X-ray crystal structures of intermediates of the stereoselective (±)-grandisol synthesis based on the remote alkylation protocol

Article abstract of DOI:10.1007/s10870-013-0411-4

Starting from easily prepared (cyclobutylsulfonyl)benzene (1), a stereoselective synthesis of (±)-grandisol, accomplished in nine steps, with an overall yield of ca. 18 %, has been presented by Monteiro and Stefani (Eur J Org Chem 14:2659-2663, 2001). Most of the synthetic intermediates were secured in good to excellent yields as crystalline compounds requiring no or minimal purification, should being amenable to scale up. The structures and absolute stereochemistry of (2), (3), (4a), (5), (8) and (9) were established by IR and NMR (¹H, ¹³C) spectroscopies and confirmed by X-ray diffraction analysis. Compound (2) crystallizes in orthorhombic Pbca, a = 16.0565(5), b = 9.5144(6), c = 23.9728(7) A, the (3) crystallizes in monoclinic P2₁/c, a = 5.6390(5), b = 17.8630(16), c = 12.8678(12) A and β = 111.928(7)°, the (4a) crystallizes in monoclinic P2₁/c, a = 5.7002(9) A, b = 17.2752(14) A, c = 14.9168(9) A and β = 109.464(8)°. The other three cyclobutylsulfonyl derivatives crystallize in the same monoclinic space group P2₁/c with cell parameters (5) a = 8.072(4), b = 11.486(9), c = 14.565(8) A and β = 101.373(4)°, (8) a = 11.3448(2), b = 7.9377(1), c = 18.5329(4) A and β = 94.147(1)° and (9) a = 37.7571(9), b = 11.4434(3), c = 8.1824(2) A and β = 90.748(1)°.

Full text of DOI:10.1007/s10870-013-0411-4

J Chem Crystallogr (2013) 43:240–249
DOI 10.1007/s10870-013-0411-4
ORIGINAL PAPER
X-ray Crystal Structures of Intermediates of the Stereoselective
(–)-Grandisol Synthesis Based on the Remote Alkylation Protocol
•
Gerimario F. de Sousa Hugo J. Monteiro
•
´
Ines S. Resck Claudia C. Gatto Javier Ellena
•
•
•
ˆ
Jose R. Sabino
´
Received: 27 April 2012 / Accepted: 4 April 2013 / Published online: 23 April 2013
Ó Springer Science+Business Media New York 2013
Abstract Starting from easily prepared (cyclobutylsulfo-
nyl)benzene (1), a stereoselective synthesis of ( )-grand-
isol, accomplished in nine steps, with an overall yield of ca.
18 %, has been presented by Monteiro and Stefani (Eur J
Org Chem 14:2659–2663, 2001). Most of the synthetic
intermediates were secured in good to excellent yields as
crystalline compounds requiring no or minimal purifica-
tion, should being amenable to scale up. The structures and
absolute stereochemistry of (2), (3), (4a), (5), (8) and (9)
were established by IR and NMR (1H, 13C) spectroscopies
and confirmed by X-ray diffraction analysis. Compound (2)
crystallizes in orthorhombic Pbca, a = 16.0565(5), b =
Keywords Grandisol Á Stereoselective synthesis Á
Alkylation Á Crystal structure
Introduction
( )-Grandisol (A), cis-2-(2-isopropenyl-1-methylcyclobutyl)etha-
nol, is one of the components of the male-produced phero-
mone of the cotton boll weevil Anthonomus grandis
Boheman, which is a very important pest in the cotton fields
in USA, Central America, Brazil and conifer infestation in
North America and Central Europe [1–3]. This monoterpe-
noide pheromone can be isolated in two enantiomeric forms,
(?)-A and (-)-A, both chemical structures show compara-
ble biological activity [3]. Two other well-known compo-
nents of pheromone are grandisal (B) and grandisoic acid
(C), being the first component was found in pheromone of
weevils of the genus Pissodes and the second one in plum
curculio Conotrachelus nenuphar Herbts [3] (Scheme 1).
Due to its high commercial value and an alternative to
classical pesticides, these cyclobutane derivatives have
been attracted the attention of many organic chemists and a
large number of syntheses of racemic and optically active
grandisol have already been published [4]. Since the cotton
boll weevil A. grandis can only recognize the natural
pheromone enantiomer (?)-grandisol [5], the synthesis of
this racemic-terpene become economically very attractive
if the product is to be used in traps for control infestation
[2]. We report the X-ray crystal structures of the interme-
diates (2), (3), (4a), (5), (8) and (9) (Scheme 2) obtained
from the reported [2] stereoselective and short synthesis
exploiting the versatile chemistry of the benzenesulfonyl
(–SO2Ph) moiety, avoiding labile intermediates and the use
of expensive reagents, which are found in many of the
reported grandisol syntheses.
˚
9.5144(6), c = 23.9728(7) A, the (3) crystallizes in
monoclinic P21/c, a = 5.6390(5), b = 17.8630(16), c =
˚
12.8678(12) A and b = 111.928(7)°, the (4a) crystallizes
˚
in monoclinic P21/c, a = 5.7002(9) A, b = 17.2752(14) A,
˚
˚
c = 14.9168(9) A and b = 109.464(8)°. The other three
cyclobutylsulfonyl derivatives crystallize in the same
monoclinic space group P21/c with cell parameters (5)
˚
a = 8.072(4), b = 11.486(9), c = 14.565(8) A and b =
101.373(4)°, (8) a = 11.3448(2), b = 7.9377(1), c =
˚
18.5329(4) A and b = 94.147(1)° and (9) a = 37.7571(9),
˚
b = 11.4434(3), c = 8.1824(2) A and b = 90.748(1)°.
G. F. de Sousa (&) Á H. J. Monteiro Á I. S. Resck Á C. C. Gatto
´ ´ ´
Instituto de Quımica, Universidade de Brasılia, Brasılia,
DF 70919-970, Brazil
e-mail: gfreitas@unb.br
J. Ellena
Instituto de Fısica de Sa˜o Carlos, Universidade de Sa˜o Paulo,
´
Sa˜o Carlos, SP 13560-970, Brazil
J. R. Sabino
Instituto de Fısica, Universidade Federal do Goias, Goiania,
´
GO 74001-970, Brazil
e-mail: jrsabino@if.ufg.br
´
ˆ
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J Chem Crystallogr (2013) 43:240–249
241
Scheme 1 Grandisol
enantiomers and their oxidized
derivatives
COOH
CHO
CH2OH
CH2OH
C
( )-A
B
(+)-A
PhSO2S
SO2Ph
SO2Ph
SO2Ph
a
b
O
O
3
2
1
c
X2
COOH
e
SO2Ph
f
O
O
SO2Ph
4
SO2Ph
5
6
4a, X = H
4b, X = N
d
g
CH2OH
SO2Me
i
CH2OH
SO2Me
h
CH2OH
PhO2S
PhO2S
SO2Ph
7
9
8
j
CH2OH
10
Scheme 2 The remote alkylation strategy in the synthesis of
grandisol (10). a i. MeLi, THF, -15 °C; ii. 2-(phenylsulfanylmeth-
yl)oxirane; iii, H2O2, HOAc; iv, Jones reagent, room temp.: b NaOH,
MeOH, room temp.: c AlMe3, CuBr, THF, 0 °C: d 2-Chloro-1-
ethylpyridinium tetrafluoroborate, NaN3, NaOAc, MeOH, 0 °C,
e Rh2(OAc)4, CH2Cl2, reflux: f i. NaOH, MeOH, reflux; ii. H?:
g Me2SÁBH3: h i. MeLi, THF, -15 °C; ii. Me2S2; iii. H2O2, HOAc:
i i. t-BuMe2SiCl, Et3N, DMAP, CH2Cl2, room temp.: ii. NaOH, MeI,
BTEAC, C6H6–H2O: iii. Dowesx 50 9 8, MeOH, room temp.:
j MeLi, THF, -15 °C
1-Phenyl-ulfonyl-3-(1-phenylsulfonylcyclobutyl)acetone
(2)
Experimental
Synthesis, IR, NMR and CHN Analyses
(15.5 g, 96.6 %), mp 130–132 °C. IR: m = 1,711, 1,320,
1,290, 1,142, 1,072, 728 cm-1 1H NMR (CDCl3): d
.
The synthesis and above physical methods have already
been described [2]. However, new NMR experiments
(COSY, HMQC and HMBC) were recorded again on a
VARIAN MERCURY PLUS spectrometer, with the aim of
locating safely all atoms of hydrogen and carbon.
1.90–2.12 (m. 2H), 2.27–2.37 (m, 2H), 2.71–2.81 (m, 2H),
3.16 (s, 2H), 4.28 (s, 2H), 7.55–7.62 (m, 4H), 7.67–7.76
(m, 2H), 7.86–7.90 (m, 4H). 13C NMR (CDCl3): d 14.9,
27.3, 46.7, 64.5, 67.4, 128.0, 129.1, 129.3, 129.7, 129.9,
123

242
J Chem Crystallogr (2013) 43:240–249
134.17, 134.3, 134.8, 138.4, 194.4. Anal.: calc. for
C19H20O5S2: C, 58.14; H, 5.14. Found: C, 57.96; H, 5.27.
139.9 (10C). Anal.: calc. for C15H22O5S2 (346.5): C, 52.00;
H, 6.40. Found: C, 51.76; H, 6.38.
1-Cyclobutylidene-3-(phenylsulfonyl)acetone (3)
(1R*, 4R*, 8R*)-2-{1-Methyl-2-[1-(methylsulfonyl)-1-
(phenylsulfonyl)-ethyl]-cyclobutyl}ethanol (9)
(4.85 g, 97.1 %), mp 71–72 °C. IR: m = 1,690, 1,628,
1,354, 1,309, 1,276, 1,173, 1,060, 895, 758 cm-1. 1H NMR
(CDCl3): d 2.13 (quint. J = 7.8 Hz, 2H), 2.86–2.93 (m,
2H), 3.08–3.16 (m, 2H), 4.15 (s, 2H), 6.23 (quint.
J = 2.4 Hz, 1H), 7.54–7.60 (m, 2H), 7.65–7.70 (m, 1H),
7.88–7.91 (m, 2H). 13C NMR (CDCl3): d 17.8, 33.0, 34.8,
67.0, 119.7, 128.0, 129.0, 129.4, 129.9, 133.9, 138.7,
172.6, 185.7. Anal.: calc. for C13H14O3S: C, 63.38; H, 5.64.
Found: C, 61.97; H, 5.39.
(2.65 g, 96 %), mp 161–172 °C. IR: 3,422 (br), 1,318,
1
1,302, 1,148, 1,072, 955 cm-1. H NMR (CDCl3): d 1.38
(s, 7CH3), 1.68–1.79/1.91–2.01 (m, 3CH2), 1.82 (s, 16CH3),
2
9
2.02–2.14 (5CH2), 2.23–2.43 (m, CH2), 3.08 (s, CH3),
3.16 (dd, 1CH), 3.71–3.89 (m, 6CH2), 7.40–7.60 (m,
11,15CH), 7.65–7.71 (m, 13CH), 7.91–7.95 (m, 12,14CH). 13
C
NMR (CDCl3): d 11.4 (16C), 22.2 (5C), 28.5 (7C), 30.8
(3C), 37.2 (2C), 38.2 (9C), 45.0 (1C), 46.7 (4C), 59.3 (6C),
88.9 (8C), 128.8 (11,15C), 129.2 (12,14C), 134.3 (13C), 139.9
(10C). Anal.: calc. for C16H24O5S2 (360.5): C, 53.31; H,
6.71. Found: C, 53.07; H, 6.53.
1-(1-Methylcyclobutyl)-3-(phenylsulfonyl)acetone (4a)
(3.4 g, 79.9 %), mp 82–83 °C. IR: m = 1,715, 1,315,
1,241, 1,144, 745 cm-1. 1H NMR (CDCl3): d 1.15 (s, 3H),
1.72–1.99 (m, 6H), 2.84 (s, 2H), 4.10 (s, 2H), 7.55–7.61
(m, 2H), 7.66–7.72 (m, 1H), 7.87–7.91 (m, 2H). 13C NMR
(CDCl3): d 15.4, 25.5, 33.3, 36.4, 55.3, 67.9, 127.9, 129.0,
133.9, 138.4, 197.0. Anal.: calc. for C14H18O3S: C, 63.13;
H, 6.81. Found: C, 62.89; H, 6.79.
Crystal Structure
The compounds (2), (3), (4a), (5), (8) and (9) were
obtained as a white product and single crystals were
obtained from MeOH by slow evaporation at room tem-
perature. The X-ray measurements were carried out in a
Enraf–Nonius Kappa-CCD diffractometer for (2), (3), (4a),
(5), (8) and on Bruker Smart Apex II-CCD instrument for
(9) with graphite monochromated Mo-Ka radiation
(1R*, 4R*, 8S*)-1-Methyl-4-
(phenylsulfonyl)bicycle[3.3.0]heptan-3-one (5)
˚
(k = 0.71073 A) at room temperature. Data of (9) have
(10.8 g, 78.8 %), mp 105–106 °C. IR: 1,745, 1,305, 1,144,
1,080, 753, 730 cm-1. 1H NMR (CDCl3): d 1.43 (s, 5CH3),
1.52–1.64/2.40–2.54 (m, CH2), 1.82–1.91/1.97–2.08 (m,
been corrected by absorption using the multiscan method.
Structure solutions were accomplished with Direct Meth-
ods and the refinements were performed using full matrix
least-squares on F2. Hydrogen atoms were placed in ide-
alized positions and refined isotropic with riding con-
straints. The compounds Ortep representations are shown
in Figs. 1, 2, 3, 4, 5 and 6 with their labeling scheme.
Crystal and refinement details are given in Tables 1 and 2
and selected bond lengths and angles with their estimated
standard deviations are compiled in Tables 3 and 4. Soft-
ware used: data collection: Collect [6]; data reduction:
DENZO-SCALEPACK [7]; multiscan absorption correction
[8]; structure solution: SHELXS97 [9]; structure refine-
ment: SHELXL97 [9], molecular graphics: ORTEP3 for
Windows [10]; preparation of material for publication:
WingX [11].
2
3CH2), 2.41/2.62 (d, J = 18 Hz, 6CH2), 3.24 (d,
1
8
J = 5,7 Hz, CH), 3.66 (s, CH), 7.45–7.61 (m, 11,13CH),
7.66–7.73 (m, 12CH), 7.81–7.85 (m, 10,14CH). 13C NMR
(CDCl3): d 21.2 (2C), 26.3 (5C), 31.8 (3C), 40.4 (4C), 41.0
(1C), 52.1 (6C), 78.5 (8C), 128.6 (10,14C), 129.0 (11,13C),
134.0 (12C), 137.3 (9C), 208.0 (7C). Anal.: calc. for
C14H16O3S (264.3 g/mol): C, 63.61; H, 6.10. Found: C,
63.17; H, 5.83.
(1R*, 4R*, 8R*)-2-{1-Methyl-2-
[(methylsulfonyl)(phenylsulfonyl)methyl]-
cyclobutyl]ethanol (8)
(5.20 g, 87.9 %), mp 160–162 °C. IR: 3,549 (br), 1,315,
1
1,150, 1,125, 1,081, 755 cm-1. H NMR (CDCl3): d 1.34
(s, 7CH3), 1.74–1.82 (m, 3CH2), 1.86–2.82 (m, 2CH2),
Results and Discussion
1
2.04–2.14/2.48–2.62 (5CH2), 2.62–2.89 (m, CH), 3.08 (s,
9CH3), 3.71–3.89 (m, 6CH2), 4.63 (d, J = 9 Hz, 8CH),
7.40–7.60 (m, 12,14CH), 7.65–7.71 (m, 13CH), 7.91–7.95
(m, 11,15CH). 13C NMR (CDCl3): d 22.6 (5C), 28.0 (7C),
30.2 (3C), 36.6 (2C), 39.7 (9C), 41.0 (1C), 43.1 (4C), 59.3
(6C), 82.3 (8C), 128.8 (12,14C), 129.2 (11,15C), 134.3 (13C),
Crystal Structure of Compound (2)
Wilson has been reported [12] that the ideal bond distances
˚
for cyclobutane is 1.54 A. The range of observed values in
˚
(2) was 1.529(3)–1.559(3) A, so there is no correlation of
123

J Chem Crystallogr (2013) 43:240–249
243
Fig. 1 ORTEP of compound (2), with 30 % probability displacement
ellipsoids
Fig. 5 ORTEP of compound (8), with 30 % probability displacement
ellipsoids
Fig. 2 ORTEP of compound (3), with 30 % probability displacement
ellipsoids
Fig. 3 ORTEP of compound (4a), with 30 % probability displace-
ment ellipsoids
Fig. 6 ORTEP of compound (9), with 30 % probability displacement
ellipsoids
this bond length with the nature of the phenylsulfonyl
group bonded to the C(1) quaternary atom. The two S(1)–
˚
C(8)aryl = 1.757(2) and S(2)–C(14)aryl = 1.766(2) A bond
lengths of each of the two phenylsulfonyl moieties have
some double bond character since they are lightly shorter
than the single S(1)–C(7) = 1.774(2) and S(2)–
˚
C(1) = 1.779(2) A bond distances. The bond length C(6)–
˚
O(1) = 1.190(3) A show the typical double-bond character
and suggest that C(6) is sp2 hybridized while the bond
Fig. 4 ORTEP of compound (5), with 30 % probability displacement
ellipsoids
angle C(5)–C(6)–C(7) = 112.73(18)° corroborate to that,
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J Chem Crystallogr (2013) 43:240–249
as expected. The four bonds S(1)–O(2) = 1.4272(18), S(1)–
O(3) = 1.4338(18), S(2)–O(4) = 1.4421(16) and S(2)–
rehybridization of C(4) atom from sp2 to sp3 during con-
struction of the quaternary centre, C(4), by a 1-4-addition of a
˚
O(5) = 1.4414(16) A observed for (2) are comparable in
˚
methyl group to acetone (3). So, the C(6)–O(1) = 1.213(2) A
length to those found in others phenylsulfonyl derivatives
[13, 14]. The two phenyl rings make a dihedral angle of
15.85(0.14)° with respect to each other and the cyclobutyl
ring make dihedral angles of 26.83(0.15)° and 12.41(0.17)°
with the phenyl rings of the C(4)-phenylsulfonyl and C(7)-
phenylsulfonyl moieties, respectively. The torsion angle
defined by C(6)–C(7)–S(1)–C(8) = 58.41(19)° is higher
than the torsion angle defined by C(6)–C(5)–C(1)–C(4) =
-52.8(3)° to minimize the possible intramolecular interac-
tions. The Cremer and Pople [15] puckering parameter
bond distance is shorter than the equivalent bond found in (3),
as expected. The cyclobutyl ring make dihedral angle of
32.06(18)° with phenyl ring while the equivalent dihedral
angle found in (3) wasof85.78(8)°. The torsion angles defined
by C(6)–C(7)–S(1)–C(8) = -168.56(12)° and by C(6)–
C(5)–C(1)–C(4) = -163.54(18)° indicate that C(8) and C(4)
atoms point roughly in opposite directions. The Cremer and
˚
Pople [15] puckering parameter (q2 = -0.230(3) A shows
that the four-membered ring is twisted, with a dihedral angle
among C(4), C(1), C(2) and C(2), C(3), C(4) of 24.0(3)°.
˚
(q2 = -0.0982(3) A shows that the cycle-butyl ring is
puckered, with a dihedral angle among C(4), C(1), C(2) and
Crystal Structure of Compound (5)
C(2), C(3), C(4) of 10.2(2)°.
In compound (5) the rings are cis-fused and the Cremer and
Pople [15] puckering parameters show that the four-mem-
Crystal Structure of Compound (3)
˚
bered ring is puckered [Q2 = -0.222(3) A] and the five-
The C(1)–C(5) = 1.330(2), C(5)–C(6) = 1.460(2) and
˚
C(6)–O(1) = 1.213(2) A bond distances values reflect the
membered ring is in an envelope conformation [Q2 =
˚
0.192(2) A and u2 = 28.3(7)°]. The seven-membered ring is
electron delocalization in the C(4)–C(5)–C(6)–O(1) chain,
indicating ethene formation at C(1)–C(5) bond due phen-
ylsulfonyl (PhSO2–) elimination from acetone (2). As
consequence of this elimination with formation of sp2-C(1)
too puckered [Q = 1.052(3), u2 = 226.07(14) and u3 =
147.3(5)°].
The geometry around the S(1) atom is described as dis-
torted tetrahedral in which the C8–S1–C9 and O1–S1–O2
bond angles values are 106.20(8) and 118.50(10)°, respec-
tively. The quaternary carbon C4 is too tetrahedrally bonded
with their angles ranging from 88.55(18) to 118.04(19)°.
Two torsion angles as a result of rotation across C8–S1bond
are C1–C8–S1–O1 = 62.37(15) and C1–C8–S1–O2 =
-66.13(16)°, indicating that the molecule adopts a alternate
gauche conformation when viewed along the C8–S1. The
four- and five-membered rings make a dihedral angles of
23.5(2)° with respect to each other and the phenyl ring makes
dihedral angles of 50.71(14) and 49.1(2)° with the four- and
five-membered rings, respectively.
˚
atom, the range of 1.498(2)–1.534(3) A for bond distances
values observed in cyclobutylidene ring of (3) shows that
these bond distances are shorter than that related ones
found in (2), as expected (see Table 2). The C(6)–
˚
˚
O(1) = 1.213(2) A bond distance is about 0.023 A longer
than the related bond found in (2), these observations
confirm the above-mentioned electron delocalization. The
S=O, S–Caryl and S–Calkyl distances are in good agreement
with equivalent bond distances observed in (2) (Table 1)
and in other related compounds [13, 14].
The torsion angle defined by C(6)–C(7)–S(1)–
C(8) = 58.65(16)° and the torsion angle defined by C(6)–
C(5)–C(1)–C(4) = -176.2(2)° is a consequence of C(1)–
C(5) double bond formation. The cyclobutyl ring make
dihedral angle of 85.82(13)° with phenyl ring while the
equivalent dihedral angle found in (2) was of 12.87(17)°.
The Cremer and Pople [15] puckering parameter
The S1–O1 = 1.4316(16), S1–O2 = 1.4343(16), C8–
˚
S1 = 1.7953(18) and C9–S1 = 1.765(2) A bond distances
are in good agreement with other related bonds previously
reported [13, 14]. The phenylsulfonyl and junction methyl
groups are in cis-positions with respect to each other. The
˚
C1–C4 = 1.566(3) and C7–O3 = 1.195(2) A bond dis-
˚
(q2 = 0.078(8) A shows that the four-membered ring is
twisted, with a dihedral angle among C(4), C(1), C(2) and
tance are consistent with the expected values [14].
C(2), C(3), C(4) of 8.4(3)°.
Crystal Structures of Compounds (8) and (9)
Crystal Structure of Compound (4a)
The substitution of the H atom in (8) by the more bulky
methyl group in (9) does not favor the modification in the
crystal packing of the molecules in each case (Figs. 5 and
6) and only the monoclinic (P21/c) crystal system was
observed. There are two crystallographically independent
molecules (denoted by a and b) for compound (9), thus
there are not significant differences in angles and distances
The C(1)–C(2) = 1.544(3), C(1)–C(4) = 1.550(3), C(1)–
˚
C(5) = 1.512(2)andC(5)–C(6) = 1.498(2)Abonddistances
are significant higher than the equivalent C(1)–C(2) =
1.498(2), C(1)–C(4) = 1.508(3), C(1)–C(5) = 1.330(2) and
˚
C(5)–C(6) = 1.460(2)
A
found in (3) due to the
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J Chem Crystallogr (2013) 43:240–249
245
Table 1 Crystallographic data for the compounds (2), (3) and (4a)
(2)
(3)
(4a)
Crystal data
Chemical formula
Chemical formula weight
Cell setting
C
19H20O5S2
C13H14O3S
250.31
C14H18O3S
266.35
392.49
Orthorhombic
Pbca
Monoclinic
P21/c
Monoclinic
P21/c
Space group
˚
a (A)
16.0565(5)
9.5144(6)
23.9728(7)
90
5.6390(5)
17.8630(16)
12.8678(12)
90
5.7002(9)
17.2752(14)
14.9168(9)
90
˚
b (A)
˚
c (A)
a (°)
b (°)
c (°)
90
111.928(7)
90
109.464(8)
90
90
3
˚
V (A )
3,662.3(3)
8
1,202.4(2)
4
1,384.9(3)
4
Z
Dx (Mg cm-3
Radiation type
)
1.424
1.383
1.278
Mo Ka
0.71073
7,853
Mo Ka
Mo Ka
˚
Wavelength (A)
0.71073
4,847
0.71073
5,261
No. Of reflections for cell parameters
h range (°)
2.9–27.5
0.32
2.9–27.5
0.26
2.9–27.5
0.23
l (mm-1
)
Temperature (K)
Crystal form
298(2)
298(2)
298(2)
Prism
Needle
Prism
Crystal size (mm)
Crystal colour
0.24 9 0.18 9 0.15
Colourless
0.43 9 0.1 9 0.1
Colourless
0.11 9 0.13 9 0.17
Colourless
Data collection
Diffractometer
Enraf–Nonius KappaCCD
x scan
Enraf–Nonius KappaCCD
x scan
Enraf–Nonius KappaCCD
x scan
Data collection method
Absorption correction
No. of measured reflections
No. of independent reflections
No. of observed reflections
Criterion for observed reflections
Rint
Multi-scan
7,821
Multi-scan
5,298
Multi-scan
5,772
4,176
2,744
3,067
3,047
2,013
2,258
I [ 2r(I)
0.029
I [ 2r(I)
0.055
I [ 2r(I)
0.033
hmax (°)
Range of h, k, l
27.5
27.6
27.5
-20 B h B 20
-12 B k B 12
-30 B l B 31
-7 B h B 7
-22 B k B 22
-16 B l B 16
-7 B h B 7
-22 B k B 21
-19 B l B 19
Refinement
Refinement on
R[F2 [ 2r(F2)]
F2
F2
F2
0.049
0.148
1.05
0.046
0.131
1.08
0.047
0.154
1.08
wR(F2)
S
Number of reflections used in refinement
No. of parameters used
H-atom treatment
4,176
235
2,744
154
3,067
164
Constrained
\0.001
0.48
Constrained
0.001
0.21
Constrained
0.001
0.21
(D/r)max
-3
˚
Dqmax (e A
)
-3
˚
Dqmin (e A
)
-0.43
None
-0.33
None
-0.28
None
Extinction method
123

246
J Chem Crystallogr (2013) 43:240–249
Table 2 Crystallographic data for compounds (5), (8) and (9)
(5)
(8)
(9)
Crystal data
Chemical formula
Chemical formula weight
Crystal system
C
14H16O3S
C15H22O5S2
346.45
C16H24O5S2
360.47
264.33
Monoclinic
P21/c
Monoclinic
P21/c
Monoclinic
P21/c
Space group
˚
a (A)
8.0720(4)
11.4860(9)
14.5650(8)
90
18.5329(4)
7.9377(1)
11.3448(2)
90
37.7935(12)
11.4478(3)
8.1883(3)
90
˚
b (A)
˚
c (A)
a (°)
b (°)
c (°)
101.373(4)
90
94.147(1)
90
90.763(1)
90
3
˚
V (A )
1,314.79(1)
4
1,664.55(5)
4
3,542.4(2)
8
Z
F(000)
Dx (Mg cm-3
Radiation type
560
736
1,536
)
1.335
1.382
1.352
Mo Ka
Mo Ka
Mo Ka
˚
Wavelength (A)
0.71073
3.13–27.52
0.244
0.71073
3.60–27.48
0.339
0.71073
3.06–25.35
0.322
h range (°)
l (mm-1
)
Temperature (K)
Crystal form
298(2)
298(2)
298(2)
Irregular
0.44 9 0.11 9 0.05
Colourless
Irregular
0.20 9 0.18 9 0.07
Colourless
Irregular
0.05 9 0.26 9 0.37
Colourless
Crystal size (mm)
Crystal colour
Data collection
Diffractometer
Enraf–Nonius Kappa-CCD
Enraf–Nonius Kappa-CCD
Smart APEX II-CCD
x/u scan
Multi-scan
23,541
Data collection method
Absorption correction
No. of measured reflections
No. of independent reflections
No. of observed reflections
Criterion for observed reflections
Rint
x scan
None
5,719
3,002
2,432
x scan
None
30,235
3,781
2,353
6,439
4,457
0.0319
0.078
0.0705
hmax (°)
27.52
27.48
25.35
Range of h, k, l
-10 B h B 10
-14 B k B 14
-18 B l B 18
-23 B h B 24
-9 B k B 10
-14 B l B 11
-45 B h B 45
-11 B k B 13
-9 B l B 9
Refinement
Refinement on
R[F2 [ 2r(F2)]
wR(F2)
F2
F2
F2
0.0507
0.0502
0.1204
1.041
3,781
201
0.0478
0.1194
1.062
6,439
421
0.1463
S
1.047
Number of reflections used in refinement
No. of parameters used
H-atom treatment
3,002
164
H-atom parameters constrained
H-atom parameters constrained
H-atom parameters constrained
Weighting scheme
(D/r)max
0.001
0.42
-3
)
˚
Dqmax (e A
0.40
0.23
-3
˚
Dqmin (e A
)
-0.31
0.082(11)
-0.39
None
-0.53
None
Extinction coefficient
123

J Chem Crystallogr (2013) 43:240–249
247
˚
˚
Table 3 Selected bond lengths (A) and angles (°) for the compounds
(2), (3) and (4a)
Table 4 Selected bond lengths (A) and angles (°) for compounds (5),
(8) and (9)
(2)
1.559(3)
(3)
1.498(2)
(4a)
1.544(3)
(5)
(8)
(9)
C(1)–C(2)
C(1)–C(2)
1.542(3)
1.535(4)
1.546(3)
1.566(3)
1.512(3)
1.513(3)
1.795(2)
1.4316(15)
1.4343(16)
1.765(2)
1.505(3)
1.195(2)
87.97(2)
88.96(18)
118.04(2)
106.20(8)
106.80(9)
118.5(1)
1.545(3)
1.550(4)
C(2)–C(3)
1.532(3)
1.529(3)
1.534(3)
1.518(3)
1.531(3)
1.539(3)
C(2)–C(3)
1.530(3)
1.547(3)
1.585(3)
1.523(3)
1.525(3)
1.812(2)
1.4293(18)
1.4334(18)
1.744(3)
1.524(4)
1.552(4)
1.590(3)
1.531(4)
1.516(4)
1.849(2)
1.431(2)
1.4404(19)
1.752(3)
C(3)–C(4)
C(3)–C(4)
C(1)–C(4)
1.556(3)
1.508(3)
1.550(3)
C(1)–C(4)
C(1)–C(5)
1.518(3)
1.330(2)
1.512(2)
C(4)–C(5)
C(5)–C(6)
1.522(3)
1.460(2)
1.498(2)
C(4)–C(6)
C(6)–C(7)
1.506(3)
1.525(2)
1.525(2)
S(1)–C(8)
O(1)–C(6)
1.190(3)
1.213(2)
1.215(2)
S(1)–O(1)
S(1)–C(7)
1.774(2)
1.7732(19)
1.7628(19)
1.4391(13)
1.4359(13)
91.63(14)
88.84(14)
89.84(14)
89.09(15)
134.06(17)
121.66(16)
114.82(15)
118.19(8)
1.7801(18)
1.7551(18)
1.4311(14)
1.4300(15)
89.58(16)
87.69(16)
88.53(16)
89.09(15)
118.09(18)
116.42(16)
116.29(15)
118.59(10)
S(1)–O(2)
S(1)–C(8)
1.757(2)
S(1)–C(9)
S(1)–O(2)
1.4338(18)
1.4272(18)
89.09(16)
89.34(17)
91.10(17)
89.56(17)
118.70(18)
116.52(18)
112.73(18)
118.12(11)
C(6)–C(7)
S(1)–O(3)
O(3)–C(7)
C(2)–C(1)–C(4)
C(1)–C(2)–C(3)
C(2)–C(3)–C(4)
C(1)–C(4)–C(3)
C(2)–C(1)–C(5)
C(1)–C(5)–C(6)
C(5)–C(6)–C(7)
O(2)–S(1)–O(3)
C(2)–C(1)–C(4)
C(2)–C(3)–C(4)
C(1)–C(4)–C(5)
C(8)–S(1)–C(9)
O(2)–S(1)–C(8)
O(1)–S(1)–O(2)
O(3)–S(2)–O(4)
C(8)–S(2)–C(10)
S(2)–C(8)–S(1)
C(1)–C(8)–S(2)
S(1)–C(8)–C(1)
C(1)–C(8)–C(7)
C(1)–C(4)–C(6)
C(2)–C(1)–C(8)
O(1)–S(1)–C(8)
S(1)–C(8)–C(7)
88.23(17)
90.15(18)
87.9(2)
90.2(2)
113.13(18)
106.19(12)
107.69(10)
117.47(11)
118.41(13)
110.48(10)
112.88(11)
109.30(15)
112.34(15)
115.9(2)
109.49(12)
105.92(12)
117.86 (12)
119.04(12)
111.93(12)
111.42(13)
106.84(17)
107.99(16)
for both structures. Both compounds exhibit intermolecular
hydrogen bonds, which helps in stabilizing the crystal
structure. In (8) two intramolecular hydrogen bonds can be
observed O5(a)–H5(a)ÁÁÁO5(b) = 1.88; O5(b)–H5(b)ÁÁÁO5(a) =
110.57(12)
105.13(15)
104.31(17)
117.56(17)
108.03(10)
111.29(12)
˚
˚
1.91 A and in (9) only one O5–H5ÁÁÁO2 = 2.27 A.
˚
The C8–S1 = 1.812(2) and C8–S2 = 1.820(2) A bond
distances, observed for compounds (8) and C8a–
˚
S1a = 1.849(2) and C8a–S2a = 1.840(2) A observed for
˚
(9), are almost equal in length to that of Calkyl–S = 1.82 A,
(9) is localized over the C8. In (8), this carbon atom pos-
sesses three tetrahedral angles ranging from 109.56(14) to
112.87(11)°, while in (9) range from 106.8(2) to
111.48(18)° (see Table 2), as expected. The C8–S1 bond
which is the sum of the covalent radii [16] for S and C
atoms. However, an increased interaction of the S2 atom
with the p-system of the phenyl ring is indicated by the
˚
˚
C10aryl–S2 distances of 1.757(2) in (8) and of 1.766(3) A
in (9), which are shorter than the average Calkyl–S distance
distances of 1.820(2) and 1.849(2) A observed for com-
pounds (8) and (9), respectively, are the most discrepant
values observed among them.
˚
(1.82 A). In compound (8), the four almost identical S=O
bond distances [1.4291(18), 1.4303(18), 1.4311(18) and
˚
1.4328(18) A] and O=S=O angles [117.48(11) and
Infrared Spectroscopy
118.42(13)°] compare quite favorably with the distances
˚
[1.431(2), 1.4409(19), 1.4323(18) and 1.4386(18) A] and
The IR spectrum of compound (1) showed characteristic
strong bands for m(CH2), d(CH2), das(O=S=O) and
dsy(O=S=O) vibrations observed at 2,950, 1,446, 1,306 and
1,087 cm-1, respectively. The bands at 763 and 690 cm-1
were assigned to out of plane ring bending, dar(C–H),
related to monosubstituted aromatic ring. In compound (2)
the m(C=O) and dar(C–H) were observed at 1,711 and
728 cm-1, while das(O=S=O) and dsy(O=S=O) were
exhibited at 1,320, 1,290 and 1,142, 1,072 cm-1. By
angles [117.86(12) and 119.04(11)°] observed for com-
pound (9). The major palpable difference between the
compounds (8) and (9) is present in the C4 quaternary
carbon atom. Methylation of this center resulted in reduc-
ing of the angles C1–C8–S1, C1–C8–S2 and S1–C8–S2 of
respectively, 4.53; 1.50 and 2.62°.
The most significant difference in the bond angles of the
compound (8) when compared to its methylated compound
123

248
J Chem Crystallogr (2013) 43:240–249
elimination reaction, appearing the m(C=C) band at
1,628 cm-1 that displaced the m(C=O) of carbonyl band to
lower frequency at 1,690 cm-1. By construction of the
C(4) quaternary centre by 1,4-addition of a methyl group to
ketone (3), the IR spectrum of (4a) showed m(C=O) typical
band at 1,715 cm-1, as expected. The das(O=S=O) and
dsy(O=S=O) vibrations were observed at 1,315 and
1,144 cm-1, respectively, while the dar(C–H) bands are
observed at 895, 752 cm-1 for sulfonyl unsaturated ketone
(3) and at 745 cm-1 for sulfonyl saturated ketone (4a).
The IR spectrum for the sulfone (5) shows the presence
of strong intensity band centered at 1,745 cm-1 which can
be assigned with confidence to stretching vibration of the
carbonyl, m(C=O), group. It is interesting to note that this
m(C=O) mode appear at higher frequencies than the cor-
responding mode observed at 1,715 cm-1 for acyclic b-
ketosulfone (4a). Usually, cyclopentanones absorbs at
1,745 cm-1 due to angular torsion promoted by five-
membered ring. Other fundamental characteristics for
sulfones are mas(O=S=O) and msy(O=S=O) vibrations
modes, observed in the 1,350–1,300 and 1,160–1,120 cm-1
regions [17], respectively. Thus, two strong absorptions
centered at 1,305 and 1,144 cm-1 can be assigned with
security to the mas(O=S=O) and msy(O=S=O) vibrations.
These stretching vibrations are located at 1,315,
1,150 cm-1 for disulfone (8) and at 1,318, 1,148 cm-1 for
disulfone (9).
15.3). The cyclobutyl hydrogens in the allylic position for
(3) were displaced to higher shifts, d 3.08–3.16 (dC 33.0
and 34.8), than the observed multiplets for cyclobutyl
hydrogens of(2) and (4a), at d 1.99–2.81(dC 27.3 and 33.3).
For all three compounds (2), (3) and (4a), the singlet aCH2
to sulfonylketones were exhibited between d 4.10 and 4.28
(dC 66.9, 67.0, 64.4), being much more deshielded than the
singlet aCH2, close to cyclobutyl ring of the compound (2)
and (4a), assigned at 3.16 (dC 46.7) and d 2.84 (dC 55.3)
and, respectively. The olefinic hydrogen of (3), coupled to
allylic of cyclobutyl ring showed as quintet at d 6.20 (dC
119.7) (J = 2.4 Hz). There was no displacement shift for
the aromatic hydrogens of those compounds (2), 3) and
(4a), as registered between d 6.60 and 7.90 (dC 127.9 and
138.7).
In the structure (5), the methyl group (C5) showed as
singlet at d 1.43 (dC 26.3). The four and five-membered
rings, respectively, exhibited the shifted displacements
between d 1.52 adn 3.66 for hydrogens and d 21.2–88.9 for
methylene (CH2) carbons. Despite of diasterotopic hydro-
gens at C6 (d 52.1) were showed at 2.41 and 2.62
(J = 18 Hz), the other ones such as C2–H and C3–H were
observed as multiplet and not doublet duplet. The chemical
shifts for the aromatic hydrogens were identified in fol-
lowing sequence for the C10 and C14 (d 7.81–7.85; dC
H
128.6), for the C11 and C13 (dH 7.45–7.61; dC 129.0) and
for the C12 (dH 7.25–7.66; dC 134.0). The aromatic qua-
ternary carbon (C9) at d 137.3 and the carbonyl group (C2)
at d 208.0 were marked by HMQC technique. Both com-
pounds (8) and (9), the chemical shifts for their hydrogens
and carbons are very closed, except to the additional
methyl group (C16, d 1.82) displaced in the structure of (9)
and their respective quaternary carbons at C8 absorbing at
d 8.23 and 88.9. The resonance hydrogen signals from d
1.34 to d 3.89 (aliphatic hydrogens) and d 7.40 to d 7.95
(aromatic hydrogens) were assigned by the homonuclear
(COSY). All carbons were matched to respective hydrogen
by the homonuclear and heteronuclear two-dimensional
experiments (COSY, HMQC and HMBC) done using the
field gradient mode.
The most significant difference in the IR spectrum of the
sulfone (5) when compared to the vibrational spectra of the
disulfones (8) and (9) is the disappearance of the m(C=O)
stretching vibration in (5) and appearance of strong
absorption centered at 3,549(sh) in (8) and at 3,422(sh)
cm-1 in (9), which are assigned to m(O–H) stretching. The
relatively strong bands centered at 1,081 in (8) and at
1,072 cm-1 in (9) can be assigned to m(C–O) stretching
vibrations.
(1H, 13C) NMR Spectroscopy
NMR spectra were recorded on a VARIAN MERCURY
1
PLUS spectrometer (7.05 T) operating at 300 MHz for H
and at 75.46 MHz for 13C. The compounds (2), (3), (4a),
(5), (8) and (9) were dissolved in CDCl3 having TMS
(Me4Si) as internal reference; the chemical shifts were
expressed in d (ppm) and coupling constants as J (Hz). All
hydrogens/carbons were matched to the numbers registered
by X-ray technique to characterize the compounds. The
methyl group of 1-methylcyclobutyl of compound (4a)
represented the shieldest hydrogens at d 1.15 (dC 25.5). The
homoallylic hydrogens of cyclobutyl ring, related to (3),
appeared as quintet at d 2.13 (dC 17.8) with J = 7.8 Hz),
when the hydrogens at same positions for (2) and (4a),
showed as multiplet between d 1.72 and 2.12 (dC 19.4 and
Supporting Information Available
Crystallographic data for the structural analysis of the
compounds have been deposited at the Cambridge Crys-
tallographic Data Center (CCDC). The CCDC numbers are
847420 (2), 847421 (3) 847422 (4a), 847984 (5), 847986
(8) and 847985 (9). Copies of the data can be obtained free
of charge on application to CCDC, 12 Union Road, Cam-
bridge CB21EZ, United Kingdom; Fax: ?44 1223 336033
or e-mail: deposit@ccdc.cam.ac.uk.
123

J Chem Crystallogr (2013) 43:240–249
249
Acknowledgments This work was sponsored by grants from CNPq
and FINEP (CT-INFRA 0970/01). GFS also gratefully acknowledges
the financial support of the Conselho Nacional de Desenvolvimento
7. Otwinowski Z, Minor W (1997) In: Carter CW Jr, Sweet RM
(eds) Processing of X-ray diffraction data collected in oscillation
mode, methods in enzymology, macromolecular crystallography,
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8. Blessing RH (1995) Acta Cryst A51:33–38
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Cientıfico e Tecnologico-CNPq (Edital Universal-2007, Processo
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9. Sheldrick GM (2008) Acta Cryst A64:112–122
10. Farrugia LJ (1997) J Appl Cryst 30:565
11. Farrugia LJ (1999) J Appl Cryst 32:837–838
12. Wilson ACJ (1992) Editor international tables of crystallography,
vol C, mathematical, physical and chemical tables. Kluwer
Academic Publishers, Dordrecht, p 693
13. Zukerman SJ, Monteiro HJ (1998) Acta Cryst C54:1673–1675
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123