Relative migratory aptitudes of hydrogen, benzoyl, 4-methoxyphenyl and 4-nitrophenyl groups in some unsaturated carbenes (vinylidenes)

Article abstract of DOI:10.1016/S0040-4020(01)00873-0

([5-¹³C] Tetrazol-5-yl)methyl ketones were prepared and subjected to oxidative fragmentation induced by lead tetraacetate. The resulting intermediate [1-¹³C]-3-oxoprop-1-en-1-ylidenes rearrange, depending on the relative migratory aptitudes of the benzoyl group and the ligands R, either to [3-¹³C]prop-2-yn-1-ones or to [2-¹³C]prop-2-yn-1-ones or to mixtures of the two isomers. The ¹H and/or ¹³C NMR spectra of the products allow the three cases to be distinguished. The relative migratory aptitudes were found to be H>PhCO, 4-MeOC₆H₄>4-O₂NC₆H ₄.

Full text of DOI:10.1016/S0040-4020(01)00873-0

TETRAHEDRON
Pergamon
Tetrahedron 57 /2001) 8889±8895
Relative migratory aptitudes of hydrogen, benzoyl,
4-methoxyphenyl and 4-nitrophenyl groups in some unsaturated
carbenes ꢀvinylidenes)
a
a,p
a,b
Ferenc Bertha, Jozsef Fetter, Karoly Lempert, Maria Kajtar-Peredy, Gabor Czira
c
d
Â
Â
Â
Â
Â
e
Í
and Erno Koltai
²
aDepartment of Organic Chemistry, Budapest University of Technology and Economics, H-1521 Budapest, Hungary
bResearch Group for Alkaloid Chemistry, Hungarian Academy of Sciences, H-1521 Budapest, Hungary
cInstitute of Chemistry, Chemical Research Center, Hungarian Academy of Sciences, H-1525 Budapest, Hungary
dGedeon Richter Chemical Works, Ltd, H-1475Budapest, Hungary
eIsotope Institute Co., Ltd, H-1121 Budapest, Hungary
Received 4 June 2001; revised 25 July 2001; accepted 23 August 2001
AbstractÐ/[5-13C] Tetrazol-5-yl)methyl ketones were prepared and subjected to oxidative fragmentation induced by lead tetraacetate. The
resulting intermediate [1-13C]-3-oxoprop-1-en-1-ylidenes rearrange, depending on the relative migratory aptitudes of the benzoyl group and
the ligands R, either to [3-13C]prop-2-yn-1-ones or to [2-13C]prop-2-yn-1-ones or to mixtures of the two isomers. The 1H and/or 13C NMR
spectra of the products allow the three cases to be distinguished. The relative migratory aptitudes were found to be H.PhCO,
4-MeOC6H4.4-O2NC6H4. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
where the relative migratory aptitudes of various groups and
hydrogen attached to C2 are well known /the order for the
singlet carbenes being in general H.aryl.alkyl13±15) very
little is known10,16 about the relative migratory aptitudes of
substituents attached to C2 of vinylidenes.
Recently tetrazol-5-ylmethyl ketones 1a±c /and a series of
analogs with other R groups and/or other electron withdraw-
ing groups replacing the benzoyl group) were found to
afford, on treatment with lead tetraacetate /LTA), the corre-
sponding ynones 3.1 3-Oxoprop-1-en-1-ylidenes 2, hitherto
scarcely known2 special types of unsaturated carbenes3
/vinylidenes) were shown to be the intermediates of the
reaction; rearrangement of the latter by [1,2] migration of
either the benzoyl group or the R group then leads to the
®nal products 3 /Scheme 1).
Equally little is known about the migratory aptitudes of acyl
/and aroyl) groups both in saturated carbenes and vinyl-
idenes. Thus, e.g. both the type 4 singlet carbenes and
singlet carbene 6 /obtained by in situ thermolysis of the
corresponding diazo compounds) rearrange with migration
of their acyl groups to afford triketones 5 and the quinoline-
2/1H)-one 7, respectively /Scheme 2).17 The observations
that migration of the acyl groups in compounds 4 takes
place in preference to migration of the methyl and hydroxyl
groups /as well as to an, in principle, equally possible Wolff
rearrangement), and in compound 6 in preference to that of
Similarly to the saturated carbenes, the vinylidenes are
known to be unstable reactive intermediates which easily
undergo [1,2] rearrangements to afford acetylenes.3±12
However, in contrast to the case of the saturated carbenes,
Scheme 1. Oxidation of tetrazolylmethyl ketones 1 with lead tetraacetate. 1±3: /a) RˆH; /b) Rˆ4-MeOC6H4 /PMP); /c) Rˆ4-O2NC6H4 /PNP).
Keywords: carbenes; benzoyl vinylidenes; migratory aptitudes; 13C labelling.
Corresponding author. Tel.: 136-1-463-2356; fax: 136-1-463-3296; e-mail: fetter.szk@chem.bme.hu
p
²
Formerly Technical University Budapest.
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020/01)00873-0

8890
F. Bertha et al. / Tetrahedron 57 12001) 8889±8895
Scheme 2. Rearrangement of in situ prepared singlet carbenes 4 and 6.
the aryl and hydroxyl group, however, do not necessarily
re¯ect the orders of the inherent migratory aptitudes of acyl,
the methyl, an aryl and the hydroxyl groups since migration
of the acyl group in compounds 4 involves, and that of the
aryl group in compound 6 would involve, in contrast to the
migration of the two other groups competing for migration,
concomitant ring contraction.
as the principal products /Scheme 3).2 Rearrangement 8!9
is clearly the reverse of rearrangement 2!3 and may, in
principle, take place by migration of either of the two groups
attached to the acetylenic carbon atoms, the situation being,
thus, similar as in rearrangement 2!3. A theoretical study
of the rearrangements of propynal /11a), but-2-ynal /11b)
and butynone /11c) into the corresponding singlet carbenes
12a±c /none of which is able to undergo cyclization to
cyclopent-2-enones) has revealed that, under thermolysis
conditions, `a H-atom or an alkyl group competes favorably
with an acyl group in the [1,2]-shift from a-alkynones to the
corresponding acylvinylidenes'.2c
On the other hand, Dreiding and coworkers have found that
gas-phase thermolysis of open-chain a-alkynones 8 and
their cyclic analogs /with R31R4 completing a ®ve- or
six-membered ring) afford, through the intermediacy of
singlet
3-oxoalk-1-en-1-ylidenes
/2-oxoalkylidene
carbenes, 9), by insertion of the carbene carbon atom into
a CH group in appropriate position, cyclopent-2-enones 10
In view of the situation outlined we decided to establish
experimentally the relative migratory aptitudes of the
benzoyl group, the hydrogen atom, the 4-methoxyphenyl
and the 4-nitrophenyl groups in 3-oxoprop-1-en-1-ylidenes
2a±c generated in situ by oxidation of tetrazole derivatives
1a±c. To this end, analogs 13a±c of compounds 1a±c,
labelled by 13C in position 5 of the tetrazole ring were
prepared and subjected to LTA oxidation. Depending on
the relative migratory aptitudes of the benzoyl group and
the ligands R, the intermediate [1-13C]-3-oxoprop-1-en-1-
ylidenes 14 should furnish either [3-13C]- /15) or [2-13C]-
prop-2-ynones /16) or mixtures of the two isomers, and the
three cases should be readily distinguished by the NMR
spectra.
Scheme 3. Alkynone cyclization. R1ˆH, D, Me, Ph, SiMe3; R2ˆH, Me.
2. Results and discussion
2.1. Preparation of the ꢀ[5-13C]tetrazol-5-yl)methyl
ketones 13a±c
The 13C-labelled tetrazole derivatives 13a±c were obtained
from the corresponding 13C-labelled nitriles 17a±c by treat-
ment with AlCl3 and NaN3 in THF, cf. Ref. 18. Nitriles
17a±c, in turn, were prepared from phenacyl bromide and
K13CN, and by benzoylating 4-methoxyphenyl- and 4-nitro-
phenyl[13C]acetonitrile, respectively, 17b and 17c existing,
according to their IR and NMR spectra, partly or exclusively
as the enols.
The reactions of the non-labelled analogs of cyanoketones
17b and 17c with AlCl3 and NaN3 in re¯uxing THF were

F. Bertha et al. / Tetrahedron 57 12001) 8889±8895
8891
is heterolytically cleaved /path a). The resulting two frag-
ments, 20 and 21 are subsequently converted into phenyl
isocyanate and 4-nitrophenylaceto[13C]nitrile, respectively.
Reaction of the isocyanate with a second molecule of
Al/N3)3 affords adduct 22 which is the aluminium derivative
of 18, the azide of a monosubstituted carbamic acid and,
therefore, in contrast to intermediate 20, does not undergo
the Curtius rearrangement.20
2.2. LTA oxidation of the ꢀ[5-13C]tetrazol-5-yl)methyl
ketones 13a±c
Oxidative fragmentations induced by LTA of tetrazole
derivatives 13a±c both afforded single products, while an
approximately 1:1 mixture of two isomers was obtained on
similar treatment of tetrazole derivative 13b. The structures
/15 and/or 16) of all these products were derived from their
1H and/or 13C NMR spectra.
found to be very slow and particularly the yield of the
resulting tetrazole derivative 1c was rather low.1 It was
now found that the conversion of the labelled cyanoketone
17b into tetrazole derivative 13b can be considerably
accelerated by increasing the amount of AlCl3 used. A care-
ful analysis of the product obtained from the reaction of the
labelled cyanoketone 17c with AlCl3 and NaN3 in THF
under the conditions used for the preparation of the non-
labelled tetrazole derivative 1c1 has, on the other hand, led to
the detection of two further products, viz phenylcarbamoyl
azide /18, 28%) and 4-nitrophenylaceto[13C]nitrile /36%) in
addition to the expected labelled tetrazole derivative 13c
/39%).
Thus, the 1H and 13C NMR spectra of the oxidation products
obtained from compound 13a and from its non-labelled
analog, compound 1a were almost identical, except for the
1
multiplicities of some signals; viz /i) in the H NMR spec-
trum /CDCl3) of the labelled oxidation product the singlet at
d 3.44 ppm of the acetylenic proton of the non-labelled
oxidation product 3a was replaced by a doublet /d
1
3.44 ppm, JC,Hˆ255 Hz). In addition, a weak singlet at d
3.44 ppm was also present, indicating that the labelled
oxidation product /and, therefore, its precursor 13a as
well) were contaminated by about 15% of non-labelled
material. /ii) In the 13C NMR spectrum /CDCl3) of the
labelled oxidation product the singlet at d 177.38 ppm of
the carbonyl carbon atom of the non-labelled oxidation
product 3a was replaced by a doublet /d 177.39 ppm,
2JC,Cˆ13.0 Hz). From these data structure 15a follows
unequivocally for the oxidation product of the labelled
compound 13a which shows that in the intermediate
The formation of the two unexpected co-products may be
understood by considering, in addition to the attack at the
nitrile group of 17c /leading to compound 13c), the
possibility of competitive attack of the azide at the carbonyl
³
carbon atom, facilitated by the powerful electron with-
[1-13C]3-phenyl-3-oxoprop-1-ene-1-ylidene
14a
/and
drawing activity of the PNP group in compound 17c and
leading to intermediate 19c which is analogous to the ®rst
intermediate of the Schmidt reaction19 of ketones with HN3.
Alternatively, 19c may be formed from the enol by attack of
the reagent at the carbon atom in b-position relative to the
[13C]cyano group. Instead of following the normal course of
the Schmidt reaction /path b) adduct 19c reacts differently:
again due to the powerful electron withdrawing ability of
the PNP group which exerts a signi®cant stabilizing effect
on the resulting anion 21, the central CC bond of the adduct
therefore in its non-labelled analog 2a as well) the
hydrogen atom migrates in preference to the benzoyl
group /Scheme 4).
Similarly, several signals in the 13C NMR spectrum /CDCl3)
of the oxidation product of compound 13c are doublets
/whereas the corresponding signals in the spectrum of its
non-labelled analog 3c are singlets), viz the signal of C1 of
the 4-nitrophenyl /PNP) group at
d
126.81 ppm
/2JC,Cˆ11.4 Hz), the common signal of C2 and C6 of the
PNP group at d 133.67 ppm /3JC,Cˆ3.0 Hz), as well as the
signals of C1 of the phenyl group at d 136.42 ppm
³
The reagent is tentatively formulated as Al/N3)3, but the same result
would be obtained if it were formulated as HN3 or N3
*
.

8892
F. Bertha et al. / Tetrahedron 57 12001) 8889±8895
Scheme 4. Rearrangement of in situ prepared vinylidenes 14a±c.
/2JC,Cˆ19.1 Hz) and of the carbonyl carbon at d 177.36 ppm
/1JC,Cˆ90 Hz). Therefore the structure of the oxidation
product of compound 13c is 16c which proves that in the
intermediate [1-13C]3-oxoprop-1-en-1-ylidene 14c /and
therefore in its non-labelled analog 2c as well) the benzoyl
group migrates in preference to the 4-nitrophenyl group.
of the products was checked, in combination with IR spec-
troscopy, by TLC on DC-Alufolien 60 PF254; the individual
compounds were detected by UV irradiation or by using
iodine or 5% ethanolic molybdophosphoric acid as the
reagents.
All new crystalline compounds described in the present
paper, except for those noted, were colorless. Mps were
determined on a Ko¯er hot-stage mp apparatus and are
uncorrected. IR spectra were recorded on a Specord 75
The oxidation product of compound 13b differs from those
of compounds 13a and 13c in that the patterns of several
signals in its 13C NMR spectrum are those of two inde-
pendent doublets of approximately equal intensities but
with different coupling constants, viz the signals of C1 of
the 4-methoxyphenyl /PMP) group at 111.92 ppm
1
spectrometer /Zeiss, Jena), H and 13C NMR spectra were
obtained with a Unity INOVA-400 spectrometer, using
tetramethylsilane as the reference. J-values are given in
Hz. Exact molecular mass determinations were made at
70 eV with a Finnigan-MAT 95 SQ hybride-tandem
instrument using a heated direct inlet system and PFK
/per¯uorokerosene) as the reference.
2
/1JC,Cˆ90.8 Hz and JC,Cˆ12.2 Hz, respectively), of C1 of
the phenyl group at 137.09 ppm /3JC,Cˆ2.3 Hz and
2JC,Cˆ19.1 Hz, respectively) and of the carbonyl carbon
1
atom at 178.00 ppm /2JC,Cˆ13.4 Hz and JC,Cˆ91.9 Hz,
respectively). This shows the oxidation product of
compound 13b to be an approximately 1:1 mixture of
isomers 15b and 16b, and the migratory aptitudes of the
PMP and the benzoyl groups in the intermediate [1-13C]3-
oxoprop-1-en-1-ylidene 14b /and therefore in its non-
labelled analog 2b as well) to be roughly equal.
The 13C content of the K13CN samples /prepared from
Ba13CO3) used for the syntheses in the a and in the other
two series was 85 and 95 atom%, respectively. The 13C
content of the various organic products prepared was
checked by mass spectrometry at 70 and/or 20 eV with
the Finnigan-MAT instrument mentioned; the values
obtained were in agreement with the 13C content of the
K13CN sample used for the synthesis of the particular
product.
Thus, the conclusion may be drawn that the order of
migratory aptitudes in the [1-13C]3-oxoprop-1-en-1-
ylidenes 14 /and their non-labelled analogs 2) is
H.PhCO, 4-MeOC6H4.4-O2NC6H4.
3.1.1. ꢀ[13C]Cyano)methyl phenyl ketone ꢀ17a). The title
compound [200 mg, 90%; mp 788C, lit.21 mp of the non-
labelled analog 78±808C; nmax /cm21) 2260 /13CuN), 1690
/CvO), non-labelled analog, prepared for comparison 2260
/CuN), 1695 /CvO), lit.22 2210, 1700] was obtained from
phenacyl bromide /300 mg, 1.5 mmol) as described22 for the
preparation of the non-labelled analog, except for using
K13CN instead of KCN.
3. Experimental
3.1. General
All reactions were monitored by TLC /DC-Alufolien 60
PF254, Merck) and allowed to go to completion. The purity

F. Bertha et al. / Tetrahedron 57 12001) 8889±8895
8893
3.1.2. ꢀ[13C]Cyano)ꢀ4-methoxyphenyl)methyl phenyl
ketone ꢀ17b). /a) 4-Methoxybenzyl [13C]cyanide was
obtained as an oil in quantitative yield essentially as
described in literature,23 except for starting with 4-methoxy-
benzyl chloride /0.73 g, 11 mmol) rather than the bromide.
17b) was added. After re¯uxing for a couple of hours, the
starting compound was consumed and the mixture was
worked up as described1 for the preparation of the non-
labelled analog to afford the title compound [72%; colorless
amorphous solid foam; HRMS, found Mz1 295.1145,
C1513CH14N4O2 requires 295.1150; nmax /cm21) /KBr)
3300±2600 /with several local maxima; NH), 1690
/CvO), practically identical with the spectrum of the
non-labelled analog prepared similarly; dH /CDCl3) 3.67
/b) A mixture of the above crude product /1.7 g, 11 mmol),
methyl benzoate /1.6 g, 12 mmol), THF /9 cm3) and 60%
NaH /in paraf®n oil; 0.89 g, 22 mmol) was re¯uxed for 1.5 h
and worked up as described1 for the preparation of the non-
labelled analog to afford the title compound as a pale yellow
oil which, in the crystalline state, exists as a mixture of the
enol and keto forms while, in CDCl3 solution, it exists in the
keto form 2.05 g, 72%; mp 818C. lit.24 mp of the non-
labelled analog 85±888C; HRMS, found Mz1 252.0976,
C1513CH13NO2 requires m/z 252.0980; nmax /cm21) /KBr)
3170 br /OH, enol), 2220 /13CuN), 1690w /CvO); non-
labelled compound /prepared according to Ref. 1) 3160 br,
2240, 1690 w; dH /CDCl3) 3.78 /3H, s, OMe), 5.55 /1H, d,
2JC,Hˆ10.4 Hz COCH13CN), 6.9017.34 /2£2H, AA0BB0,
JOˆ8.6 Hz, PMP), 7.45 /2H, m, 3-H15-H, Ph), 7.58 /1H,
m, 4-H, Ph), 7.94 /2H, m, 2-H16-H, Ph); dC /CDCl3) 45.96
2
/3H, s, OMe), 6.76 /1H, d, JC,Hˆ7.2 Hz, COCH13C),
6.7717.34 /2£2H, AA0BB0, JOˆ8.8 Hz, PMP), 7.41 /2H,
m, 3-H15-H, Ph), 7.54 /1H, m, 4-H, Ph), 8.02 /2H, m,
2-H16-H, Ph), 13.5 /br, NH), except for the multiplicity
of the 6.76 ppm signal, practically identical with the spec-
trum of the non-labelled analog;1 dC /CDCl3) 48.69 /d,
1JC,Cˆ58.7 Hz, COCH13C), 55.23 /OMe), 115.22
2
/C31C5, PMP), 125.94 /d, JC,Cˆ3.8 Hz, C1, PMP)
128.97 and 129.33 /C31C5 and C21C6, Ph), 129.46 /d,
3JC,Cˆ2.3 Hz, C21C6, PMP), 134.30 /C4, Ph), 134.53 /d,
3JC,Cˆ1.5 Hz, C1, Ph), 154.88 /13C5, tetrazole), 159.72 /C4,
2
PMP), 194.97 /d, JC,Cˆ2.3 Hz, CvO)].
1
/d, JC,Cˆ61.8 Hz, CO±C±13C), 55.36 /OMe), 115.10
3.1.6. ꢀ4-Nitrophenyl) ꢀ[5-13C]tetrazol-5-yl)methyl phenyl
ketone ꢀ13c), phenylcarbamoyl azide and 4-nitrophenyl-
aceto[13C]nitrile. Compound 17c /0.93 g, 3.5 mmol) was
allowed to react with AlCl3 and NaN3 in dry THF under
argon as described1 for the preparation of the non-labelled
analog of compound 13c, except that the reaction time was
increased to 6 days. The mixture was evaporated to dryness;
the residue was triturated with water and acidi®ed with
conc. HCl. The resulting thick emulsion was extracted
with EtOAc. The EtOAc solution was dried /MgSO4) and
worked up by ¯ash chromatography /Kieselgel 60 G,
Merck; CH2Cl2!CH2Cl2±MeOH, 1:1) to obtain ®rst a
mixture /0.41 g) of phenylcarbamoyl azide [0.16 g, 28%;
mp 102±1038C; HRMS, found Mz1 162.0534 and
119.0371, C7H6N4O requires 162.0541, C7H5NO /phenyl
isocyanate, apparently formed in the mass spectrometer by
2
/C31C5, PMP), 116.77 /13CN), 122.18 /d, JC,Cˆ3.8 Hz,
C1, PMP), 128.99 and 129.44 /C31C5 and C21C6, Ph),
3
129.50 /d, JC,Cˆ3.0 Hz, C21C6, PMP), 133.72 /C1, Ph),
134.30 /C4, Ph), 160.15 /C4, PMP), 189.09 /d,
2JC,Cˆ2.3 Hz, CO).
3.1.3. ꢀ[13C]Cyano)ꢀ4-nitrophenyl)methyl phenyl ketone
ꢀ17c). /a) Phenylaceto[13C]nitrile was obtained from benzyl
chloride and K13CN as described25 for the preparation of the
non-labelled analog.
/b) 4-Nitrophenylaceto[13C]nitrile /off-white crystals, 95%,
crude; mp 105±1068C, lit.26 mp of the non-labelled analog
115±1168C) was obtained by nitration of the above product
as described26 for the preparation of the non-labelled analog.
thermolysis of the azide) requires 119.0371; nmax /cm21
)
/c) The title compound /yellowish crystals, 45%; mp 163±
1648C; HRMS, found Mz1 267.0723, C1413CH10N2O3
requires 267.0725) which, in the crystalline state, exists as
the pure enol [nmax /cm21) /KBr) 3050 br /OH), 2200
/13CuN), 1540 vs11340 vs /NO2)] was obtained as
described27 for the preparation of the non-labelled analog
[mp27 163.58C; nmax /cm21) /KBr) 3025br /OH), 2260
/CuN), 1530 vs11340 vs /NO2)].
/KBr) 3330 /NH), 2160 /N3), 1695 /CvO); dH
/CDCl31DMSO-d6) 7.08 /1H, m, 4-H, Ph), 7.29 /2H, m,
3-H15-H, Ph), 7.52 /2H, br d, JOˆ8.2 Hz, 2-H16-H, Ph),
8.75 /br, NH); dC /CDCl31DMSO-d6) 119.35 /C21C6, Ph),
124.05 /C4, Ph), 128.87 /C31C5, Ph), 137.75 /C1, Ph),
154.05 /CvO)] and 4-nitrophenylaceto[13C]nitrile [off-
white crystals, 0.21 g, 36%; mp 1108C /MeOH), lit.26 mp
of the non-labelled analog 115±1168C; HRMS, found Mz1
163.0460 C713CH6N2O2 requires 163.0463; nmax /cm21
)
3.1.4. Phenyl ꢀ[5-13C]tetrazol-5-yl)methyl ketone ꢀ13a).
[94%, crude; mp, crude 184±1878C, lit. mp1 of the non-
labelled analog 187±1888C /MeOH); Rf values in TLC. of
the labelled and non-labelled compound were identical] was
obtained from compound 17a as described1 for the prepara-
tion of its non-labelled analog, except for starting with the
13C-labelled nitrile 17a instead of its non-labelled analog.
/KBr) 2220 /13CuN), 1520 vs11350 vs /NO2); dH
/CDCl3) 3.89 /2H, d, 2JC,Hˆ10.8 Hz, CH213CN),
7.5518.26 /2£2H, AA0BB0, JOˆ8.6 Hz, PNP); dC
1
/CDCl3) 23.60 /d, JC,Cˆ59.5 Hz, CH213CN), 116.40
/13CN), 124.39 /C31C5, PNP), 128.97 /d, JC,Cˆ3.8 Hz,
3
2
C21C6, PNP), 137.00 /d, JC,Cˆ3.0 Hz, C1, PNP), 147.91
/C4, PNP)] which were separated by preparative TLC
/Kieselgel PF2541366, Merck; hexane±EtOAc, 7:2), and
compound 13c [0.42 g, 39%, brownish yellow amorphous
product; HRMS, found Mz1 310.0887, C1413CH11N5O3
requires 310.0895; nmax /cm21) 3600±2300 /NH), 1700
/CvO), 1530 vs11355 vs /NO2), in good agreement with
the IR spectrum of the non-labelled analog; dH /DMSO-d6)
3.1.5. ꢀ4-Methoxyphenyl) ꢀ[5-13C]tetrazol-5-yl)methyl
phenyl ketone ꢀ13b). A mixture of compound 17b /2.0 g,
7.9 mmol), AlCl3 /1.33 g, 10 mmol), NaN3 /2.35 g,
36 mmol) and dry THF /40 cm3) was re¯uxed for 6 days.
Since, according to TLC, considerable amounts of
unchanged starting 17b were still present, a further amount
of AlCl3 /1.0 g, 7.5 mmol; total amount 2.2 mmol/mmol
7.08 /1H, d, JC,Hˆ8.6 Hz, COCH13Ctetrazole), 7.52 /2H, m,
2
3-H15-H, Ph), 7.64 /1H, m, 4-H, Ph), 7.7218.24 /2£2H,

8894
F. Bertha et al. / Tetrahedron 57 12001) 8889±8895
AA0BB0, JOˆ8.4 Hz, PNP), 8.04 /2H, m, 2-H16-H, Ph),
except for the multiplicity of the 7.08 ppm signal,
practically identical with the spectrum of the non-
labelled analog;1 dC /DMSO-d6) 48.99 /d,1JC,Cˆ58.0 Hz,
COCH13Ctetrazole), 124.00 /C31C5, PNP), 129.12 and
129.18 /C31C5 and C21C6, Ph), 130.96 /d,
3JC,Cˆ1.5 Hz, C21C6, PNP), 134.22 /C4, Ph), 134.91
129.47 /C21C6, Ph), 133.88 /C4, Ph), 135.13 /d,
2
3JC,Cˆ2.7 Hz, C21C6, PMP), 137.09 /d, JC,Cˆ19.1 Hz,
1
C1, Ph), 161.76 /C4, PMP), 178.00 /d, JC,Cˆ91.9 Hz,
CvO)] from compound 13b /2.95 g, 1.1 mmol).
3.2.3. 3-ꢀ4-Nitrophenyl)-1-phenyl-[2-13C]prop-2-yn-1-one
ꢀ16c). [43%, pale yellow crystals, mp 150±1518C, lit. mp of
the non labelled analog 152±1548C1 and 148±148.58C;30
HRMS, found Mz1 252.0611, C1413CH9NO3 requires
252.0616; nmax /cm21) /KBr) 2185 /13CuC), 1650
/CvO), 1540 vs11350 vs /NO2), non-labelled analog, lit.
2225, 1650, 1540 vs11335 vs1 and /in CCl4 solution) 2207,
1653;30 dH /CDCl3) 7.55 /2H, m, 3-H15-H, Ph), 7.67 /1H,
m, 4-H, Ph), 7.8418.29 /2£2H, AA0BB0, JOˆ8.6 Hz, PNP),
8.20 /2H, m, 2-H16-H, Ph), identical with the spectrum1 of
the non-labelled analog; dC /CDCl3), 89.88 /CO13CuC),
2
/C1, Ph), l42.63 /d, JC,Cˆ2.3 Hz, C1, PNP), 147.29 /C4,
PNP), 155.43 /13Ctetrazole), 193.98 /d, JC,Cˆ2.3 Hz, CvO),
2
except for the multiplicities of the 48.99, 130.96, 142.63 and
193.98 signals, in good agreement with the spectrum of the
non-labelled analog1].
3.2. Oxidation of compounds 13a±c with lead
tetraacetate
2
The oxidations were carried out as described1 for the oxida-
tions of the non-labelled analogs of compounds 13a±c. The
following products were obtained.
123.85 /C31C5, PNP), 126.81 /d, JC,Cˆ11.4 Hz, C1,
PNP), 128.84 /C31C5, Ph), 129.65 /C21C6, Ph), 133.67
3
/d, JC,Cˆ3.0 Hz, C21C6, PNP), 134.67 /C4, Ph), 136.42
2
/d, JC,Cˆ19.1 Hz, C1, Ph), 148.57 /C4, PNP), 177.36 /d,
1JC,Cˆ90.0 Hz, CvO); due to the high intensity of the
89.88 ppm signal, the low intensity CO13CuC signal
/which appears at 89.18 ppm in the spectrum of the non-
labelled analog1) could not be identi®ed; except for the
multiplicities of the 126.81, 133.67, 136.42 and the
177.36 ppm signals, the spectrum is identical with that of
the non-labelled analog1] from compound 13c /0.30 g,
0.97 mmol).
3.2.1. 1-Phenyl-[3-13C]prop-2-yn-1-one ꢀ15a). [65%; mp.
49±508C, lit. mp of the non-labelled analog 47±488C1 and
49±508C28; HRMS, found Mz1 131.0448, C813CH6O
requires 131.0452; nmax /cm21) /KBr) 3280 /u13C±H),
2110/2090d /Cu13C), 1650 /CvO), non-labelled analog
3280, 2100, 1650, lit.29 3311, 2109, 1666; dH /CDCl3)
1
3.44 /0.85H, d, JC,Hˆ255.3 Hz, u13CH). 3.44 /0.15H, s,
u12CH), 7.50 /2H, m, 3-H15-H, Ph), 7.63 /1H, m, 4-H,
Ph), 8.17 /2H, m, 2-H16-H, Ph); except for the doublet at
3.44 ppm and the intensity of the singlet at 3.44 ppm,
identical with the spectrum of the non-labelled analog;1
dC /CDCl3) 80.77 /u13CH), 128.69 /C31C5, Ph), 129.70
/C21C6, Ph), 134.51 /C4, Ph), 136.17 /C1, Ph), 177.39 /d,
2JC,Cˆ13.0 Hz, CvO); due to the high intensity of the
80.77 ppm signal and the presence of spinning side bands,
the low intensity COCu13C signal /which appears at
80.30 ppm in the spectrum of the non-labelled analog1)
could not be identi®ed; except for the multiplicity of the
177.39 ppm signal, the spectrum is identical with that of
the non-labelled analog1] from compound 13a /244 mg,
1.28 mmol).
Acknowledgements
The authors thank Miss K. Ofalvi for the IR spectra. F. B., J.
F. and K. L. are grateful to OTKA [Hungarian Scienti®c
Research Fund, /Grant No. T-029035)] and to the
Hungarian Ministry of Education /Grant No. FKFP 0028/
1999) for ®nancial assistance.
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