Preparation and structures of isoindolone- or pyrimidone-condensed heterocycles containing a hydroxy group on a cyclohexane or norbornane moiety

Article abstract of DOI:10.2174/157017809787893136

With DL-valinol, 3-amino-1-propanol and o-aminothiophenol, aroyl(bi/tri)cyclic lactones 1 and 2 were cyclized to isoindole- 4-6, 8, 9, pyrimidinone- 10 or thiazepine- 7 condensed heterocycles. The ketal lactone 3 furnished the benzthiazoloisoindole 9 and

Full text of DOI:10.2174/157017809787893136

252
Letters in Organic Chemistry, 2009, 6, 252-257
Preparation and Structures of Isoindolone- or Pyrimidone-Condensed
Heterocycles Containing a Hydroxy Group on a Cyclohexane or Norbor-
nane Moiety
Ferenc Miklós1, Pál Sohár*,2,3, Antal Csámpai3, Reijo Sillanpää4 and Géza Stájer*,1
1Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös u. 6,H-6720 Szeged, Hungary
2Protein Modelling Group, Hungarian Academy of Sciences – Eötvös Loránd University, P.O. Box 32, H-1518 Budapest
112, Hungary
3Institute of Chemistry, Loránd Eötvös University, P.O. Box 32, H-1518 Budapest-112, Hungary
4Department of Chemistry, University of Jyväskylä, P.O. Box 35, 40351 Jyväskylä, Finland
Received July 09, 2008: Revised February 13, 2009: Accepted February 13, 2009
Abstract: With DL-valinol, 3-amino-1-propanol and o-aminothiophenol, aroyl(bi/tri)cyclic lactones 1 and 2 were cy-
clized to isoindole- 4-6, 8, 9, pyrimidinone- 10 or thiazepine- 7 condensed heterocycles. The ketal lactone 3 furnished the
benzthiazoloisoindole 9 and mixtures of epimeric hydroxyphthalazinoquinazolinones 11 and 12. The structures were es-
tablished by means of 1H and 13C NMR spectroscopy and in some cases by X-ray crystallography.
Keywords: Cycloalkane lactones, Isoindolones, 1,3-oxazines, Thiazoles, Stereostructure, NMR, X-ray.
INTRODUCTION
rated 7-hydroxyoxazolo- 4 and 8-hydroxy[1,3]oxaz-ino[2,3-
a]isoindolone 5. Through the reaction of and o-
1
We have recently developed a method with which to syn-
thetize (bi)cycloalkane aroyl lactones and ketal lactones [1],
which seemed to be applicable as starting compounds for the
preparation of derivatives with the hydroxy group at differ-
ent sites on the saturated carbocycle. Our first attempts fo-
cused on the hydrolysis and hydrazonolysis of the lactones,
which resulted in hydroxylated products on a preparative
scale [2]. Until recently, no simple method was known for
the introduction of a hydroxy group onto a saturated ring.
The results emphasized the advantageous features of this
reaction. The literature procedures [3-7] for preparation of
the starting synthons involved either electrophilic addition
following lactonization and elimination of the undesired
group or oxidation with perbenzoic acid [8] and lithiation
[9,10]. Epoxidation on the olefinic bond [11,12] or the pho-
tolysis and reduction of nitrosamines [13] are not general
routes to hydroxy-substituted derivatives.
aminothiophenol, a mixture of two products was obtained:
the partially saturated isoindolo[1,2-b]benzthiazolone 6 and
dibenzo[b,f][1,4]thiazepine 7, which were separated by col-
umn chromatography and their structures established by
means of NMR spectroscopic methods. For the formation of
7, the amino attacks on the oxo group, giving a Schiff base;
the thiol then reacts at the cyclohexane ꢀ-carbon. The inter-
mediate is stabilized by the formation of OH and formyl
groups, the latter subsequently being eliminated (Scheme 1).
A compound analogous to 7, clothiapine, was synthetized
earlier [13], and partially saturated thiazepines are also
known in the literature [14]. With 3-amino-1-propanol, di-
endo-norbornanelactone 2 cyclizes to the saturated methano-
8-hydroxy-1,3-oxazinoisoindolone 8 (Scheme 2). From lac-
tone 1, with diexo-3-aminonorbornane-2-carbohydrazide, the
pentacyclic methano-2-hydroxyphthalazinoquinazolinone 10
was obtained (Scheme 3).
In the present paper, our earlier-developed procedure is
extended by reacting the lactones 1-3 with bifunctional rea-
gents: aminoalcohols, 2-aminothiophenol and diexo- norbor-
nane-2-aminocarbohydrazides.
On opening with 2-aminophenyl-1-mercaptan, ketal lac-
tone 3 yielded the tetracyclic 3-hydroxy-benzthiazoloi-
soindolone 9 (Scheme 3). In the reaction of 3 with diexo-3-
aminobicyclo[2.2.1]heptane-2-carbohydrazide, different mix-
tures of the pentacyclic hydroxyphthalazinopyrimidinone
isomers 11 and 12 were isolated after purification by column
chromatography. The X-ray data revealed that the products
contain a 3-hydroxy group on a cis-condensed cyclohexane
ring, equatorial [86(1)%] for 11 (Fig. 1) and axial [72(1)%]
for 12. These mixtures are thermodynamically stable and the
products could not be separated in pure form.
RESULTS AND DISCUSSION
In the presence of PTSA as catalyst, cis-2-toluoyl-
cyclohexane lactone 1 was refluxed with 2-amino-3-methyl-
butan-1-ol or 3-amino-1-propanol in xylene to yield the satu-
*Address correspondence to these authors at the Institute of Pharmaceutical
Chemistry, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary;
E-mail: stajer@pharm.u-szeged.hu
Institute of Chemistry, Loránd Eötvös University, P.O.Box 32, H-1518
Budapest 112, Hungary; E-mail: sohar@chem.elte.hu
To summarize, the reactions of lactones 1 or 2 and ketal
lactone 3 [12] with bidentate nucleophiles can be utilized for
the transannulational hydroxylation of cyclohexane- or
1570-1786/09 $55.00+.00
© 2009 Bentham Science Publishers Ltd.

Preparation and Structures of Isoindolone- or Pyrimidone-Condensed
Letters in Organic Chemistry, 2009, Vol. 6, No. 3
253
1
2
Ar
H
O
10
3
10b
9
8
10a
N
4
6a
6
5
HO
7
H
O
5
HO
NH2
6
Ar
H
1
Ar
H
5
SH
O
S
4b
N
9
6
2
3
7
8
4
9b
N
5
NH2
O
NH2
OH
7
4
10
9
HO
11
Ar
HO
2
H
1
H
O
O
O
4
O
6
1
Ar
Ar
11
Ar
10
N
HO
3
1
N
N
2
– H2CO
HO
S
O
HS
S
5
4
O
H
6
O
7
Ar = p-tolyl
Scheme 1.
1
2
Ar O
10
3
HO
NH2
9
O
N
4
5
7
Ar
8
6
O
O
OH
O
2
8
Ar = p-tolyl
Scheme 2.
O
8
O
9
6
N
7
NHNH2
5
O
Ar
N
NH2
H
N
Ar
12
H
4
O
H
H
O
1
1
3
10
2
OHeq
6
Ar
H
5
S
SH
7
8
4
HO
3
O
O
4a
11a
N
N
NHNH2
10
NH2
Ar
O
N
9
11
O
NH2
H
N
H
H
O
O
H
H
9
Ar
3
11: 86% eq
12: 72% ax
OH
Ar = p-tolyl
Scheme 3.

254 Letters in Organic Chemistry, 2009, Vol. 6, No. 3
Miklós et al.
Fig. (1). ORTEP perspective views of compounds 8, 10-12.
Table 1. Characteristic IR Frequenciesa and 1H NMR Datab of Compounds 4-11c
d
i
ꢀOH
ꢀC=O ꢁCAr
H
CH3
CH2
CHe
CHf
CHg
2’,6’- H
3’,5’- H
CH2
CH(CO)j CHꢀN=k
Com-
pound
Band
Band
Band
810
s(3H)
Cyclohexane/ene
Tolyl(2ꢂ2H)h
2ꢂd(2ꢂ1H)
Norbornane Ring
4
5
3480
3425l
3485
3363
3360
3440
3330
3265o
1701
1701
1703
ꢀ
2.37
2.38m
2.32m
2.45m
2.39
1.2- 2.3
0.7- 2.1
1.4-2.5m
1.8-3.0m
0.8-1.9m
1.2-2.4m
1.2-2.1
2.40
2.37m
2.80
ꢀ
3.05
2.88
2.85
ꢀ
3.99
3.87
4.08
4.25
4.24
3.58
3.77m
3.92
7.34
7.13, 7.40
7.22
7.19
7.19, 7.26
7.14
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
814
814
839l
814
805
827
ꢀ
6
ꢀ
ꢀ
ꢀ
7
7.35
7.28
ꢀ
ꢀ
ꢀ
8
1677
1690
1704l
1710l
2.36
2.92
3.3
3.44
2.78
2.87
2.95
7.04, 7.43
7.21
7.18, 7.29
7.14
0.94, 1.24l
ꢀ
3.44
ꢀ
2.36
ꢀ
9
2.31m
10
11
2.38
2.38m
7.64
7.30
1.21, 1.36
1.26, 1.40n
2.77
2.79
3.77m
3.79
1.2-2.9m
3.06
7.78
7.22
aIn KBr discs (cmꢀ1). Further bands, ꢀNH: 3500-2500, very broad, in overlap with the ꢀOH (11); ꢀC-O: 1032 (4), 1061 (5), 1064 (6), 1068 and 1046 (7), 1058 (8), 1073 (9), 968 (10),
1079 (11); bIn CDCl3 solution (in DMSO-d6 for 10) at 500 MHz. Chemical shifts in ppm (ꢀTMS = 0 ppm), coupling constants in Hz. Further signals: CH3 (i-Pr, 4): 0.74, 1.11, 2ꢀd, J =
6.7; CH (i-Pr, 4): 1.33 m; OCH2, 2ꢀdd: 3.60 and 4.33, J = 8.5, 7.4 and 7.0 (4), 3.67 and 3.76, J = 12.3, 2.3 and 5.0 (5, 8); NCH2, dd + dt: J = 13.2, 3.6 and 5.2 (5, 8), NCH, m (1H):
3.68 (4); CH (norbornene, 2ꢀ~s (2ꢀ1H): 1.24m and 2.65 (8, Pos. 7, 10), 2.38m; Condensed benzene ring, 3-H”: 7.04 (6, 9), 7.13 (7), 4”-H: 7.03 0.02, 5”-H: 7.12 0.02 (coalesced
c
with the d of 3’,5’-H for 6), 6”-H: 7.86 (6, 9), 7.55 (7); Assignments were supported by HMQC, HMBC (except for 11), DIFFNOE (for 4, 6-9), for 5, 8, 9, 11 also by 2D-COSY
measurements; dMultiplets, total intensity: 6H, 4H (8): norbornane-CH2 (Pos. 9) and CCH2C (Pos. 3), 8H (5): in overlap with CCH2C (Pos. 3), with norbornane-CH2 (Pos. 10, 11);
eCH bound to CquatAr, td (4, 6, 9, 11, J = 11.5 and 6.2 for 4, 12.5 and 5.6 for 9), d, J = 8.1 (8) and m (10); fCH bound to C=O (4-9) or C(N)=N dt, J = 6.5, 2.2 (4), 7.5, 5.5 (5), t, J = 6.2
(6), 5.6 (9), d, J = 8.1 (8), 8.7 (10, 11); gCH(OH) group, broad m for 4, 7 and 8, ꢁꢀ: 5 Hz (4), tt, J = 5.7, 2.9 (5), qi, J = ~3 (6), 11.3, 3.7 (9), d, J = 8.7 (11); h2ꢀ~d, J = 8.0 (4, 8, 10,
11), one (6, 7) or both (9) broadened, ~d and dd for 5; iBridging CH2 in norbornene, J = 10.8 (8, 11), 10.5 (10); jd, J = 8.1 (8), 8.7 (10, 11); kVicinal to quaternary C(tolyl) for (8), d, J
= 8.1, for 11 dd, J = 8.6, 2.5; lSplit band with the second maximum at 3395 (5), 829 (7), and 1672 (11), probably coupled with ꢀC=O (11); mOverlapped signals; nIn overlap with one
m of the two vicinal norbornane-CH2 groups; oHidden by the signal of the solvent.
diexo-norbornane-fused heterocycles. The opening of the
ketal lactone 3, however, led to a mixture of conformers,
separation of which did not succeed.
In compound 4, the carbonyl is attached axially to the cy-
clohexane, in accordance with our earlier experience [15,16],
which points to similar cis-annelated perhydroisoindolones.
This is unambiguous from the triple doublet split (td) of 9a-
H and confirms the axial orientation of this H and the equa-
torial position for 5a-H (in the CHCO group): only one
diaxial coupling (9Hax,9a-H) is present. DIFFNOE meas-
urements proved the sterically close arrangement of the or-
Structure
The spectral data (IR and1H and 13C NMR) prove the
structures given in Tables 1 and 2.

Preparation and Structures of Isoindolone- or Pyrimidone-Condensed
Letters in Organic Chemistry, 2009, Vol. 6, No. 3
255
Table 2. 13C NMR Chemical Shiftsa of Compounds 4-11b,c
Compound C-Tyl C=O C-1
C-2
C-3
C-4
C-5
C-6 C-1’ C-2’ C-3’ C-4’ C-5’ C-6’ CH3 C-1” C-2”,6” C-3”,5” C-4”
Cyclohexane/ened or Norbornanee Ring
Condensed Aromatic Ring f
Tolyl (Tyl) Group
4
5
102.4 180.5 48.6 41.9 29.6 64.9 29.9 17.0
96.2 179.7 43.5 39.7 31.5 66.0 30.0 19.8
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
21.47 139.5
21.5 133.9
125.6
127.5g
124.5
130.1
129.5 139.6
129.3g 138.4
129.8 138.3
129.26 137.4
6
87.0 175.1 48.2 41.8 29.7 64.4 30.2 22.0 131.1 134.7 116.7 125.7 126.1 123.1 21.4 142.5
122.9 107.4 123.6 31.3 68.0 31.9 19.9 135.6 131.3 123.9 122.8 124.9 113.3 21.5 129.33
97.3 179.9 53.4 43.4 45.6 71.6 39.1 40.0
7
ꢀ
8
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
21.5 134.4 127.76g 129.0g 138.3
9
85.7 172.9 48.2 42.8 21.3 32.0 69.3 38.7 130.5 134.3 116.3 125.5 125.8 122.8 21.1 142.1
158.2 165.1 62.5 49.9 44.2 29.9 26.5 46.1 34.8 36.6 31.9 22.4 66.1 33.4 21.8 133.4
124.1
127.6
126.7
129.5 138.1
129.8 140.2
10
11h
?
?
63.1 49.9 44.9 29.2 26.8 46.2 35.8 36.3 34.7 24.9 65.1 35.5 21.7
?
129.8
?
aIn ppm (ꢀTMS = 0 ppm) at 125.7 MHz. Solvent: CDCl3 (for 10 DMSO-d6). Further signals, CH3 (i-Pr, 4): 19.2 and 21.49; CCH2C: 25.3 (5), 25.8 (8); CH2(norbornane): 33.2 (8), 34.8
(10 and 11); NCH2: 38.0 (5 and 8); OCH2: 73.1(4), 62.4 (5), 62.8 (8), NCH: 61.3; bAssignments were supported by DEPT (except for 11), HMQC and also HMBC (except for 11)
measurements; cHere, C-1,1’,1”,2,2’,4” indicate the substituted carbons, C-1 bound to the C-tolyl group and the N atom for the cyclohexane ring and norbornane, and C-1’ to the S
e
atom; dFor 4-6, 9/7; For 8, 10-11; fFor 10-11 cyclohexane; gDue to hindered rotation of the tolyl group, two separated lines. The counterparts of the lines given in the Table are at
128.9 and 130.3 (5), 127.82 and 130.6 (8); hDue to the very poor solubility, the 13C NMR shifts of protonated carbons were determined from the HMQC measurements. The same
possibility, of course, does not exist for quaternary carbon atoms.
tho tolyl-H’s and the annelational H’s (5a,9a-H), and also of
the former H’s and the isopropyl methyl-H’s. The hydroxy
group must be axial (cis to the carbonyl), because the gemi-
nal CH exibits a narrow signal (ꢂꢃ ꢄ 5 Hz), which demon-
strates its equatorial position. In 4, a stable 7-membered
intramolecular H-bridge can exist. This is supported by the
higher ꢃOH frequency (3480 cm-1 for 4 and 3485 cm-1 for 6,
as compared with 3360-3440 cm-1 for the further com-
pounds) and the sharp contour of the ꢃOH band [17]. The
stereostructure for 4 is given in Scheme 1 and Fig. (2).
Similar values of the shifts of the hydroxy-substituted
and annelational carbons of the cyclohexane ring, and also
the narrow CH(OH) signal (2-H), suggest analogous stereo
structures for 6 and 4. The same holds for the skeleton of 9.
Similarly as in 4, the sterically close positions of the annela-
tional H's 4a,11a-H and the ortho-tolyl H's were demon-
strated by the DIFFNOE results. The position (Pos. 3) of the
hydroxy group, however, is different in 9. It is equatorial as
in 5 and the geminal H gives a triple triplet signal. The 13C
1
NMR shifts of the annelational carbons and the H NMR
chemical shifts are very similar to those observed for 6,
which (in accordance with the DIFFNOE measurements)
supports the analogous orientation of the tolyl group, and
hence the postulated structure of 9 (Scheme 3).
Me
H
O
O
O
O
5a
9a
H
N
6a
N
O
HO
As compound 7 contains only one chiral centre, this pre-
cludes the possibility of the formation of different isomers.
From the presence of only one methyne carbon (DEPT
measurement) and (besides twelve aromatic carbons) three
further sp2-type carbons, the structure depicted in Scheme 1
follows.
8
H
10
Me
10a
Me
Me
4
5
Fig. (2).
The X-ray stereostructures of 8, 10 and 11 show that the
norbornane annelations to the condensed heteroring are
diexo, due to the doublet split of the signal of the annela-
tional H’s, in accord with our “splitting rule” [19, 20]. In
diendo isomers, the dihedral angles of the latter and their CH
neighbours (Pos. 7 and 10 in 8 and Pos. 9 and 12 in 10 and
11) are ~30°; consequently, a further split leads to the double
doublet split of the signals of the annelational H’s in ques-
tion. In the diexo compounds, these dihedral angles are ~90°;
no split occurs, and only the interaction of annelational H's
leads to a doublet, as observed for 8, 10 and 11. Due to the
distorted skeleton of 11 (as a consequence of the crowded
steric structure), the 12,12a-H interaction leads to a small
splitting, resulting in a dd. The exo 9-H of 8 gives a ddd
split. The J(8-H,9-H) interaction (4.8 Hz) is evidence [21] of
the exo position of 8-H and thus an endo OH (in Pos. 8).
This is in accord with the X-ray results (Fig. 1), the latter
also confirming the close-lying position of the tolyl group
relative to the bridging CH2 in the norbornane moiety. (The
Compound 5 has a skeleton analogous to that of 4 (cis-
annelated perhydroisoindolone) as indicated by the similar
sums of the carbon chemical shifts of the cyclohexane ring
(230.5 ppm for 5, and 231.9 ppm for 4). For trans annela-
tion, a significantly higher value would be expected [18a].
Furthermore, the shifts of the annelational carbons are also
similar [43.5 and 39.7 ppm (5) and 48.6 and 41.9 ppm (4)];
either smaller, while higher values would be expected for a
trans-annelated structure [18a]. In accord with this, the cou-
plings of CHCO (6a-H) are all smaller (ꢀ 7.5 Hz) than the
data characteristic of a diaxial interaction (ꢁ 9-10 Hz). The
OH must be equatorial: the geminal H (8-H) gives a triple
triplet signal due to the two diaxial and two axial-equatorial
couplings with the neighbouring H’s. NOE was not observed
between the aromatic and annelational H's, and the axial 10-
methylene-H is much more shielded than in 4 because of the
anisotropic shielding of the tolyl group [18b], which is near
to the H in question and consequently trans to the annela-
tional H’s (Fig. 2).

256 Letters in Organic Chemistry, 2009, Vol. 6, No. 3
Miklós et al.
O
O
2
Me
N
N
N
N
N
N
H
Me
1
H
H
OH
H
H
H
H
H
HO
H
1
10
11
Fig. (3).
DIFFNOE results were not convincing because of signal
overlaps).
the skeleton (ꢁꢁꢀꢀ configuration) and the angle made by the
C–1ax-H bond to the plane of the :N=C–C moiety is ~60°
(Fig. 3).
For 11, the cis annelation of the cyclohexanole to the
pyridazine follows from the splittings of the annelational H
signals. Further supporting data are the relatively small car-
bon shifts of the annelational carbons [18a], which are very
similar to those measured for 10. Thus, diexo and cis annela-
tions are present in 10 and 11. In both compounds, the posi-
tion of the hydroxy group is unambiguous because of the
structures of the starting materials. The equatorial position
(trans to the annelational H's in the cyclohexane ring) of the
Because of the poor solubility, the NMR spectra of com-
pound 12 provided only dubious results. Here, the
stereostructure was determined by X-ray diffraction (Fig. 1).
EXPERIMENTAL
IR spectra were run in KBr disks on a Bruker IFS-55 FT-
1
spectrometer controlled by Opus 3.0 software. The H and
1
13C NMR spectra were recorded in CDCl3 solution in 5 mm
tubes at RT, on a Bruker DRX-500 spectrometer at 500.13
(1H) and 125.76 (13C) MHz, with the deuterium signal of the
solvent as the lock and TMS as internal standard. The stan-
dard Bruker micro program NOEMULT to generate NOE
[22] and to get DIFFNOE spectra [18d, 23] was used with a
selective pre-irradiation time. DEPT spectra [24] were run in
a standard manner [25], using only a ꢀ = 135 C pulse to
separate the CH/CH3 and CH2 lines phased “up” and
“down”, respectively. The 2D-COSY [26a,27a], HMQC
[26b,27b] and HMBC [28,29] spectra were obtained by us-
ing the standard Bruker pulse programs COSY-45
INV4GSSW and INV4GSLRNDSW.
OH group in 11 follows from the H NMR signal of the
geminal H, which is a sextet with a half signal width of ~25
1
Hz. Due to the very similar chemical shifts in the H and 13
C
NMR spectra of the CH(OH) group for 10 and 11, the equa-
torial orientation of the OH group is also unambiguous in
10. A strikingly large difference was observed for a methyl-
ene-H in the cyclohexane of 11. While all six such H’s gave
signals in the interval 1.2-2.2 ppm for 10, as did five of them
in 11, the sixth in 11 gave a signal at 2.83 ppm. The signifi-
cant downfield shift of this H (1eq-H) can be explained by
the anisotropy of the lone electron pair on the N atom [18c]
(cf. Fig. 3). This arrangement requires the same positions for
the two annelational H’s in each of the pyrimidone and the
pyridazine (the four annelational H’s must lie on the same
side of the skeleton: ꢁꢁꢁꢁ; Scheme 3 and Figs. (1 and 3) as
the annelation (cis) of the cyclohexane and the orientation
(eq) of the OH group are identical in 10 and 11, and the
above-mentioned downfield signal of a CH2 group (at ~2.83
General Procedure for Preparation of Compounds 4-12
A mixture of 1 or 3 (1.22 g, 5 mmol) or 2 (1.28 g, 5
mmol), a bidentate nucleophile (DL-valinol 0.77 g, 1-amino-
3-propanol 0.56 g, 2-aminothiophenol 0.94 g, 7.5 mmol) or
diexo-3-aminobicylo[2.2.1]heptane-2-hydrazide (1.27 g, 7.5
1
ppm) is absent in the H NMR spectrum of 10. In this com-
pound, two each of the annelational H’s must lie opposite to
Table 3. Physical and Analytical Data on Compounds 4-12
Analysis
Compd.
Mp. (°C)
Yield (%)
Formula (Mw.)
Found %
H
Calcd %
C
N
C
H
N
4
5
154-156a
176-178a
165-167a
178-180b
252-254c
204-205b
241-243d
276-277b
296-297b
43
52
28
13
47
36
32
16
17
C20H27NO3 (329.44)
C18H23NO3 (301.39)
C21H21NO2S (351.47)
C20H19NOS (321.44)
C19H23NO3 (313.40)
C21H21NO2S (351.47)
C23H27N3O2 (377.49)
C23H27N3O2 (377.49)
C23H27N3O2 (377.49)
72.15
72.45
71.05
74.28
72.11
71.99
72.70
73.59
73.01
8.45
7.82
6.55
5.72
7.12
6.11
7.38
7.05
7.46
4.05
4.51
72.92
71.73
71.77
74.73
72.82
71.77
73.18
73.18
73.18
8.26
7.69
6.02
5.96
7.40
6.02
7.21
7.21
7.21
4.25
4.65
6
3.81
3.99
7
4.15
4.36
8
4.58
4.47
9
3.87
3.99
10
11
12
10.88
11.18
10.79
11.13
11.13
11.13
Crystallization solvent: aEt2O. – bEtOAc. – cEtOH. – di-Pr2O.

Preparation and Structures of Isoindolone- or Pyrimidone-Condensed
Letters in Organic Chemistry, 2009, Vol. 6, No. 3
257
mmol), and 0.04 g PTSA in xylene (15 mL) was refluxed for
10 h. Monitoring by TLC: aluminium sheets, silica gel 60
Cambridge Crystallographic Data Centre, Union Road,
Cambridge CB2 1EZ, UK; Fax: (internat) + 44-1223-336-
033; E-mail: deposit@ccdc.cam.ac.uk].
F
254, EtOAc–n-hexane 2:1 for 4, 6, 7 and 9, EtOAc for 5, 8,
10, 11 and 12, developed in iodine vapour. After evapora-
tion, the residue was dissolved in CHCl3, transferred to a
silica gel column (Kieselgel 60 Merck, 0.040-0.063 mm) and
eluted with EtOAc-n-hexane (2:1) for 4 and 9, n-hexane-
EtOAc (2:1) for 10, n-hexane-EtOAc (1:1) for 6 and 7, and
EtOAc for 5, 8, 11 and 12. The residues of the eluates were
crystallized. Data on compounds 4-12 are listed in Table 3.
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X-Ray Study
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Crystal Data for 8
C19H23NO3, Mr = 313.38, triclinic, space group P-1 (no.
2), a = 8.2662(4), b = 10.7774(5), c = 10.7966(5) Å, ꢀ =
62.872(2), ꢁ = 70.659(3), ꢅ = 85.255(2)°, V = 805.05(7) Å3,
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Crystal Data for 11
C23H27N3O2, Mr = 377.48, triclinic, space group P-1 (no.
2), a = 9.5765(10), b = 9.8653(8), c = 10.7500(11) Å, ꢀ =
80.164(5), ꢁ = 72.851(5), ꢅ = 87.055(6)°, V = 956.19(16) Å3,
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Crystal Data for 12
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The structures were solved by a direct method, applying
the SHELXS-97 program [31]. Full matrix, least squares
refinements on F2 were performed [31]. In all cases, the CH
hydrogen atoms were included at fixed distances with fixed
displacement parameters from their host atoms. The OH hy-
drogen atoms were refined isotropically with fixed dis-
placement factors. The Figures were drawn with ORTEP-3
for Windows [32]. The deposition numbers CCDC 682347-
682350 contain the supplementary crystallographic data for
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