Selective catalytic oxidative carbonylation of amino alcohols to ureas

Article abstract of DOI:10.1021/jo0521908

Amino alcohols undergo W(CO)₆-catalyzed oxidative carbonylation to the corresponding hydroxyalkylureas without protection of the hydroxyl group. Selected examples of 1,2-, 1,3-, 1,4-, and 1,5-amino alcohols were converted to the ureas in good to excellent yields, with only small amounts of the cyclic carbamates being formed. In contrast, the phosgene derivatives CDI and DMDTC undergo stoichiometric reactions with the amino alcohol substrates to afford ureas and cyclic carbamates with variable selectivity.

Full text of DOI:10.1021/jo0521908

Selective Catalytic Oxidative Carbonylation of Amino
Alcohols to Ureas
Delmy J. D ´ı az, Keisha-Gay Hylton, and Lisa McElwee-White*
Department of Chemistry and Center for Catalysis, UniVersity of Florida, GainesVille, Florida 32611-7200
lmwhite@chem.ufl.edu
ReceiVed October 20, 2005
6
Amino alcohols undergo W(CO) -catalyzed oxidative carbonylation to the corresponding hydroxyalkylureas
without protection of the hydroxyl group. Selected examples of 1,2-, 1,3-, 1,4-, and 1,5-amino alcohols
were converted to the ureas in good to excellent yields, with only small amounts of the cyclic carbamates
being formed. In contrast, the phosgene derivatives CDI and DMDTC undergo stoichiometric reactions
with the amino alcohol substrates to afford ureas and cyclic carbamates with variable selectivity.
Introduction
SCHEME 1
Conversion of amines to ureas commonly involves nucleo-
philic displacement of leaving groups from phosgene or a
phosgene derivative.1 Phosgene and its derivatives are not
selective for the carbonylation of amines, reacting with other
functionalities such as hydroxyl groups. In fact, phosgene reacts
with both functional groups of amino alcohols to form products
2
such as cyclic carbamates or isocyanate chloroformates (Scheme
3
,4
5
1
). Although transamination of ureas, selenium-catalyzed
6
carbonylation, and condensation with S,S′-dimethyl dithiocar-
bonate (DMDTC) have been used to generate hydroxyalkyl-
7
ureas from amino alcohols under circumstances where formation
of the cyclic carbamate is disfavored, selective reactivity of
amino alcohols with a phosgene derivative often requires
protection of one functional group to avoid forming mixtures
of ureas and carbamates.
A functional group compatibility study demonstrated that the
catalyst was tolerant of -OH groups (eq 1), at least in the case
As an alternative to phosgene and phosgene derivatives, we
recently reported the catalytic carbonylation of aliphatic amines
8
-11
to ureas using W(CO)6 as the catalyst and I2 as the oxidant.
(
1) Hegarty, A. F.; Drennan, L. J. In ComprehensiVe Organic Functional
Group Transformations; Katritzky, A. R., Meth-Cohn, O., Rees, C. W.,
Eds.; Pergamon: Oxford, UK, 1995; Vol. 6, pp 499-526.
of [4-(aminomethyl)phenyl]methanol, in which the correspond-
ing urea was produced without competing carbamate or carbon-
(
(
(
2) Scholtissek, C. Chem. Ber. 1956, 89, 2562-2565.
8
3) Hayashi, K.; Iwakura, Y. Makromol. Chem. 1966, 94, 132-139.
4) Kurita, K.; Matsumura, T.; Iwakura, Y. J. Org. Chem. 1976, 41,
ate formation. However, in the carbonylation reaction of eq 1,
the -OH group is para with respect to the amine so as to
2
070-2071.
5) Kielbania, A. J.; Kukkala, P.; Lee, S.; Leighton, J. C. U.S. Patent
,858,549, 1999.
6) Sonoda, N.; Yamamoto, G.; Natsukawa, K.; Kondo, K.; Murai, S.
Tetrahedron Lett. 1975, 1969-1972.
7) Leung, M. K.; Lai, J. L.; Lau, K. H.; Yu, H. H.; Hsiao, H. J. J. Org.
Chem. 1996, 61, 4175-4179.
8) McCusker, J. E.; Main, A. D.; Johnson, K. S.; Grasso, C. A.;
McElwee-White, L. J. Org. Chem. 2000, 65, 5216-5222.
eliminate the possibility of intramolecular formation of a cyclic
(
5
(
(9) McCusker, J. E.; Qian, F.; McElwee-White, L. J. Mol. Catal. A:
Chem. 2000, 159, 11-17.
(
(10) McCusker, J. E.; Abboud, K. A.; McElwee-White, L. Organome-
tallics 1997, 16, 3863-3866.
(
(11) McCusker, J. E.; Logan, J.; McElwee-White, L. Organometallics
1998, 17, 4037-4041.
10.1021/jo0521908 CCC: $33.50 © 2006 American Chemical Society
7
34
J. Org. Chem. 2006, 71, 734-738
Published on Web 12/21/2005

Carbonylation of Amino Alcohols
carbamate. We now report the catalytic carbonylation of a series
of amino alcohols of varying tether lengths and substitution
patterns to evaluate the selectivity of the W(CO)6/I2 carbonyl-
ation system for reactivity of alcohols vs amines. These results
are compared to reaction of the same amino alcohol substrates
with the phosgene derivatives DMDTC and 1,1′-carbonyldi-
imidazole (CDI).
TABLE 1. Carbonylation of Amino Alcohols to Ureas and
Carbamates
Results and Discussion
The amino alcohol substrates for this study were chosen with
varying tether lengths between the functional groups and varying
steric hindrance at the active sites. The substrates were then
subjected to W(CO)6-catalyzed oxidative carbonylation for
evaluation of the selectivity of the W(CO)6/I2 system toward
formation of the ureas or carbamates, either cyclic or acyclic.
As a comparison of the stoichiometric reactions of phosgene
derivatives to the catalytic W(CO)6/I2 methodology, 1,1′-
carbonyldiimidazole (CDI) and dimethyl dithiocarbonate (DM-
DTC) were also used for the carbonylation of the amino alcohol
substrates.
Carbonylation of 5-Aminopentanol. Carbonylation of 5-ami-
nopentanol (1) was investigated to determine the preference of
a 1,5-amino alcohol to form the corresponding acyclic urea 2
or the eight-membered cyclic carbamate 3 (eq 2). The optimal
The selectivity of the W(CO)6-catalyzed carbonylation of
5-aminopentanol is comparable to the selectivity when phosgene
derivatives are used as the carbonylation agents. Carbonylation
of amino alcohol 1 with CDI afforded urea 2 in 80% yield,
while just trace amounts of the cyclic carbamate 3 and none of
the acyclic carbamate 4 were observed. The other phosgene
derivative, DMDTC, produced urea 2 from amino alcohol 1 in
reaction conditions of a substrate concentration of 4 M, 40 °C,
8
0 atm CO and a reaction time of 18 h afforded the bis-
(hydroxyalkyl)urea 2 in 64% yield and the cyclic carbamate 3
in only 2% yield. The acyclic carbamate 4 was not detected in
the reaction mixtures. However, the presence of unreacted
starting material was observed by TLC prior to purification of
the products.
4
1
5% yield with no evidence of the formation of 3 or 4 (Table
, entry 1).
Carbonylation of 4-Amino-2-methylbutan-1-ol. The selec-
tivity between conversion of a 1,4-amino alcohol to a seven-
membered cyclic carbamate, an acyclic carbamate, or the
corresponding urea was investigated with use of 4-amino-2-
methylbutan-1-ol (5) as a representative substrate. The optimal
reaction conditions were found to be the same as for 5-amino-
pentanol; with a substrate concentration of 4 M, 40 °C, and a
reaction time of 18 h producing urea 6 in 93% yield. Compounds
7 and 8 were not detected in the reaction mixtures by NMR or
IR.
To compare the carbonylation of 5 to results by using
phosgene derivatives, 4-amino-2-methylbutanol was treated with
CDI at a concentration of 4 M or DMDTC at a concentration
of 4.5 M. All three carbonylation methods produced similar
selectivity for the formation of urea 6 over products 7 and 8.
When CDI was used as the carbonylating agent, compound 6
was formed in 70% yield as the major component of the product
mixture while 7 was detected in trace amounts (eq 3). There
was no evidence for the formation of 8. Likewise, in the case
When potassium carbonate was used as the base, as was
8,12
reported in prior studies, formation of urea 2 was confirmed
by various spectroscopic methods. No evidence of the acyclic
carbamate 4 was found. Purification of 2 by the previously
described method proved difficult. The problem is similarity in
the solubilities of the hydroxyalkylurea product and potassium
iodide, which is a byproduct of carbonylation in the presence
of K2CO3. Consequently, it was difficult to purify the urea by
methods such as chromatography or selective extraction. These
difficulties with the workup could be avoided by changing the
base to pyridine, which allowed purification of the products to
be carried out without chromatography. The modified workup
for the recovery of the urea and carbamate is described in detail
in the Experimental Section.
(12) McCusker, J. E.; Grasso, C. A.; Main, A. D.; McElwee-White, L.
Org. Lett. 1999, 1, 961-964.
J. Org. Chem, Vol. 71, No. 2, 2006 735

Diaz et al.
of DMDTC, urea 6 was produced in 93% yield as the only
product (Table 1, entry 2).
1, entry 3). Urea 11 was isolated in 95% yield with carbamate
12 formed in trace amounts as a minor product. Acyclic
carbamate 13 was not observed. To compare the carbonylation
results to phosgene derivatives, 10 was treated with DMDTC
and CDI, respectively. In contrast to the excellent yield of urea
1
1
1 from the W(CO)6-catalyzed carbonylation, reaction of amine
0 with DMDTC afforded 11 and 12 in yields of 30% and 8%,
respectively. Compound 13 was once again not detected. The
reaction also produced a number of side products which were
detected by TLC analysis. When CDI was used as the carbo-
nylating agent, 11 and 12 were produced with 12 being the major
product (60% yield) while 11 was formed in 36% yield. Once
again, compound 13 was not observed (Table 1, entry 3).
A second example of the preference for conversion of 1,3-
amino alcohols to the urea vs the cyclic carbamate was obtained
by carbonylation of 1-phenyl-3-aminopropanol (14). Amino
alcohol 14 was synthesized by treating benzaldehyde with
acetonitrile under basic conditions followed by reduction of the
Carbonylation of 1,3-Amino Alcohols. The carbonylation
of a 1,3-amino alcohol to a six-membered cyclic carbamate or
an acyclic carbamate vs formation of the corresponding urea
was first investigated with use of 3-amino-4-phenylbutanol (10)-
as a representative substrate. Substrate 10 was synthesized by
reduction of DL-â-homophenylalanine (9) with BH3‚THF at 0
13
resulting cyanohydrin with borane dimethyl sulfide. Carbo-
nylation of 14 with use of the W(CO)6/I2 catalytic conditions
provided the corresponding urea 15 in 72% yield, with the minor
product being cyclic carbamate 16 in 14% yield after crystal-
lization. The acyclic carbamate 17 was not formed in the
reaction.
1
7
°
C (eq 4).
Amino alcohol 10 was then subjected to oxidative carbonyl-
ation with use of the W(CO)6/I2 catalytic system under the
previously determined optimal reaction conditions (eq 5, Table
For comparison, 1-phenyl-3-aminopropanol was subjected to
carbonylation with the phosgene derivatives CDI and DMDTC
(
Table 1, entry 4). When CDI was used as carbonylating agent,
the urea 15 was formed in 49% yield, and the cyclic carbamate
6 in 30% yield. Once again, the acyclic carbamate was not
1
observed in the product mixture. In contrast, when DMDTC
was used as carbonylating agent, cyclic carbamate 16 was the
major product (47% yield), while the urea was recovered in
3
4% yield.
Finally, 3-amino-2,2-dimethylpropanol (18) was studied under
the optimal W(CO)6/I2 catalytic conditions (eq 7). Compound
(
13) Koenig, T. M.; Mitchell, D. Tetrahedron Lett. 1994, 35, 1339-
1
342.
(
14) Hylton, K.-G.; Main, A. D.; McElwee-White, L. J. Org. Chem. 2003,
6
8, 1615-1617.
(15) Hylton, K.-G. Ph.D. Dissertation, Department of Chemistry, Uni-
versity of Florida, 2004.
16) Pierce, M. E.; Harris, G. D.; Islam, Q.; Radesca, L. A.; Storace, L.;
Waltermire, R. E.; Wat, E.; Jadhav, P. K.; Emmett, G. C. J. Org. Chem.
996, 61, 444-450.
17) Ueno, K.; Ogawa, A.; Ohta, Y.; Nomoto, Y.; Takasaki, K.; Kusaka,
H.; Yano, H.; Suzuki, C.; Nakanishi, S. WO Patent 2001047931, 2001.
(
18 was chosen to examine the effect of steric bulk at the position
â to the nucleophilic nitrogen and the Thorpe-Ingold effect of
the gem-dimethyl substituents at C3. Accordingly, the carbamate
was expected to be favored by the presence of the gem-dimethyl
1
(
736 J. Org. Chem., Vol. 71, No. 2, 2006

Carbonylation of Amino Alcohols
substituents. However, when carried out under the W(CO)6/I2
carbonylation conditions, the reaction did not go to completion
and 12% of the starting material was recovered. This may be
due in part to steric bulk in the substrate. Nevertheless, urea 19
and carbamate 20 were obtained in 60% and 5% yield,
respectively (Table 1, entry 5). There was no evidence for the
formation of the acyclic carbamate 21.
In contrast, when 3-amino-2,2-dimethylpropanol (18) was
treated with CDI or DMDTC, much higher proportions of
carbamate were generated than with the W(CO)6-catalyzed
carbonylation (Table 1, entry 5). Urea 19 was still the major
product for both carbonylation reactions, being isolated in 55%
yield and 32% yield, respectively. However, cyclic carbamate
produced only low yields of a roughly equal mixture of urea
27 and carbamate 28.
To further investigate the carbonylation of 1,2-amino alcohol
substrates, catalytic carbonylation of (R)-(-)-2-amino-1-phen-
ylethanol (29) was also subjected to the W(CO) -catalyzed
6
carbonylation (eq 10). Urea 30 and cyclic carbamate 31 were
obtained in 79% and 14% yield, respectively. As observed for
1,2-amino alcohol 26, there was a high selectivity for conversion
of 29 to the urea in preference to the oxazolidinone.
2
0 was recovered in 28% yield from the reaction with CDI and
in 29% yield when DMDTC was used in the carbonylation.
Overall, there is a strong selectivity favoring formation of urea
over carbamate in the W(CO)6-catalyzed carbonylation for all
three 1,3-amino alcohols that were investigated. In comparison,
the selectivity for formation of the urea over formation of the
carbamate is significantly lower when CDI or DMDTC is used
as the carbonylating agent.
Carbonylation of 1,2-Amino Alcohols. Our interest in the
carbonylation of 1,2-amino alcohols began with our preparation
of the core structure of the HIV protease inhibitors DMP 323
and DMP 450 by W(CO)6-catalyzed carbonylation of O-
protected derivatives of diamine diol 22.14 As part of these
investigations, it was determined that under the initially reported
conditions, oxidative carbonylation of 22 afforded oxazolidi-
nones 24 and 25 instead of the diol urea 23 (eq 8).15 A similar
preference had previously been reported for the reactions of 22
with CDI and phosgene.16
The phosgene derivatives CDI and DMDTC were also used
in the carbonylation of 29 for comparison. In the former reaction,
the cyclic carbamate 31 was the major product (52% yield) while
the urea 30 was recovered in 30% yield from the mixture. On
the other hand, when DMDTC was used as the carbonylating
agent, urea 30 was the major product of the reaction (73% yield)
while oxazolidinone 31 was isolated in just trace amounts (Table
1
, entry 7). Note that for 1,2-amino alcohols 26 and 29, both
the W(CO)6-catalyzed carbonylation and DMDTC afforded the
hydroxyalkyl ureas as the major products but carbonylation with
CDI favored the cyclic carbamate.
Conclusions
In summary, the W(CO)6/I2 methodology can be applied to
carbonylation of amino alcohols to the ureas without protection
of the hydroxyl group. The W(CO)6-catalyzed oxidative car-
bonylation is consistently selective for the urea over the cyclic
carbamate in all cases studied. Acyclic carbamates are not
detected in the reaction mixtures. In contrast, reactions of the
phosgene derivatives CDI and DMDTC with 1,3- and 1,2-amino
alcohol substrates exhibit variable selectivities between ureas
and cyclic carbamates.
Experimental Section
General. All experimental procedures described were carried
out under nitrogen and in oven-dried glassware unless stated
otherwise. Solvents used for carbonylation reactions were passed
through a solvent purification system18 prior to use. Most of the
amino alcohol substrates were commercially available and were
used without further purification. The amino alcohols 3-amino-4-
phenylbutanol and 3-amino-1-phenylpropanol were prepared as
described in the literature.
Procedure A for Carbonylation of Amino Alcohols with CDI.
The amino alcohol (2 equiv) was dissolved in dry THF and placed
These prior results provided motivation for additional study
of 1,2-amino alcohols. The initial substrate was â-amino alcohol
6 (eq 9), chosen for its structural similarity to half of 22. To
further investigate formation of the oxazolidinone ring vs
coupling to the urea, oxidative carbonylation of â-amino alcohol
6 was carried out with use of the W(CO)6/I2 catalytic system
eq 9). The conditions were the same as described for the
2
17
13
2
(
into the flask under a flow of N
added. The reaction was left to stir for 18 h, then the solvent was
evaporated under a flow of N . The residue was dissolved in a 1:1
mixture of CH Cl :H O. The mixture was placed in a separatory
funnel. After the layers were separated, the aqueous layer was
washed with CH Cl , then with a 2:1 solution of chloroform/ethanol.
2
. One equivalent of CDI was then
2
2
2
2
2
2
The combined organic layers were dried and filtered, then the
solvent was removed. The crude product was purified by flash
previous amino alcohol substrates. Upon carbonylation of 26,
urea 27 and cyclic carbamate 28 were obtained in 78% and 10%
yield, respectively, with urea formation once again strongly
preferred (Table 1, entry 6). Although the phosgene derivative
DMDTC afforded similar results, carbonylation of 26 with CDI
chromatography on silica gel with 5% MeOH/CH
2 2
Cl as eluent for
the carbamate and 30% MeOH/CH Cl for the urea.
2
2
(18) Pangborn, A. B.; Giardello, M. A.; Grubbs, R. H.; Rosen, R. K.;
Timmers, F. J. Organometallics 1996, 15, 1518-1520.
J. Org. Chem, Vol. 71, No. 2, 2006 737

Diaz et al.
Procedure B for Carbonylation of Amino Alcohols with
DMDTC. The amino alcohol (2 equiv) was dissolved in dry
Authentic Samples of N,N′-Bis(1-benzyl-3-hydroxypropyl)-
urea (11) and 4-Benzyl-1,3-oxazinan-2-one (12). Procedure B
afforded compounds 11 and 12 from 10 (600 mg, 2.97 mmol) as
methanol and placed into the flask under a flow of N
equiv) was then added and the reaction was left to stir for 18 h
under N . The solvent was then evaporated under N and the product
was immediately chromatographed on silica gel with use of a
mixture of 5% to 30% MeOH/CH Cl as eluent to recover the
2
. DMDTC (1
1
white solids in 30% and 8% yield, respectively. For urea 11: H
2
2
NMR (CDCl ) δ 1.22 (m, 2H), 1.77 (m, 2H), 2.70 (m, 4H), 3.42
3
13
(
3
m, 4H), 4.10 (s, 2H), 4.82 (s, 2H); C NMR (CDCl ) δ 38.4,
2
2
4
V
2.0, 48.0, 58.6, 126.6, 128.6, 129.2, 138.2, 159.9; IR (CH
Cl
)
2
2
carbamate and urea, depending on the substrate.
-1
+
CO 1600 cm ; MS (LSIMS) [M + H] calcd for C21
28
H N
2
O
3
1
Procedure C for Catalytic Carbonylation of Amino Alcohols
257.2178, found 257.2161. For carbamate 12: H NMR (CDCl ) δ
3
with W(CO)
glass vial in a multicompartment Parr high-pressure vessel contain-
ing 1.9 mL of CH Cl were added 1 (800 mg, 7.7 mmol), W(CO)
136 mg, 0.38 mmol), pyridine (0.93 mL, 12 mmol), and I (977
6
2
/I : 1,3-Bis(5-hydroxypentyl)urea (2). To a 15 mL
1.68 (m, 1H), 1.87 (m, 1H), 2.78 (m, 1H), 2.89 (m, 1H), 3.67 (m,
1
3
1H), 4.14 (m, 1H), 4.27 (m, 1H), 6.81 (s, 1H), 7.24 (m, 5H);
C
2
2
6
NMR (CDCl ) δ 26.5, 42.3, 51.8, 65.4, 126.8, 128.6, 129.1, 136.2,
3
(
2
-1
+
1
54.5; IR (CH
2
Cl
2
) VCO 1710 cm ; MS (LSIMS) [M + H] calcd
mg, 3.8 mmol). The vessel was then charged with 80 atm of CO
and heated at 40 °C for 18 h. The pressure was released and
methylene chloride (5 mL) was added to the reaction mixture to
further dissolve the crude product. The solution was washed
successively with saturated sodium sulfite, then saturated sodium
bicarbonate. Each of the collected aqueous layers was washed with
for C11
H13NO
2
192.1024, found 192.1020.
1,3-Bis(3-hydroxy-3-phenylpropyl)urea (15) and 6-Phenyl-1,3-
oxazinan-2-one (16). Procedure C afforded urea 15 from 14 (320
1
mg, 2.12 mmol) in 72% yield. H NMR (CDCl
3
) δ 1.87 (m, 4H),
.30 (m, 2H), 3.6 (m, 2H), 4.72 (t, 2H), 6.19 (s, 2H), 7.32 (m,
0H); 13C NMR (CDCl
) δ 38.4, 38.7, 72.3, 125.8, 127.5, 128.4,
43.8, 160.1; IR (CHCl
3
1
1
3
2
:1 CHCl
were dried with MgSO
3
/EtOH (4 × 30 mL). The combined CHCl
3
/EtOH layers
and the solvents removed by evaporation
-1
3
) VCO 1646 cm . Cyclic carbamate 16 was
recovered in 14% yield; it was identified by comparison with
4
to afford urea 2 as a white solid in 64% yield. To recover the
carbamate, the methylene chloride layer from the original extrac-
literature data.20
tions was washed with 0.1 M aqueous HCl, then dried with MgSO
The solvent was removed under vacuum to afford carbamate 3 in
% yield. The urea was identified by comparison with literature
4
.
N,N′-Bis(3-hydroxy-2,2-dimethylpropyl)urea (19) and 5,5-
Dimethyl-1,3-oxazinan-2-one (20). Procedure C afforded urea 19
2
from 18 (600 mg, 5.81 mmol) as a white solid in 60% yield.
1
H
19
1
data (elemental analysis and melting point). Urea 2: H NMR
NMR (CDCl ) δ 0.73 (s, 12H), 2.85 (d, 4H, 6.3 Hz), 3.03 (d, 4H,
3
(
3
D
2
O) δ 1.22 (m, 4H), 1.37 (m, 4H), 1.52 (m, 4H), 2.88 (m, 4H),
13
6
3
Hz), 4.61 (t, 2H, 6 Hz), 6.02 (t, 2H, 6.3 Hz); C NMR (CDCl )
δ 22.3, 36.6, 46.2, 67.6, 159.7; IR (CHCl ) VCO 1666 cm ; MS
LSIMS) [M + H] calcd for C11
Anal. Calcd for C11 : C 56.89, H 10.41, N 12.06. Found:
C 57.69, H 10.63, N 12.01. Carbamate 20: yield 5%; H NMR
CDCl ) δ 0.96 (s, 6H), 2.88 (s, 2H), 3.80 (s, 2H), 7.12 (br s, 1H);
C NMR (CDCl
702 cm ; MS (LSIMS) [M + H] calcd for C
found 130.0867.
+
.42 (m, 4H). MS (LSIMS) [M + H] calcd for C11
H
24
N
2
O
3
232.18,
-1
3
-
1
found 232.18. IR (CHCl
: C 56.87, H 10.41, N 12.06. Found: C 56.96, H 10.80,
N 11.89. Mp reported 106.6-108.5 °C (found 106.3-108.5 °C).
3
) VCO 1654 cm . Anal. Calcd for
+
(
24 2 3
H N O 233.1751, found 233.1750.
11 24 2 3
C H N O
24 2 3
H N O
1
1
Carbamate 3: H NMR (CDCl
1
3
) δ 1.49 (m, 2H), 1.50 (m, 2H),
(
3
13
.52 (m, 2H), 3.30 (m, 2H), 3.65 (t, 2H), 5.9 (br, 1H); C NMR
13
3
) δ 22.1, 27.3, 50.6, 75.1, 152.4; IR (CHCl
3
) VCO
(
CDCl
3
) δ 22.9, 29.3, 32.1, 41.2, 62.6, 147.2; IR (CH
2
Cl
2
) VCO 1708
-1
+
1
6
H
11NO
2
130.0868,
-
1
+
cm ; MS (LSIMS) [M + H] calcd for C
1
6
H
11NO
2
130.08, found
30.08.
1,3-Bis(1-benzyl-2-hydroxyethyl)urea (27) and 6-Phenyl-6-
1
,3-Bis(4-hydroxy-3-methylbutyl)urea (6). Procedure C af-
oxazolidin-2-one (28). Procedure C afforded urea 27 from 26 (800
mg, 5.3 mmol) in 78% yield. Carbamate 28 was recovered in 10%
yield. The products were identified by comparison with literature
data.21
1
forded 6 from 5 (0.20 mL, 1.8 mmol) in 93% yield. H NMR
CDCl ) δ 0.86 (d, 6H, J ) 6.6 Hz), 1.22 (m, 2H), 1.59 (m, 4H),
(
3
1
3
.07 (m, 4H), 3.38 (m, 4H), 6.08 (s, 2H); 1 C NMR (CDCl
3
3
) δ
-
1
6.4, 33.0, 33.4, 38.4, 67.4, 161.0; IR (CHCl
3
) VCO 1648 cm
;
+
MS (LSIMS) [M + H]
33.1913.
-Amino-4-phenyl-1-butanol (10). DL-â-homophenylalanine
1000 mg, 5.57 mmol) was added to 2.2 mL of THF and the mixture
was cooled to 0 °C. BH ‚THF (1 M, 8.36 mL, 8.36 mmol) was
C
11
H N
24 2
O
3
calcd 233.1865, found
1,3-Bis(3-hydroxy-2-phenylethyl)urea (30) and 5-Phenylox-
azolidine-2-one (31). Procedure C afforded urea 30 from 29 (800
2
1
3
mg, 5.83 mmol) in 79% yield. H NMR (CDCl
3
) δ 2.85 (m, 2H),
1
3
(
3.08 (m, 2H), 4.78 (t, 2H), 5.64 (br, 2H), 7.38 (m, 10H); C NMR
(CDCl ) δ 49.2, 74.2, 125.8, 127.5, 128.4, 147.2, 159.5; IR (CHCl
CO 1649 cm . Cyclic carbamate 31 was isolated in 14% yield; it
3
3
)
3
-
1
added dropwise to the suspension. The resulting mixture was stirred
at room temperature for 4.5 h. The mixture was then cooled to 0
V
22
was identified by comparison with literature data.
°
C, 4 mL of 3 N sodium hydroxide was slowly added, and the
mixture was stirred at room temperature overnight. The pH of the
solution was adjusted to 11 by adding a few pellets of sodium
hydroxide. The aqueous phase was saturated with potassium
carbonate, the THF phase was separated, and the aqueous phase
was extracted with (6 × 50 mL) diethyl ether. The combined
organic layers were dried over magnesium sulfate. The solvents
were evaporated and the product was obtained in 82% yield. The
Acknowledgment. Funding was provided by the donors of
the Petroleum Research Fund, administered by the American
Chemical Society.
Supporting Information Available: 1H NMR spectra for
compounds 3, 6, 11, 12, 15, 20, 30, and 31. This material is
available free of charge via the Internet at http://pubs.acs.org.
17
product was identified by comparison with literature data.
N,N′-Bis(1-benzyl-3-hydroxypropyl)urea (11) and 4-Benzyl-
,3-oxazinan-2-one (12). Procedure C afforded urea 11 from 10
JO0521908
1
(
1
760 mg, 4.6 mmol) as a pale yellow oil in 95% yield. Carbamate
2 was recovered in trace amount. The products were identified
by comparison with authentic samples prepared as described below.
(
20) Masuyama, A.; Tsuchiya, K.; Okahara, M. Bull. Chem. Soc. Jpn.
1985, 58, 2855-2859.
21) Dondoni, A.; Perrone, D.; Rinaldi, M. J. Org. Chem. 1988, 63,
(
9
252-9264.
(
19) Mckay, A. F.; Skulski, M.; Garmaise, D. L. Can. J. Chem. 1958,
(22) Kubota, T.; Kodaka, M.; Tomohiro, T.; Okuno, H. J. Chem. Soc.,
Perkin 1 1993, 5-6.
3
6, 147-150.
738 J. Org. Chem., Vol. 71, No. 2, 2006