),
2.12 (m, 1 H), 2.75 (1.5 H), 2.92 (1.5 H), 3.06 (m, 6 H), 3.17
(m, 1 H), 3.51 (m, 1 H), 5.03 (s, 4 H), 6.88 (d, 4 H, J ) 8 Hz),
7.03 (d, 2 H, J ) 8 Hz), 7.12 (d, 2 H), J ) 8 Hz), 7.25-7.60 (m,
14 H); 13C NMR (CDCl3) 22.17 (23.65), 27.76, 32.47, 36.80
(37.06), 38.16 (38.65), 44.66, 47.37, 51.44, 69.83, 114.10, 126.92,
127.21, 127.44, 127.82, 128.02 (128.09), 128.44, 130.22, 135.29
(135.00), 137.00 (137.10), 141.50 (141.88), 156.59, 166.06
(166.18), 171.03 (170.48); IR (cm-1) 3062, 3033, 1668, 1633,
1244, 1181, 1089, 1018; HRMS calcd for C42H44N2O4S (M +
H) 673.3100, found 673.3089.
1
[G-4]-Am id e (24): yield 84% (1 g scale); H NMR (CDCl3)
δ 1.20-1.90 (m, 75 H), 2.10-2.25 (m, 30 H), 2.48 (s, 1.5 H),
2.69 (s, 1.5 H), 3.02 (m, 6 H), 3.25 (m, 1 H), 3.45 (m, 1 H), 3.84
(m, 24 H), 4.20-4.25 (m, 4 H), 5.01 (s, 32 H), 6.74 (d, 28 H, J
) 9 Hz), 6.87 (d, 32 H, J ) 9 Hz), 7.00-7.20 (m, 62 H), 7.25-
7.50 (m, 82 H); 13C NMR (CDCl3) 22.62, 22.91, 23.65, 24.20,
24.91, 27.43, 27.85, 28.82, 29.11, 29.28, 29.60, 30.24, 31.83,
36.80, 38.03, 38.26, 38.61, 44.40, 44.53, 44.69, 64.88, 68.05,
68.18, 69.86, 113.22, 113.64, 114.06, 127.02, 127.25, 127.44,
127.67, 127.83, 128.22, 128.47, 128.70, 130.80, 132.35, 135.19,
135.29, 137.07, 141.08, 141.37, 141.56, 141.75, 141.95, 156.62,
156.78, 157.13, 167.67, 171.03; IR (cm-1) 3070, 3029, 1672,
1607, 1509, 1245, 1811, 1025. Anal. Calcd for C378H380N2O32S:
C, 82.62; H, 6.97. Found: C, 82.53; H, 7.02.
Gen er a l P r oced u r e for Syn th esis of Den d r itic Th iol
([G-n ]-SH, 25-28). A flask containing [G-n]-amide 21-24 (1
equiv) and sodium hydroxide (3 equiv) was flushed with
nitrogen, and then a mixture of methanol and tetrahydrofuran
(1:1) was added. This heterogeneous mixture was further
degassed for 2 h by flushing with nitrogen. The reaction
mixture was then refluxed overnight under nitrogen. After it
was cooled, the reaction mixture was quenched with 20 mL of
1 N HCl. Then the mixture was partitioned between meth-
ylene chloride and water. The organic layer was dried over
anhydrous magnesium sulfate, filtered, and evaporated to
dryness. The crude product was purified by flash chromatog-
raphy, eluting with 2% diethyl ether in methylene chloride.
[G-1]-SH (25): yield 78% (2 g scale); 1H NMR (CDCl3) δ
1.25-1.50 (m, 2 H), 1.54 (s, 1.5 H), 1.61 (s, 1.5 H), 1.82 (m, 1
H), 2.10 (m, 1 H), 2.74 (s, 1.5 H), 2.92 (s, 1.5 H), 3.15 (m, 1 H),
3.49 (m, 1 H), 3.52 (s, 1 H), 5.03 (s, 4 H), 6.88 (d, 4 H, J ) 9
Hz), 6.95-7.30 (m, 8 H), 7.30-7.50 (m, 10 H); 13C NMR (CDCl3)
23.72 (22.17), 27.72, 32.70 (37.09), 38.29 (38.61), 44.62, 51.60
(47.47), 69.83, 114.09, 127.41, 127.70, 127.83, 128.02, 128.44,
128.60, 132.90 (133.06), 136.97, 141.46 (141.92), 156.62, 171.16
(170.61); IR (cm-1) 3054, 3033, 2563, 1633, 1505, 1244, 1811,
1016; HRMS calcd for C39H39NO3S (M + H) 602.2729, found
602.2747. Anal. Calcd for C39H39NO3S: C, 77.84; H, 6.53; N,
2.33; S, 5.33. Found: C, 77.56; H, 6.57; N, 2.24; S, 5.14.
[G-2]-SH (26): yield 86% (1 g scale); 1H NMR (CDCl3) δ
1.25-1.90 (m, 15 H), 2.05-2.17 (m, 2 H), 2.17 -2.30 (m, 4 H),
2.77 (m, 1.5 H), 2.94 (m, 1.5 H), 3.16 (m, 1 H), 3.49 (m, 1 H),
3.53 (s, 1 H), 3.89 (t, 4 H, J ) 6 Hz), 5.04 (s, 8 H), 6.77 (d, 4 H,
J ) 8 Hz), 6.90 (d, 8 H, J ) 9 Hz), 6.95-7.20 (m, 14 H), 7.25-
7.50 (m, 22 H); 13C NMR (CDCl3) 24.17, 24.95, 27.89, 28.24,
37.97, 38.29, 38.68, 44.59, 44.72, 53.38, 68.21, 69.89, 113.67,
114.10, 127.47, 127.73, 127.86, 128.15, 128.25, 128.51, 128.80,
130.90, 137.10, 141.24, 141.66, 141.98, 156.65, 156.78, 171.16;
IR (cm-1) 3063, 3034, 2562, 1608, 1510, 1244, 1181, 1016;
HRMS calcd for C87H87NO7S (M + H) 1290.6282, found
1290.6267. Anal. Calcd for C87H87NO7S: C, 80.96; H, 6.79;
N, 1.09; S, 2.48. Found: C, 81.01; H, 6.85; N, 1.07; S, 2.36.
[G-2]-Am id e (22): yield 93% (2.8 g scale); 1H NMR (CDCl3)
δ 1.30-1.90 (m, 15 H), 2.00-2.15 (m, 2 H), 2.15-2.30 (m, 4
H), 2.77 (s, 1.5 H), 2.93 (1.5 H), 3.05 (m, 6 H), 3.19 (m, 1 H),
3.51 (m, 1 H), 3.88 (t, 4 H, 6 Hz), 5.03 (s, 8 H), 6.77 (d, 4 H, J
) 8 Hz), 6.89 (d, 8 H, J ) 9 Hz), 6.98-7.20 (m, 14 H), 7.30-
7.60 (m, 22 H); 13C NMR (CDCl3) 24.88, 25.17, 27.82, 28.18,
32.47, 36.84, 37.09, 38.23, 38.68 (38.58), 44.69 (44.62), 47.37,
51.44, 68.18, 69.86, 113.67, 114.03, 126.99, 127.21, 127.44,
1
[G-3]-SH (27): yield 85% (1.5 g scale); H NMR (CDCl3) δ
1.25-1.90 (m, 35 H), 2.10-2.30 (m, 14 H), 2.60-2.90 (m, 3
H), 3.00-3.40 (m, 2 H), 3.50 (s, 1 H), 3.70-3.90 (m, 12 H),
5.02 (s, 16 H), 6.75 (d, 12 H, J ) 8 Hz), 6.88 (d, 16 H, J ) 8
Hz), 7.00-7.20 (m, 30 H), 7.25-7.50 (m, 42 H); 13C NMR

Synthesis of Organothiol Dendrons
J . Org. Chem., Vol. 61, No. 26, 1996 9235
(CDCl3) 24.98, 25.59, 27.92, 38.32, 38.61, 44.59, 44.79, 45.04,
60.36, 67.95, 68.24, 69.92, 113.71, 114.13, 127.50, 127.89,
128.05, 128.18, 128.54, 128.73, 137.13, 141.63, 142.01, 156.68,
156.84, 156.91, 171.13 (170.93); IR (cm-1) 3033, 1607, 1510,
1244, 1180. Anal. Calcd for C183H183NO15S: C, 82.37; H, 6.91;
N, 0.52; S, 1.20. Found: C, 82.13; H, 6.94; N, 0.50; S, 1.06.
C375H375NO31S: C, 83.04; H, 6.97; N, 0.26; S, 0.59. Found: C,
82.81; H, 7.09; N, 0.27; S, 0.56.
Ack n ow led gm en t. This work was supported in part
by NC State start-up funds and the U.S. Army Research
Office under Grant No. 34422MS-YIP. We thank Pro-
fessor Dominic McGrath at the University of Con-
necticut for helpful advice on the choice of several
synthetic conditions and Wendy Su and Brandon
Parkhurst for checking this manuscript. Mass spectra
were obtained at the Mass Spectrometry Laboratory for
Biotechnology. Partial funding for the Facility is from
NSF Grant No. 94-2.
1
[G-4]-SH (28): yield 73% (0.5 g scale); H NMR (CDCl3) δ
1.30-1.90 (m, 75 H), 1.90-2.30 (m, 30 H), 2.92 (s, 1.5 H), 2.74
(s, 1.5 H), 3.13 (m, 1 H), 3.31 (m, 1 H), 3.88 (m, 28 H), 5.04 (s,
32 H), 6.78 (d, 28 H, J ) 8 Hz), 6.91 (d, 32 H, J ) 9 Hz), 7.05-
7.25 (m, 62 H), 7.30-7.50 (m, 82 H); 13C NMR (CDCl3) 23.04,
24.91, 25.30, 27.89, 28.40, 29.11, 34.09, 38.26, 38.90, 44.07,
44.53, 44.66, 44.72, 49.79,68.18, 69.51, 69.86, 113.67, 114.06,
114.71, 127.44, 127.83, 128.22, 128.47, 137.07, 141.08, 141.43,
141.59, 141.95, 156.62, 156.78, 156.94, 162.53; IR (cm-1) 3063,
3035, 2540, 1666, 1511, 1244, 1181, 1025. Anal. Calcd for
J O961527Q