Facile Preparation of 3, 7-Diazabicyclo[3.3.0]octane and 3, 7, 10-Triheterocyclic [3.3.3]Propellane Ring Systems from 1, 5-Diazacyclooctane 3, 7-Derivatives

Article abstract of DOI:10.1021/jo9614755

The cyclodimerization ofp-toluenesulfonamide and 3-chloro-2-(chloromethyl)-l-propene to prepare W, Ar-bis(p-toluenesulfonyl)-3, 7-bis(methylene)-l, 5-diazacyclooctane (la) and its ozonation to the corresponding 3, 7-dione 2a are reported. Unusual transannular cyclizations initiated by lithium aluminum hydride treatment or bromination of la and oxidative coupling of the dioxime derived from 2a are described. These reactions lead, respectively, to the following derivatives of the littlestudied 3, 7-diazabicyclo[3.3.0]octane ring system: l, 5-dimethyl-3, 7-diazabicyclo[3.3.0]octane (5), Ar/'-bis(p-toluenesulfonyl)-l, 5-bis(bromomethyl)-3, 7-diazabicyclo[3.3.0]octane (8), and N, N'-bis(ptoluenesulfonyl)-l, 5-dinitro-3, 7-diazabicyclo[3.3.0]octane, (12). Acid-catalyzed hydration of la, in contrast, gives the expected 5-methyl-3, 7-diazabicyclo[3.3.1]nonan-l-ol (10). Reaction of the dibromide 8 with the nucleophiles, sodium sulfide, sodium oxide, and sodium p-toluenesulfonamide conveniently delivers the corresponding novel 3, 7, 10-triheterocyclic [3.3.3]propellanes.

Full text of DOI:10.1021/jo9614755

J . Org. Chem. 1996, 61, 8897-8903
8897
F a cile P r ep a r a tion of 3,7-Dia za bicyclo[3.3.0]octa n e a n d
3,7,10-Tr ih eter ocyclic [3.3.3]P r op ella n e Rin g System s fr om
1,5-Dia za cycloocta n e 3,7-Der iva tives1
Paritosh R. Dave* and Farhad Forohar
GEO-CENTERS, INC at ARDEC, Building 3028, Picatinny Arsenal, New J ersey 07806-5000
Theodore Axenrod, Kajal K. Das, Lida Qi, Clara Watnick, and Hamid Yazdekhasti
Department of Chemistry, The City College of the City University of New York,
New York, New York 10031
Received August 1, 1996X
The cyclodimerization of p-toluenesulfonamide and 3-chloro-2-(chloromethyl)-1-propene to prepare
N,N′-bis(p-toluenesulfonyl)-3,7-bis(methylene)-1,5-diazacyclooctane (1a ) and its ozonation to the
corresponding 3,7-dione 2a are reported. Unusual transannular cyclizations initiated by lithium
aluminum hydride treatment or bromination of 1a and oxidative coupling of the dioxime derived
from 2a are described. These reactions lead, respectively, to the following derivatives of the little-
studied 3,7-diazabicyclo[3.3.0]octane ring system: 1,5-dimethyl-3,7-diazabicyclo[3.3.0]octane (5),
N,N′-bis(p-toluenesulfonyl)-1,5-bis(bromomethyl)-3,7-diazabicyclo[3.3.0]octane (8), and N,N′-bis(p-
toluenesulfonyl)-1,5-dinitro-3,7-diazabicyclo[3.3.0]octane, (12). Acid-catalyzed hydration of 1a , in
contrast, gives the expected 5-methyl-3,7-diazabicyclo[3.3.1]nonan-1-ol (10). Reaction of the
dibromide 8 with the nucleophiles, sodium sulfide, sodium oxide, and sodium p-toluenesulfonamide
conveniently delivers the corresponding novel 3,7,10-triheterocyclic [3.3.3]propellanes.
Sch em e 1
In tr od u ction
The chemistry of 1,5-diazacyclooctanes has been in-
vestigated in these laboratories as part of a continuing
program to synthesize novel high density energetic
materials derived from functionalized small-2 and medium-
ring nitrogen heterocycles. As a class,3 1,5-diazacyclooc-
tanes are versatile compounds important as pharmaceu-
tical intermediates, polymerization accelerators, antiknock
agents in motor fuels, and energetic materials.4,5 In the
course of this work, 1,5-diazacyclooctanes exhibited a
marked propensity to undergo unusual transannular
cyclizations to form the 3,7-diazabicyclo[3.3.0]octane ring
system. With one notable exception, this same unex-
pected bicyclic ring system was formed by treatment of
1,5-diazacyclooctanes with several dissimilar reagents
under conditions that doubtless proceed through different
intermediates and by quite distinct reaction mechanisms.
These cyclizations have been exploited to provide facile
entry into the little-studied 3,7-diazabicyclo[3.3.0]octane
ring system, which is easily transformed into polyhet-
eroatom-containing tricyclic compounds conjoined in a
carbon-carbon single bond (propellanes).6 In this paper,
we detail new synthetic routes to the 1,5-diazacyclooc-
tane, 3,7-diazabicyclo[3.3.0]octane, and 3,7,10-trihetero-
cyclic [3.3.3]propellane6 ring systems that now become
conveniently accessible.
Resu lts a n d Discu ssion
1,5-Dia za cycloocta n es. Conspicuously absent from
the many known 1,5-diazacyclooctanes are the 3,7-
dimethylene and 3,7-diketo derivatives. These com-
pounds were initially targeted as simple intermediates
useful for the facile functionalization of the 3,7-ring
positions. The sequence of steps outlined in Scheme 1
illustrates the synthetic method that was used to prepare
these 3,7-dimethylene and 3,7-diketo derivatives. In this
approach, when either p-toluenesulfonamide or meth-
anesulfonamide was allowed to react with 3-chloro-2-
(chloromethyl)-1-propene in the presence of potassium
carbonate the corresponding cyclodimeric 3,7-bis(meth-
ylene)-1,5-diazacyclooctane derivatives 1 were easily
obtained and isolated in moderate to good yields (∼50%).
The use of sulfonamides in this procedure is found to
be superior to the previously described reactions of
amines with 3-halo-2-(halomethyl)-1-propenes7,8 or other
bifunctional allylic compounds where the product is
frequently a complex mixture consisting of the 3-meth-
ylene-1-azetidines, 3,7-bis(methylene)-1,5-diazacyclooc-
tanes, and higher cyclic oligomers as well as noncyclic
materials.9,10 Ozonation of the exocyclic double bonds in
X Abstract published in Advance ACS Abstracts, November 15, 1996.
(1) For a preliminary communication see: Dave, P. R.; Forohar, F.
F.; Axenrod, T.; Qi, L.; Watnick, C.; Yazdekhasti, H. Tetrahedron Lett.
1994, 35, 8965.
(2) Axenrod, T.; Watnick, C.; Yazdekhasti, H.; Dave, P. R. Tetrahe-
dron Lett. 1993, 34, 6677.
(3) For a review see Perlmutter, H. D. Adv. Heterocycl. Chem. 1989,
46, 1.
(4) Cichra, D. A.; Adolph, H. G. Synthesis 1983, 830.
(5) Li-Hua, X.; Ming-xuan, W.; En-pu, W.; Hui-min, T.; BØ-ren, C.
Propellants, Explos., Pyrotech. 1988, 13, 21.
(6) For a discussion of the use of this trivial nomenclature, see
Knowles, P.; Harris, N. V. J . Chem. Soc., Perkin Trans. 1 1983, 1475.
Altman, J .; Babad, E.; Itzchaki, J . Ginsburg, D. Tetrahedron, Suppl.
8, Part I, 1966, 279.
(7) Schulze, K.; Winkler, G.; Dietrich, W.; Mu¨hlsta¨dt, M. Prakt.
Chem. 1977, 319, 463.
(8) Schulze, K.; Vetter, A.; Dietrich, W.; Mu¨hlsta¨dt, M. Z. Chem.
1977, 17, 174.
(9) Lukin, S. S.; Levashova, V. I.; Bunina-Krivorukova, L. I.; Zlotskii,
S. S. J . Org. Chem. USSR 1989, 2210.
S0022-3263(96)01475-2 CCC: $12.00 © 1996 American Chemical Society

8898 J . Org. Chem., Vol. 61, No. 25, 1996
Dave et al.
Sch em e 2
Sch em e 3
Ta ble 1. Resu lts of An a lysis of Deu ter iu m Con ten t of
1,5-Dim eth yl-3,7-d ia za bicyclo[3.3.0]octa n es-d x 5 Obta in ed
in Hyd r id e Red u ction of 1a
the 3,7-bis(methylene)-1,5-diazacyclooctanes 1 produced
the corresponding 1,5-diazacyclooctane-3,7-diones 2 in
excellent yields.
products, 5
Analysis of the respective 1H and 13C NMR spectra
together with their mass spectra confirms that the
cyclodimerization products of the reaction of p-toluene-
sulfonamide or methanesulfonamide with 3-chloro-2-
(chloromethyl)-1-propene are the 3,7-bis(methylene)-1,5-
diazacyclooctane derivatives 1 and not azetidines or some
higher cyclic oligomers that are possible.
Although the stereoisomeric 1,5-diazacyclooctane-3,7-
diols 3 are readily prepared from the reaction of p-
toluenesulfonamide anion with epichlorohydrin or 1,3-
dihalo-2-propanols, this route to the 1,5-diazacyclooctane-
3,7-diones 2 is unsatisfactory because of the failure of
the latter diols to undergo complete oxidation. Rather,
as outlined in Scheme 2, chromic anhydride oxidation is
reported11 to give the transannular hemiketal 4 and, in
our hands, oxidation under Swern conditions gives the
same product.
LRMSb
(M + 1)+
δ
13C{1H}, ppm
methyl CH2
reactanta
hydride/quench m/zc
Cq
LAH/H2O
LAH/D2O
LAD/H2O
LAD/D2O
141 C8H17N2
142 C8H16DN2
142 C8H16DN2
20.4,-
51.7 62.6
20.4, 20.0d 51.5 62.3
20.4, 20.0d 51.5 62.3
143 C8H15D2N2- -, 20.0d
51.5 62.1
a
b
Compound 1a in THF treated with indicated reagents. Low
resolution chemical ionization (NH3) mass spectrum. c Base peak
(100%); other isotopomeric (M + 1)+ ions less than 10%. Triplet,
d
1J (13C-2H) ) 19.0 Hz.
formation, shown in Scheme 3, had occurred to afford 1,5-
dimethyl-3,7-diazabicyclo[3.3.0]octane 5 in 82% yield.
This conclusion is also supported by the measured mass
spectrum of 5.
To probe further the nature of this rather unexpected
reductive cyclization, a series of experiments with lithium
aluminum hydride and lithium aluminum deuteride was
carried out, and the reaction mixtures were quenched
with either H2O or D2O. The deuterium content of the
several labeled reaction products was determined from
the m/ z value of the prominent (M + 1)+ ion in the
chemical ionization (NH3) mass spectra of the 1,5-
dimethyl-3,7-diazabicyclo[3.3.0]octanes. Before mass mea-
surement, azeotropic distillation of the reduction products
with benzene containing added H2O was employed to
exchange any N-D species and convert them to the
corresponding N-H compounds. The position of deute-
rium incorporation was determined by analysis of the
carbon chemical shifts and multiplicities in the 13C{1H}
spectra. These results are summarized in Table 1.
Analysis of the (M + 1)+ ions in the mass spectra of
the various reaction products indicated that either one
or two deuterium atoms were quantitatively introduced.
Thus, reduction of 1a with LAH and quenching with D2O
or reduction with LAD and quenching with H2O afforded
material having an m/ z value equal to 142 corresponding
to C8H15DN2. Similarly, reduction with LAD followed by
D2O resulted in material having the composition
C8H14D2N2. The isotope shifts and multiplicities in the
13C{1H} spectra establish unequivocally that the deute-
rium atoms appear, as the case may be, in either one or
both of the methyls and then only as isotopically labeled
CH2D groups.
In apparent contrast, the transannular hemiketal of
5-hydroxycyclooctanone is converted to the corresponding
dione by J ones oxidation.12
3,7-Dia za b icyclo[3.3.0]oct a n es. The convenient
preparation of N,N′-bis(p-toluenesulfonyl) derivative 1a ,
suggested N-detosylation followed by alkylation with
appropriate electrophiles as a potential synthetic route
to a variety of N,N′-disubstituted-3,7-bis(methylene)-1,5-
diazacyclooctanes and their corresponding diketones.
Precedents for the hydrolysis of sulfonamides13 or their
smooth reductive cleavage by hydride reagents14 are
available in the literature.
When 1a was treated with lithium aluminum hydride,
in an attempted reductive detosylation to prepare the
parent 3,7-bis(methylene)-1,5-diazacyclooctane, the first
indication of the pronounced tendency toward transan-
nular cyclization in this system was detected. This
normally predictable hydride reduction was found to
follow an unexpected course. The reductive cleavage of
the tosyl group proceeded smoothly as evidenced by the
disappearance of the tosyl signals in the NMR spectrum
of the product. However, surprisingly, this was ac-
companied by the simultaneous disappearance of the
vinyl proton resonances at δ 5.19 and the emergence of
a singlet at δ 0.99 in the methyl region along with an
AB pattern centered at δ 2.71 and δ 2.92 (J ) 11.2 Hz).
The complete structure of this product was arrived at by
While we are aware of no precedent, the formation of
this bicyclic system can be rationalized, mechanistically,
in terms of a hydride attack at one of the exocyclic
methylene carbons followed by carbanion addition to the
proximal transannular double bond. The ring closure
process is then completed by transfer of a proton to the
newly generated intermediate methyl carbanion. This
proposed interpretation is consistent with the results of
these deuterium labeling experiments.
1
analysis of its H and 13C NMR spectra including record-
ing the DEPT and HETCORR spectra. From these
determinations it was concluded that transannular bond
(10) Suzuki, M.; Lim, J .-C., Oguni, M.; Eberhardt, M.; Saegusa, T.
Polym. J . 1990, 22, 815.
(11) Paudler, W. W.; Gapski, G. R.; Barton, J . M. J . Org. Chem.
1966, 31, 277.
(12) Bishop, R. J . Chem. Soc. Perkin Trans. 1 1974, 2364.
(13) A mixture of acetic acid and
6 N hydrochloric acid has
successfully been used to remove the N-tosyl groups in 3,7-disubsti-
tuted octahydrodiazocines over a four-week period; see for example,
reference 16.
On the other hand, the smooth reduction of alkenes
by LiAlH4 in combination with catalytic quantities of such
first-row transition metal salts as CoCl2, NiCl2, and TiCl3
(14) Gold, E. H.; Babad. E. J . Org. Chem. 1972, 37, 2208.

Facile Preparation of 3,7-Diazabicyclo[3.3.0]octane
J . Org. Chem., Vol. 61, No. 25, 1996 8899
Sch em e 4
nonane skeleton. In this connection, it is interesting to
note that 1a reacts with H2SO4 in a manner that parallels
the behavior exhibited by carbocycle 6 toward electro-
philic reagents. Thus, by treatment with acid, 1a is
quantitatively converted to the expected 5-methyl-3,7-
diazabicyclo[3.3.1]nonan-1-ol 10.
is well-known. However, the low deuterium incorpora-
tion found when the product mixtures were quenched
with D2O suggests that the reactive intermediates arise
from the homolytic dissociation of a transition metal-
alkyl which subsequently abstracts hydrogen from the
solvent.15 This pathway is quite different from the
present case where good yields and essentially quantita-
tive deuterium incorporation are obtained in the absence
of any added transition metal salts.
The 3,7-diazabicyclo[3.3.0]octane ring system has
scarcely been investigated. The one reported example
in the literature, of which we are aware, was prepared
by a lengthy multistep synthesis.6 While ring contrac-
tions to diazepines and piperidines have previously been
observed in diazocine chemistry,16 transannular cycliza-
tions to bicyclic systems appear to be unknown. Thus, a
significant contrast in behavior is observed in the elec-
trophilic addition of bromine to the carbocycle, 1,5-bis-
(methylene) cyclooctane 6, and its diaza analog 1a .
1
The structure of 10 has been deduced from its H and
13C NMR properties as well as analysis of its mass
spectrum. The reaction path that leads to the formation
of 10 highlights the apparent disparity in the behavior
of 1a toward acid-catalyzed hydration compared with the
product of what is presumed to be electrophilic addition
of bromine.
Transannular cyclizations in the diazacyclooctane sys-
tem offer an attractive and viable synthetic route to the
inaccessible 3,7-diazabicyclo[3.3.0]octane ring system.
This property was utilized in the synthesis of 1,3,5,7-
tetranitro-3,7-diazabicyclo[3.3.0]octane (13) shown in
Scheme 5. Compound 2a was converted to the corre-
sponding dioxime 11 by standard method. NMR analysis
showed the dioxime product so obtained to be a mixture
of the syn (minor) 11a and anti (major) 11b stereoiso-
mers, from which the latter could be isolated in pure form
by recrystallization from 95% ethanol. Treatment of the
stereoisomeric mixture of the dioximes 11 with N-
bromosuccinimide in aqueous dioxane or with m-chlo-
roperbenzoic acid in a buffered medium leads in both
instances to ring-closure giving N,N′-bis(p-toluenesulfo-
nyl)-1,5-dinitro-3,7-diazabicyclo[3.3.0]octane 12. NMR
and mass spectroscopic data provide evidence for the
structure of compound 12.
Both systems are disposed to undergo transannular
cyclizations, but quite dissimilar ring skeletons are
obtained. For example, carbocycle 6 is transformed by
bromine into bridgehead substituted bicyclo[3.3.1]nonane
derivatives,12 whereas, as outlined in Scheme 4, 1a gives
an unexpected mixture of the 1,2- and 1,4-dibromo
addition products, N,N′-bis(p-toluenesulfonyl)-3-bromo-
3-(bromomethyl)-7-methylene-1,5-diazacyclooctane (7) and
N,N′-bis(p-toluenesulfonyl)-1,5-bis(bromomethyl)-3,7-
diazabicyclo[3.3.0]octane (8) together with very small
quantities of the tetrabromide, N,N′-bis(p-toluenesulfo-
nyl)-3,7-dibromo-3,7-bis(bromomethyl)-1,5-diazacyclooc-
tane (9). The relative amounts of 7 and 8 formed are
sensitive to the reaction conditions. Combination of
molar equivalents by rapid dropwise addition of a solu-
tion of bromine to 1a in CH2Cl2 at 0 °C affords mainly 7,
whereas slow addition of the bromine reverses the
situation leading to 8 as the major product. Attempts
to convert 7 to 8 by heating in DMSO at 110 °C for 16 h
were unsuccessful, and the starting material was recov-
ered.
In a recent parallel report 3,7-dinitrotricyclo[3.3.1.03,7]-
nonane has been prepared17 from the dioxime of the
corresponding bridgehead bicyclic diketone by oxidative
coupling with m-chloroperbenzoic acid. Similar transan-
nular reactions of bisoximes have also been described by
Paquette18 and Camps et al.19
Treatment of 12 with trifluoroacetyl nitrate in CH2-
Cl2 results in the nitrolysis of the tosyl groups affording
the tetranitro compound 13. The structure of 13 is
supported by the presence of the expected AB system
centered at δ 4.99 and δ 5.14 (J ) 13.9 Hz) in the 1H
spectrum. Alternatively, compound 13 could be prepared
directly from 11 by nitrolysis with 100% HNO3. In this
case considerable nitration of the tosyl groups was
observed, but it proved possible to isolate pure 13 in 25%
yield by preparative scale thin-layer chromatography.
These assignments and the structure of 13 were further
substantiated by X-ray crystallographic analysis.20
The structures assigned to compounds 7-9 are con-
firmed by their 1H and 13C NMR properties and their
mass spectra.
From carbonium ion considerations, the reaction of 1a
with bromine to give 7 and 8 is exceptional and clearly
at variance with the anticipated and more readily
rationalized formation of the 3,7-diazabicyclo[3.3.1]-
(17) Camps, P.; Munoz-Torrero, D. Tetrahedron Lett. 1994, 35, 3187;
See also, Chapman, R. D.; Archibald, T. G.; Baum, K. Report No. ONR-
7-1 (Interim), 1989; Fluorochem Inc., Azusa, CA; AD-A214106; avail-
able from the National Technical Information Service, U.S. Department
of Commerce, Springfield, VA 22161.
(18) Waykole, L. M.; Shen, C. C.; Paquette, L. A. J . Org. Chem. 1988,
53, 4969.
(19) Camps, P.; Munoz-Torrero, D., Munoz-Torrero, V. Tetrahedron
Lett. 1995, 36, 1917. Camps, P.; Font-Bardia, M.; Munoz-Torrero, D.;
Solans, X. Liebigs Ann. Chem. 1995, 523.
(20) Ammon, H. L.; Zuyue, D.; Gilardi, R.; Dave, P. R.; Forohar, F.;
Axenrod, T. Acta Crystallogr. Sect. B 1996, 52, 352.
(15) See for example, Ganem, B.; Osby, J . O. Chem. Rev. 1986, 86,
763 and references cited therein.
(16) Paudler, W. W.; Zeiler, A. G.; Gapski, G. R. J . Org. Chem. 1969,
34, 1001.

8900 J . Org. Chem., Vol. 61, No. 25, 1996
Dave et al.
Sch em e 5
Sch em e 6
diazacyclooctanes is described. Unusual transannular
cyclizations in these systems leading to the little known
3,7-diazabicyclo[3.3.0]octane system have been examined.
Procedures were developed that permit the ready conver-
sion of the latter ring system to novel 3,7,10-trihetero-
cyclic [3.3.3]propellanes. The methods reported consti-
tute simple and efficient syntheses of otherwise
inaccessible 3,7-diazabicyclo[3.3.0]octanes and various
3,7,10-triheterocyclic [3.3.3]propellanes.
Exp er im en ta l Section
The chemical shifts in CDCl3, DMSO-d6, and acetone-d6 are
reported in δ (ppm) relative to TMS and were measured
against the solvent as an internal standard. Melting points
are uncorrected. THF was distilled from Na/benzophenone
immediately prior to use. Other solvents and reagents were
obtained from commercial sources and used without further
purification.
N,N′-Bis(p-tolu en esu lfon yl)-3,7-bis(m eth ylen e)-1,5-d i-
a za cycloocta n e (1a ). To a suspension of p-toluenesulfona-
mide (27.5 g, 160 mmol) and anhydrous K2CO3 (45.0 g) in
anhydrous acetonitrile (250 mL) was added 3-chloro-2-(chlo-
romethyl)-1-propene (20.0 g, 160 mmol) in acetonitrile (25.0
mL) over a 15 min period. After stirring the mixture at reflux
for 4 h, the solvent was evaporated in vacuo, and the solid
residue was extracted with hot ethyl acetate. Cooling the
extract gave 21.5 g (60%) of colorless crystalline N,N′-bis(p-
toluenesulfonyl)-3,7-bis(methylene)-1,5-dia za cycloocta ne
(1a ): mp 194-197 °C; 1H NMR (CDCl3) δ 2.43 (s, 6H), 3.82 (s,
8H), 5.19 (s, 4H), 7.67 (d, J ) 8.3 Hz, 4H), 7.31 (d, J ) 8.3 Hz,
4H); 13C NMR (CDCl3) δ 21.5, 53.0, 118.1, 127.1, 129.7, 135.8,
141.8, 143.5. HRMS (FAB) calcd for C22H27N2O4S2 (MH)+
3,7,10-Tr ih et er ocyclic [3.3.3]P r op ella n es. Poly-
amines, having the appropriate three-dimensional struc-
ture, such as that represented by the parent propellanes
of 14-16, have possible application as bifunctional
catalysts in 1,3-proton transfer reactions. Thus, they are
potentially important as mimics of transaminases in
biological processes.21 It has previously been observed
that heterocyclic propellanes are difficult to prepare. In
particular, it has been reported that angular halomethyl
groups which form part of substituted neopentyl systems
fail to undergo cyclization to the corresponding hetero-
cyclic propellanes.6 The ready availability of appropriate
precursors in the present work prompted us to examine
anew these ring-closures, which, if successful, would open
a facile route to these desired heterocyclic propellanes.
Although the reaction of 8 with nucleophiles was slug-
gish, this difficulty was surmounted by heating the
reactants in dimethyl sulfoxide. Thus, as shown in
Scheme 6, when 8 was heated with either Na2S, Na2O,
or the preformed sodium salt of p-toluensulfonamide,
cyclization could be induced to give the corresponding
triheterocyclic propellanes. In this manner, propellanes
14, 15, and 16 were conveniently prepared in 80%, 75%,
and 78% yield, respectively.
447.1412; found m/ z, 447.1402. Anal. Calcd for C22H26
-
N2O4S2: C, 59.17; H, 5.87; N, 6.27. Found: C, 59.21; H, 5.98,
N, 6.54.
N,N′-Bis(m et h a n esu lfon yl)-3,7-b is(m et h ylen e)-1,5-d i-
a za cycloocta n e (1b). To a well-stirred refluxing suspension
of methanesulfonamide (15.2 g, 160 mmol) and anhydrous K2-
CO3 (48.5 g) in acetonitrile (150 mL) was added 3-chloro-2-
(chloromethyl)-1-propene (20.0 g, 160 mmol). The mixture was
heated at reflux for 4 h and then cooled and filtered, and the
filtrate was concentrated to give a solid residue, which was
extracted with CH2Cl2 (100 mL). The CH2Cl2 solution was
washed with 5% NaOH (50 mL) and water, dried (MgSO4),
and evaporated to give 4.96 g (22%) of crude N,N′-bis-
(methanesulfonyl)-3,7-bis(methylene)-1,5-diazacyclooctane (1b).
Recrystallization from ethyl acetate afforded a colorless crys-
talline solid: mp 136-137 °C; 1H NMR (CDCl3) δ 2.88 (s, 6H),
3.99 (s, 8H), 5.28 (s, 4H); 13C NMR (CDCl3) δ 38.1, 52.8, 119.3,
141.2. HRMS (FAB) calcd for C10H19N2O4S2 (MH)+ 295.0786;
found m/ z, 295.0781. Anal. Calcd for C10H18N2O4S2: C, 40.80;
H, 6.16; N, 9.52. Found: C, 41.11; H, 5.87, N, 9.32.
The 1H and 13C NMR spectral properties of these
propellanes were consistent with the expected structures.
The chemical shifts observed for the different carbons
attached to nitrogen, oxygen, and sulfur in these propel-
lanes also compare favorably with the trends reported
for other related heteropolycycloalkanes.22
In conclusion, a convenient preparation of 3,7-func-
tionalized N,N′-diarylsulfonyl and dialkylsulfonyl-1,5-
N,N′-Bis(p-tolu en esu lfon yl)-1,5-d ia za cycloocta n e-3,7-
d ion e (2a ). A mixture of ozone in oxygen was bubbled
through
a solution of N,N′-bis(p-toluenesulfonyl)-3,7-bis-
(21) Wu, Y.; Ahlberg, P. Acta Chem. Scand. 1992, 46, 60.
(22) Breitmaier, E.; Voelter, W. Carbon-13 NMR Spectroscopy; VCH
Publishers: New York, 1987; p 277.
(methylene)-1,5-diazacyclooctane (1a ) (1.0 g, 2.24 mmol) in
CH2Cl2 (20 mL) at -78 °C until the blue color persisted. The

Facile Preparation of 3,7-Diazabicyclo[3.3.0]octane
J . Org. Chem., Vol. 61, No. 25, 1996 8901
mixture was stirred for 1 h and then allowed to warm to 0 °C.
Oxygen was bubbled through the mixture to remove excess
ozone, and then excess dimethyl sulfide was added. After
stirring at rt for 1 h the mixture was concentrated, and the
residue was dissolved in CH2Cl2, washed with water and brine,
dried (MgSO4), and concentrated. The residue was recrystal-
lized from acetone/hexanes to give pure N,N′-bis(p-toluene-
sulfonyl)-1,5-diazacyclooctane-3,7-dione (2a ) (0.86 g, 85%): mp
275 °C dec; 1H NMR (CDCl3) δ 2.45 (s, 6H), 4.08 (s, 8H), 7.72
(d, J ) 8.3 Hz, 4H), δ 7.36 (d, J ) 8.3 Hz, 4H); 13C NMR
(CDCl3) δ 21.6, 59.9, 127.1, 130.3, 133.9, 145.1, 204.3; HRMS
(FAB) calcd for C20H23N2O6S2 (MH)+ 451.0998; found m/ z
451.0990. Anal. Calcd for C20H22N2O6S2: C, 53.32; H, 4.92;
N, 5.93. Found: C, 53.61; H, 5.09, N, 5.93.
1,5-Dim eth yl-3,7-d ia za bicyclo[3.3.0]octa n e-d 1. The pro-
cedure used to prepare 5 was modified by the use of deuterated
reagents in two separate experiments.
(a) N,N′-Bis(p-toluenesulfonyl)-3,7-bis(methylene)-1,5-diaza-
cyclooctane (1a ) (0.223 g, 0.50 mmol) in THF (50 mL) was
treated with LiAlH4 (0.25 g, 6.6 mmol). Quenching of the
reaction mixture with D2O (1.0 mL) followed by 40% NaOD
(0.5 mL) gave, after workup, 0.052 g (82%) of 5-d1 as a colorless
oil.
(b) Procedure a was repeated using LiAlD4 and H2O followed
by 40% NaOH to give 0.57 g of 5-d1 (82%).
Prior mass spectral measurement, the crude products were
dissolved in benzene (25 mL) to which was added H2O (3 × 1
mL), and the mixtures were independently subjected to
azeotropic distillation using a Dean-Stark trap. Analysis of
these samples by a DEPT experiment and their respective
mass spectra confirmed the presence of only one deuterium
atom and a CH2D group. LRMS (EI) 141 (M).
1,5-Dim eth yl-3,7-d ia za bicyclo(3.3.0)octa n e-d 2. A sus-
pension of N,N′-bis(p-toluenesulfonyl)-3,7-bis(methylene)-1,5-
diazacyclooctane (1a ) (0.446 g, 1.00 mmol) in THF (50 mL)
and LiAlD4 (0.427 g, 10.2 mmol, 99% 2H atom-enrichment) in
THF (50 mL) afforded 0.152 g of crude product after quenching
with D2O, followed by NaOD, and workup as described for the
preparation of 5. Prior to mass spectral measurement, the
crude product was azeotropically distilled with benzene and
water as described above.
If the reaction mixture was not worked up until the next
day, a sticky white substance was obtained; addition of CH2-
Cl2 or ether resulted in the formation of a white precipitate in
6% yield, that was identified as the cyclic hydrate of the
diketone: 1H NMR (acetone-d6) δ 2.42 (s, 6H), 2.30 (d, J ) 11
Hz, 4H), 3.66 (d, J ) 11 Hz, 4H), 7.45 (d, J ) 7.3 Hz, 4H),
7.65 (d, J ) 7.3 Hz, 4H); 13C NMR (acetone-d6) δ 21.4, 52.0,
93.7, 128.6, 130.4, 133.1, 145.5. Heating the hydrate with
benzene with azeotropic removal of water resulted in smooth
dehydration to 2a .
N,N′-Bis(m et h a n esu lfon yl)-1,5-d ia za cyclooct a n e-3,7-
d ion e (2b). A mixture of ozone in oxygen was bubbled
through a suspension of N,N′-bis(methanesulfonyl)-3,7-bis-
(methylene)-1,5-diazacyclooctane (1b) (1.0 g, 3.34 mmol) in
CH2Cl2 (50 mL) at -78 °C until the blue color of ozone
persisted. The mixture was stirred for 1 h and then allowed
to warm to 0 °C. Oxygen was then bubbled through the
reaction mixture to remove excess ozone. Excess dimethyl
sulfide was then added, and the mixture was stirred at rt for
1 h to decompose the ozonide. The mixture was then filtered,
and the collected solid was washed with a small amount of
CH2Cl2 to give 0.94 g of N,N′-bis(methanesulfonyl)-1,5-diaza-
cyclooctane-3,7-dione (2b) (93%): mp 305 °C dec; 1H NMR
(DMSO-d6) δ 3.36(s, 6H), 4.18 (s, 8H); 13C NMR (DMSO-d6)) δ
38.7, 59.1, 206.5. HRMS (FAB) calcd for C8H15N2O6S2 (MH)+
N,N′-Bis(p-tolu en esu lfon yl)-3-br om o-3-(br om om eth yl)-
7-m eth ylen e-1,5-d ia za cycloocta n e (7), N,N′-Bis(p-tolu -
en esu lfon yl)-1,5-bis(br om om eth yl)-3,7-diazabicyclo[3.3.0]-
octa n e (8), a n d N,N′-Bis(p-tolu en esu lfon yl)-3,7-d ibr om o-
3,7-bis(br om om eth yl)-1,5-diazacyclooctan e (9). A solution
of bromine (3.2 g, 20 mmol) in CH2Cl2 (50 mL) was added
dropwise over a 4 h period to a stirred solution of 1a (8.92 g,
20 mmol) in CH2Cl2 (250 mL) at 0 °C. The reaction mixture
was then stirred for an additional 6 h and then it was washed
successively with 5% Na2S2O3 (100 mL), saturated NaHCO3
(100 mL), and water. The organic phase was dried (MgSO4)
and concentrated at reduced pressure to give a residue which
was treated with ice-cold acetone (15 mL). Pure 8 (8.2 g, 68%)
was isolated as crystalline material which remained insoluble
299.0372; found m/ z, 299.0379. Anal. Calcd for C8H14
-
N2O6S2: C, 32.21; H, 4.73; N, 9.39. Found: C, 32.47; H, 4.48,
N, 9.81.
1
in the acetone: mp 228-231 °C; H NMR (CDCl3) δ 2.45 (s,
6H), 3.16 (d, J ) 10.5 Hz, 4H), 3.31 (d, J ) 10.5 Hz, 4H), δ
7.33 (d, J ) 8.4 Hz, 4H), δ 7.64 (d, J ) 8.3 Hz, 4H); 13C NMR
(CDCl3) δ 21.6, 34.0, 56.0, 57.3, 127.7, 130.0, 131.9, 144.5;
HRMS (FAB) calcd for C22H27N2O4S2Br2 (MH)+ 604.9778,
found m/ z, 604.9768. Anal. Calcd for C22H26N2O4S2Br2: C,
43.58; H, 4.32; N, 4.62. Found: C, 43.66; H, 4.73, N, 4.96.
Concentration of the acetone mother liquor deposited the
tetrabromide 9 (0.30 g, 2%) as colorless crystals: mp 210-
Oxid a tion of Ster eoisom er ic N,N′-Bis(p-tolu en esu lfo-
n yl)-1,5-d ia za cycloocta n e-3,7-d iols (3). A solution of py-
ridine sulfur trioxide complex (0.88 g, 5.54 mmol), triethy-
lamine (0.82 g, 8.72 mmol), and a stereoisomeric mixture of
the N,N′-bis(p-toluenesulfonyl)-1,5-diazacyclooctane-3,7-diols
(0.20 g, 0.44 mmol) in DMSO (6.91 g, 88.5 mmol) stirred at rt
for 1 h and then poured over ice and extracted with ethyl
acetate (4 × 10 mL). The combined extracts were washed with
water (5 × 10 mL), dried (MgSO4), and concentrated to give
an oil which solidified on standing. Recrystallization from
ethanol/hexane gave 0.41g (41%) of 4 as a colorless solid: mp
215-217 °C (lit. mp11 217 °C); 1H NMR (CDCl3) δ 2.42 (s, 6H),
2.53 (d, 2H), 2.88 (m, 2H), 3.51 (d, J ) 11 Hz, 2H), 3.71 (d, J
) 11 Hz, 2H), 4.21 (m, 1H), 7.69 (d, J ) 8.2 Hz, 4H), 7.33 (d,
J ) 8.2 Hz, 4H); 13C NMR (CDCl3) δ 21.6, 46.1, 52.3, 68.8,
90.4, 128.1, 129.9, 132.1, 144.2. LRMS (CI-NH3) 453 (M + 1),
470 (M + 18).
1,5-Dim eth yl-3,7-d ia za bicyclo[3.3.0]octa n e (5). A slurry
of N,N′-bis(p-toluenesulfonyl)-3,7-bis(methylene)-1,5-diazacy-
clooctane (1a ) (2.22 g, 4.98 mmol), in THF (75 mL) containing
LiAlH4 (1.90 g, 50 mmol), was stirred under N2 for 42 h. The
reaction mixture was quenched with 20% NaOH (4.5 mL) with
external cooling. Stirring was continued at rt for 3 h, and the
white granular precipitate that formed was removed by
filtration and washed with anhydrous ether (3 × 50 mL). The
combined organic extracts were concentrated to give 0.574 g
(82%) of 5 as a colorless oil which slowly solidified: mp ∼ 30
°C; 1H NMR (CDCl3) δ 0.99 (s, 6H), 2.71 (d, J ) 11.2 Hz, 4H),
2.92 (d, J ) 11.2 Hz, 4H), 2.61 (s, 2H, br); 13C NMR (CDCl3) δ
20.4, 51.7, 62.6. HRMS (FAB) calcd for C8H17N2 (MH)+
141.1392; found m/ z, 141.1388. Treatment of an ethanolic
solution of 5 with picric acid afforded the picrate as a yellow
solid, mp 258 °C.
1
212 °C; H NMR (CDCl3) δ 2.48 (s, 6H), 3.33 (d, J ) 15.6 Hz,
4H), 4.18 (s, 4H), 4.35 (d, J ) 15.6 Hz, 4H), 7.38, 7.40, 7.75,
7.77; 13C NMR (CDCl3) δ 21.61, 39.85, 61.13 67.07, 127.93,-
130.22, 133.96,144.89; LRMS (EI) 762 (M).
After separating the undissolved 9, column chromatography
of the mother liquor on silica gel using hexane-ethyl acetate
(4:1) as the elution solvent afforded the dibromide 7 (3.6 g,
1
30%): mp 192-197 °C; H NMR (CDCl3) δ 2.45 (s, 6H), 3.45
(d, J ) 12.6 Hz, 2H), 3.88 (d, J ) 12.6 Hz, 2H), 3.56 (d, J )
15.7 Hz, 2H), 3.85 (d, J ) 15.7 Hz, 2H), 4.11 (s, 2H), 5.24 (s,
2H), 7.33, 7.35, 7.69, 7.72; 13C NMR (CDCl3) δ 21.55, 42.61,
55.28, 55.58, 67.29, 124.23, 127.66, 130.03, 134.04, 139.33,
144.27; HRMS (FAB) calcd for C22H27N2O4S2Br2 (MH)+
604.9779; found m/ z, 604.9779. Anal. Calcd for C22H26
-
N2O4S2Br2: C, 43.58; H, 4.32; N, 4.62. Found: C, 43.25; H,
4.95, N, 4.90.
Attempts to convert 7 to its isomer 8 by heating at 110 °C
for 16 h in anhydrous DMSO lead to the recovery of the
starting material.
Ra p id Ad d ition of Br om in e to 1a . To an ice-cooled (-5
to 0 °C) solution of N,N′-bis(p-toluenesulfonyl)-3,7-bis(meth-
ylene)-1,5-diazacyclooctane (1a ) (2.68 g, 6.0 mmol) in CH2Cl2
(80 mL) was added a solution of bromine (0.96 g, 6.0 mmol) in
CH2Cl2 (15 mL) over a 30 min period. The reaction mixture
was stirred at 0 °C for an additional 5 h and then was washed
successively with 5% sodium bicarbonate (30 mL), 5% sodium

8902 J . Org. Chem., Vol. 61, No. 25, 1996
Dave et al.
bisulfite (30 mL), brine, and water. The organic layer was
dried (MgSO4), and the solvent was removed on a rotary
evaporator to give 2.07 g of a crude mixture of 7 and 8. NMR
analysis showed this material to be an 88:12 mixture of 7 and
8.
1,3,5,7-Tetr a n itr o-5,7-d ia za bicyclo[3.3.0]octa n e (13) by
Nitr olysis of 12. Over a 2 min period 100% nitric acid (0.9
g, 14.2 mmol) was added to a stirred solution of trifluoroacetic
anhydride (2.9 g, 14.1 mmol) in CH2Cl2 (10 mL) at -10 °C. To
this mixture, maintained at -10 °C, was added a solution of
12 (0.36 g, 0.7 mmol) in CH2Cl2 (4 mL) was added over 0.5 h,
and stirring was continued for 2.5 h. The reaction mixture
was poured into ice-water (35 g) and extracted with CH2Cl2
(35 mL). The combined organic layers were washed succes-
sively with 5% sodium carbonate (50 mL) and water (50 mL),
dried (Na2SO4), and evaporated to give a crude yellowish
product (0.26 g) which was chromatographed on silica gel and
eluted with acetone-hexane to give 0.06 g of 13 (36%), as
colorless crystals: mp 222-224 °C; 1H NMR (acetone-d6) δ 5.14
(d, J ) 13.9 Hz, 4H), 4.99 (d, J ) 13.9 Hz, 4H); 13C NMR
(acetone-d6) δ 56.6, 94.0.
1,3,5,7-Tet r a n it r o-5,7-d ia za b icyclo[3.3.0]oct a n e (13)
fr om th e Nitr olysis of N,N′-Bis(p-tolu en esu lfon yl)-1,5-
d ia za cycloocta n e-3,7-d ion e Dioxim e (11). A solution of
98% nitric acid (5 mL) in CH2Cl2 (10 mL) containing catalytic
quantities of urea and ammonium nitrate was added to a
refluxing solution of dioxime 11 (0.3 g, 0.6 mmol) in CH2Cl2
(50 mL). The reaction mixture was heated under reflux for 1
h, initially developing a blue-green color which changed to dark
brown as the reaction progressed. The reaction mixture was
cooled to rt and poured over ice, and the organic layer was
washed with water (50 mL), saturated sodium bicarbonate
solution (50 mL), dried (MgSO4), and concentrated under
reduced pressure. The residue was chromatographed on silica
gel and eluted with acetone-hexane. The appropriate frac-
tions were combined and recrystallized from acetone-hexane
to give 13 (0.045 g, 25%) which was identical in all respects
with the material isolated from the reaction of 12 with
trifluoroacetyl nitrate. Although no other pure material was
isolated, NMR evidence indicated byproducts arising from
nitration of the aromatic rings.
N,N′-Bis(p -t olu en esu lfon yl)-3-t h ia -7,10-d ia za [3.3.3]-
p r op ella n e (14). To a solution of 8 (150 mg, 0.25 mmol) in
DMSO (15 mL) was added sodium sulfide (100 mg, 0.42 mmol).
After heating at 125 °C for 1.5 h, the mixture was cooled to rt
and poured into water (45 mL). The aqueous medium was
extracted with ethyl acetate (2 × 20 mL), the combined organic
layers were washed with brine, dried (Na2SO4), and concen-
trated in vacuo, and the resulting residue was recrystallized
from acetone/hexanes to give 14 (0.95 g, 80%): mp 195-6 °C;
1H NMR (CDCl3) δ 2.45 (s, 6H), δ 2.96 (d, J ) 9.5 Hz, 4H),
3.01 (d, J ) 9.5 Hz, 4H), 2.73 (s, 4H), 7.33 (d, J ) 8.0 Hz, 4H),
7.58 (d, J ) 8.0 Hz, 4H); 13C NMR (CDCl3) δ 21.61, 42.22,
57.15, 65.88, 127.93, 129.93, 131.10, 144.34; HRMS (FAB)
calcd for C22H27N2O4S3 (MH)+ 479.1133; found m/ z, 479.1119.
Anal. Calcd for C22H26N2O4S3: C, 55.21; H, 5.47; N, 5.85.
Found: C, 55.37; H, 5.29, N, 6.14.
N ,N ′-Bis(p -t olu e n e su lfon yl)-3-oxa -7,10-d ia za [3.3.3]-
p r op ella n e (15). To a solution of 8 (0.20 g, 0.33 mmol) in
anhydrous DMSO (15 mL) was added anhydrous sodium oxide
(0.021 g, 3.3 mmol). The reaction mixture was heated for 20
h at 120 °C under N2. The solvent was removed under vacuum
and the residue taken up in water (30 mL) which was extracted
with ethyl acetate (2 × 25 mL). The combined organic extracts
were washed with water (2 × 25 mL) and dried (Na2SO4), and
the solvent was removed under vacuum. After triturating the
residue with cold ethyl acetate, 15 was obtained as a white
solid (0.114 g, 75%): mp 212-216 °C; 1H NMR (CDCl3) δ 2.45
(s, 6H), 2.95 (d, J ) 9.5 Hz, 4H), 3.01 (d, 9.5 Hz, 4H), 3.62
(2H), 7.33 (d, J ) 8.0 Hz, 4H), 7.59 (d, J ) 8.0 Hz, 4H); 13C
NMR (CDCl3) δ 21.62, 56.03, 63.53, 76.19, 127.95, 129.99,
131.05, 144.45; HRMS (FAB) calcd for C22H27N2O5S2 (MH)+
5-Meth yl-3,7-d ia za bicyclo[3.3.1]n on a n -1-ol (10). A so-
lution of 1a (112 mg, 0.25 mmol) in chloroform (2.0 mL) was
stirred at rt for 24 h with concd H2SO4 (4.0 mL). The reaction
mixture was poured into ice-water (60 mL) and extracted with
chloroform (3 × 25 mL). The chloroform layer was washed
with saturated sodium bicarbonate, dried (MgSO4), and evapo-
rated to leave 115 mg of crude product which was essentially
pure 10. Recrystallization from alcohol afforded needle-shaped
crystals: mp 238-240 °C; 1H NMR (CDCl3) δ 0.91 (s, 3H), 1.33
(s, 2H), 1.62 (s, br, 1H), 2.32 (d, 2H, J ) 11.2 Hz), 2.41 (s, 6H),
2.48 (d, 2H, J ) 10.7 Hz), 3.43 (d, 2H, J ) 11.2 Hz), 3.66 (d,
2H, J ) 10.7 Hz), 7.30, 7.33, 7.67, 7.69; 13C NMR (CDCl3) δ
21.54, 24.76, 33.19, 45.38, 54.08, 54.35, 66.57, 127.91, 129.78,
133.03, 143.67. HRMS (FAB) calcd for C22H29N2O5S2 (MH)+
465.1518; found m/ z, 465.1510. Anal. Calcd for C22H28
-
N2O5S2: C, 56.88; H, 6.07; N, 6.03. Found: C, 56.68; H, 5.78,
N, 5.72.
Ster eoisom er ic Mixtu r e of N,N′-Bis(p-tolu en esu lfo-
n yl)-1,5-d ia za cycloocta n e-3,7-d ion e Dioxim es (11).
A
suspension of N,N′-bis(p-toluenesulfonyl)-1,5-diazacyclooctane-
3,7-dione (2a ) (0.900 g, 2.00 mmol), hydroxylamine hydrochlo-
ride (0.556 g, 8.00 mmol), and sodium acetate trihydrate (2.18
g, 16.0 mmol) in ethanol (70 mL) was stirred under reflux for
5 d. The ethanol was removed, and the residue was washed
with water and dried over P2O5 in vacuo to give 0.710 g (74%)
of 11 as a colorless solid comprised of two geometric isomers
(syn, minor, 11a and anti, major, 11b).
A sample of crude 11 was recrystallized from ethanol to give
1
the pure anti isomer 11b: mp 239 °C dec; H NMR (DMSO-
d6) δ 2.41 (s, 6H), 3.84 (s, 4H), 4.09 (s, 4H), 7.46 (d, J ) 7.9
Hz, 4H), 7.69 (d, J ) 7.9 Hz, 4H), 11.3 (s, 2H); 13C NMR
(DMSO-d6) δ 21.0, 47.0, 52.3, 126.6, 130.0, 134.6, 143.9, 152.9.
HRMS (FAB) calcd for C20H25N4O6S2 (MH)+ 481.1216; found
m/ z, 481.1198.
N,N′-Bis(p-tolu en esu lfon yl)-1,5-din itr o-3,7-diazabicyclo-
[3.3.0]octa n e (12) by N-Br om osu ccin im id e Oxid a tion of
11. A mixture of sodium bicarbonate (7.4 g, 88.1 mmol), NBS
(6.6 g, 37.1 mmol), and a stereoisomeric mixture of the
dioximes 11 (3.5 g, 7.3 mmol) in 5% aqueous dioxane (200 mL)
was stirred at rt for 4 d. The reaction mixture was partitioned
between CH2Cl2 (150 mL) and 5% sodium hydroxide (150 mL),
and the organic layer was separated. The aqueous layer was
further extracted with CH2Cl2 (2 × 50 mL), and the combined
organic layers were successively treated with 5% NaOH (2 ×
50 mL), water (2 × 100 mL), and brine, dried (Na2SO4), and
concentrated in vacuo to give 2.06 g of a slightly yellow solid,
most of which dissolved on treatment with acetone (70 mL).
The acetone solution was concentrated in vacuo to give 1.89 g
of 12 as a slightly yellow solid (48%). Recrystallization from
acetone/water gave crystalline needles of 12: mp 154-156 °C;
1H NMR (CDCl3) δ 2.47 (s, 6H), 3.89 (d, J ) 11.5 Hz, 4H),
4.00 (d, J ) 11.5 Hz, 4H), 7.40 (d, J ) 8.3 Hz, 4H), 7.70 (d, J
) 8.3 Hz, 4H); 13C NMR (CDCl3) δ 21.7, 55.1, 94.0, 127.5, 130.4,
131.8, 145.5. HRMS (FAB) calcd for C20H23N4S2O8 (MH)+
511.0957; found m/ z, 511.0955.
N,N′-Bis(p-tolu en esu lfon yl)-1,5-din itr o-3,7-diazabicyclo-
[3.3.0]octa n e (12) by m -CP BA Oxid a tion of 11. A mixture
of urea (0.02 g, 0.3 mmol), disodium hydrogen phosphate (0.8
g, 5.6 mmol), and the dioxime 11 (0.240 g, 0.5 mmol) in
anhydrous acetonitrile (5.0 mL) was stirred at reflux for 10
m, and then m-chloroperbenzoic acid (0.3 g, 1.8 mmol) was
slowly added over 1 h. The suspension was heated under
reflux for 2 h and concentrated at reduced pressure, and the
residue was extracted with CH2Cl2 (3 × 20 mL). The combined
extracts were washed with a saturated sodium bicarbonate
solution (4 × 15 mL), water (4 × 15 mL), and brine (2 × 30
mL), dried (Na2SO4), and concentrated to give compound 12
(0.064 g, 24%). The properties of 12 obtained in this experi-
ment were identical with those exhibited by compound 12
isolated from the NBS oxidation of 11.
463.1361; found m/ z, 463.1349. Anal. Calcd for C22H26
-
N2O5S2: C, 57.12; H, 5.67; N, 6.06. Found: C, 56.93; H, 5.89,
N, 6.41.
N,N,′N′′-Tr is(p -t olu en esu lfon yl)-3,7,10-t r ia za [3.3.3]-
p r op ella n e (16). p-Toluenesulfonamide (0.865 g, 5.05 mmol)
was added to a solution of metallic sodium (115 mg, 5.05 mmol)
in anhydrous methanol (50 mL), the solvent was removed
under vacuum, and the residue was dissolved in DMSO (50
mL). The freshly prepared sodium salt solution was added

Facile Preparation of 3,7-Diazabicyclo[3.3.0]octane
J . Org. Chem., Vol. 61, No. 25, 1996 8903
dropwise to a heated solution of dibromide 8 (1.0 g, 1.65 mmol)
in anhydrous DMSO (25 mL) under N2. After heating the
solution for 16 h at 110 °C the solvent was removed and the
residue taken up in chloroform (50 mL), washed with water
(3 × 50 mL), and dried (MgSO4). Removal of the solvent under
Drs. T. DeAngelis, G. Doyle, and R. Surapaneni for their
support. Financial support for this work was provided
in part by ARDEC, and in part by the Office of Naval
Research and the Ballistic Missile Defense Organiza-
tion.
1
vacuo gave pure 16 (0.79 g, 78%): mp 208-210 °C; H NMR
(CDCl3) δ 2.41 (s, 9H), 2.99 (s, 12H), 7.29 (d, J ) 8.3 Hz, 6H),
7.51 (d, J ) 8.3 Hz, 6H); 13C NMR (CDCl3) δ 21.47, 56.08,
60.73, 127.70, 129.92, 130.85, 144.44; HRMS (FAB) calcd for
C29H34N3O6S3 (MH)+ 616.1610; found m/ z, 616.1606. Anal.
Calcd for C29H33N3O6S3: C, 56.57; H, 5.40; N, 6.82. Found:
C, 56.73; H, 5.56, N, 7.05.
Su p p or tin g In for m a tion Ava ila ble: Copies of the 1H
NMR spectra of 5, 9, 11, and 13 as well as 13C NMR spectra
of 5, 7-9, 10, and 12-16 (14 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.
Ack n ow led gm en t. The assistance of Mr. William
Cao is gratefully acknowleged. P.R.D. and F.F. thank
J O9614755