Reactive Carbon-Chain Molecules
A R T I C L E S
times with diethyl ether. The filtrate was concentrated under reduced
2,4-Pentadiynal-1-d Tosylhydrazone (7c). The procedure described
for the synthesis of the protio compound 7a was followed (on 2/3 scale).
pressure to remove remaining NH
with anhydrous MgSO , filtered, and concentrated to reveal a reddish-
brown oil. This oil was purified via flash chromatography (5% EtOAc/
CH Cl ) to afford 2,4-pentadiynol (11) (1.69 g, 21.1 mmol; 70% yield)
3
. The remaining mixture was dried
4
The product was purified via flash chromatography (5% EtOAc/CH
Cl ) to reveal two separate white solids (0.813 g, 3.29 mmol, 75% yield
over two steps).
2
-
2
2
2
1
as an amber oil. H NMR δ 4.34 (dd, J ) 6.5, 0.9 Hz, 2 H), 2.21 (t,
J ) 0.9 Hz, 1 H), 1.79 (t, J ) 6.3 Hz, 1 H). MS (ESI, m/z) 81 (M +
H), 63 (M - OH).
1
syn-2,4-Pentadiynal-1-d Tosylhydrazone (syn-7c). (0.369 g) H
NMR δ 8.79 (s, 1 H), 7.83 (d, J ) 7.4 Hz, 2 H), 7.34 (d, J ) 7.4 Hz,
+
2
,4-Pentadiynal Tosylhydrazone (7a). Dry CH
2
Cl
2
(40 mL) was
2 H), 2.84 (s, 1 H), 2.44 (s, 3 H). HRMS (ESI, m/z) C12
H
9
DN
2
O
2
SNa
added to a flask containing 2,4-pentadiynol (11) (0.532 g, 6.64 mmol).
To this stirring mixture was added Dess-Martin periodinane (3.72 g,
calcd 270.0423, found 270.0423.
1
anti-2,4-Pentadiynal-1-d Tosylhydrazone (anti-7c). (0.444 g) H
8
.76 mmol). This mixture was stirred at room temperature for 1.5 h
2 6
NMR (Me SO-d ) δ 12.32 (s, 1 H), 7.68 (d, J ) 7.4 Hz, 2 H), 7.43 (d,
(until complete by TLC), at which point 50 mL of diethyl ether was
J ) 7.1 Hz, 2 H), 4.24 (s, 1 H), 2.39 (s, 3 H). MS (ESI, m/z) 270
added. This mixture was rinsed through a short silica gel column with
diethyl ether into a flask containing p-toluenesulfonhydrazide (1.24 g,
+
+
(C
12
H
9
DN
-Diazo-2,4-pentadiyne (6a). anti-Tosylhydrazone anti-7a (0.075
Cl (5 mL). NaH (11.5 mg, 0.30
2 2 9 2 2 2
O SNa ), 517 ((C12H DN O S) Na ).
6
.64 mmol). After being stirred at room temperature for 24 h, the
1
contents were suction filtered to remove remaining insoluble Dess-
Martin byproducts. The filtrate was washed with saturated aqueous
g, 0.30 mmol) was dissolved in CH
2
2
mmol), as a 60% dispersion in mineral oil, was added. The reaction
stirred for 1 h at room temperature. The flask was cooled to -40 °C,
and the solvent was removed under vacuum (0.2 mmHg). Once the
solvent was removed, the flask was warmed to room temperature and
left under vacuum for an additional 30 min. The remaining solid was
briefly heated to 35 °C then placed in a preheated (70 °C) oil bath. A
liquid N cooled trap was used to collect the resulting yellow solid
2
during sublimation. After 1 h of sublimation, the trap was closed and
was transferred to the matrix isolation apparatus.
NaHCO
layer was neutralized with NH
diethyl ether to recover any tosylhydrazone that may have been lost as
the salt in the NaHCO wash. The organic layers were combined, dried
with MgSO , filtered, and concentrated under reduced pressure to reveal
an oily white solid. The product was purified via flash chromatography
5% EtOAc/CH Cl ) to reveal two separate white solids (1.52 g, 6.18
mmol, 93% yield over two steps). The assignment of syn vs anti is
based on the observation that treatment of the syn isomer with D O/
3
to quench AcOH remaining from the oxidation. The aqueous
4
Cl and extracted once with 30 mL of
3
4
(
2
2
2
NaOH results in immediate cyclization to pyrazole, while treatment of
the anti isomer affords H/D exchange (see below).
Extinction coefficients were determined by preparing a stock solution
of diazo compound in a known volume of CD OD containing a known
3
1
syn-2,4-Pentadiynal Tosylhydrazone (syn-7a). (0.57 g) H NMR
concentration of CH
3
CN as an internal standard. The concentration of
δ 8.77 (s, 1 H), 7.84 (d, J ) 8.7 Hz, 2 H), 7.34 (d, J ) 8.4 Hz, 2 H),
.62 (s, 1 H), 2.84 (s, 1 H), 2.44 (s, 3 H). 1 C NMR (Me
3
) δ
3
1
6
2
SO-d
6
diazo compound was determined, relative to CH
gration. Subsequent dilution with CH
bance values of 1-2. The extinction coefficients represent lower limits,
CN, by H NMR inte-
OH afforded solutions with absor-
1
44.0, 135.7, 129.7, 127.5, 124.6, 84.2, 81.3, 66.9, 65.0, 21.1. HRMS
3
+
(ESI, m/z) C12
H N
10 2
O
2
SNa calcd 269.0361, found 269.0367.
1
anti-2,4-Pentadiynal Tosylhydrazone (anti-7a). (0.95 g) H NMR
as the diazo compound decomposes slowly during the measurement
δ 8.23 (s, 1 H), 7.82 (d, J ) 9.9 Hz, 2 H), 7.35 (d, J ) 8.1 Hz, 2 H),
procedure.
undergoes exchange in CD
42 (65), 302 (13,969), 288 (19,843), 277 (16,841), 221 (33,947) nm.
IR (N , 10 K; relative intensity): 3320 (17), 3312 (9), 2188 (8), 2085
100), 2065 (37), 1374 (8), 581 (3), 496 (3), 489 (2) cm-1. UV/vis
, 10 K): λmax 305.4, 300.7, 288.9, 285.1, 274.6, 271.6, 261.6, 248.3
1
H NMR (CD OD) δ 3.40 (s, 1 H); the other resonance
3
3
6
.94 (s, 1 H), 2.56 (s, 1 H), 2.45 (s, 3 H). 1 C NMR (Me
2
SO-d
6
) δ
-1
-1
3 3
OD. UV/vis (CH OH): λmax (ꢀ, M cm )
1
44.2, 135.8, 130.1, 128.3, 127.4, 78.6, 76.5, 70.2, 66.9, 21.2. EIMS
4
+
(70 eV) m/z: M 246 (45), 182 (85), 155 (55), 91 (100), 65 (70). HRMS
2
+
(ESI, m/z) C12
H N
10 2
O
2
SNa calcd 269.0361, found 269.0356.
(
(
anti-2,4-Pentadiynal-5-d Tosylhydrazone (anti-7b). anti-Tosylhy-
drazone anti-7a (303 mg, 1.23 mmol) was dissolved in 5 mL of dry
CH Cl . Deuterium oxide (5 mL) was added, creating a biphasic system.
N
2
nm.
2
2
NaOH (0.01 g, 0.25 mmol) was added, and the mixture was stirred at
room temperature for 24 h under nitrogen. The layers were separated.
1-Diazo-2,4-pentadiyne-5-d (6b). IR (N , 10 K; relative intensity):
2
3
(
321 (17), 3312 (9), 2587 (12), 2583 (11), 2185 (11), 2087 (100), 2064
The aqueous layer was neutralized with NH
Cl . The organic layers were combined and washed once with 25 mL
saturated aqueous NH Cl. After separation, the organic layer was dried
with MgSO , filtered, and concentrated to reveal the recovered
4
Cl and extracted with CH
2
-
26), 1373 (9), 496 (6), 489 (5) cm-1
.
2
1
2
-Diazo-2,4-pentadiyne-1-d (6c). IR (N , 10 K; relative intensity):
4
3320 (11), 3311 (7), 2218 (2), 2214 (2), 2174 (5), 2094 (22), 2088
(100), 2065 (9), 2058 (7), 2055 (7), 2034 (2), 1337 (5), 652 (3), 648
(2), 605 (2), 594 (2), 581(3) cm-1.
4
tosylhydrazone as a white solid. The initial base-catalyzed exchange
presumably produces the dideuterio isotopomer (N-D, C-D). Sub-
sequent aqueous workup affords the monodeuterio isotopomer (N-H,
C-D). Isotopic incorporation of ca. 60-80% was typical, as established
1
1
Acknowledgment. The Wisconsin group gratefully acknowl-
edges the National Science Foundation for financial support of
this project (CHE-0412707 and CHE-0110769), the Depart-
mental parallel computing center (CHE-0091916), and the
electron paramagnetic resonance spectrometer (CHE-9013030).
The Texas group was supported by the National Science and
Welch Foundations.
by H NMR spectroscopy. H NMR δ 8.43 (s, 1 H), 7.82 (d, J ) 8.4
Hz, 2 H), 7.35 (d, J ) 7.8 Hz, 2 H), 6.95 (s, 1 H), 2.56 (s, 0.37 H;
residual protio material) 2.45 (s, 3 H). MS (ESI, m/z) 270 (C12
H
9
DN
2
O
2
-
+
+
+
SNa ), 517 ((C12H DN O
9 2 2
S)
2
Na ). EIMS (70 eV) m/z: M 247 (8),
1
83 (30), 155 (25), 91 (100), 65 (25). Note: under identical reaction
conditions, syn-tosylhydrazone 7a yields only pyrazole, the product of
intramolecular conjugate addition.
2
,4-Pentadiynol-1,1-d
synthesis of the protio compound 11 was followed (on 2/3 scale),
substituting paraformaldehyde-d (CD O) for paraformaldehyde (CH O)
Purification via flash chromatography (5% EtOAc/CH Cl ) affords 2,4-
pentadiynol-1,1-d (11-d ) (0.36 g, 4.4 mmol; 22% yield) as an amber
oil. H NMR δ 2.20 (s, 1 H), 1.90 (br s, 1 H).
2 2
(11-d ). The procedure described for the
2
2
n
2
n
.
Supporting Information Available: Details concerning ex-
perimental techniques; experimental procedure for the initial
synthesis of 1-diazo-2,4-pentadiyne (6a) (Scheme 3); infrared
2
2
2
2
1
J. AM. CHEM. SOC.
9
VOL. 128, NO. 10, 2006 3301