Photochemistry of 1-allyl-4-aryltetrazolones in solution; Structural effects on photoproduct selectivity

Article abstract of DOI:10.1039/c2pp25210d

The photochemistry of tetrazolones derived from the carbocyclic allylic alcohols cyclohex-2-enol and 3-methylcyclohex-2-enol and from the natural terpene alcohol nerol was investigated in solution with the aim of assessing the effect of solvent and of structural constraints imposed by bulky allylic moieties on photoproduct selectivity and stability. Photolysis of tetrazolones derived from nerol and cyclohex-2-enol afforded the corresponding pyrimidinones as major products through a pathway that appears to be similar to that proposed for other 1-allyl-4-phenyl-1,4-dihydro-5H-tetrazol-5-ones derived from acyclic and unhindered allylic alcohols previously investigated but photolysis of the tetrazolone derived from the bulkier 3-methylcyclohex-2-enol 4c leads to formation of a benzimidazolone, indicating that, in this case, cyclization of the biradical formed upon extrusion of N₂ involves the phenyl substituent and not the allylic moiety. Theoretical calculations (DFT(B3LYP)/3-21G*) were conducted to support the interpretation of the experimental results and mechanistic proposals. Laser flash photolysis experiments were conducted with the aim of clarifying the nature of the intermediate involved in the primary photocleavage process.

Full text of DOI:10.1039/c2pp25210d

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Photochemistry of 1-allyl-4-aryltetrazolones in
solution; structural effects on photoproduct selectivity†
Amin Ismael,a Carlos Serpab and M. Lurdes S. Cristiano*a
Cite this: Photochem. Photobiol. Sci., 2013,
12, 272
The photochemistry of tetrazolones derived from the carbocyclic allylic alcohols cyclohex-2-enol and
3-methylcyclohex-2-enol and from the natural terpene alcohol nerol was investigated in solution with
the aim of assessing the effect of solvent and of structural constraints imposed by bulky allylic moieties
on photoproduct selectivity and stability. Photolysis of tetrazolones derived from nerol and cyclohex-2-enol
afforded the corresponding pyrimidinones as major products through a pathway that appears to be similar
to that proposed for other 1-allyl-4-phenyl-1,4-dihydro-5H-tetrazol-5-ones derived from acyclic and unhin-
dered allylic alcohols previously investigated but photolysis of the tetrazolone derived from the bulkier
3–methylcyclohex-2-enol 4c leads to formation of a benzimidazolone, indicating that, in this case, cycliza-
tion of the biradical formed upon extrusion of N2 involves the phenyl substituent and not the allylic
moiety. Theoretical calculations (DFT(B3LYP)/3-21G*) were conducted to support the interpretation of the
experimental results and mechanistic proposals. Laser flash photolysis experiments were conducted with
the aim of clarifying the nature of the intermediate involved in the primary photocleavage process.
Received 21st June 2012,
Accepted 24th August 2012
DOI: 10.1039/c2pp25210d
www.rsc.org/pps
The photochemistry of tetrazoles in solution has been
reviewed in the context of potential applications to organic
1. Introduction
Tetrazole1 and its derivatives are applied in major areas, such synthesis.28 Analysis of the literature reveals that, through a
as medicine, agriculture, food chemistry and imaging technol- careful selection of the solvent and other reaction conditions,
ogy. Most applications of tetrazoles derive from the acid/base the photofragmentation of some derivatives of tetrazole may
properties of the tetrazolic acid fragment, –CN4H, which acts be tuned to grant selectivity and high yield, affording
as a surrogate for the carboxylic acid group, –CO2H, due to its stable and synthetically useful photoproducts that may be
comparatively higher metabolic stability at physiological pH.2
isolated and stored, or trapped in the reaction media. A diver-
The photochemistry of tetrazole and a range of its deriva- sity of photoproducts such as 9H-pyrimido(4,5-b)indoles,24
tives has been studied, in solution and/or isolated in cryogenic diaziridinones,16,25 iminoaziridines,26,27 carbodiimides,22,25
matrices.3–27 Photodecomposition of tetrazoles involves clea- oxazines,14 benzimidazolones22 and pyrimidinones10,11 may
vage of the tetrazolyl ring, leading to a variety of photopro- be obtained from photolysis of tetrazole derivatives in
ducts. Azides, isocyanates or aziridines are generally obtained, solution. Of the 7 classes mentioned, 3 (diaziridinones,
but the presence of labile hydrogen atoms, either directly benzimidazolones and pyrimidinones) result from photolysis
linked to the tetrazole ring or in substituent groups, may open of 1,4-disubstituted-1,4-dihydro-5H-tetrazol-5-ones (tetrazo-
additional photocleavage pathways or allow for secondary lones), illustrating their versatility as starting materials
photochemical reactions to take place concomitantly with the for the preparation of other scaffolds and the relevance of
main primary photoprocesses.4–8,20–26 The photochemistry of
tetrazoles is also influenced by the chemical nature and con- particular class.
a
deep investigation of the photochemistry of this
formational flexibility of substituents linked to the heterocycle,
The synthesis of benzimidazolones from photolysis of
which may favor or exclude certain reaction channels,9–14 4-substituted-1,4-dihydro-1-phenyl-5H-tetrazol-5-ones
was
determining the nature and relative amount of the final reported in 1985.22 The authors described that irradiation of
photoproducts.
1-phenyl-tetrazolones substituted at N-4 by hydrogen, phenyl,
alkyl, propenyl and butenyl, in methanol, acetonitrile or 2-pro-
panol leads to benzimidazolones as final products in nearly
quantitative yields and proposed a mechanism involving
photoextrusion of molecular nitrogen with formation of a bi-
radical intermediate that, upon cyclization involving the
phenyl substituent, gives rise to the product.22
aCCMAR and Department of Chemistry and Pharmacy, F.C.T., University of Algarve,
P-8005-039 Faro, Portugal. E-mail: mcristi@ualg.pt
bDepartment of Chemistry, University of Coimbra, P-3004-535 Coimbra, Portugal
†Electronic supplementary information (ESI)
available. See DOI:
10.1039/c2pp25210d
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In this publication, we describe the photochemistry of tetrazo-
lones derived from the natural terpene nerol 4a (see Scheme 2)
and from the cyclic allyl alcohols cyclohex-2-enol 4b and
3-methylcyclohex-2-enol 4c (Scheme 3). Tetrazolones 4a–c were
prepared and subsequently irradiated in methanol, acetonitrile
Scheme 1 Proposed synthetic route to pyrimidinones from allylic alcohols,
based on photolysis of tetrazolones in alcohols.
The photochemistry in solution of a small range of 1-allyl-4-
phenyl-1,4-dihydro-5H-tetrazol-5-ones was investigated in our
group.10,11 Tetrazolones 4 (Scheme 1; R = H, CH3, Ph) were
irradiated in cyclohexane, acetonitrile, methanol, 1-propanol
and 1-hexanol. Photolysis of the compounds in all solvents
tested resulted in formation of 3,4-dihydro-6-substituted-3-
phenylpyrimidin-2(1H)-ones 5 as the sole primary photopro-
ducts. Based on the observed photosensitizing effect of oxygen
and on the observation that an increase in solvent viscosity
leads to a decrease in quantum yields we proposed that photo-
excitation of 1-allyl-4-phenyl-1,4-dihydro-5H-tetrazol-5-ones 4
would lead to photoextrusion of molecular nitrogen with poss-
ible formation of a caged triplet biradical that after T–S conver-
sion would cyclize to form pyrimidinones 5 that, in the protic
solvents, remained photostable even after extended periods of
irradiation.11 Besides, formation of a biradical from tetrazo-
lones, through photolysis, had already been postulated.22
When irradiation was conducted in cyclohexane, carbon tetra-
chloride or acetonitrile, the primary photoproducts 5 under-
Scheme 2 Proposed photodegradation pathways of 1-(3,7-dimethylocta-1,6-
dien-3-yl)-4-phenyl-1H-tetrazol-5(4H)-one 4a in solution.
went rapid photodecomposition to afford
a mixture of
products identified as allyl amine 7, aniline 8 phenyl-, and
allyl-isocyanates (6, 9, Scheme 1).
Given the observed selectivity and stability of compounds 5
in alcohols, we postulated that the novel synthetic route to
pyrimidinones from allylic alcohols in only 3 steps (Scheme 1)
should be further explored. Besides, 5-allyloxy-1-aryl tetrazoles
3 are prepared in high yields from the reaction of the required
allylic alcohol 2 with 5-chloro-1-phenyl tetrazole 129 and
1-allyl-4-aryl-tetrazolones 4 are obtained from 5-allyloxy-1-aryl
tetrazoles 3, in quantitative yields, through a thermally-
induced sigmatropic isomerisation that proceeds via a con-
certed [3,3′]-sigmatropic Claisen-type mechanism.30–33
Considering the relevance of pyrimidinones as scaffolds in
heterocyclic synthesis34 and the importance of developing
mild and efficient synthetic routes to these compounds, we
aimed at a deeper investigation of the scope of this photo-
chemically based synthetic methodology. In particular, we
propose to study the effect of steric constraints imposed by
bulky allylic moieties on photoproduct selectivity and stability.
Scheme 3 Proposed photodegradation pathways of 1-cyclohexenyl-4-phenyl
tetrazolones 4b,c in solution.
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and cyclohexene. Results show that photolysis of tetrazolones (red). As shown, the UV spectral assignments for compounds
4a,b leads to formation of compounds 10a,b through a 4a–c are similar, with absorption maxima around 249 nm,
pathway that appears to be similar to that proposed for other indicating that, for these 3 compounds, the structure of the
1-allyl-4-phenyl-1,4-dihydro-5H-tetrazol-5-ones previously inves- N-allyl substituents attached to the tetrazolyl ring has a negli-
tigated,10,11 but photolysis of the tetrazolone derived from the gible effect on the absorbance of the chromophore. UV spectra
bulkier 3-methylcyclohex-2-enol 4c leads to formation of benz- for compounds 10a,b exhibit similar patterns, with maxima of
imidazolone 11, indicating that, in this case, cyclization of the 241 and 238 nm respectively, and are also similar to spectra
transient intermediate species formed upon extrusion of N2 of pyrimidinones previously obtained from photolysis of other
involves the phenyl substituent and not the allylic moiety. This 1-allyl-4-phenyltetrazolones.10,11 Note that the photoproduct
unexpected cyclization pathway is ascribed to steric constraints 10a shows absorbance at the excitation wavelength and thus
imposed by the methyl group attached to the allylic carbon in photolysis yields will decrease at higher conversions, which
4c, which hinders the cyclization pathway involving the inter- may explain why photolysis of tetrazolone 4a is comparatively
mediate formed from 4c and the allylic system, that would slower. Photoproduct 10b also shows absorbance at the exci-
lead to formation of the expected pyrimidinone. Interpretation tation wavelength, and photolysis yield would also be expected
of the experimental results was assisted by theoretical calcu- to decrease at higher conversions. However, it was observed
lations (DFT(B3LYP)/3-21G*). Laser flash photolysis experi- that photofragmentation through route B (Scheme 3) is higher,
ments were conducted with the aim of clarifying the nature of resulting in an overall faster photodegradation of tetrazolone
the transient intermediate species involved in the primary 4b when compared to 4a (see Fig. S9, ESI†).
photocleavage.
As observed, the UV spectrum of compound 11, resulting
from photolysis of 4c, shows a different pattern from those
exhibited by photoproducts 10a and 10b. As discussed below,
the intermediate species formed from photolysis of 4c
2. Results and discussion
2.1. Synthesis of tetrazolones 4a–c
follows an alternative cyclisation pathway, leading to
benzimidazolone.
a
Synthesis of 1-allyl-4-phenyltetrazolones 4a–c (Schemes 2 and
3) was conducted following the methodology depicted in
Scheme 1. The carbocyclic allylic alcohols cyclohex-2-enol and
3-methylcyclohex-2-enol and nerol were converted into the
allylic alkoxides through reaction with sodium hydride in
anhydrous conditions. Subsequent addition of 5-chloro-1-
phenyltetrazole29 resulted in nucleophilic displacement of
chloride leading to formation of 5-allyloxy-1-phenyltetrazoles
3a–c. Ethers 3a,b could be isolated and characterised.
However, putative ether 3c could not be isolated, as it readily
isomerised to the corresponding tetrazolone 4c, under the con-
ditions used for etherification. It was also observed that iso-
merization of ether 3a occurs very easily at room temperature.
N-Allyl-tetrazolones 4a,b were quantitatively obtained from the
The molar absorption coefficients (ε) for tetrazolones 4a–c
and photoproducts 10a,b and 11, calculated at λmax, are pro-
vided in Table S11.† A detailed description of the results
obtained for steady-state photolysis of compounds 4a–c is pro-
vided below.
2.2.1. Photolysis of 1-(3,7-dimethylocta-1,6-dien-3-yl)-4-
phenyl-1H-tetrazol-5(4H)-one (4a). Photolysis of tetrazolone 4a
was initially conducted in methanol. The major photoproduct,
identified as 4-methyl-4-(4-methylpent-3-enyl)-1-phenyl-3,4-
dihydropyrimidin-2(1H)-one 10a (Scheme 2), was isolated in
83% yield after purification by column chromatography on
silica gel. This primary photoproduct is formed by extrusion of
molecular nitrogen from the tetrazolyl ring system in 4a
through photo-induced cleavage of the two formally single
N–N bonds of the heterocycle followed by cyclization of the
resulting transient intermediate involving the allylic fragment
(route A; Scheme 2). GC-MS analysis of this primary photopro-
duct shows a peak with a shoulder that we assumed to result
1
corresponding ethers 3a,b by heating a neat sample. H-NMR
spectra for compounds 4a–c are presented in Fig. S1–S3 (ESI†).
2.2. Photolysis of 1-allyl-4-phenyltetrazolones 4a–c
Solutions of N-allyl-tetrazolones 4a–c in methanol, acetonitrile from the presence of a mixture of conformers, which was sup-
1
and cyclohexane were irradiated with a low-pressure mercury ported by analysis of the H NMR spectrum where two sets of
lamp (λ = 254 nm) and the reaction was monitored by GC-MS. signals with small differences in chemical shifts are observed
Irradiation was continued until no starting material was (see Fig. S4 and S8; ESI†).
detected. GC-MS analysis of irradiated solutions led to the
Traces of other primary photoproducts were identified:
identification of one major primary photoproduct for each of phenyl-isocyanate (6; m/z = 119), that is subsequently con-
the three derivatives. Preparative-scale irradiations were con- verted to N-phenyl methylcarbamate (13; m/z = 151), through
ducted, followed by purification of the photoproducts by methanolysis, or aniline (8; m/z = 93), through hydrolysis fol-
column chromatography on silica gel. Analysis of the isolated lowed by decarboxylation, and a peak that matches the MS
1
products by mass spectrometry (EI) and H-NMR (see Fig. S4– trace of 3,7-dimethyl-1,3,6-octatriene (12a; m/z = 136) resulting
S6; ESI†) confirmed their structures. No degradation of the from 3-azido-3,7-dimethyl-1,6-octadiene through elimination
photoproducts during storage was observed.
of azide. Phenyl isocyanate, aniline and N-phenyl methylcarb-
Fig. S7 (ESI†) shows the UV spectra of methanolic solutions amate were identified by comparing their GC-MS spectra
of tetrazolones 4a–c (blue) and of photoproducts 10a,b and 11 with those of standard samples of the compounds. The
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identification of these minor photoproducts on the GC/MS 1-phenyl-3a,4,5,6-tetrahydro-1H-benzoimidazol-2(3H)-one 10b
spectra from the beginning of irradiation clearly indicates that (Scheme 3). This compound results from route A, a pathway
two photo-fragmentation pathways (A and B; Scheme 2) for that involves photoextrusion of molecular nitrogen from the
tetrazolone 4a are at play. In order to confirm that compounds tetrazolyl ring followed by cyclization of the resulting transient
6, 8, 12a and 13 were generated from an alternative photo- intermediate involving the allylic moiety. In order to dis-
cleavage of 4a and not by photocleavage of the major primary tinguish the photoproducts resulting from different cyclization
photoproduct resulting from pathway A, a pure sample of com- pathways, with the allylic moiety or the phenyl ring, we shall
pound 10a was irradiated in methanol, using the experimental class photoproduct 10b as a pyrimidinone.
conditions applied to photolysis of 4a. Even with extended
As observed for photolysis of 4a, a second photocleavage
irradiation, no secondary photoproducts were detected, con- pathway (route B) leading to phenyl-isocyanate (6 m/z = 119)
firming that compounds 6, 8, 12a, 13 result from tetrazolone and corresponding products of solvolysis N-phenyl methylcarb-
photodegradation and demonstrating that pyrimidinone 10a is amate (13 m/z = 151) and aniline (8 m/z = 93), together with
photostable in methanol. Thus, a minor photofragmentation cyclohex-2-enimine (12b m/z = 95), was also observed for com-
route B, involving photocleavage of the formally single N–N pound 4b (Scheme 3). As previously reported,35 cyclohex-2-
and C–N bonds on tetrazolone 4a and leading to trace enimine is formed from 3-azido-cyclohexene via elimination of
amounts of phenyl-isocyanate and 3-azido-3,7-dimethyl-1,6- nitrogen followed by rearrangement.
octadiene, operates concomitantly with the major photofrag-
mentation/cyclisation pathway A.
Photolysis of tetrazolone 4b in acetonitrile and cyclohexane
led to formation of a new photoproduct identified as N-1,3-
Based on previous work,35 we expected to observe extrusion cyclohexadienyl-N-phenylamine 14, arising from photocleavage
of molecular nitrogen from the putative primary photoproduct of primary photoproduct 10b (Scheme 3). Proposal of this
3-azido-3,7-dimethyl-1,6-octadiene, followed by rearrangement, pathway was confirmed through irradiation experiments using
leading to the corresponding imine derivative. As will be a pure sample of pyrimidinone 10b (isolated previously from
described below, this was observed for tetrazolones 4b and 4c. photolysis in methanol) in acetonitrile and cyclohexane. In the
However, with tetrazolone 4a no imine was ever detected. We course of these experiments, formation of this new photopro-
believe that the preferential elimination of azide from 3-azido- duct was detected, confirming that it results from photodegra-
3,7-dimethyl-1,6-octadiene results from the high stability of dation of the primary photoproduct 10b.
the conjugated diene system formed in the 12a photoproduct.
In general terms, the outcome of photolysis in compounds
The photoreactivity of N-allyl-tetrazolone in acetonitrile and 4a and 4b appears to be similar, despite the cyclic nature of
cyclohexane was also investigated and proved to be similar to the allylic moiety in 4b. The difference is the relative extent of
that in methanol. Photolysis of 4a may occur through pathway photocleavage through route B, which represents around 40%
A, leading to compound 10a as the major primary photopro- in 4b against less than 10% in 4a, as shown from kinetics (dis-
duct, and through pathway B, leading to phenyl-isocyanate cussed below).
and subsequently to aniline. The relative concentrations of
2.2.3. Photolysis of 4-(3-methylcyclohex-2-enyl)-1-phenyl-
phenyl-isocyanate and aniline are higher than those obtained 1H-tetrazol-5(4H)-one (4c). Photolysis of 4-(3-methylcyclohex-
when photolysis was conducted in methanol. It has been 2-enyl)-1-phenyl-1H-tetrazol-5(4H)-one 4c in methanol resulted
reported that pyrimidinones undergo easy photocleavage in in a main photoproduct isolated in 76% yield and identified
non-alcoholic solvents.10,11 Thus, the higher formation of as 3-(1-methylcyclohex-2-enyl)-benzoimidazol-2(1H)-one 11. As
phenyl-isocyanate and aniline can be explained by ring photo- observed for the other allyltetrazolones studied, the primary
cleavage of pyrimidinone 10a (Scheme 2). This was confirmed photofragmentation route for compound 4c involves photo-
by irradiating solutions of pyrimidinone 10a, isolated pre- extrusion of molecular nitrogen from the tetrazolyl ring system,
viously as the major product of photolysis in methanol, in leading to a transient intermediate species. However, a distinct
acetonitrile and cyclohexane. These experiments led to for- process of cyclization of the intermediate appears to take place
mation of phenyl-isocyanate and aniline, confirming that the in this case (route C), leading to formation of benzimidazolone
two products also result from pyrimidinone photodegradation. 11 (Scheme 3). Thus, the intermediate does not cyclise using
The formation of phenyl-isocyanate and aniline by photoclea- the allyl moiety but, instead, uses the phenyl ring system.
vage of 10a will be concomitant with formation of two other
Results obtained for photolysis of tetrazolone 4c in aceto-
possible secondary products (7a, 9a, respectively). However, nitrile and cyclohexane were similar to those obtained in
these photoproducts were never detected, due possibly to their methanol. Irradiation experiments using a pure sample of
high volatility, fast photodecomposition into low molecular benzimidazolone 11 (isolated previously from photolysis in
weight products, or fast elution under the chromatographic methanolic solution) in acetonitrile and cyclohexane showed
conditions used.
that benzimidazolone 11 is a photostable product in all sol-
2.2.2. Photolysis of 4-(cyclohex-2-enyl)-1-phenyl-1H-tetra- vents tested.
zol-5(4H)-one (4b). Photolysis in 4-(cyclohex-2-enyl)-1-phenyl-
A previous investigation on the UV-induced photochemistry
1H-tetrazole-5-one 4b in methanol using the experimental con- (λ ≥ 235 nm) of 1-phenyl-4-allyl-tetrazolone isolated in solid
ditions applied with 4a led to formation of a main primary argon showed a photofragmentation pathway involving a
photoproduct, isolated in 56% yield and identified as [3 + 2] pericyclic molecular nitrogen elimination reaction,
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leading to 1-allyl-2-phenylaziridinone that subsequently forms led to formation of a new secondary photoproduct (14,
the corresponding benzimidazolone.12 Thus, in the cryogenic Scheme 3), identified in Fig. S10† as an amine.
matrix, cyclization with phenyl appears more favorable than
Kinetics for the photodecomposition of tetrazolones 4a–c
with allyl. However, when photolysed in solution, this and two in cyclohexane exhibits a similar profile to that observed in
other 4-allyl-tetrazolones investigated afforded pyrimidinones acetonitrile.
as the sole primary photoproducts in almost quantitative
yields, and no trace of benzimidazolone was ever detected.10,11
2.4. Theoretical analysis of proposed routes; interpretation of
This trend is followed by tetrazolones 4a and 4b, as explained
above, but not by tetrazolone 4c. A search in the literature
revealed similarities between the UV spectrum of compound
11 (Fig. S7†) and typical UV spectra of benzimidazolones,36
adding further evidence to the identification of the photo-
product resulting from photolysis of tetrazolone 4c as benzimi-
dazolone 11.
In order to shed some light on the effect of structural con-
straints in the allylic system on the mechanism of cyclization,
and product selectivity, molecular orbital calculations at the
DFT level of theory were carried out. Tetrazolones 4b and 4c
have high structural similarity, differing only in a methyl
group strategically attached to the allylic carbon. For pyrimidi-
none formation, the allylic system is involved in ring closure of
the transient intermediate formed from photo-extrusion of
nitrogen, and this cyclisation requires prior rotation of the
allylic fragment on the putative biradical. In the case of 4c the
bulky methyl group attached to the allylic carbon appears to
hinder rotation of the allylic system, preventing ring closure to
the expected pyrimidinone. Instead, cyclization involving the
phenyl ring is preferred, leading to the observed photoproduct
11. Results obtained from DFT calculations will be discussed
in detail.
substituent effects on route selectivity
The major primary photoproducts arising from photolysis of
4b and 4c, pyrimidinone 10b and benzimidazolone 11,
respectively, result from elimination of nitrogen from the tetra-
zole ring followed by two distinct processes of cyclization.
Differences in photoreactivity for the two tetrazolones can be
ascribed to substitution at the allylic carbon; replacement of
hydrogen by methyl clearly affects the reactivity and stability of
the intermediate species involved.
In order to gather more information regarding the mechan-
isms involved in each case and on the specific nature of substi-
tuent effects on route selectivity, quantum chemical
calculations were performed at the DFT level of theory for com-
pounds 4b and 4c, considering all steps from starting tetra-
zolone
to
observed
products,
pyrimidinone
and
benzimidazolone. Two possibilities were explored for cycliza-
tion of the transient intermediates: rotation and ring closure
involving either the allylic system or the phenyl ring. Results
are schematically presented in Fig. 2 and 5.
The starting compounds, 4-allyl tetrazolones 4b and 4c,
have three intramolecular rotational degrees of freedom (desig-
nated in Fig. 1 by arrows) that may result in different confor-
mers. These include: (i) relative orientation of the phenyl and
tetrazolyl rings (dihedral angle A); (ii) relative orientation of
the cyclohex-2-enol and tetrazole rings (dihedral angle B). It is
important to note that the carbon atom C(20) is chiral. In the
present study all calculations were carried out for the S-enan-
tiomer of the starting compound; (iii) conformation of the
cyclohex-2-enol ring (dihedral angle C).
2.3. Kinetics for the photodecomposition of tetrazolones 4a–c
Fig. S9† shows the kinetics for the photodecomposition of tetr-
azolones 4a–c in methanol, along with the kinetics of photo-
products formation. After 10 min of irradiation, about 90% of
the tetrazolones 4a–c had been consumed. Complete photo-
decomposition of tetrazolones 4b and 4c occurs after 15 and
20 min, respectively, but for tetrazolone 4b formation of photo-
products through route B is more significant. After total con-
version, 40% of photoproducts derived from route B were
formed from tetrazolone 4b, against 15% from tetrazolone 4c.
For tetrazolone 4a complete photodecomposition was com-
paratively slower, probably due to its absorbance wavelength,
as previously discussed. After 40 min of irradiation the reagent
was totally consumed, and photoproducts arising from route B
corresponded to less than 10%.
Extensive chemical calculations for initial structures 4b and
4c were previously reported by our group.33 Calculations at
DFT level predict that in all conformers the phenyl and tetr-
azole rings have planar geometries and are coplanar to each
Fig. S10† shows the kinetic profiles for the photodecompo-
sition of tetrazolones 4a–c in acetonitrile, along with those for
photoproducts formation. It can be deduced that photolysis in
acetonitrile follows the global pattern observed in methanol,
with two significant changes: the first corresponds to a signifi-
cant increase in the amount of isocyanate and aniline that
results from photolysis of 4a, in keeping with previous obser-
vations showing that these photoproducts also result from
photodegradation of the primary photoproduct 10a. Also, as
Fig. 1 Structure of the tetrazolones 4b (X = H) and 4c (X = CH3) with chosen
atom numbering. Carbon atom C(20) of the cyclohex-2-enyl ring is chiral.
Arrows accompanied by the letters A, B and C show intramolecular confor-
discussed above, photolysis of tetrazolone 4b in acetonitrile mationally revelant degrees of freedom.
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Fig. 3 Structure of the biradicalar intermediate B1b calculated at the DFT
(B3LYP)/3-21G* level. The two new rotational degrees of freedom involve dih-
edrals E [OCN(3)C(20)] and F [OCN(5)C(6)] (see Fig. 1 for atom numbering).
Model structure a illustrates the relative proximity of the nitrogen radical and
the H-allylic system when rotation about E is in cis orientation.
Fig. 2 Relative energies of the structures corresponding to the most stable
stationary points for the photochemical formation of pyrimidinone 10b and
putative benzoimidazolone 10b’ from tetrazolone 4b, calculated at the DFT
(B3LYP)/3-21G* level.
other (dihedral angle A). The exchange of the substituent X (H
or CH3) does not influence this parameter. The calculated
values of the dihedral angle C were found to fall in a narrow Fig. 4 Structures corresponding to minima for biradical intermediates B1bH
and B2b, resulting from rotation of dihedral E, corresponding to cis and trans
range, which indicates the rigidity of the cyclohex-2-enol ring.
Dihedral angle B has the most flexible conformational degree.
For tetrazolone 4b two minima were found, corresponding to
orientations, respectively. Considering that C(18) approaches N(5) in B2b
through rotation of dihedral B with formation of a new C–N single bond leads
to 10b, the structure of pyrimidinone experimentally obtained.
the cis and trans orientations of the CNCH (dihedral angle B),
the cis conformer being the most stable. The methylated tetr-
azolone 4c exhibits three minima for the rotation of the CNC-
(20)C(21) (dihedral angle B), the trans and gauche orientations,
the gauche (+61.4°) conformer being the most stable.
In calculations undertaken for both routes, the relative zero
level of energy was chosen to be the energy of the most stable
conformer of starting tetrazolones. The proposed reaction
pathways and relative energies of species involved, for for-
mation of pyrimidinone 10b and benzimidazolone 11, from 4b
and 4c respectively, are presented in Fig. 2 and 5.
From internal rotation about the B dihedral angle, when
dihedral E is in the cis orientation (structure B1bH) confor-
mations where the cyclohex-2-enol ring is directed to the carb-
onyl group of the tetrazole moiety can be expected, although
corresponding to high energy structures due to steric hin-
drance. The relevant low energy forms result from this B
internal rotation in the trans orientation of the dihedral E (see
structure B2b), since only in this case the allylic fragment is
properly aligned for ring closure. For the minima found, B2b,
with two possible directions of internal rotation of dihedral B,
a clockwise rotation of the cyclohex-2-enol moiety is essential
for ring closure, due to higher steric hindrance through the
counterclockwise rotation when the cyclohex-2-enol ring is
directed to the phenyl group. Subsequent reaction coordinate
calculations, considering that C(18) approaches N(5) through
rotation of dihedral B and formation of a new C–N single
bond, provided the expected structure of pyrimidinone 10b, in
an exothermic process (see Fig. 2 and 4).
The possibility of rotation and ring closure involving the
phenyl ring was also studied, although the putative photopro-
duct (10b′) was never detected experimentally. For this alterna-
tive route involving rotation of dihedral angle F (Fig. 2 and 3),
two minima were found, corresponding to the cis and trans
orientations (B2b′). Calculations show that this pathway is
energetically more demanding as compared with the former
one. The energy calculated for intermediate (B2b′) is 60 kJ
mol−1 and 50 kJ mol−1 higher than that for intermediates
B1bH and B2b, respectively. Thus, although putative benzimid-
azolone 10b′ is calculated to be thermochemically more stable
than pyrimidinone 10b by around 100 kJ mol−1, only the pyri-
midinone is formed, through kinetic control.
2.4.1. Theoretical investigation of the photodegradation of
4-(cyclohex-2-enyl)-1-phenyl-1H-tetrazol-5(4H)-one
(4b). The
mechanism of photocleavage of compound 4b was investi-
gated. Calculations were performed for the 2 putative routes.
For each pathway, structures of the species proposed/observed
were optimized. Fig. 2 presents a diagram of the relative ener-
gies of species corresponding to the most stable stationary
points for both pathways.
Based on the literature,11,22 we postulated that cleavage of
the tetrazole ring with N2 extrusion leads to a biradicalar inter-
mediate B1b (see Fig. 3). This intermediate has two new
rotational degrees of freedom, the OCN(3)C(20) (dihedral angle
E) and the OCN(5)C(6) (dihedral angle F).
Two minima were found for rotation of dihedral E, corre-
sponding to cis and trans orientations. In the cis orientation,
the relative proximity of the nitrogen radical and the H-allylic
system is noteworthy (see structure a). Under such circum-
stances, the H-migration involving the allylic system can be
easily established (see structure B1bH, Fig. 4). We can assume
that the expected H-migration is intramolecular, since it
occurred in the aprotic solvents acetonitrile and cyclohexane
as well as in protic methanol.
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Fig. 6 Structure of the biradicalar intermediate B1c calculated at the DFT
(B3LYP)/3-21G* level. Rotational degrees of freedom are related to dihedrals E
[OCN(3)C(20)] and F [OCN(5)C(6)] (see Fig. 1 for atom numbering). In the
minimum of B2c rotation of dihedral B, essential for ring closure through the
approach of C(18) to N(5), occurs far from the plane of the carbamide moiety,
preventing formation of putative pyrimidinone.
Fig. 5 Relative energies of structures corresponding to the most stable station-
ary points in the pathway leading to formation of benzoimidazolone 11 from
tetrazolone 4c, calculated at the DFT(B3LYP)/3-21G* level.
2.4.2. Theoretical analysis of the photodegradation of 4-(3-
methylcyclohex-2-enyl)-1-phenyl-1H-tetrazol-5(4H)-one
(4c).
The mechanism of photolysis of compound 4c was investi-
gated. As above, calculations were performed for the 2 putative
routes and all structures for species proposed/observed were
optimized. Fig. 5 presents a diagram of the relative energies
calculated for species corresponding to the most stable station-
ary points for both pathways.
Again, cleavage of the tetrazole ring with N2 extrusion is
assumed to lead to a biradicalar intermediate B1c, with two
new rotational degrees of freedom, the dihedral angle E and
the dihedral angle F (Fig. 6).
Fig. 7 Relative orientation of the cyclohex-2-enol and tetrazole rings (dihedral
angle B) of the starting compounds, 4-allyl tetrazolones 4b and 4c, as a result of
their different substituents H and CH3 respectively.
Three minima were found for anticlockwise rotation of
dihedral E: the cis orientation, −60° and −90°. Interestingly in
this structure, for the clockwise rotation of dihedral E, no
structures corresponding to minima were found. Analysis of
the initial structures 4b and 4c reveals a clear difference in the
relative orientation of the cyclohex-2-enol and tetrazole rings
(dihedral angle B) imposed by the two different substituents
(Fig. 7). As mentioned above, the methylated tetrazolone 4c
exhibits three minima for the rotation of the CNC(20)C(21)
(dihedral angle B), the trans and gauche orientations, the
gauche (+61.4°) being the most stable conformer. This gauche
conformation of the dihedral angle B prevents clockwise
rotation around dihedral E in the intermediate B1c, due to
steric hindrance caused by the methyl, justifying the observed
product selectivity when the outcome of photolysis of com-
pounds 4b and 4c is compared.
In both minima corresponding to dihedral E orientations
of −60° and −90° (B2c, Fig. 6), rotation of dihedral B, essential
for ring closure through the approach of C(18) to N(5), occurs
far from the plane of the carbamide moiety. Thus, rotation of
dihedral B is prevented due to steric hindrance and to
increased difficulties in the ring closure process imposed by
the geometry of B2c.
Fig. 8 Minimum energy structure obtained for biradicalar intermediate B2c’,
found from the rotation of dihedral F, corresponding to the trans orientation.
Minimum energy structure obtained for the expected structure of benzimidazo-
lone 11, obtained from B2c’ by ring closure, through the approach of C(7) to
N(3).
The experimental data are in agreement with results from
theoretical calculations, showing a selective preference for the
route leading to formation of benzimidazolone.
2.5. Investigation of the nature of the intermediate; flash
photolysis experiments
Based on results of our preliminary investigation of the photo-
chemistry of selected allyl tetrazolones (4; Scheme 1) we
proposed a mechanism of photolysis involving initial photo-
extrusion of nitrogen with formation of a triplet biradical. This
proposal was based on the observed photosensitizing effect of
oxygen and also on the observation that an increase in solvent
viscosity led to a decrease in quantum yields.11 It was thus pro-
posed from this evidence that photoexcitation of 1-allyl-
4-phenyl-1,4-dihydro-5H-tetrazol-5-ones 4 would lead to for-
mation of a caged triplet biradical that after T–S conversion
For the alternative route involving rotation of dihedral F in
B1c, two minima were found, corresponding to the cis and
trans orientations (B2c′; Fig. 8). Ring closure requires the
approach of C(7) to N(3), providing the expected structure of
benzimidazolone (11), in an exothermic process (Fig. 5 and 8).
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would cyclize to the product.11 Quast and co-workers had
already postulated on the involvement of a transient biradical
in formation of benzimidazolones from aryl-tetrazolones and
tetrazole-thiones.22 However, no flash photolysis or spin trap
experiments were ever conducted to confirm the nature of the
transient intermediate species involved.
In recent years, we undertook a mechanistic examination of
the photodecomposition of 5-allyloxytetrazoles.14 For this
class, results from laser flash photolysis experiments revealed
involvement of an excited triplet state and implicated the inter-
mediacy of a triplet biradical in photolysis of allyloxy tetr-
azoles. More recently, Rayat and collaborators investigated the
mechanism of photolysis of tetrazolethiones.8 Based on the
absence of an appreciable effect of the presence of triplet sen-
sitizers (benzophenone, acetophenone and acetone) and
triplet quenchers (biphenyl and oxygen) on the nature and
quantities of photodecomposition products obtained from
tetrazolethiones, the authors concluded against the involve-
ment of a triplet excited state and (probably) triplet biradicals
in the photolysis of tetrazolethiones.8
In order to gather further information on the nature of the
intermediate involved in photolysis of 1-allyl-4-phenyl-1,4-
dihydro-5H-tetrazol-5-ones we undertook laser flash photolysis
experiments for compounds 4a–c. A direct observation of the
possible transient formed upon excitation at 266 nm was
undertaken and its kinetics was followed in the presence and
absence of oxygen and with addition of the radical trap N-tert-
butyl-α-phenylnitrone.37,38 A biradical with a relatively long
lifetime should be very sensitive to quenching by this agent39
and such a study should provide further information on the
spin nature of the intermediate involved in photodecomposi-
tion of 1-allyl-4-aryltetrazolones.
Fig. 10 Transient decay at 270 nm (depletion) and 300 nm observed in the
presence of oxygen for tetrazolone 4c.
appreciably over a long period of time, as the transient spectra
taken 20 and 200 μs after the laser pulse excitation completely
overlap. The same happens on both observed bands, indicat-
ing the observation of a unique transient over the spectrum.
The decays observed for tetrazolone 4c at the two transient
absorption maxima (270 nm and 300 nm, Fig. 10) confirm the
long lifetime of the transients. The same long-lived species is
observed either in the presence or in the absence of oxygen.
We did not observe any growth component on the kinetic
traces taken, which indicates that the transient observed is
formed within the 8 ns excitation laser pulse. In order to
further investigate on the nature of the 300–360 nm absorbing
transient, gathering evidence for either a neutral triplet state
or radical species, the effect of N-tert-butyl-α-phenylnitrone on
the transient species lifetime was also examined. Because com-
petitive absorption of phenylnitrone did not allow us to collect
the full range spectra we concentrated on the transient decay
at 340 nm. Results have shown that the presence of phenyl-
nitrone (concentration up to 1 × 10−4 M) does not change the
observed decay at 340 nm, indicating that the transient
observed may not be a triplet biradical. Similar behavior was
observed for the three studied compounds (4a–c).
Fig. 9 shows the typical transient absorption spectra
obtained for tetrazolone 4b.
A depletion band with a
maximum at 270 nm is observed, followed by a band with a
maximum at 300 nm that spreads until 360 nm. This figure
shows that the transient absorption intensity does not change
Thus, our present results did not confirm the involvement
of triplet states in photolysis of 1-allyl-4-aryltetrazolones. This
observation is in keeping with results obtained for the photo-
lysis of tetrazolethiones where participation of triplet states
was also discarded.8 However the evidence gathered is not
sufficient to discard a triplet pathway. The DFT calculations
assumed a biradical intermediate, and theoretical data comply
with the nature of products obtained. Thus, the nature of the
long-lived transient intermediate observed by flash photolysis
remains to be clarified.
3. Conclusions
The photochemistry of tetrazolones derived from the carbo-
cyclic allylic alcohols cyclohex-2-enol and 3-methylcyclohex-2-enol
Fig. 9 Transient absorption for tetrazolone 4b, following excitation at 266 nm.
Circles: 20 μs after excitation; open circles: 200 μs after excitation.
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and from the natural terpene alcohol nerol was investigated in at a distance of 10 to 40 cm from the lamp. A 16 W low-
solution with the aim of assessing the effect of solvent and of pressure Hg lamp (254 nm) was used as a source of UV radi-
structural constraints imposed by bulky allylic moieties on ation. Generally, 10−4 M starting solutions were used.
photoproduct selectivity and stability. Photolysis of tetrazo-
4.2. Computational details
lones derived from nerol and cyclohex-2-enol afforded the cor-
responding pyrimidinones as major products through
a
Quantum chemical calculations were performed using the
pathway that appears to be similar to that proposed for other Gaussian 03 program package40 at the DFT level of theory with
1-allyl-4-phenyl-1,4-dihydro-5H-tetrazol-5-ones derived from the 3-21G* basis set and the three-parameter density func-
acyclic and unhindered allylic alcohols previously investigated tional, abbreviated as B3LYP, which includes Becke’s gradient
by us but photolysis of the tetrazolone derived from the exchange correction41 and the Lee, Yang, Parr correlation func-
bulkier 3-methylcyclohex-2-enol 4c leads to formation of a ben- tional.42 No symmetry restrictions were imposed on the initial
zimidazolone, indicating that, in this case, cyclization of the structures.
transient intermediate species formed upon extrusion of N2
involves the phenyl substituent and not the allylic moiety.
4.3. Flash photolysis
Interpretation of the experimental results and of mechanistic Flash photolysis experiments were carried out on an Applied
pathways proposed was assisted by theoretical calculations Photophysics LKS.60 laser-flash-photolysis spectrometer, with
(DFT(B3LYP)/3-21G*). This unexpected cyclization pathway is a Spectra-Physics Quanta-Ray GCR-130 Nd:YAG laser (fourth
ascribed to steric constraints imposed by the methyl group harmonic, 266 nm) for excitation and a Tektronix TDS3052B
attached to the allylic carbon in 4c, which hinders the cycliza- oscilloscope for transient decay capture. Sample solutions in
tion pathway involving the transient intermediate formed from acetonitrile were pumped through a quartz cell at a 0.9 mL
4c and the allylic system, that would lead to formation of the min−1 flow rate using an SSI chromatographic pump.
expected pyrimidinone. Laser flash photolysis experiments
4.4. Synthesis of 5-allyloxytetrazoles and 4-allyltetrazol-4-ones
were conducted with the aim of clarifying the nature of the
intermediate involved in the primary photocleavage process. A
unique long-lived transient was observed but its nature tetrazole
4.4.1. (E)-5-(3,7-Dimethylocta-2,6-dienyloxy)-1-phenyl-1H-
(3a). (E)-3,7-Dimethylocta-2,6-dien-1-ol (nerol;
remains elusive.
2.15 g; 13.9 mmol) in dry THF (20 mL) was added to a slurry of
sodium hydride (60% in mineral oil; 0.60 g; 14.6 mmol) in dry
THF (20 mL). When effervescence (hydrogen) had ceased
(30 min) 5-chloro-1-phenyl-1H-tetrazole (2.5 g; 13.9 mmol), in
dry THF (20 mL), was added, and the reaction was stirred at
≈10 °C for 12 h. Work-up followed by crystallization of the
4. Experimental section
4.1. Equipment and experimental conditions
All chemicals were used as purchased from Aldrich. Solvents solid residue from ethanol gave the required product as white
for extraction and chromatography were of technical grade. crystals (1.0 g; 24% yield), mp 43–45 °C. IR νmax: 2967, 2912,
When required, solvents were freshly distilled from appropri- 2858, 1592, 1570, 1506, 1460, 1443, 939; 1H NMR (400 MHz,
ate drying agents before use. Analytical TLC was performed CD3OD): δ 1.56 (3H, s, CH3), 1.60 (3H, s, CH3), 1.81 (3H, s,
with silica gel 60 F254 plates from Merck. Melting points were CH3), 2.09–214 (2H, q, CH2), 2.21–2.25 (2H, t, CH2), 5.09, 5.10
recorded on a Stuart Scientific SMP3 melting point apparatus (3H, d,vCH–, CH2), 5.58–5.61 (1H, t,vCH–), 7.48–7.52 (1H,
and are uncorrected. UV absorption spectra were recorded on a m, ArH), 7.55–7.58 (2H, t, ArH), 7.70,7.72 (2H, d, ArH).
Varian CARY 50 Bio UV-visible spectrophotometer, using 1 ×
4.4.2. 1-(3,7-Dimethylocta-1,6-dien-3-yl)-4-phenyl-1H-tetra-
1 cm quartz cells. Mass spectra were obtained on a VG 7070E zol-5(4H)-one (4a). A neat sample of (E)-5-(3,7-dimethylocta-
mass spectrometer by electron ionization (EI) or chemical ion- 2,6-dienyloxy)-1-phenyl-1H-tetrazole (0.8 g; 2.7 mmol) was
ization (CI, NH3) at 70 eV. 1H-NMR (400 MHz) spectra were heated at 40 °C for 1 h to give 1-(cyclohex-2-enyl)-4-phenyl-1H-
obtained on a Bruker AM-400 spectrometer using TMS as the tetrazol-5(4H)-one as a yellow oil (quantitative yield). IR νmax
internal reference (δ = 0.0 ppm). Elemental analyses were per- 1725, 1598, 1560, 1502, 1376, 757 cm−1 1H NMR (400 MHz,
formed on an EA1108-Elemental Analyzer (Carlo Erba Instru- CDCl3): δ 1.54 (3H, s, CH3), 1.57 (3H, s, CH3), 1.77 (3H, s,
ments). Infrared spectra were obtained on Bruker CH3), 1.98–2.37 (4H, m, –CH2CH2–), 5.01–5.07 (1H, t,vCH–),
FTIR-TENSOR 27 spectrometer. GC-MS analyses were carried 5.16–5.25 (2H, m,vCH2), 623–6.30 (1H, m,vCH–), 7.36–7.40
out on a 6890-N Network GC System gas chromatograph with a (1H, t, ArH), 7.48–7.52 (2H, t, ArH), 7.85, 7.87 (2H, d, ArH); 13
:
;
a
C
5973 inert Mass Selective Detector (EI 70 eV) from Agilent NMR (100 MHz, CD3OD): δC 16.37, 21.69, 22.19, 24.54, 36.97,
Technologies, using a DB-35MS capillary column with 30 m 64.95, 113.63, 119.38, 122.75, 127.53, 129.03, 131.75, 134.55,
length and 0.25 mm ID (J & W Scientific, Agilent). The initial 139.51, 148.76; MS (EI), m/z 299 [M + H]+; Anal. Calcd for
temperature of 50 °C was maintained during 3 min and then a C17H22N4O: C, 68.43; H, 7.43; N, 18.78%. Found: C, 68.22; H,
heating rate of 10 °C min−1 was applied, until a final temp- 7.75; N, 18.30%.
erature of 250 °C was reached.
4.4.3. 5-(Cyclohex-2-enyloxy)-1-phenyl-1H-tetrazole
(3b).
Photolysis studies were carried out in analytical grade aceto- Cyclohex-2-enol (1.36 g; 13.9 mmol) in dry THF (30 mL) was
nitrile, cyclohexane and methanol using 1 × 1 cm quartz cells added to a slurry of sodium hydride (55% in mineral oil;
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0.65 g; 14.9 mmol) in dry THF (5 mL). When effervescence of compound was collected as a colorless oil (0.038 g; 83% yield)
hydrogen had ceased (30 min), 5-chloro-1-phenyl-1H-tetrazole and identified as 4-methyl-4-(4-methylpent-3-enyl)-1-phenyl-
(2.5 g; 13.9 mmol) in dry THF (20 mL) was added and the final 3,4-dihydropyrimidin-2(1H)-one, 10a. IR νmax: 2973, 2870,
mixture was stirred at room temperature for about 3 h. Work- 1669, 1592, 1262 cm−1 1H-NMR (400 MHz, CD3OD): δ 1.26
;
up and crystallization of the crude from ethanol gave the (3H, s); 1.41 (3H, s); 1.57 (3H, s); 1.75–1.86 (2H, m); 2.01–2.39
5-(cyclohex-2-enyloxy)-1-phenyl-1H-tetrazole as white crystals (2H, m); 4.06–4.12 (1H, m); 5.06 (1H, d, J = 10.5 Hz); 5.23 (1H,
(2.1 g; 61% yield), mp 60–62 °C. IR νmax: 2927, 1591, 1549, d, J = 4.9 Hz); 6.88–6.92 (3H, m); 7.15 (2H, t, J = 7.8 Hz); 13C
1504, 1457, 910 cm−1; 1H NMR (400 MHz, CD3OD): δ 1.66–1.83 NMR (100 MHz, CD3OD): δC 23.40, 23.77, 24.78, 25.95, 43.71,
(2H, m, –CH2–), 2.04–2.18 (4H, m, –CH2–), 5.47–5.48 (1H, m, 51.21, 63.72, 71.06, 112.36, 123.58, 127.96, 128.51, 142.79,
CH–O–), 5.98, 6.00 (1H, d, –CHv), 6.09–6.13 (1H, m,vCH–), 148.06, 151.54; MS (EI), m/z 270 [M]+.
7.47–7.51 (1H, t, ArH), 7.54–7.58 (2H, t, ArH), 7.70–7.72 (2H, d,
ArH); 13C NMR (100 MHz, CD3OD): δC 18.06, 24.64, 27.87,
Similarly, the other compounds were prepared and isolated.
4.5.2. 1-Phenyl-3a,4,5,6-tetrahydro-1H-benzoimidazol-2(3H)-
78.52, 121.85, 123.44, 128.98, 129.44, 133.47, 134.91, 159.85; one (10b). 4-(Cyclohex-2-enyl)-1-phenyl-1H-tetrazol-5(4H)-one
MS (EI), m/z 242 [M]+.
4b (0.05 g; 0.20 mmol), irradiated for 15 min, gave a brown
4.4.4. 4-(Cyclohex-2-enyl)-1-phenyl-1H-tetrazol-5(4H)-one solid (0.025 g; 56% yield). IR νmax: 3327, 3063, 2937, 2867,
(4b). A neat sample of 5-(cyclohex-2-enyloxy)-1-phenyl-1H- 1690, 1548 cm−1; 1H-NMR (400 MHz, CD3OD): δ 0.90–0.95 (1H,
tetrazole (1.0 g; 4.1 mmol) was heated at 40 °C for 2 h to give m); 1.27–1.32 (5H, m); 3.34–3.38 (1H, t); 5.09(1H, m); 6.99–7.02
1-(cyclohex-2-enyl)-4-phenyl-1H-tetrazol-5(4H)-one as a yellow (1H, t, ArH); 7.25–7.29 (2H, t, ArH); 7.40–7.42 (2H, d, ArH); MS
oil (quantitative yield). IR νmax: 2927, 1724, 1595, 1552, 1504, (EI), m/z 214 [M]+.
1
1459, 904 cm–1; H NMR (400 MHz, CD3OD): δ 1.71–2.23 (6H,
4.5.3. 3-(1-Methylcyclohex-2-enyl)-benzoimidazol-2(1H)-one
m, –CH2–), 4.88–4.91 (1H, m, CH–N), 5.71–5.74 (1H, d, –CHv), (11). 4-(3-Methylcyclohex-2-enyl)-1-phenyl-1H-tetrazol-5(4H)-one
6.08–6.10 (1H, mvCH–), 7.39–7.42 (1H, t, ArH), 7.50–7.54 (2H, 4c (0.05 g; 0.19 mmol) was irradiated for 20 min. Isolation
t, ArH), 7.87–7.89 (2H, d, ArH); 13C NMR (100 MHz, CDCl3): δC afforded a yellow powder (0.034 g; 76% yield). IR νmax: 3124,
20.14, 24.78, 28.70, 52.03, 77.14, 77.45, 77.77, 119.71, 124.31, 3006, 2921, 1687, 1475, 1360 cm−1
;
1H-NMR (400 MHz,
127.98, 129.73, 133.45, 135.19; MS (EI), m/z 243 [M + H]+.
CD3OD): δ 1.52–1.75 (4H, m); 1.83 (3H, s); 2.11–2.15 (2H, m);
4.4.5. 4-(3-Methylcyclohex-2-enyl)-1-phenyl-1H-tetrazol-5- 6.02 (1H, dt, J = 10.1 Hz, J = 3.5 Hz); 6.09 (1H, d, J = 10.1 Hz);
(4H)-one (4c). 3-Methyl-cyclohex-2-enol (0.62 g; 5.54 mmol) in 6.91–7.01 (3H, m); 7.60 (1H, d, J = 8.0 Hz); 13C NMR (100 MHz,
dry THF (30 mL) was added to a slurry of sodium hydride CD3OD): δC 18.78, 24.58, 26.55, 33.18, 58.31, 108.56, 112.08,
(55% in mineral oil; 0.32 g; 7.4 mmol) in dry THF (5 mL). 120.16, 120.68, 128.55, 129.12, 130.92, 132.72, 155.47; MS (EI),
When effervescence (hydrogen) had ceased (20 min) 5-chloro- m/z 228 [M]+.
1-phenyl-1H-tetrazole (1.0 g; 5.54 mmol) in dry THF (10 mL)
was added, and the mixture was stirred at ≈10 °C for 4 h.
4-(3-Methylcyclohex-2-enyl)-1-phenyl-1H-tetrazol-5(4H)-one was
obtained as a light yellow oil (1.1 g; 71% yield), indicating that
Acknowledgements
the synthesised ether readily isomerises to the corresponding The authors acknowledge Fundação para a Ciência e Tecnolo-
tetrazolone 4c. IR νmax: 2927, 1721, 1596, 1504, 1460, 1367, gia (FCT) and FEDER [Projects PTDC/QUI/67674/2006 and
1095, 904 cm−1 1H NMR (400 MHz, CD3OD): δ 1.69 (3H, s, PTDC/QUI/71203/2006] for financial support.
;
CH3), 1.79–1.86 (4H, m, –CH2CH2–), 2.09–2.11 (2H, m, CH2),
5.97–6.03 (2H, m, CHvCH), 7.38–7.42 (1H, t, ArH), 7.50–7.54
(2H, t, ArH), 7.85–7.87 (2H, d, ArH); 13C NMR (100 MHz,
CD3OD): δC 18.34, 24.21, 25.29, 32.78, 60.16, 119.63, 127.59,
128.15, 129.05, 130.50, 134.59, 148.71; MS (EI), m/z 257
[M + H]+.
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