Baran Group Meeting
Apr. 21, 2012
Flash Vacuum Pyrolysis
Flash vacuum pyrolysis (FVP) or flash vacuum thermolysis (FVT) is a
process by which a substrate is distilled through a hot tube and the products
are collected afterwards in a cold trap.
–Unimolecular conditions
–High temperatures (200–1000 ºC), but short exposure times (~ms)
Therefore, there are only a few parameters to optimize, namely temperature,
time of exposure (related to initial heating, pressure, and carrier gas), and
occassionally solid-phase packing material.
Reactions typically fall into the following catagories:
–Pericyclic processes (entropy often favors "reverse" direction)
–Cleavage of small molecules (N2, CO2, CO, ethylene, etc.)
–Cleavage of the weakest bond in the molecule to afford free radicals
Since these processes are dominated by cleavage mechanisms, FVP
reactions are oxidative rather than reductive.
Ionic mechanisms are never encountered under FVP due to high ionization
energies in the absense of solvation.
"FVP should not be considered a molecular sledgehammer, even if
apparently extreme temperatures are employed."
Dane Holte
"The destructive distillation of mineral or organic material was one of the few
preparative methods available to the alchemists and the first chemists."
ferrous sulfate
urine
oil gas
!
sulfuric acid
Basil Valentine, 15th century
!
phosphorous
Brand, 1669
!
benzene
Faraday, 1825
glowing iron tube
pumice packing
N
N
Ber. Dtsch. Chem. Ges. 1899, 22, 3339.
Justus Liebigs Ann. Chem. 1891, 1, 49.
Cost of FVP apparatus?
–Standard laboratory vacuum
–Quartz tubing (<$100, www.technicalglass.com)
–Tube furnace ($2500.00+, www.coleparmer.com)
–Typical glassware
Notable Reviews:
Angew. Chem. Int. Ed. Engl. 1977, 16, 365.
Brown, R.F.C. Pyrolytic Methods in Organic Chemistry, Academic
Press, 1980.
Tetrahedron, 1986, 42, 2135.
Thermochimica Acta 1987, 112, 31.
Pure & Appl. Chem. 1990, 62, 1981.
Contemp. Org. Syn. 1996, 3, 373.
Eur. J. Org. Chem. 2001, 2209.
Aldrichimica Acta 2004, 37, 19.
"Pyrolysis, Flash Vacuum," in Kirk-Othmer Encyclopedia of
Chemical Technology, 2006; pp 134–158.
Aust. J. Chem. 2010, 63, 1002.
Aldrichimica Acta 1984, 17, 31.
Baran Group Meeting
Apr. 21, 2012
Flash Vacuum Pyrolysis
O2
S
Alkane formation
O
O
660 ºC
O
0.05 mmHg
56% yield
Bull. Chem. Soc. Jap. 1993, 66, 1239.
69% yield
Me
Me
S
A
Me
660 ºC
O
B
S
Cl
Cl
Me
O2
S
Me
Me
S
S
550 ºC
S
O2
S
+
O
O
700 ºC
S
O2
0.05 mmHg
[1 gram scale]
O
Dane Holte
Me
0.5–1.0
mmHg
Me
Me
0.05 mmHg
O
Cl
+
Cl
Cl
J. Am. Chem. Soc. 1968, 90, 2839.
S
O2S S
470 ºC
1.5–2 mmHg
S
(1.00:2.04:1.00, A:B:C)
3% yield
10-5
O
mmHg
A. mesitylene, 220 ºC
Angew. Chem. Int. Ed. 1992,
31, 307.
CO2Me
B. 550 ºC, 0.1 mmHg
CO2Me
10-5 mmHg
note: the products were
obtained as mixtures, but at
each temperature, the shown
product is the major component
MeO2C
MeO2C
O
620 ºC
O
J. Org. Chem.
1992, 57, 4654.
Alkene formation
MeO2C CO2Me
25% yield
O
O2S S
7% over three steps
O
610 ºC
1. NBS
2. Na2S!9H2O
3. mCPBA
Cl
C
Me
25% yield
A. decomposition
B. 80% yield
J. Am. Chem. Soc. 1991, 113, 636.
20% yield
O
O
650 ºC
OTMS
O
10-5 mmHg
D
550 ºC
OTMS
0.01 mmHg
31% yield
D
D
D
J. Chem. Soc. Perkin Trans. 1 1976, 371.
D
55% forbidden
suprafacial 1,3-shift
OTMS
D
+ 3% retro DA, 37% enol hydrolysis
Baran Group Meeting
Apr. 21, 2012
Flash Vacuum Pyrolysis
S
780 ºC,
0.2 mmHg
Cl
Me
Dane Holte
85% yield
-HCl
[10 g / 30 min.]
S
Synthesis, 1992, 1265.
400 ºC
S
10-4 mmHg
[5 gram scale]
86% yield
150 ºC
S
OAc
OAc
neat
O
FVP
Cl
1
630
14
28
2
630
5
53
3
780
5
59
4
780
5
60
6
800
1.75
32
7
800
1.5
75
8
780
0.5
80
Ph
Ph
[30g / 2 hr]
Cl
O
Cl
90% yield
+ 7% PhH
N
Ac
O
600 ºC
OTs
OHC
O
nBu
CO2Me
Atisane
Sealed tube (180 ºC, 30 min): decomp.
Reflux in collidine (180 ºC, 18h): n.r.
Sublimation (300 ºC, 0.1 mmHg): low conversion
Aconane
N
Ac
O
H
77% after
two passes
J. Chem. Soc., Perkin Trans. 1 1972,1490.
nBu
4
500 ºC
0.01 mmHg
CO2Me
>80% yield,
(based on RCHO)
O
4
nBu
then, TsOH
MgO
Me
0.3–0.5 mmHg
CO2Me
4
"easily"
O
H
F
83% yield
nBuMgCl,
[25g / 2 hr]
Ph
0.1 mmHg
81% yield
J. Org. Chem. 1989, 54, 5811.
Me
Ph
CuCl
Cl
O
305 ºC
An approach toward the prostainoids
700 ºC, <1 mmHg
TsO
Ph
83% yield
Tetrahedron Lett. 1994, 35, 4851.
Tetrahedron Lett. 1994, 35, 4853.
87% yield
[60g / 3.5 hr]
F
F
525 ºC, <1 mmHg
S
O
0.1 mmHg
O
S
HO
Cl
508 ºC
Ph
O
700 ºC, <1 mmHg
MeS
S
F
Tetrahedron Lett. 1998, 39, 1695.
HO
OH
O
5
780
1.75
35
20% yield
J. Org. Chem. 1986, 51, 114.
[200 gram scale]
Me
Run
Column Temp. (ºC)
Pressure (mmHg)
Yield (%)
O
nBu
O
Li(OtBu)3AlH
CO2Me
4
>60% yield
over 4 steps
J. Chem. Soc., Chem. Commun. 1976, 12, 446.
For more on the concept of "transient chirality" utilizing
retro-DA methodology, see: Chem. Rev. 1999, 99, 1163.
Baran Group Meeting
Apr. 21, 2012
Flash Vacuum Pyrolysis
O
Me
Me
O
H Me
Me
500 ºC, 1.0 mmHg Me
hirsutene
100% yield
O
H
O
740 ºC
630 ºC
O
Cl
0.05 mmHg
70–75% yield
Tetrahedron Lett. 1992, 33,1825.
J. Chem. Soc., Chem. Commun. 1973, 123.
Alkyne formation
O
Me Me
H H
Me Me
capnellene
O
O
600 ºC
33% yield
Me
Me
O
H
Helv. Chim. Acta 1982, 65, 2413.
Me H
Me
Me
550 ºC, 0.5 mmHg
Me
O
N
SO2
9x10-3 mmHg
83% yield
J. Org. Chem. 1997, 62, 2767.
Me
CHO
+
HN
O
95% yield
O
Angew. Chem. Int. Ed. 1978, 17, 609.
750 ºC
10-3 mmHg
N
H
97% yield
HN
Me O
Me O
220 ºC
Helv. Chim. Acta 1980, 63, 1703.
O
S
(10:1 sm:pdt)
Synthesis, 1993, 1067.
2-ethynylpyrrole polymerizes at room temperature,
yet is thermodynamically stable in the gas phase
up to 1000 ºC.
550 ºC,
R
10-3 mmHg
N
Helv. Chim. Acta 1994, 77, 36.
SO2
PhS
O
Me
Me
800 ºC
Me
O
H
10-3 mmHg
68% yield
O
PhS
~45% yield
[35 g scale]
O
72% yield
500 ºC,
H
620 ºC, 14 mmHg
O
0.1 mmHg
Aust. J. Chem. 1984, 37, 2295.
Cl
Me Me O
H H
Me
O
65% yield
Tetrahedron, 1981, 37, 4543.
See also: Weidner, Triquinane GM, 2012.
The Brown Reaction
Me O
0.2 mmHg
HO
H
Dane Holte
Ph3P
H
80% yield
NOT FVP
H
R
H
500 ºC,
10-3 mmHg Bu
O
Bu
Ph
66% yield
J. Chem. Soc., Perkin Trans. 1, 1994, 2473.
700 ºC,
10-3 mmHg Bu
Ph
Ph
Baran Group Meeting
Apr. 21, 2012
Flash Vacuum Pyrolysis
Dane Holte
Aromatic Chemistry
Me O
MeO
O
O
Me
Me
Me
MeO
650 ºC,
0.01 mmHg
OH
99% yield
Me
O
Aust. J. Chem. 1995, 48, 1055.
Me
OH
Corannulene
OH
700 ºC,
15 mmHg
1000 ºC, 10-4 mmHg
10% yield, 30–50 mg scale
J. Am. Chem. Soc. 1991, 113, 7082.
Me
Br
Helv. Chim. Acta 1986, 69, 560.
870 ºC, 0.2 mmHg
N
N
N
Na
N
Br
Br
Br
Br
Br
70% yield
J. Chem. Soc, Chem. Commun. 1972, 1219.
SO2Ar
Br
Br
250 ºC, FVP
900 ºC, 10-4 mmHg
1000 ºC, FVP
18% yield, 60 mg scale
23% yield, 50 mg scale
J. Am. Chem. Soc. 1992, 114, 1920. J. Am. Chem. Soc. 1992, 114, 1921.
30% yield
J. Am. Chem. Soc., 1969, 91, 7754.
TMS
Cl
Cl
FVP
13C-label
J. Am. Chem. Soc., 1977, 99, 4506.
400–500 ºC, 1-2 hr
or FVP >800 ºC
Experientia, 1947, 3, 70.
Extensive 13C-labelling studies and DFT calculations show that multiple
mechanisms are operative, which are interesting, complex, and out of the
scope of this group meeting. For a thorough discussion, see:
Acc. Chem. Res. 1982, 15, 52.
J. Am. Chem. Soc. 2003, 125, 5375.
TMS
900 ºC, FVP, H2 carrier gas
15% yield, 20–40 mg scale
Tetrahedron Lett. 1994, 35, 4747.
1100 ºC, 1.0 mmHg
N2 carrier gas, 1.0 g scale, 40% yield
J. Am. Chem. Soc. 1997, 119, 10963.
For a higher-yielding, solution-phase approach based on similar
disconnections, see: J. Am. Chem. Soc. 2000, 122, 6323.
For additional synthesis of and studies on geodesic polyarenes,
see: Chem Rev. 2006, 106, 4868.
Baran Group Meeting
Apr. 21, 2012
Flash Vacuum Pyrolysis
Me O
Me
Me O
600 ºC
H
O
Heterocyclic Chemistry
H
–CH4
40% yield
H
H
Dane Holte
H
H
KOtBu [1 mol]
N3
Cl
0.1 mmHg
80 ºC, 0.1 mmHg
[0.17 mol, 17.9 g]
HO
J. Chem. Soc., Chem. Commun. 1983, 238.
J. Am. Chem. Soc. 1950, 72, 4531.
Ph
585 ºC
Ph
OH
NH2
O
N
(S)-phenylalanine
CHO
10-4
mmHg
Ph
O
CHO
Chem. Ber. 1990, 123, 635.
Angew. Chem. Int. Ed. 1991, 30, 893.
C
A
N
500 ºC
10-3
700 ºC
P
mmHg
10-3
mmHg
Me
J. Chem. Soc., Chem. Commun. 1992, 1799.
S
Me
O
major product
S
O
720 ºC
S
~10-5 mmHg
O
J. Org. Chem. 1990, 55, 2596.
mmHg
Ph
CN
N
E
A
B
C
D
E
100%
some
–
–
>64%
–
–
some
some
–
some
some
–
some
–
(+ charred material)
J. Chem. Soc., Perkin Trans. 1, 1975, 45.
800 ºC
O
CN
HS
0.1 mmHg
N
H
S
O
550 ºC
O
38% yield
Tetrahedron Lett. 1999, 40, 9271.
H
C
+
O
J. Chem. Soc., Perkin Trans. 1 1991, 3225.
1000 ºC
N
B
O
600 ºC
Me
Me ~10-5 mmHg
95% yield
O
400
420–450
>500
P
P
10-3
D
temp. (ºC)
P
H
temp.
N
83% yield N
54% from phenylalanine
C
[0.1 mol, 4.1g]
59% yield
N
Ph
3 steps
N
Ph
Heteroatom Containing Functional Groups
O
400 ºC
N3
O
NH
0.1 mmHg
80% yield
S
H
6% yield
HO
S
53% yield
CHO
HS
SH
OH
750 ºC
10-3
Angew. Chem. Int. Ed. 1994, 33, 465.
mmHg
S
S
60% yield
Baran Group Meeting
Apr. 21, 2012
Flash Vacuum Pyrolysis
Dane Holte
N
N
590 ºC
O
N
O
O
0.01 mmHg
CO2Et
N
O
0.01 mmHg
–CO2
N
Ar
87% yield
CO2Et
N
NO2
Ar
N
N
N
H 11% yield
EtO2C
O
O
O
N
N
Me
Me
Me
Me
O
OAc
MeO
CO2Et
MeO
Me
N
O
~0.05 mmHg
CO2Et
O
O
Cl
66% yield
70% mixture,
1.0:2.7 ratio
Me
600 ºC
Me
FVP
N
O
O
J. Chem. Soc., Chem. Commun. 1993, 1570.
90% yield
Cl
Me
Cl
O
NH
N
OAc
O
Me
N
OH
O
O
O
~500 ºC
N
O
750 ºC
O
J. Chem. Soc., Chem. Commun. 1993, 794.
O
82% yield
CO2Et
10-3 mmHg
Tetrahedron, 1993, 49, 8147.
O
Me Me
O
CO2Et
N
0.02 mmHg
[4 g scale]
Tetrahedron 1992, 48, 8947.
NH
EtO2C
550 ºC
CO2Et
N
EtO2C
O
O
CO2Et
N
99% yield
O
N
NO2
Ar
O N
J. Chem. Soc., Chem. Commun. 1994, 2661.
NO2
~550 ºC
10-4 mmHg
Me
92% yield
CO2Me
N
O
Me
475 ºC
O
N
N
490 ºC
O
0.1 mmHg
O
J. Chem. Soc., Perkin Trans. 1 1997, 2665.
O
O
Cl
N
Me
18% yield
Me
O
O
O
N
H
O
Me
500–550 ºC
Me
0.01 mmHg
O
Tetrahedron, 1996, 52, 3163.
O
N
Me
77% yield
Baran Group Meeting
Apr. 21, 2012
Flash Vacuum Pyrolysis
Dane Holte
O
O
O
Me2N
Me
500 ºC
Me
10-3 mmHg
630 ºC
O
N3
N
Me
O
SO2
+
3 mmHg, N2 carrier
N
H
N
65% yield
11% yield
64% yield
J. Chem. Soc., Chem. Commun. 1987, 140.
J. Chem. Soc., Perkin Trans. 1 1989, 425.
H
N
For a review containing an overview of FVP with Meldrum's acid
derivatives, see: Aldrichimica Acta 2004, 37, 19.
SO2
N
Me
N
Me
N
650 ºC
N
HO
0.03 mmHg
N
N
Me
N N
J. Am. Chem. Soc. 1975, 97, 676.
>90% yield
O
Aust. J. Chem. 1994, 47, 991.
O
O
900 ºC
O
10-3 mmHg
J. Am. Chem. Soc. 1964, 86, 2741.
J. Am. Chem. Soc. 1967, 89, 2413.
925 ºC
N
0.01 mmHg
MeO2C
J. Chem. Soc., Perkin Trans. 1 1999, 2047.
N
79% yield
Me
N
O
CO2Me
O
P
–CO
700 ºC
10-3 mmHg
CO2H
Ph
100%
Me
N
+
74%
+
CO2Me
60%
O
P
J. Chem. Soc., Chem. Commun. 1993, 1295.
–PhCO2H
P
40% yield
retro ene
Me
N
CO2Me
H
NMe
retro ene
H
MeO2C
Tetrahedron Lett. 1989, 30, 5977.