Iminodiaziridines by regio- and stereoselective cyclization of diastereomeric singlet triazatrimethylenemethane diradicals generated through photolysis of 5-imino-4,5-dihydro-1H-tetrazoles

Article abstract of DOI:10.1021/jo702697f

(Chemical Equation Presented) 1,4-Dialkyl-5-(N-alkylimino)-4,5-dihydro-1H- tetrazoles were prepared in high yields by deprotonation with sodium hydride of 1,4-dialkyl-5-(N-alkylamino)tetrazolium salts that were adorned with two or three different alkyl gr

Full text of DOI:10.1021/jo702697f

Iminodiaziridines by Regio- and Stereoselective Cyclization of
Diastereomeric Singlet Triazatrimethylenemethane Diradicals
Generated Through Photolysis of 5-Imino-4,5-dihydro-1H-tetrazoles†
Helmut Quast* and Lothar W. Bieber‡
Institut für Organische Chemie der UniVersität Würzburg, Am Hubland, D-97074 Würzburg, Germany
hquast@uni-osnabrueck.de
ReceiVed December 19, 2007
1,4-Dialkyl-5-(N-alkylimino)-4,5-dihydro-1H-tetrazoles were prepared in high yields by deprotonation
with sodium hydride of 1,4-dialkyl-5-(N-alkylamino)tetrazolium salts that were adorned with two or three
different alkyl groups, including methyl, trideuteriomethyl, and tert-butyl groups. Direct irradiation (λ >
255 nm) at -60 °C yielded molecular nitrogen and mixtures of 1,2-dialkyl-3-(N-alkylimino)diaziridines
(83–87%) along with carbodiimides (13–17%) arising by 1,3-dipolar cycloreversion. The missing 1,3-
dipoles, alkyl azides, did not survive photolysis. Each member of a pair of isotopomers and of a pair of
isomers, and an iminodihydrotetrazole, whose three nitrogens were tagged, yielded a characteristic mixture
of three isomeric iminodiaziridines that allowed the mode of formation to be deduced. The results are
interpreted in terms of photodenitrogenation of the iminodihydrotetrazoles to furnish diastereomeric singlet
triazatrimethylenemethane diradicals that retain the inherited configurations before ring closure to
iminodiaziridines, presumably in two steps via mono-orthogonal diradicals.
Introduction
in organic matrixes at low temperatures, viz., trimethylene-
methanes (TMMs), including Dowd’s famous parent system12
and Berson’s bridged TMMs,13 a diazaTMM,7e and triaza-
TMMs.14
Photoextrusion of molecular nitrogen from five-membered
heterocyclic azo compounds with unconjugated exocyclic double
bonds affords three-membered rings (Scheme 1, top).1–10 In
addition, certain dihydrotetrazole derivatives yield small amounts
of alkyl azides and isocyanates8b,9 or carbodiimides9 by
photochemical 1,3-dipolar cycloreversion.11 Besides these pho-
toproducts, triplet diradicals were detected by EPR spectroscopy
The results of direct irradiation of cyclic azo compounds of
the general type in Scheme 1 may be interpreted in terms of
spin-conservative cleavage into molecular nitrogen and singlet
TMM-type diradicals. These undergo intersystem crossing to
ground-state triplet diradicals or cyclize to three-membered
rings,13b unless certain structural features provide alternative
reaction channels.15 In principle, this photocleavage may proceed
in a concerted way or in steps.16 The latter mechanism would
lead to diazenyl allyl diradicals, which might lose molecular
nitrogen to yield singlet TMM-type diradicals, cyclize again to
* To whom correspondence should be addressed. Current address: Hoetger-
strasse 10, D-49080 Osnabrück, Germany. Fax +49-(0)541/8141935.
† This paper is dedicated to Professor Dieter Seebach on the occasion of his
70th birthday.
‡ Current address: Departamento de Química Fundamental, Universidade
Federal de Pernambuco, Cidade Universitária, 50670-901 Recife, Brazil.
3738 J. Org. Chem. 2008, 73, 3738–3744
10.1021/jo702697f CCC: $40.75 2008 American Chemical Society
Published on Web 04/17/2008

Iminodiaziridines by Photolysis of Iminodihydrotetrazoles
turn-around isomers, or close a three-membered ring by radical
substitution of the diazenyl group (Scheme 1, bottom). However,
convincing evidence for stepwise cleavage exists only for
Berson’s bicyclic TMM precursor, 7-isopropylidene-2,3-
diazabicyclo[2.2.1]hept-3-ene, and only on thermal but not on
photochemical excitation.17,18
Long-standing, continued interest in singlet diradicals19
prompts us to report on the regio- and stereoselectivity of
iminodiaziridine formation during irradiation of iminodihy-
drotetrazoles 1. We irradiated a number of iminodihydrotetra-
zoles whose nitrogens were labeled by substituents, including
methyl, trideuteriomethyl, and tert-butyl groups, and determined
the structures of their products formed at low temperatures. The
results are consistent with intermediate diastereomeric singlet
triazaTMM diradicals whose geometries resemble those of the
precursors 1 and are reluctant to undergo change of configuration.
SCHEME 1. Products (Top) and Possible Mechanisms
(Bottom) of the Photolysis of Five-Membered Heterocyclic
Azo Compounds with Unconjugated Exocyclic Double Bonds
Results
Deuterium labeling has been used to study the formation of
methylenecyclopropanes by photolysis1i 1k 1m 1n and thermoly-
sis20 of 4-alkylidenedihydropyrazoles. We employed the same
method to investigate the pathways of product formation on
photolysis of 5-imino-4,5-dihydro-1H-tetrazoles 1. These were
prepared from 1,4-dialkyl-5-(N-alkylamino)tetrazolium salts
which were synthesized on various, in principle known routes
(Scheme 2). Because alkylation of 5-aminotetrazoles21 affords
mixtures of isomers,22 the synthesis of each salt was optimized.
Detailed experimental procedures are given in the Supporting
Information.
,
,
,
Deprotonation of 1·HX with sodium hydride in inert solvents
gave 1 as low-melting, hygroscopic, colorless crystals in high
1
yields. H and 13C NMR spectra of 1a showed temperature-
dependent ring methyl signals due to exchange by inversion of
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Soc. 1964, 368. (b) Mock, W. L. Ph.D. Thesis, Harvard University, 1965. (c)
Day, A. C.; Whiting, M. C. J. Chem. Soc. (C) 1966, 464. (d) Andrews, S. D.;
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Rule, M.; Lazzara, M. G.; Berson, J. A. J. Am. Chem. Soc. 1979, 101, 7091. (k)
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1989, 45, 259. (b) Reference 7a.
(10) Diaziridinones: (a) Quast, H.; Bieber, L. Chem. Ber. 1981, 114, 3253.
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(2) Iminocyclopropanes: (a) Quast, H.; Fuss, A.; Heublein, A. Angew. Chem.,
Int. Ed. Engl. 1980, 19, 49. (b) Quast, H.; Meichsner, G. Chem. Ber. 1987, 120,
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(17) (a) Cichra, D. A.; Platz, M. S.; Berson, J. A. J. Am. Chem. Soc. 1977,
99, 8507. (b) Cichra, D. A.; Duncan, C. D.; Berson, J. A. J. Am. Chem. Soc.
1980, 102, 6527. (c) Kelley, D. F.; Rentzepis, P. M.; Mazur, M. R.; Berson,
J. A. J. Am. Chem. Soc. 1982, 104, 3764.
(3) Cyclopropanones: (a) Quast, H.; Fuss, A Angew. Chem., Int. Ed. Engl.
1981, 20, 291. (b) Adam, W.; Fuss, A.; Mazenod, F. P.; Quast, H. J. Am. Chem.
Soc. 1981, 103, 998. (c) Sander, W.; Wrobel, R.; Komnick, P.; Rademacher, P.;
Muchall, H. M.; Quast, H. Eur. J. Org. Chem. 2000, 91. (d) Moiseev, A. G.;
Abe, M.; Danilov, E. O.; Neckers, D. C. J. Org. Chem. 2007, 72, 2777.
(4) Alkylideneoxiranes (allene oxides): reference 3c.
(5) Alkylidenethiiranes: (a) Schaumann, E.; Behr, H.; Adiwidjaja, G.;
Tangerman, A.; Lammerink, B. H. M.; Zwanenburg, B. Tetrahedron, 1981, 37,
219. (b) Quast, H.; Fuss, A.; Jakobi, H. Chem. Ber. 1991, 124, 1747. (c) Reference
3a.
(18) The only reported turn-around photoisomer of this type1t has met with
skepticism16b and could not be reproduced.1v
(19) See, for example: (a) Borden, W. T., Ed. Diradicals; Wiley: New York,
1982. (b) Borden, W. T. In Magnetic Properties of Organic Materials; Lahti,
P., Ed.; Marcel Dekker: New York, 1999; pp 61–102. (c) Giese, B.; Barbosa,
F.; Stahelin, C.; Sauer, S.; Wettstein, P.; Wyss, C. Pure Appl. Chem. 2000, 72,
1623. (d) Griesbeck, A. G. Synlett. 2003, 4, 451. (e) Abe, M.; Adam, W.; Borden,
W. T.; Hattori, M.; Hrovat, D. A.; Nojima, M.; Nozaki, K.; Wirz, J. J. Am.
Chem. Soc. 2004, 126, 574. (f) Creary, X. Acc. Chem. Res. 2006, 39, 761. (g)
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Ser. 2006, 917, 81. (h) Abe, M.; Hattori, M.; Takegami, A.; Masuyama, A.;
Hayashi, T.; Seki, S.; Tagawa, S. J. Am. Chem. Soc. 2006, 128, 8008. (i) Zhou,
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(6) Alkylideneseleniranes: Muchall, H. M.; Kowski, K.; Rademacher, P.; Fuss,
A.; Neuberger, R.; Quast, H.; Komnick, P.; Sander, W. Tetrahedron 1996, 52,
1965.
(7) Iminoaziridines: (a) Quast, H.; Bieber, L. Angew. Chem., Int. Ed. Engl.
1975, 14, 428. (b) Quast, H.; Bieber, L.; Meichsner, G. Chem. Ber. 1988, 121,
2117. (c) Quast, H.; Regnat, D. Chem. Ber. 1990, 123, 2195. (d) Quast, H.;
Hergenröther, T. Chem. Ber. 1992, 125, 2095. (e) Quast, H.; Fuss, A.; Nüdling,
W. Eur. J. Org. Chem. 1998, 317.
(20) (a) Crawford, R. J.; Cameron, D. M.; Tokunaga, H. Can. J. Chem. 1974,
52, 4025. (b) Chang, M. H.; Crawford, R. J. Can. J. Chem. 1981, 59, 2556. (c)
Crawford, R. J.; Chang, M. H. Tetrahedron 1982, 38, 837. (d) Bushby, R. J.
J. Chem. Soc., Perkin Trans. 2 1985, 1211. (e) LeFevre, G. N.; Crawford, R. J.
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(8) Aziridinones (R-lactams): (a) Quast, H.; Seiferling, B. Tetrahedron Lett.
1982, 23, 4681. (b) Quast, H.; Meichsner, G.; Seiferling, B. Chem. Ber. 1987,
120, 225.
(21) For a summary of general routes to 5-aminotetrazoles, see: Katritzky,
A. R.; Rogovoy, B. V.; Kovalenko, K. V. J. Org. Chem. 2003, 68, 4941.
J. Org. Chem. Vol. 73, No. 10, 2008 3739

Quast and Bieber
SCHEME 3. Products Formed During Irradiation of 1a
SCHEME 2. Synthetic Routes to
1,4-Dialkyl-5-(N-alkylamino)tetrazolium Salts
13-17% dimethylcarbodiimide (2),7a,9 which was identified by
comparison of its IR and 1H NMR spectra with those reported in
the literature (Scheme 3). Methyl azide (3) is expected to arise by
1,3-dipolar cycloreversion of 1a along with 2 but escaped detection,
most probably, because it was photolyzed and the product formed
a polymer (CH2NH)n.24 No attempts were made to separate 4 from
the solvent because of the high volatility of 4 and its propensity to
undergo nucleophilic ring opening. The same properties frustrated
attempts to isolate the other iminodiaziridines in pure form.
However, NMR spectra and the very characteristic IR bands around
1800 cm-1 of iminodiaziridines25 permitted unequivocal identifica-
tion. In particular, observation of a long-range 1H,1H coupling of
5J ) 0.5 Hz between the protons of the ring methyl groups of 4
and 7 left no doubt about these structures.
The objective of the present study necessitated that several
conditions were met. (i) Except for photochemical decomposition,
the iminotetrazoles 1b-(E)-1f remained unchanged on irradiation,
i.e., they neither rearranged to turn-around isomers nor showed
photochemical inversion of predominant configurations. (ii) Imi-
nodiaziridines are known to undergo inversion of the imino group
and valence isomerization, which interchanges one of the ring
nitrogens and the exocyclic nitrogen.25b,c Consequently, irradiation
was performed at -60 °C, at which temperature both isomerizations
were slow so that the ratios of the iminodiaziridines remained
unaltered for days. (iii) When irradiated samples were allowed to
attain room temperature in the cavity of the NMR spectrometer,
rapid E/Z equilibration permitted unequivocal assignment of NMR
signals to a certain diastereomer. In contrast, thermal valence
isomerization was slow at room temperature.26 (iv) Persistence of
the iminodiaziridines toward irradiation could not be anticipated
since their photochemistry has not yet been investigated. However,
irradiation of 1 at -60 °C showed that the compositions of the
resulting mixtures remained essentially unaltered as long as
significant amounts of 1 were still present. Thereafter, the imino-
diaziridines underwent slow photochemical E/Z diastereomerization
and valence isomerization.27
the imino group (Tc ) 28 °C at 60 MHz in [D8]THF; ∆ν ) 34
Hz at -50 °C; ∆Gq28°C ) 62.6 kJ/mol). In contrast, 1d did not
1
show splitting of the N-methyl H NMR singlet down to -70
°C. The asymmetrically ring-substituted imines 1e and 1f exist
as single diastereomers to which we attribute the E-configura-
tion.
Photolysis experiments were performed by direct irradiation,
using Corex-filtered (λ > 255 nm)23 light of a medium-pressure
mercury arc lamp. Without Corex filter, slow [2 + 1] cycloe-
limination of the iminodiaziridines afforded methyl or tert-butyl
1
isocyanide as indicated by the characteristic 1:1:1 triplet H
(22) (a) Herbst, R. M.; Roberts, C. W.; Harvill, E. J. J. Org. Chem. 1951,
16, 139. (b) Herbst, R. M.; Percival, D. F. J. Org. Chem. 1954, 19, 439. (c)
Murphy, D. B.; Picard, J. P. J. Org. Chem. 1954, 19, 1807. (d) Henry, R. A.;
Finnegan, W. G. J. Am. Chem. Soc. 1954, 76, 923. (e) Henry, R. A.; Finnegan,
W. G.; Lieber, E. J. Am. Chem. Soc. 1954, 76, 2894. (f) Hattori, K.; Lieber, E.;
Horwitz, J. P. J. Am. Chem. Soc. 1956, 78, 411. (g) Percival, D. F.; Herbst,
R. M. J. Org. Chem. 1957, 22, 925. (h) Herbst, R. M.; Froberger, C. F. J. Org.
Chem. 1957, 22, 1050. (i) Wilson, K. R.; Herbst, R. M.; Haak, W. J. J. Org.
Chem. 1959, 24, 1046. (j) Butler, R. N.; Scott, F. L. J. Org. Chem. 1966, 31,
3182. (k) Scott, F. L.; Tobin, J. C. J. Chem. Soc. (C) 1971, 703. (l) Spear, R. J.
Aust. J. Chem. 1984, 37, 2453.
NMR signals. Both E/Z diastereomerization and valence isomer-
ization of iminodiaziridines appear to be catalyzed by acid.
Hence it was essential for the observation of unaltered primary
photoproducts to avoid any traces of acid at the walls of the
NMR sample tubes. Otherwise, equilibrated mixtures were
obtained. The irradiation experiments took a very clean course
1
up to high conversion. Monitoring by H NMR spectroscopy
allowed complete conversion to be approached, which mini-
mized signal overlap, and irradiation to be terminated, before
(23) (a) Freeman, P. K.; Johnson, R. C. J. Org. Chem. 1969, 34, 1746. (b)
Dauben, W. G.; Shaffer, G. W. J. Org. Chem. 1969, 34, 2301.
1
isomerization of primary products became noticeable. The H
(24) Currie, C. L.; Darwent, B. de B. Can. J. Chem. 1963, 41, 1552.
(25) (a) Quast, H.; Schmitt, E. Angew. Chem., Int. Ed. Engl. 1969, 8, 448.
(b) Quast, H.; Schmitt, E. Angew. Chem., Int. Ed. Engl. 1969, 8, 449. (c) Quast,
H.; Schmitt, E. Chem. Ber. 1970, 103, 1234.
NMR spectra were integrated many times on an expanded scale
by using both the high f low field and the low f high field
sweep direction. The yields given in Schemes 4-6 represent
average values from at least two independent experiments. The
error was estimated at 1-2%, which is a size that compels
neglect of remote deuterium isotope effects.
(26) Thermal equilibration of a mixture of (E)-, (Z)-11; (E)-, (Z)-12; and
(E)-, (Z)-13 required several days and gave a mixture in which (E)-, (Z)-12 made
up only 3-4%.
(27) For example, irradiation for 3 d at -60 °C converted about half of (E)-8
into (Z)-8. Under these conditions, 13 [(E):(Z) ca. 1:1] underwent degenerate
valence isomerization to 11 [(E):(Z) ca. 1:1]. Similar photochemical rearrange-
ments of methylenecyclopropanes are known, see: Creary, X.; Losch, A; Sullivan,
W. J. Org. Chem. 2007, 72, 7930. and references cited therein.
Irradiation of degassed solutions of 1a in [D8]tetrahydrofuran,
enclosed in sealed NMR sample tubes, gave 83-87% 4 along with
3740 J. Org. Chem. Vol. 73, No. 10, 2008

Iminodiaziridines by Photolysis of Iminodihydrotetrazoles
SCHEME 4. Iminodiaziridines Formed During Irradiation of 1b (First Row) and 1c (Second Row)
SCHEME 5. Iminodiaziridines and Carbodiimides Formed During Irradiation of 1d (First Row) and (E)-1e (Second Row)
By contrast to the iminodiaziridines 4, 5, and 7, whose
SCHEME 6. Iminodiaziridines Formed During Irradiation
of (E)-1f
1
structures can be immediately read from the H NMR spectra,
the iminodiaziridines 6, 8, and 11-13 exist as pairs of E/Z
diastereomers. Provided that both diastereomers can be observed,
a most convenient and reliable criterium for the configuration
of N-alkylimines is the relative asymmetric solvent-induced shift
(ASIS).28 Asymmetric solvation by aromatic solvents shifts
resonances of protons at the side of the imino alkyl group
stronger to high field than those of protons at the side of the
lone pair.29 Therefore, we irradiated 1 not only in [D8]THF but
also in [D8]toluene as solvent. The nature of the solvent hardly
influenced the differential chemical shifts of the imino methyl
signals of the E- and Z-diastereomers but strongly influenced
those of their ring methyl signals (Table 1). Thus each
diastereomer could be assigned the E- or Z-configuration.30 Very
similar ratios of photoproducts were observed in both solvents,
except that the ratios in [D8]toluene were somewhat shifted
toward those of the room temperature equilibria (hence they
are only reported in the Supporting Information).
Irradiation of the isotopomers 1b and 1c gave the iminodi-
aziridines 5, (E)-6, and (Z)-6 in total yields of 87% (Scheme 4)
along with 13% dimethylcarbodimides [D3]2 and (2 + [D3]2),
respectively. When the main photoproduct arises from 1b, the
Me-N-CsNsMe moiety, fixed in the tetrazole ring of 1b,
mutates into the Me-NsCdNsMe partial structure of (Z)-6,
i.e., without change of the original geometry. In the minor
product (E)-6, this geometry has been inverted. We are reluctant,
however, to attribute this N-inversion to an intermediate, because
we cannot exclude that a small fraction of (Z)-6 underwent light-
induced N-inversion.
obtained from 1b. Iminodiaziridine 5 arises from both diaster-
eomers by bond formation between the nonlabeled nitrogens.
Provided that light-induced N-inversion is unimportant, (E)-1c
affords exclusively (E)-6, while (Z)-1c may yield (E)-6 as well
as (Z)-6. This explains why (E)-6 predominates.
Formal exchange of the [D3]methyl groups of 1b and 1c for
tert-butyl groups leads to 1d and 1e, respectively, and strongly
altered the results. The tert-butyl group of 1e coerces the
molecule into adopting exclusively the E-configuration. Irradia-
tion of 1d and (E)-1e afforded the expected iminodiaziridines
7 and 8 along with small amounts of carbodiimides 2 and 9
(Scheme 5). Most probably, the missing 1,3-dipoles methyl azide
(3)24 and tert-butyl azide (10)31,32 were photolyzed and hence
could not be detected.
Irradiation of the 1:1 mixture of (E)-1c and (Z)-1c furnished
yields of 5, (E)-6, and (Z)-6 that strongly differed from those
Small amounts of photoproducts, viz., (E)-8 from 1d and (Z)-8
from (E)-1e, had inverted imino groups. As before, this can be
rationalized in terms of light-induced E/Z isomerization of the
(28) Quast, H.; Aldenkortt, S.; Freudenreich, B.; Schäfer, P.; Hagedorn, M.;
Lehmann, J.; Banert, K. J. Org. Chem. 2007, 72, 1659.
(29) (a) Karabatsos, G. J.; Lande, S. S. Tetrahedron 1968, 24, 3907. (b)
Karabatsos, G. J.; Taller, R. A. Tetrahedron 1968, 24, 3923. (c) Rummens,
F. H. A.; Krystynak, R. H. J. Am. Chem. Soc. 1972, 94, 6914.
(30) Surprisingly, (E)-8 is slightly less stable than (Z)-8 [(E):(Z) ) (47.5 (
0.5):(52.5 ( 0.5)]. Each diastereomer is more stable than 7 [7:8 ) (3.5 (
0.5):(96.5 ( 0.5) at 25 °C].
(31) Photolysis of 10 yields N-isopropylidene-N-methylamine,32 which shows
three multiplets in the 1H NMR spectrum.33 In view of the low yield of the
1,3-dipolar cycloreversion, these could not be expected to emerge from the noise.
(32) (a) Solar, S.; Koch, E.; Lietich, J.; Margaretha, P.; Polansky, O. E.
Monatsh. Chem. 1973, 104, 220. (b) Dunkin, I. R.; Thomson, P. C. P. Tetrahedron
Lett. 1980, 21, 3813.
J. Org. Chem. Vol. 73, No. 10, 2008 3741

Quast and Bieber
1
TABLE 1. Chemical Shifts [ppm] (Relative to TMS) and H,1H
TABLE 2. Ratios of Yields yi of Iminodiaziridines That Were
Obtained From Iminodihydrotetrazoles 1 by Cyclizations of
5
1
Coupling Constants J [Hz] in 60 or 90 MHz H NMR Spectra
Intermediate Diradicals at Their Sites a, b, and c
compd dNsR
δH
>NsRsyn
δH
>NsRanti
δH
a
compd
ratios of Yields
4
Me
3.04
3.03
1.18
3.05
3.02
3.05
3.03
Me
2.79b
2.58c
2.80b
2.79
Me
2.68b
2.55c
2.64b
1.08
A
B
A
A
C
A
C
1b
1d
(E)-1e
(E)-1f
ya: (yb + yc) ) 23:77
ya: (yb + yc) ) 4:96
(ya + yb): yc ) 42:58
ya:yb:yc ) 26:21:53
Scheme 4
Scheme 5
Scheme 5
Scheme 6
7
t-Bu
Me
Me
Me
Me
t-Bu
(E)-8
2.58c
1.13
1.10
(Z)-8
Me
t-Bu
Me
2.69
1.04
2.56c
remote deuterium isotope effects allows the different diradicals
that may originate from 1b, (E)-1c, and (Z)-1c to be considered
degenerate with respect to their energy.
a Solvent:
A
) [D8]THF, B ) [D6]benzene, C ) [D8]toluene.
b
Quartet, J ) 0.5 Hz. c The chemical shifts may be exchanged.
5
Singlet triazaTMMs 16 may be invoked as intermediates. In
principle, they may arise by concerted or stepwise photodeni-
trogenation. The latter mechanism would involve diazenyl 1,3-
diazaallyl diradicals 14 and 15. These could not only form
triazaTMMs 16 but also cyclize directly to iminodiaziridines
by radical substitution of the diazenyl group, or close again the
tetrazole ring affording turn-around isomers, which were not
observed, however. We note that both types of hypothetical
intermediates, 14/15 and 16 (see below; for the substituent key,
see 1), differ by their propensities to undergo changes of
prevailing diastereomers. The origin of 7 by bond formation
between the two methyl-substituted nitrogens of 1d and (E)-1e
is obvious. Likewise, the two possible routes to the major
product of 1d, (Z)-8, are straightforward. However, the second
product of (E)-1e, (E)-8, may arise on two different routes, viz.,
by bond formation between the two ring nitrogens and between
the tert-butyl-substituted and the exocyclic nitrogen. To distin-
guish these paths, we labeled the ring methyl group of (E)-1e
and obtained (E)-1f. As expected, the product distribution for
(E)-1f in Scheme 6 closely resembles that for (E)-1e in Scheme
5, except that all iminodiaziridines 11-13 revealed their mode
of formation and adopted the E-configuration, which portrays
the geometry of the precursor (E)-1f. Only tiny amounts, if any,
of 11 and 13 possessed the Z-configuration. Besides the
iminodiaziridines, [D3]dimethylcarbodiimide ([D3]2, 4%) and
1
9 (8%) made their appearance in the H NMR spectra.
Discussion
geometry. The former possess a CN single bond with a probably
low rotational barrier while 16 resembles the guanidinium ion.
A priori, the diradicals may close the diaziridine ring at each
of their three sites, referred to as a, b, and c. These differ by
the degree of repulsion between the substituents and, in case of
14 and 15, by the mechanisms of cyclization. To support a
choice between 14/15 and 16, we assigned the yields given in
Schemes 4-6 to the corresponding sites and compiled the ratios
of these yields in Table 2.
Inspection of the results listed in Table 2 shows that they are
consistent with intermediate diazenyl 1,3-diazaallyl diradicals
14 and 15 only on the basis of a number of questionable
assumptions. Therefore, we propose singlet triazaTMM diradi-
cals 16 as crucial intermediates en route from iminodihydrotet-
razoles 1 to iminodiaziridines.
Ring-closure of 16b at site a is less favorable than cyclizations
at sites b and c (1st entry). The ratio of yields of the tert-butyl-
substituted iminodiaziridines 7 and 8, formed from iminodihy-
drotetrazole 1d, reflects the relative stabilities of 7 and 8 (2nd
entry),30 while this ratio, observed for the isomeric precursor
(E)-1e, does not (3rd entry). Cyclization of 16d at site a (f7)
is strongly disfavored compared to that at sites b and c [f(Z)-
8]. Presumably, cyclizations at the latter two sites are more rapid,
because the tert-butyl-substituted nitrogen of 16d is predisposed
to ring closure owing to twisting of the tert-butyl group from
the molecular plane. Ring closure of 16e at site c predominates
but yields the less stable isomer 7; cyclizations at both sites a
and b afford the minor but more stable product (E)-8 (3rd entry).
However, all three sites become distinguishable when the labeled
diastereomer (E)-1f is irradiated. Diradical 16f cyclizes at cites
a, b, and c in the approximate ratios 1:1:2 (4th entry). The
preference for cyclization at site c of all diradicals 16 indicates
that relief of allylic strain is an important factor.
In the absence of photophysical and computational evidence,
an interpretation of the photolysis of iminodihydrotetrazole 1
must remain tentative, in particular, since even the type of
excitation, n,π* and/or π,π*, is unknown. Triplet species do
not appear to be involved in the formation of iminodiaziridines,
because these arise at a temperature as low as 12 K,9a while
triplet triazaTMMs are persistent at 77 K.14
The observed bifurcation in photodenitrogenation and light-
induced 1,3-dipolar cycloreversion of 1 is found in organic
solvents at room temperature as well as in nitrogen matrix at
12 K.9 The share of the latter reaction remained unchanged in
the presence of tert-butyl substituents. In the 1,3-dipolar
cycloreversions, the NN bonds by the side of the tert-butyl
groups of (E)-1e and (E)-1f were broken more readily (f9)
than the NN bonds alongside of the ring methyl groups (f2).
This could be explained if strongly asynchronous or even
stepwise mechanisms via diazenyl 1,3-diazaallyl diradicals 14
and 15 would be postulated. Following each of the two
mechanistic alternatives, formation of 9 would be more favorable
compared to 2 because the onset of NN bond breaking that
affords 9 develops less allylic strain.
The regio- and stereoselectivity of the photochemical forma-
tion of iminodiaziridines indicate that any conceivable inter-
mediates do not exist long enough to attain equilibrium
structures. Instead short-lived intermediates retain geometries
that closely resemble those of the iminodihydrotetrazoles 1.34
This is particularly obvious from Scheme 4 where neglect of
(33) Colebourne, N.; Foster, R. G.; Robson, E. J. Chem. Soc. (C) 1967, 685.
(34) It goes without saying that the stereochemical information of the two
nitrogens is lost when they close the diaziridine ring, and only the E/Z ratios of
the iminodiaziridines 6, 8, and 11-13 reveal the reluctance of the intermediates
to undergo change of configuration.
3742 J. Org. Chem. Vol. 73, No. 10, 2008

Iminodiaziridines by Photolysis of Iminodihydrotetrazoles
SCHEME 7. Three-Membered Rings Formed During
Irradiation of Some Heterocyclic Azo Compounds with
Unconjugated Exocyclic Double Bonds
structure in Scheme 1 where each letter X, Y, and Z stands for
carbon or nitrogen. The results depicted in Scheme 7 and those
of this investigation indicate that both photochemical generation
and cyclization of intermediates are stereochemically well-
defined. As inferred from the structures of the photolysis
products, configuration and geometric features inherent in the
heterocyclic azo precursors translate to intermediates that
maintain the configuration during their lifetime and cyclize
regio- and stereoselectively to three-membered rings with
exocyclic double bonds. Details of photochemical generation,
structures, and cyclization of these intermediates, which most
probably are singlet TMM-type diradicals, may be challenges
for photophysical and computational research. Finally, we note
that the photolyses described here offer a convenient access to
sensitive iminodiaziridines.
Experimental Section
Equivalent masses were determined by titration with 0.1 M
perchloric acid in acetic acid.35
Irradiation experiments were performed by using NMR sample
tubes whose walls had been carefully freed from traces of acids
followed by drying under vacuum at 150 °C. The sample tubes
were attached to a vacuum line (10-5 Torr) and the iminodihy-
drotetrazoles (kept under Ar) allowed to sublime into the tubes.
This took 1-4 h at 10-5 Torr for a 20-50 mg sample. Deuterated
solvents were kept over LiAlH4, degassed by several pump-
freeze–thaw cycles, and condensed into the sample tubes, which
were cooled with liquid N2 and sealed under high vacuum. A 150
W medium-pressure mercury arc lamp (TQ 150 by Heraeus, Hanau,
Germany) was placed into a vacuum-insulated water-cooled quartz
immersion well, which was fixed in a large Dewar vessel filled
with methanol whose temperature was kept at -60 °C with the
help of a stainless steel coil connected to a low-temperature
thermostat. The NMR sample tube was kept in a Corex filter glass
tube,23 which was directly attached to the immersion well and
suffused by a stream of cold methanol.
We restrain ourselves from detailing speculations about the
timing of the two rotations around CN bonds involved in the
ring closure of 16 assumed to be planar. However, a stepwise
process via mono-orthogonal triazaTMMs that arise by 90°
rotation of one of the two sterically interacting imino groups at
site c seems reasonable. It explains, for example, the nearly
statistical ratio 1:1:2 of the ring closure at sites a, b, and c of
16f. In contrast to a stepwise process, two concerted rotations
in 16f should occur only at site c, but would be unlikely at
site a.
It is interesting to compare the present results with those from
photodenitrogenations of related heterocyclic azo compounds
(Scheme 7). The two alkylidene heterocycles 17 and 19 afford
exclusively the three-membered ring imines (E)-187b and (E)-
20,2b respectively, certainly because the alternative paths of
cyclization would lead to much less stable three-membered rings.
The same is true for the photolysis of iminodihydrotriazole (E)-
22. However, (E)-22 yields isomeric iminoaziridines (E)-21 and
(Z)-23, which immediately reveal the site of ring-closure.7c All
photoproducts of 17, 19, and (E)-22 portray the geometries of
their precursors. This indicates that hypothetical intermediate
azaTMM and diazaTMM diradicals retain the inherited con-
figurations, just like the triazaTMM intermediates 16 of the
present study. Likewise, bisorthogonal TMMs, which have been
advocated by Andrews and Day1d,e and Bushby et al.,1n,p,20d
and monoazaTMM diradicals with persistent configurations are
to be invoked as intermediates to explain stereoretention on
product formation from the dihydropyrazoles 251w and 27.2c
1,4-Dialkyl-5-(N-alkylimino)-4,5-dihydro-1H-tetrazoles (1),
General Procedure. 1,4-Dimethyl-5-(N-methylimino)-4,5-dihy-
dro-1H-tetrazole (1a). Under Ar, 1a·HBF4 (2.15 g, 10 mmol) or
1a·HClO4 (2.28 g, 10 mmol) was slowly added to a stirred
suspension of NaH (1.2 g, 50 mmol) in dry THF (20 mL), contained
in an 80 mL centrifuge tube, which was equipped with a septum
and connected via syringe to an Ar supply and a vacuum line. The
suspension was stirred overnight. The solid was removed with
the help of a centrifuge and washed with pentane. Distillation of
the solvent from the clear solution under vacuum with strict
exclusion of air and moisture yielded a colorless residue. Sublima-
tion at 30–40 °C/10-3 Torr into a directly attached flask, cooled to
-78 °C, furnished hygroscopic colorless crystals (1.15 g, 91%),
mp 52-53 °C (sealed tube) (ref 22c mp <100 °C). MS (EI 70
eV): m/z (rel intensity) 127 (32) [M+], 126 (17), 71 (10), 70 (51)
[M+ - CH3N3], 69 (100), 44 (8), 43 (18), 42 (59). UV (hexane)
λmax [nm] (log ꢀ) 216 (3.878), 279 (3.286) [UV (DMSO and 0.01
1
M aq NaOH): ref 36]. IR (Nujol) 1682 cm-1 (CdN). H NMR
([D8]THF, 60 MHz) δ 3.13 (s, 3 H, CH3), 3.55 [br s, 6 H, 2 CH3;
splits into 2 signals at Tc ) 28 °C, ∆ν ) 34 Hz (-50 °C), ∆Gcq
)
62.6 kJmol-1]; 1H NMR (C6D6, 250 MHz) δ 3.037 (s, 3 H, CH3),
3.064 (s, 6 H, 2 CH3). 13C NMR (C6D6, 63 MHz) δ 31.4 (broadened
by exchange, CH3), 33.1 (CH3), 34.7 (broadened by exchange, CH3),
142.8 (quat C, C-5). Anal. Calcd for C4H9N5: equivalent mass,
127.1. Found: equivalent mass, 127.9.
Conclusion
(35) Huber, W. Titrations in Nonaqueous SolVents; Academic Press: New
York, 1967.
The present study describes the photolysis of the last type of
heterocyclic azo compounds that is represented by the general
(36) Bianchi, G.; Boulton, A. J.; Fletcher, I. J.; Katritzky, A. R. J. Chem.
Soc. (B) 1971, 2355.
J. Org. Chem. Vol. 73, No. 10, 2008 3743

Quast and Bieber
1,4-Dimethyl-5-(N-[D3]methylimino)-4,5-dihydro-1H-tetrazole
(1b). (a) 1b was prepared from 1b·HBF4 (2.18 g, 10 mmol) and
NaH; colorless crystals (1.16 g, 89%), mp 52–53 °C (sealed tube).
(b) A mixture of 5-(N-benzoyl-N-[D3]methylamino)-1,4-dimeth-
yltetrazolium tosylate (16.3 g, 40 mmol) and conc aq HCl (30 mL)
was heated under reflux for 0.5 h. The solvent was distilled under
vacuum. Aq NaOH (4 M, 30 mL) was added to the residue and
the resulting mixture was extracted with CH2Cl2 (5 × 100 mL).
The organic layers were filtered under Ar through a pad of Na2SO4
(4 × 10 cm) into a flask containing NaH (2–3 g). After the
suspension was stirred for 1 h and the solid material filtered under
Ar, the solvent was distilled under vacuum with strict exclusion of
air and moisture. Sublimation as described for 1a afforded
hygroscopic colorless crystals (4.51 g, 87%), mp 52.5–54 °C (sealed
tube).
1-tert-Butyl-4-methyl-5-(N-methylimino)-4,5-dihydro-1H-tet-
razole (1e) was obtained from 1e·HBF4 (2.57 g, 10 mmol) and
NaH as colorless crystals (1.45 g, 86%), mp 61–62 °C (sealed tube).
MS (EI 70 eV) m/z (rel intensity) 169 (20) [M+], 114 (100), 113
(87), 112 (46), 71 (53), 70 (51), 69 (36), 57 (100), 56 (35). UV
(hexane) λmax [nm] (log ꢀ) 219 (3.692), 27 (3.234). IR (Nujol) 1675
cm-1 (CdN). 1H NMR ([D8]THF, 60 MHz) δ 1.53 (s, 9 H, t-Bu),
3.14 (s, 3 H, CH3), 3.79 (s, 3 H, CH3). Anal. Calcd for C7H15N5:
N, 41.43. Found: N, 41.78.
1-tert-Butyl-4-[D3]methyl-5-(N-methylimino)-4,5-dihydro-1H-
tetrazole (1f) was obtained from 1f·HBF4 (2.60 g, 10 mmol) and
NaH as colorless crystals (1.48 g, 86%), mp 61–62 °C (sealed tube).
Acknowledgment. We thank Dres. Markus Heubes and
Wolfgang Nüdling for recording the high-field NMR spectra
and Dr. Gerda Lange for taking the mass spectra. Financial
support by the Deutsche Forschungsgemeinschaft and the Fonds
der Chemischen Industrie, Frankfurt an Main, is gratefully
acknowledged.
1-[D3]Methyl-4-methyl-5-(N-methylimino)tetrazole (1c) was
obtained from 1c·HBF4 (2.18 g, 10 mmol) and NaH as hygroscopic
colorless crystals (1.18 g, 91%), mp 52–53 °C (sealed tube).
5-(N-tert-Butylimino)-1,4-dimethyl-4,5-dihydro-1H-tetra-
zole (1d) was obtained from 1d·HClO4 (2.70 g, 10 mmol) and
NaH as colorless crystals (1.63 g, 96%), mp 24–25 °C (sealed tube).
MS (EI 70 eV) m/z (rel intensity) 169 (13) [M+], 154 (67), 112 (1)
[M+ - CH3N3], 98 (6), 97 (100), 69 (6), 57 (13), 56 (12). UV
(hexane) λmax [nm] (log ꢀ) 208 (3.989), 278 (3.258). IR (Nujol)
Supporting Information Available: General experimental
details; synthetic procedures, elemental analyses, and NMR
spectra for 5-aminotetrazolium salts; UV and NMR spectra of
iminodihydrotetrazoles; detailed results of all irradiation experi-
ments; and IR and 1H NMR spectra of photolysis products. This
material is available free of charge via the Internet at
http://pubs.acs.org.
1
1668 cm-1 (CdN). H NMR ([D8]THF, 60 MHz) δ 1.28 (s, 9 H,
t-Bu), 3.53 (s, 6 H, 2 CH3; shows no splitting into 2 signals down
to -70 °C); 1H NMR (C6D6, 250 MHz) δ 1.28 (s, 9 H, t-Bu), 3.15
(s, 6 H, 2 CH3). 13C NMR (C6D6, 63 MHz) δ 33.8 (3 CH3), 34.2
(2 CH3), 50.2 (quat. C), 138.5 (quat. C, C-5). Anal. Calcd for
C7H15N5: N, 41.43; equivalent mass, 169.2. Found: N, 41.82;
equivalent mass, 170.3.
JO702697F
3744 J. Org. Chem. Vol. 73, No. 10, 2008