S,S-dimethyl dithiocarbonate: A convenient reagent for the synthesis of symmetrical and unsymmetrical ureas

Full text of DOI:10.1021/jo9522825

J . Org. Chem. 1996, 61, 4175-4179
4175
above observations, we concluded that DMDTC is a very
selective reagent toward amines. By taking advantage
of its selectivity, we successfully obtained the bisaniline
14 directly from DMDTC and 4-aminobenzylamine (13)
without the need for protection and deprotection proce-
dures. Furthermore, heating DMDTC with 2 equiv of
3-aminopropanol (15) in methanol afforded a mixture of
bis(3-hydroxypropyl)urea 16 and the cyclic urethane 17
in a ratio of 7:3. More interesting is the fact that 16 is
a highly crystalline compound which was readily purified
by recrystallization from chloroform. Nevertheless, be-
cause of the proximity of the amino group and the
hydroxy group, preparation of bis(2-hydroxyethyl)urea
(19) in methanol was less successful, rendering oxazoli-
done (20) as the major product. Since the product ratio
of the symmetrical urea to the cyclic carbamate is
dependent on the reaction concentration of the corre-
sponding amino alcohol, we carried out the synthesis
at higher concentration, obtaining the desired sym-
metrical bis(hydroxyalkyl)ureas 16 and 19 in satisfactory
yields.
Further experiments with DMDTC (Table 2) revealed
that aliphatic amines bearing a hydroxy or an amino
substituent at the â or γ position react in dilute
solution to provide predominantly cyclic ureas or car-
bamates. In particular, reaction of (()-3-aminopropane-
1,2-diol (21) with DMDTC afforded exclusively 5-
(hydroxymethyl)oxazolidin-2-one (22), the kinetically
favored isomer. On the other hand, 1,3-diamino-2-
propanol (23) reacted under the same conditions to give
24 as the major product. Also formed was 5-(aminom-
ethyl)oxazolidin-2-one (25) as a minor component. We
attribute the regioselectivity of the cyclization to the
greater nucleophilicity of the amino group, which favors
the six-membered ring closure over oxazolidone forma-
tion.
S,S-Dim eth yl Dith ioca r bon a te: A
Con ven ien t Rea gen t for th e Syn th esis of
Sym m etr ica l a n d Un sym m etr ica l Ur ea s
Man-kit Leung,* J un-Liang Lai, King-Hang Lau,
Hsiao-hua Yu, and Hsiang-J u Hsiao
Department of Chemistry, National Taiwan University,
Taipei, Taiwan, Republic of China
Received December 28, 1995
The condensation of primary amines with phosgene or
isocyanates is a classic method for the synthesis of
organic ureas.1 However, due to their high toxicity and
reactivity, phosgene and isocyanates are difficult to
handle in the laboratory. Although several substitutes
for phosgene such as triphosgene and carbonyldiimid-
azole have been developed during the last few decades,2,3
these reagents are themselves prepared from phosgene.
Alternative methods involving drastic reaction conditions,
such as direct reactions of amines with dialkyl carbonates
at high temperature4 and the reaction of amines with
N,N′-diphenylurea in the presence of Et3N in refluxing
DMF,5 have been reported previously. Our efforts are
therefore directed toward the development of mild re-
agents that can be used instead of phosgene or its
derivatives in urea synthesis. Since S,S-dimethyl dithio-
carbonate (DMDTC) is structurally similar to phosgene
and can be prepared from methanol, carbon disulfide,
and dimethyl sulfate by a two-step sequence,6 DMDTC
was deemed an appropriate candidate for our investiga-
tion. Although dimethyl sulfate is a suspected human
carcinogen, the substance is relatively nonvolatile (bp
188 °C) and can be handled safely with care in the
laboratory.
In an effort to ascertain the scope of DMDTC applica-
tion to the synthesis of unsymmetrical ureas, we exam-
ined the possibility of preparing N-alkyl-S-methyl thio-
carbamate by mono aminolysis of DMDTC. First,
benzylamine was allowed to react with excess DMDTC
(1.6 molar equiv), affording N-benzyl-S-methyl thiocar-
bamate (36) and dibenzylurea (6) in a ratio of 1:30. This
result implies that the formation of dibenzylurea (6) at
the second stage of the reaction is faster than N-benzyl-
S-methyl thiocarbamate (36) formation from DMDTC. To
To explore the feasibility of using DMDTC in urea
synthesis, we first reacted DMDTC with 2 equiv of
primary alkyl amines 1, 3, and 5 using methanol or
ethanol as the solvent at 60 °C and obtained, respectively,
the desired symmetrical ureas 2, 4, and 6 as the only
products (Table 1). No incorporation of methanol or
1
ethanol into the products occurred according to the H
NMR analyses. While the above procedure is quite
successful for primary alkylamines, we discovered that
DMDTC is relatively sensitive to steric environment and
the nucleophilicity of the amino group. Thus, R-substi-
tuted amines 7 and 9 react with DMDTC at much slower
rates. Furthermore, reaction of tert-butylamine with
DMDTC does not proceed under the same conditions.
Although piperidine (11) is considered to be a good
nucleophile, it only reacts with DMDTC at a moderate
rate, affording thiocarbamate 12 as the product. At-
tempts to extend our procedure to less nucleophilic
aromatic amines such as aniline were unsuccessful,
resulting in recovery of the starting materials. From the
(1) (a) Hegarty, A. F. In Comprehensive Organic Chemistry; Barton,
D., Ollis, W. D., Eds.; Pergamon Press: New York, 1979; Vol. 2, p 1067.
(b) Sandler, S. R.; Karo, W. Organic Functional Group Preparations;
Academic Press: New York, 1971; Vol. 2, p 135.
(2) Staab, H. A. Angew. Chem., Int. Ed. Engl. 1962, 1, 531.
(3) Eckert, H.; Forster, B. Angew. Chem., Int. Ed. Engl. 1987, 26,
894.
(4) Flyes, T. M.; J ames, T. D.; Pryhitka, A.; Zojsji, M. J . Org. Chem.
1993, 58, 7456.
(5) Ramadas, K.; Srinivasan N. Org. Prep. Proc. 1993, 25, 600.
(6) (a) Degani, I.; Fochi, R.; Regondi, V. Synthesis 1980, 375. (b)
Degani, I.; Fochi, R.; Regondi, V. Synthesis 1981, 149.
prevent thiocarbamate 36 from converting to dibenzyl-
urea, we carried out the reaction under basic conditions,
in the course of which 36 should be deprotonated im-
mediately after being formed. Since the anion 37 is
relatively stable toward nucleophilic substitution at
ambient temperature and will not react further to give
S0022-3263(95)02282-1 CCC: $12.00 © 1996 American Chemical Society

4176 J . Org. Chem., Vol. 61, No. 12, 1996
Notes
Ta ble 1. P r ep a r a tion of Sym m etr ica l Ur ea s fr om Con d en sa tion of Va r iou s Am in es w ith DMDTC
2RNH2 + (MeS)2CO f RNHCONHR
a
b
Initial concentration of the starting amine. Isolated yield.
dibenzylurea (6), quenching of 37 led to the thiocarbam-
ate 36 in high yield. Further condensation of 36 with
The foregoing methodology offers a new approach to
the synthesis of symmetrical and unsymmetrical ureas.
It is particularly attractive for the preparation of hy-
droxy- and amino-substituted ureas that are not easy to
obtain by conventional methods. In addition, unsym-
metrical ureas have been prepared from DMDTC and two
different amines through a two-step sequence. This
method is especially useful when the corresponding
isocyanates are unavailable.
Exp er im en ta l Section
Ma ter ia ls. Amines (Aldrich, J anssan, Tokyo Kasei) were
commercially available and used as received. S,S-Dimethyl
dithiocarbonate (DMDTC) was prepared according to the pro-
cedures reported in the following section. Carbon disulfide is
highly toxic, while benzene and dimethyl sulfate are suspected
human carcinogens; these reagents should be handled in a
properly ventilated fume hood, and rubber gloves should be
worn.
tetrahydrofurfurylamine furnished the unsymmetrical
urea 38 (Table 3). This synthetic strategy was extended
to the preparation of bisureas, a new class of guest-host
molecules that has been developed recently for molecular
recognition,7 by using bisthiocarbamate 39 as the key
intermediate.
P r ep a r a tion of S,S-Dim eth yl Dith ioca r bon a te (DM-
DTC). To a suspension of granulated KOH (21.5 g, 0.33 mol)
in anhydrous Et2O and benzene (1:1, 140 mL) was added
methanol (10.5 g, 0.33 mmol), followed by dropwise addition of
a solution of CS2 (24.7 g, 0.33 mol) in benzene (15 mL) at 0 °C.
The reaction mixture was kept at 0 °C for 5 h, and Me2SO4 (41
g, 0.33 mol) was added. The reaction was allowed to react at
ambient temperature for 20 h. The organic layer then was
decanted, washed sequentially with dilute HCl solution and
saturated NaCl solution, dried over anhydrous Na2SO4, and
(7) (a) Nishizawa, S.; Bu¨hlmann, P.; Iwao, M.; Umezawa, Y.
Tetrahedron Lett. 1995, 36, 6483. (b) Fan, E.; Van Arman, S. A.;
Kincaid, S.; Hamilton, A. D. J . Am. Chem. Soc. 1993, 115, 369. (c)
Albert, J . S.; Hamilton, A. D. Tetrahedron Lett. 1993, 34, 7363.

Notes
J . Org. Chem., Vol. 61, No. 12, 1996 4177
Ta ble 2. Con d en sa tion of Va r iou s Dia m in es or Am in o Alcoh ols w ith DMDTC
a
b
Initial concentration of the starting amine. Isolated yield.
concentrated using simple distillation to afford crude O,S-
dimethyl dithiocarbonate (39 g). The oily crude product was
then subjected to thermal rearrangement at 100-110 °C, using
tetrabutylammonium iodide (3 mol %) as a catalyst. After being
heated for 18 h, the yellowish crude oil was fractionally distilled
under reduced pressure to give DMDTC as a colorless oil (25 g,
58%): bp 60-62 °C (20 mmHg) (lit.6 bp 58-59 °C, 16 Torr); 1H
NMR (200 MHz, CDCl3) δ 2.43 (s, 6H) (lit.6 1H NMR (CCl4) δ
2.40 (s, 6H)); 13C NMR (75 MHz, CDCl3) δ 189.8, 12.7.
N,N′-Diben zylu r ea (6). Recrystallization from CHCl3-
hexane yielded 6 as colorless crystals: mp 166-168 °C (lit.10
mp 167-170 °C).
N,N′-Cycloh exylu r ea (10). Recrystallization from MeOH
yielded 10 as colorless crystals: mp 230-231 °C (lit.1b mp 229-
230 °C from MeOH).
S-Meth yl 1-P ip er id in eca r both ioa te (12). Flash chroma-
tography on silica gel, using MeOH-CH2Cl2 (1:7) as the eluent,
afforded 12 as a colorless oil: 1H NMR (200 MHz, CDCl3) δ 3.52-
3.40 (m, 4H), 2.32 (s, 3H), 1.70-1.49 (m, 6H); 13C NMR (50 MHz,
CDCl3) δ 167.1, 45.7 (broad peak), 25.6, 24.4, 12.8; IR (neat,
Typ ica l Syn th etic P r oced u r es for Sym m etr ica l Ur ea s.
N,N′-Bis(isobu tyl)u r ea (2) (Meth od A). To a stirred solution
of isobutylamine (1) (0.18 g, 2.6 mmol) in methanol (1.5 mL)
was added DMDTC (0.16 g, 1.3 mmol). The mixture was heated
at 60 °C for 24 h. The released malodorous methyl sulfide by
product was absorbed and oxidized by NaOCl solution. When
the reaction was complete, the reaction mixture was concen-
trated under reduced pressure, providing a crude solid which
was further purified by recrystallization from methanol-H2O
(1:1) to give 2 as colorless crystals (92%): mp 130-132 °C (lit.8
NaCl) cm-1 1734; MS (EI, 70 eV) m/e 159 (M+, 28), 112 (M+
CH3S, 81), 69 (100); HRMS (EI, 70 eV) calcd for C7H13NOS
159.0719, obsd 159.0722.
-
N,N′-Bis(4-a m in oben zyl)u r ea (14). Flash chromatography
on silica gel, using MeOH-CHCl3 (1:20) as the eluent afforded
14 as colorless crystals: mp 200-202 °C; 1H NMR (200 MHz,
DMSO-d6) δ 6.90 (d, J ) 8.2 Hz, 4H), 6.50 (d, J ) 8.2 Hz, 4H),
6.04 (broad triplet, 5.6 Hz, 2H), 4.90 (bs, 4H), 4.02 (d, J ) 5.6
Hz, 4H); 13C NMR (50 MHz, DMSO-d6) δ 158.2, 147.4, 128.2,
127.8, 113.9, 43.0; IR (KBr) cm-1 3416, 3318, 1606, 1560; MS
(EI, 70 eV) m/e 270 (M+, 40), 177 (32), 164 (61), 121 (100), 106
(45), 94 (20); HRMS (EI, 70 eV) calcd for C15H18N4O 270.1480,
obsd 270.1479. Anal. Calcd for C15H18N4O: C, 66.64; H, 6.71;
N, 20.72. Found: C, 66.34; H, 6.67; N, 20.59.
N,N′-Bis(2-h yd r oxyeth yl)u r ea (19) (Meth od B). Excess
ethanolamine and DMDTC were mixed and heated at 60 °C for
15 h. The released malodorous methyl sulfide by product was
absorbed and oxidized by NaOCl solution. When the reaction
was complete, the unreacted ethanolamine was removed under
reduced pressure by simple distillation, providing a crude
1
128-130 °C); H NMR (200 MHz, CDCl3) δ 5.54 (broad triplet,
2H), 2.91 (t, J ) 6.1 Hz, 4H), 1.72-1.56 (m, 2H), 0.84 (d, J )
6.6 Hz, 12 H); 13C NMR (75 MHz, CDCl3) δ 159.4, 47.7, 29.0,
20.1; IR (KBr) cm-1 3347, 1623, 1572; MS (EI, 70 eV) m/e 172
(M+, 100), 157 (M+ - CH3, 20), 129 (M+ - C3H7, 25), 72 (29), 58
(81); HRMS calcd for C9H20N2O 172.1576, obsd 172.1573. Anal.
Calcd for C9H20N2O: C, 62.75; H, 11.70; N: 16.26. Found: C,
62.49; H, 11.67; N; 16.21.
N,N′-Dia llylu r ea (4): colorless crystals; mp 93-95 °C (lit.9
mp 92-94 °C).
(8) Franz, R. A.; Applegath, F.; Morriss, F. V.; Baiocchi, F. J . Org.
Chem. 1961, 26, 3306.
(9) Laufer, D. A.; Al-Farhan, E. J . Org. Chem. 1991, 56, 891.
(10) Pihuleac, J .; Bauer, L. Synthesis 1989, 61.

4178 J . Org. Chem., Vol. 61, No. 12, 1996
Ta ble 3. P r ep a r a tion of Un sym m etr ica l Ur ea s fr om DMDTC
Notes
R2NH2
R1NHLi + (MeS)2CO (1) LDA8 R1NHCOSMe
8 R1NHCONHR2
(2) H+
a
Overall isolated yield.
mixture of oxazolidone and bis(2-hydroxyethyl)urea which was
further purified by recrystallization from methanol-ethyl ace-
tate (1:4.5) to give 19 as colorless crystals: mp 82-84 °C; 1H
NMR (200 MHz, DMSO-d6) δ 5.96 (broad triplet, 2H), 4.62 (bs,
2H), 3.33 (bs, 4H), 3.02 (q, J ) 6 Hz, 4H); 13C NMR (75 MHz,
DMSO-d6) δ 158.4, 60.8, 42.1; IR (KBr) cm-1 3343, 1621; MS
(EI, 70 eV) m/e 149 (M+ + H, 5), 148 (M+, 2), 118 (100), 117
(60), 70 (40); HRMS (EI, 70 eV) calcd for C5H12N2O3 148.0848,
obsd 148.0842. Anal. Calcd for C5H12N2O3: C, 40.53; H, 8.17;
N, 18.91. Found: C, 40.08; H, 8.16; N, 18.78.
N,N′-Bis(3-h ydr oxypr opyl)u r ea (16). Recrystallization from
MeOH-CHCl3 provided 16 as colorless crystals: mp 83-86 °C
(lit.4 mp 93-94 °C from CH3CN); 1H NMR (200 MHz, DMSO-
d6) δ 5.82 (t, J ) 6.0 Hz, 2H), 4.00-4.50 (bs, 2H), 3.38 (t, J )
6.0 Hz, 4H), 3.00 (q, J ) 6 Hz, 4H), 1.48 (quintet, J ) 6 Hz, 4H)
(lit.4 1H NMR (90 MHz, D2O) δ 3.5 (t, J ) 7.0 Hz, 4H), 3.1 (q, J
) 7 Hz, 4H), 1.6 (m, 4H)); 13C NMR (50 MHz, DMSO-d6) δ 158.5,
58.4, 36.4, 33.2 (lit.4 13C NMR (62.89 MHz, D2O) δ 160.7, 59.2,
36.7, 31.8); IR (KBr) cm-1 3339 (br), 1613, 1584; MS (EI, 70 eV)
m/e 176 (M+, 20), 146 (65), 132 (90), 102 (40), 74 (100), 57 (91);
HRMS (EI, 70 eV) calcd for C7H16N2O3 176.1161, obsd 176.1155.
N,N′-Bis(1-m eth ylp r op yl)u r ea (8). Recrystallization from
CHCl3-hexane yielded 8 as colorless crystals: mp 131-132.5
°C (lit.8 mp 135 °C); 1H NMR (300 MHz, CDCl3) δ 4.30 (bs, 2H),
3.62 (m, 2H), 1.48 (m, 4H), 1.07 (d, J ) 6.7 Hz, 6H), 0.87 (t, J )
7.4 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ 157.6, 47.3, 30.3, 21.0,
10.3; IR (KBr) cm-1 3339 (br), 1613, 1584; MS (EI, 70 eV) m/e
172 (M+, 12), 143 (M+ - C2H5, 63), 72 (20), 58 (100); HRMS (EI,
70 eV) calcd for C9H20N2O 172.1576, obsd 172.1573. Anal. Calcd
for C9H20N2O: C, 62.74; H, 11.70; N, 16.26. Found: C, 62.49;
H, 11.57; N, 16.39.
4.8 (bs, 2H), 4.6 (m, 1H), 3.25-3.80 (m, 4H)); 13C NMR (50 MHz,
DMSO-d6) δ 159.4, 76.4, 62.3, 41.6 (lit.11 13C NMR (CD3OD) δ
78.5, 63.5, 42.9); IR (KBr) cm-1 3320 (br), 3297, 1731; MS (EI,
20 eV) m/e 118 (M+ + H, 5), 100 (M+ - OH, 24), 86 (M+ - CH2-
OH, 100); HRMS (EI, 70 eV) calcd for C4H7NO3 117.0426, obsd
117.0420.
Tetr a h yd r o-5-h yd r oxy-2(1H)-p yr im id in on e (24). Recrys-
tallization of the crude product from MeOH-acetone afforded
24 as colorless crystals: mp 210-213 °C; 1H NMR (200 MHz,
DMSO-d6) δ 6.16 (bs, 2H), 5.07 (d, J ) 4 Hz, 1H), 3.79-3.82 (m,
1H), 3.05-3.20 (m, 2H), 2.80-3.00 (m, 2H); 13C NMR (50 MHz,
DMSO-d6) δ 156.1, 60.4, 46.2; IR (KBr) cm-1 3344, 3297, 3217,
1645; MS (EI, 20 eV) m/e 116 (M+, 90), 88 (30), 59 (100); HRMS
(EI, 70 eV) calcd for C4H8N2O2 116.0586, obsd 116.0583. Anal.
Calcd for C4H8N2O2: C, 41.37; H, 6.94; N, 24.13. Found: C,
41.03; H, 6.84; N, 23.99.
4,4-Dim eth yl-2-im id a zolid in on e (29). Recrystallization
from CH2Cl2-hexane (4:1) afforded 29 as colorless crystals: mp
139-141 °C; 1H NMR (200 MHz, CDCl3) δ 5.63 (bs, 2H), 3.20
(s, 2H), 1.33 (s, 6H); 13C NMR (50 MHz, CDCl3) δ 163.5. 54.9,
53.8, 28.1; IR (KBr) cm-1 3281, 1704, 1688; MS (EI, 70 eV) m/e
114 (M+, 10), 99 (100), 56 (30); HRMS (EI, 70 eV) calcd for
C5H10N2O 114.0793, obsd 114.0787. Anal. Calcd for
C5H10N2O: C, 52.61; H, 8.83; N, 24.54. Found: C, 52.28; H, 8.81;
N: 24.42.
Tetr a h yd r o-5,5-d im eth yl-2(1H)-p yr im id in on e (31). Re-
crystallization of 31 from CH2Cl2-hexane afforded colorless
crystals: mp 254-256 °C (lit.12 255-257 °C); 1H NMR (200 MHz,
CDCl3) δ 5.19 (bs, 2H), 2.94 (d, J ) 2.2 Hz, 4H), 1.05 (s, 6H);
13C NMR (50 MHz, CDCl3) δ 157.0, 52.3, 28.3, 24.7; IR (KBr)
cm-1 3228, 1697; MS (EI, 70 eV) m/e 128 (M+, 70), 113 (M+
-
Typ ica l Syn t h et ic P r oced u r es for Cyclic Ur ea s a n d
Ca r ba m a tes. 5-(Hyd r oxym eth yl)oxa zolid in -2-on e (22). To
a stirred solution of 3-aminopropane-1,2-diol (21) in methanol
was added DMDTC. After being heated at 60 °C for 24 h, the
reaction mixture was concentrated under reduced pressure,
providing a crude oil which was further purified by flash
chromatography, using MeOH-CH2Cl2 (1:10) as the eluent to
give 22 as colorless oil: 1H NMR (200 MHz, DMSO-d6) δ 7.38
(bs, 1H), 5.06 (t, J ) 5.6 Hz, 1H), 4.45-4.57 (m, 1H), 3.33-3.58
(m, 3H), 3.21 (dd, J ) 8.4, 6.6 Hz, 1H) (lit.9 1H NMR (CD3OD) δ
CH3 ), 56 (100); HRMS (EI, 70 eV) calcd for C6H12N2O 128.0950,
obsd 128.0950. Anal. Calcd for C6H12N2O: C, 56.23; H, 9.44;
N, 21.86. Found: C, 55.96; H, 9.40; N, 21.76.
Hexa h yd r o-3H-oxa zolo[3,4-a ]p yr id in -3-on e (33). Flash
chromatography on silica gel, using MeOH-CH2Cl2 as the
(11) Cardillo, G.; Orena, M.; Sandri, S.; Tomasini, C. Tetrahedron
1987, 43, 2505.
(12) Skinner, G. S., Hall, R. H.; Susi, P. V. J . Am. Chem. Soc. 1957,
79, 3786.

Notes
J . Org. Chem., Vol. 61, No. 12, 1996 4179
eluent, yielded 33 as a colorless oil: 1H NMR (200 MHz, CDCl3)
δ 4.38 (t, 8.1 Hz, 1H), 3.88-3.96 (m, 2H), 3.50-3.70 (m, 1H),
2.90-2.70 (m, 1H), 1.78-1.98 (m, 2H), 1.66-1.75 (m, 1H), 1.20-
1.55 (m, 3H) (lit.13 1H NMR (neat) δ 4.8 (m, 1H), 4.2 (m, 3H),
3.25 (m, 1H), 2.1 (m, 6H)); 13C NMR (50 MHz, CDCl3) δ 156.8,
67.9, 54.2, 41.1, 30.2, 24.0, 22.3; IR (neat, NaCl) cm-1 1739; MS
(EI, 70 eV) m/e 141 (M+, 100), 126 (20), 97(30), 83 (95), 69 (40),
55 (55); HRMS (EI, 70 eV) calcd to C7H11NO2 141.0790, found
141.0799.
mL) was added tetrahydrofurfurylamine (0.12 g, 1.1 mmol). After
being heated at 60 °C for 24 h, the reaction mixture was
concentrated under reduced pressure, providing a crude solid.
Recrystallization of the solid from CHCl3-hexane gave 38 as
colorless crystals (0.14 g, 88%): mp 78-80 °C; 1H NMR (300
MHz, CDCl3) δ 7.18-7.30 (m, 5H), 5.86 (broad triplet, 1H), 5.55
(broad triplet, 1H), 4.27 (d, J ) 6 Hz, 2H), 3.90 (m, 1H), 3.60-
3.80 (m, 2H), 3.39 (m, 1H), 3.03 (m, 1H), 1.75-1.95 (m, 3H), 1.51
(m, 1H); 13C NMR (100 MHz, CDCl3) δ 158.7, 139.3, 128.5, 127.4,
127.2, 78.8, 68.0, 44.5, 44.4 28.2, 25.9; IR (KBr) cm-1 3339, 1615;
MS (EI, 70 eV) 234 (M+, 31), 190 (17), 164 (40), 151 (20), 106
(58), 91 (80), 71 (100); HRMS calcd for C13H18N2O2 234.136, obsd
234.1369. Anal. Calcd for C13H18N2O2: C, 66.64; H, 7.74; N,
11.95. Found: C, 66.67; H, 7.75; N, 11.93.
3,4-Dih yd r o-2(1H)-qu in a zolin on e (35). Recrystallization
of 35 from MeOH-CH2Cl2 led to colorless crystals: mp 222-
223 °C; 1H NMR (200 MHz, DMSO-d6) δ 8.98 (bs, 1H), 7.03-
7.14 (m, 2H), 6.78-6.87 (m, 3H), 4.28 (s, 2H) (lit.14 1H NMR
(DMSO-d6) δ 9.08 (bs, 1H), 6.80-7.50 (m, 5H), 4.40 (s, 2H)); 13
C
NMR (50 MHz, DMSO-d6) δ 154.8, 138.3, 127.8, 125.9, 121.1,
118.3, 113.7, 42.7; IR (KBr) cm-1 3248, 1718; MS (EI, 70 eV)
m/e 148 (M+, 100), 147 (M+ - H, 90), 104 (20); HRMS (EI, 70
ev) calcd for C8H8N2O 148.0637, obsd 148.0638. Anal. Calcd
for C8H8N2O: C, 64.85; H, 5.54; N: 18.91. Found: C, 64.68; H:
5.42; N: 18.90.
N,N′′-(p-Xylylen e)bis[N′-(3-h ydr oxypr opyl)u r ea] (40). Re-
crystallization of 40 from DMSO-EtOAc afforded colorless
crystals: mp 219-221 °C dec; 1H NMR (200 MHz, DMSO-d6) δ
7.16 (s, 4H), 6.28 (t, J ) 6.0 Hz, 2H), 5.89 (t, J ) 6.0 Hz, 2H),
4.45 (t, J ) 6.0 Hz, 2H), 4.15 (d, J ) 6.0 Hz, 4H), 3.35-3.42 (q,
J ) 6.0 Hz, 4H), 3.05 (q, J ) 6.0 Hz, 4H), 1.50 (quintet, J ) 6.0
Hz, 4H); 13C NMR (75 MHz, DMSO-d6) δ 158.2, 139.2, 126.9,
58.4, 42.7, 36.4, 33.2; IR 3325, 1606, 1574; FAB (NBA) 339.2
(M+ + H). Anal. Calcd for C14H22N4O4: C, 56.78; H, 7.74; N,
16.55. Found: C, 56.55; H, 7.87; N, 16.50.
Typ ica l Syn th etic P r oced u r es for S-m eth yl N-Alk ylth io-
ca r ba m a tes. S-Meth yl N-Ben zylth ioca r ba m a te (36). To a
solution of benzylamine (0.93 g, 0.87 mmol) and diisopropyl-
amine (0.89 g, 8.8 mmol) in THF (20 mL) at -78 °C under
nitrogen atmosphere was added n-BuLi (1.6 M, 10.9 mL, 17.5
mmol) in hexane. After addition, the solution was stirred at -78
°C for 0.5 h, followed by addition of a solution of DMDTC (1.07
g, 8.8 mmol). The solution was then allowed to react at room
temperature for 20 h. The reaction was quenched by pouring it
into a mixture of ice-dilute HCl solution. The crude solid was
dissolved into EtOAc, washed with aqueous Na2CO3 and brine,
dried over anhydrous MgSO4, concentrated under reduced
pressure, and recrystallized from hexane to provide 36 as
colorless crystals (0.95 g, 62%): mp 76-79 °C; 1H NMR (300
MHz, CDCl3) δ 7.20-7.34 (m, 5H), 5.67 (bs, 1H), 4.45 (d, J ) 6
Hz, 2H), 2.35 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 167.9, 137.7,
128.45, 127.4, 127.3, 45.1, 12.2; IR (KBr) cm-1 3305, 1639; MS
(EI, 70 eV) 181 (M+, 30), 133 (30), 91 (100); HRMS (EI, 70 eV)
calcd for C9H11NOS 181.0562, obsd 181.0559. Anal. Calcd for
C9H11NOS: C, 59.64; H, 6.12; N, 7.73. Found: C, 59.65; H, 6.12;
N, 7.78.
N,N′′-(p-Xylylen e)bis[N′-(2-m eth ylp r op yl)u r ea ] (41). Re-
crystallization from DMSO-EtOAc afforded 41 as colorless
crystals: mp 237-240 °C dec; 1H NMR (300 MHz, DMSO-d6) δ
7.15 (s, 4H), 6.19 (broad triplet, 2H), 5.92 (broad triplet, 2H),
4.14 (d, J ) 6 Hz, 4H), 2.82 (t, J ) 6 Hz, 4H), 1.60 (m, 2H), 0.81
(d, J ) 6.6 Hz, 12 H); 13C NMR (50 MHz, DMSO-d6) δ 158.1,
139.2, 126.9, 46.8, 42.6, 28.6, 20.0; IR (KBr) cm-1 3318, 1613,
1562; FAB (NBA) 335.2 (M+
18H30N4O2: C, 64.64; H, 9.04; N, 16.75. Found: C, 64.36; H,
8.97; N, 16.70.
+ H). Anal. Calcd for
C
N,N′′-(p-Xylylen e)bis(N′-ben zylu r ea ) (42). Recrystalliza-
tion from DMSO-EtOAc afforded 42 as colorless crystals: mp
258-261 °C dec; 1H NMR (300 MHz, DMSO-d6) δ 7.20-7.33 (m,
10H), 7.17 (s, 4H), 6.39 (m, 4H), 4.21 (d, J ) 6 Hz, 4H), 4.19 (d,
J ) 6 Hz, 4H); 13C NMR (50 MHz, DMSO-d6) δ 158.0, 140.9,
139.2, 128.2, 128.1, 127.0, 126.6, 42.9, 42.7; IR (KBr) cm-1 3319,
1619; FAB (NBA) 403.2 (M+
24H26N4O2: C, 71.62; H, 6.51; N, 13.91. Found: C, 71.52; H,
6.50; N, 13.90.
+ H). Anal. Calcd for
S-Meth yl N,N′-(p-Xylylen e)bis(th ioca r ba m a te) (39). Re-
crystallization from EtOAc-hexane yielded 39 as colorless
crystals: mp 201-203 °C; 1H NMR (200 MHz, DMSO-d6) δ 8.64
(broad triplet, J ) 6.0 Hz, 2H), 7.17 (s, 4H), 4.25 (d, J ) 6.0 Hz,
4H), 2.20 (s, 6H); 13C NMR (50 MHz, DMSO-d6) δ 166.4, 137.8,
127.3, 43.7, 11.6; IR (KBr) cm-1 3244, 1629; MS (EI, 70 eV) 284
(M+, 1), 236 (10), 193 (46), 188 (16), 180 (37), 146 (100), 91 (48);
C
Ack n ow led gm en t. We thank the National Science
Council of the Republic of China for the financial
support (NSC 85-2113-M-002-013 and NSC 85-2815-
C002-01-010M).
HRMS (EI, 70 eV) calcd for
C12H16N2O2S2 284.0653, obsd
284.0652. Anal. Calcd for C12H16N2O2S2: C, 50.70; H, 5.68; N,
9.86. Found: C, 51.30; H, 5.74; N, 9.70.
Typ ica l Syn th etic P r oced u r es for Un sym m etr ica l Ur ea s
fr om S-Meth yl N-Alk ylth ioca r ba m a tes. N-Ben zyl-N′-tet-
r a h yd r ofu r fu r ylu r ea (38). To a stirred solution of S-methyl
N-benzylthiocarbamate (36) (0.11 g, 0.63 mmol) in methanol (2
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of DMDTC and compounds 4, 6, 8, 12, 14, 16, 19, 22,
24, 29, 31, 33, 35, 36, and 38-42 (38 pages). This material is
contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
(13) Hall, H. K. J r.; El-Shekiel, A. J . Org. Chem. 1980, 45, 5325.
(14) Yoshida, T.; Kambe, N.; Murai, S.; Sonoda, N. J . Org. Chem.
1987, 52, 1611.
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