Convenient synthesis of more complex 2-substituted 4(3H)-quinazolinones via lithiation of 2-alkyl-4(3H)-quinazolinones

Article abstract of DOI:10.1135/cccc19990515

2-Methylquinazolin-4(3H)-one has been doubly lithiated, at nitrogen and in the 2-methyl group, with n-butylithium. The lithium reagent thus obtained reacts with a variety of electrophiles (iodomethane, D₂O, phenyl isocyanate, benzaldehyde, benzophenone, cyclopentanone, 2-butanone, carvone) to give the corresponding 2-substituted derivatives in very good yields. Reaction of the dilithio reagent with acetonitrile gives an α,β-unsaturated imine by tautomerization of the initial addition product. Double lithiation of 2-ethyl-and 2-propyl-4(3H)-quinazolinones can be achieved using lithium diisopropylamide and the lithiated reagents thus obtained react with similar electrophiles to give the corresponding products in very good yields. In the reaction of the dianion of the 2-ethyl-4(3H)-quinazolinone with iodine, an oxidatively dimerised product was obtained. Lithiation of 2-unsubstituted 4(3H)-quinazolinone does not take place on C-2 under similar conditions.

Full text of DOI:10.1135/cccc19990515

Convenient Synthesis of Quinazolinones
515
CONVENIENT SYNTHESIS OF MORE COMPLEX
2-SUBSTITUTED 4(3H)-QUINAZOLINONES via LITHIATION
OF 2-ALKYL-4(3H)-QUINAZOLINONES
b
Keith SMITHa1, Gamal A. EL-HITIa2,*, Mohamed F. ABDEL-MEGEED
b
and Mohamed A. ABDO
Department of Chemistry, University of Wales Swansea+, Swansea SA2 8PP, U.K.;
a
1
2
e-mail: k.smith@swansea.ac.uk, g.el-hiti@swansea.ac.uk
b
Department of Chemistry, Faculty of Science, Tanta University, Tanta, Egypt
Received Jun e 30, 1998
Accepted Decem ber 11, 1998
2-Meth ylquin azolin -4(3H)-on e h as been doubly lith iated, at n itrogen an d in th e 2-m eth yl
group, with n -butylith ium . Th e lith ium reagen t th us obtain ed reacts with a variety of
electroph iles (iodom eth an e, D2O, ph en yl isocyan ate, ben zaldeh yde, ben zoph en on e, cyclo-
pen tan on e, 2-butan on e, carvon e) to give th e correspon din g 2-substituted derivatives in very
good yields. Reaction of th e dilith io reagen t with aceton itrile gives an α,β-un saturated im in e
by tautom erization of th e in itial addition product. Double lith iation of 2-eth yl- an d
2-propyl-4(3H)-quin azolin on es can be ach ieved usin g lith ium diisopropylam ide an d th e
lith iated reagen ts th us obtain ed react with sim ilar electroph iles to give th e correspon din g
products in very good yields. In th e reaction of th e dian ion of th e 2-eth yl-4(3H)-
quin azolin on e with iodin e, an oxidatively dim erised product was obtain ed. Lith iation of
2-un substituted 4(3H)-quin azolin on e does n ot take place on C-2 un der sim ilar con dition s.
Key w ord s: Quin azolin on es; Metallation ; Double lith iation ; Nucleoph ilic addition s; Keton es;
Carban ion s.
Th e rapid expan sion of th e list of fun ction alities capable of directin g
m etalation 1 h as m ade th is an im portan t strategy for th e syn th esis of
regiospecifically substituted ben zen es an d h eterocycles, but th ere are rela-
tively few reports con cern in g th e m etalation of pyrim idin e com poun ds2–13
.
In a con tin uation of our own in terests in h eterocyclic ch em istry14, particu-
larly in th e use of directed lith iation for h eterocyclic syn th esis15, we h ave
recen tly sh own th e lith iation of 3-acylam in o-, 3-am in o- an d 3-m eth yl-
am in o-2-alkyl-4(3H)-quin azolin on es16–18. Lith iation of 3-un substituted
+ Form erly kn own as th e Un iversity College of Swan sea.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

516
Smith, El-Hiti, Abdel-Megeed, Abdo:
2-m eth yl-4(3H)-quin azolin on e h as been reported previously19, but th e
lith iated species h as been reacted with on ly a lim ited ran ge of electroph iles
an d oth er 2-alkyl-4(3H)-quin azolin on es were n ot in vestigated at all. We
n ow report th e exten sion of th is approach to en com pass a wider ran ge of
products.
2-Alkyl-4(3H)-quin azolin on es (1–3) were prepared accordin g to th e liter-
ature procedures20. Double lith iation of 2-m eth yl-4(3H)-quin azolin on e (1)
occurred sm ooth ly an d rapidly with 2.2 equivalen ts of n -BuLi at –78 °C in
THF with n o n ucleoph ilic attack at eith er th e carbon yl or th e im in e group
of th e quin azolin on e rin g. In itial addition of n -BuLi provided a reddish so-
lution un til approxim ately on e equivalen t h ad been added, th en gave a
very deep red solution of th e dian ion 4 as th e rem ain in g n -BuLi was added.
Reaction s of th e dian ion 4 with a ran ge of electroph iles (iodom eth an e,
D2O, ph en yl isocyan ate, ben zaldeh yde, ben zoph en on e, cyclopen tan on e,
2-butan on e, R-(–)-carvon e) resulted in th e production of th e correspon din g
2-substituted 4(3H)-quin azolin on e derivatives 2 an d 5–11, respectively
(Sch em e 1) in very good yields (Table I).
OLi
O
N
O
(i) Electrophile
5
8
4
4a
8a
6
7
o
o
C
N
3
NH
Me
-78
C
20
NH
2
2.2 eq. n-BuLi
o
(ii) NH Cl aq.
4
THF, -78
C
N
CH Li
2
N
1
CH E
2
4
1
2, 5-11
SCHEME 1
Th e yields of isolated, purified products were extrem ely good. No N-sub-
stitution was observed, even with excess iodom eth an e (3.3 equivalen ts) as
electroph ile.
Reaction of th e dilith io reagen t of com poun d 1 with excess aceton itrile
(2 equivalen ts) proceeded in an in terestin g m an n er to give com poun d 12 in
72% isolated yield (Sch em e 2).
O
N
O
5
8
o
(i) n-BuLi, THF, -78
C
4
4a
8a
6
7
NH
C
3
NH
Me
NH
o
o
(ii) 2.2 eq. CH CN, -78
3
C
20 C
2
N
H
CH
Me
(iii) NH Cl aq.
4
1
1
12 (72%)
SCHEME 2
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Convenient Synthesis of Quinazolinones
517
Th e NMR an d m ass spectra con firm th e structure of com poun d 12. Th e
1H NMR spectrum sh ows th e presen ce of th ree exch an geable sin glets due to
th ree NH proton s wh ich reson ate in th e 11.40–9.26 ppm region , wh ile th e
13C NMR spectrum sh ows all th e appropriate carbon reson an ces. Th e CI
m ass spectrum sh ows an in ten se pseudo m olecular ion peak (MH+) at m/z
202, an d th ere is a m olecular ion peak at m/z 201 in th e EI spectrum . Th e
accurate m ass of th e m olecular ion con firm s th e form ula as C11H11N3O. Th e
un usual stability of com poun d 12 is presum ably a result of in tram olecular
h ydrogen bon din g.
Atten tion was n ext turn ed to lith iation of 2-eth yl-4(3H)-quin azolin on e (2)
an d 2-propyl-4(3H)-quin azolin on e (3). It was h oped th at lith iation would
take place as for com poun d 1, wh ich would suggest th at th e process was
toleran t of a variety of prim ary alkyl groups at position 2, but attem pts to
lith iate com poun d 2 with n -BuLi gave on ly low yields of th e products of re-
action with a n um ber of electroph iles (D2O, Ph 2CO an d MeI). However,
successful lith iation was ach ieved with 2.2 equivalen ts of LDA in THF at
TABLE I
Products from th e reaction s of th e dilith io reagen t 4 with electrophiles according to Schem e 1a
Com poun d
Electroph ile
E
Yieldb, %
2
5
6
7
8
MeI
Me
D
89
90
80
77
79
D2O
Ph NCO
Ph CHO
Ph 2CO
Ph NHCO
Ph CH(OH)
Ph 2C(OH)
(OH)
9
10
11
81
80
O
EtCOMe
EtC(OH)Me
2'
1'
82c
O
3'
(OH)
*
4'
6'
*
5'
a
b
c
See Experim en tal for details. Yields reported are for isolated, purified m aterials. NMR
spectra in dicate a m ixture of two diastereoisom ers in a ratio 1 : 4.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

518
Smith, El-Hiti, Abdel-Megeed, Abdo:
–78 °C un der n itrogen for 2 h . In itial addition of LDA provided a brown ish
yellow solution wh en approxim ately on e equivalen t h ad been added an d
th en a red solution of th e dilith io reagen t 13 or 14 as th e rem ain in g LDA
was added. Addition of iodom eth an e to 13 or 14 gave th e correspon din g
C-m eth yl com poun ds 15 an d 16 in 82 an d 79% isolated yields, respectively,
with n o N-substitution , as h ad been observed with dian ion 4. In order to
test th e versatility of th e in term ediate dilith io reagen ts 13 an d 14, th ey
were reacted with several electroph iles (Sch em e 3) to give th e correspon d-
in g 2-substituted 4(3H)-quin azolin on e derivatives 15–25 in very good
yields (Table II).
OLi
O
O
(i) Electrophile
o
5
8
4
4a
8a
6
7
o
N
3
NH
CH R
-78
C
20
C
NH
2
2.2 eq. LDA
o
(ii) NH Cl aq.
4
THF, -78
C
N
CHLi
R
N
N
1
CHR
E
2
2 R = Me
3 R = Et
13 R = Me
14 R = Et
15-25
SCHEME 3
TABLE II
Products from th e reaction s of th e dilith io reagen ts 13 an d 14 with electroph iles accordin g
to Sch em e 3a
Com poun d
R
Electroph ile
E
Yieldb, %
15
16
17
18
19
20
21
22
23
24
25
Me
Et
MeI
Me
Me
D
82
MeI
79
Me
Et
D2O
87
D2O
D
77
Me
Et
Ph 2CO
Ph 2CO
Ph COMe
Ph COMe
Ph CHO
Ph CHO
Ph NCO
Ph 2C(OH)
Ph 2C(OH)
Ph C(OH)Me
Ph C(OH)Me
Ph CH(OH)
Ph CH(OH)
Ph NHCO
78
88
Me
Et
70
77c
73c
79c
62
Me
Et
Me
a
b
c
See Experim en tal for details. Yields reported are for isolated, purified m aterials. NMR
spectra in dicate a m ixture of two diastereoisom ers.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Convenient Synthesis of Quinazolinones
519
Th e NMR spectra of com poun ds 22–24 sh ow th e expected presen ce of
two racem ic diastereoisom ers in un equal proportion s. However, for com -
poun d 21 th e spectra in dicate on ly on e racem ic diastereoisom er, wh ich is
clearly n ot expected wh en two asym m etric cen tres are in troduced durin g
th e reaction . Sim ilar observation s h ave been m ade previously for
3-am in oquin azolin on e derivatives18. We are curren tly attem ptin g to estab-
lish th e cause of th e diastereoselectivity.
Reaction of th e dilith io reagen t of com poun d 2 with iodin e resulted in
oxidative dim erization to give com poun d 26 in 71% crude yield (Sch em e 4).
Th e EI spectrum of com poun d 26 sh ows an in ten se m olecular ion peak
(M+) at m/z 346. After extraction with h ot m eth an ol, th e yield was reduced
to 60%. 1H an d 13C NMR spectra of th e product, before or after wash in g
suggested th at it was a sin gle racem ic diastereoisom er. We h ave n ot deter-
m in ed wh ich on e because of th e low solubility of th e com poun d, wh ich
preven ted crystallisation to obtain suitable crystals for X-ray studies an d
also im paired th e use of a ch iral sh ift reagen t in NMR studies.
O
N
O
O
o
5
8
5'
8'
(i) 2.2 eq. LDA, THF, -78
o
C
4
4'
3'
HN
4a
8a
4'a
8'a
6
7
6'
7'
NH
Et
3
NH
o
(ii) 2.2 eq. I , -78
2
C
20 C
2
2'
N
1
CH CH
Me Me
N
1'
(iii) NH Cl aq.
4
2
26 (60%)
SCHEME 4
Atten tion was n ext turn ed to lith iation of 4(3H)-quin azolin on e itself, to
see if substitution of th e h ydrogen at position 2 could be ach ieved. It was
foun d th at th e double lith iation of 4(3H)-quin azolin on e did n ot take place
un der con dition s sim ilar to th ose used for lith iation of com poun ds 1–3
with n -BuLi an d LDA. No furth er attem pts were m ade to try to fin d con di-
tion s un der wh ich such lith iation s could be effected.
EXPERIMENTAL
Meltin g poin t determ in ation s were perform ed by th e open capillary m eth od usin g a
Gallen kam p m eltin g poin t apparatus an d are reported un corrected. Th e laboratories of th e
Un iversity of W ales Cardiff carried out m icroan alyses. IR spectra were recorded on
a
Perkin –Elm er 1725X spectrom eter. 1H an d 13C NMR spectra (ppm , δ-scale; J in Hz) were re-
corded on a Bruker AC spectrom eter operatin g at 400 MHz for 1H an d 100 MHz for 13C m ea-
surem en ts. Ch em ical sh ifts are reported relative to tetram eth ylsilan e. Assign m en ts of sign als
are based on couplin g pattern s an d expected ch em ical sh ift values an d h ave n ot been rigor-
ously con firm ed. Sign als with sim ilar ch aracteristics m igh t be in terch an ged. Low-resolution
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

520
Smith, El-Hiti, Abdel-Megeed, Abdo:
m ass spectra were recorded on a VG 12-253 spectrom eter, electron im pact (EI) at 70 eV an d
ch em ical ion ization (CI) by th e use of am m on ia as ion ization gas. Accurate m ass data were
obtain ed on a VG ZAB-E in strum en t. Colum n ch rom atograph y was carried out usin g Merck
Kieselgel 60 (230–400 m esh ). Lith ium diisopropylam ide, n -butyllith ium an d oth er ch em icals
were obtain ed from Aldrich Ch em ical Com pan y an d n -butyllith ium was estim ated prior to
use by th e m eth od of Watson an d Easth am 21. THF was distilled from sodium ben zoph en on e
ketyl. Oth er solven ts were purified by stan dard procedures22,23. Th e IR spectra were in agree-
m en t with th e assign ed structure.
2-Substituted 4(3H)-Quin azolin on es 2 an d 5–12. Gen eral Procedure
A 1.6 M solution of n -BuLi (2.75 m l, 4.4 m m ol) was added in a dropwise m an n er to a stirred
solution of 1 (0.32 g, 2.0 m m ol) in an h ydrous THF (40 m l) m ain tain ed at –78 °C un der n i-
trogen . Form ation of th e dian ion was observed as a very deep red solution . Th e m ixture was
stirred at –78 °C for an addition al 1 h , after wh ich an electroph ile (2.2 m m ol), in THF (8 m l)
if solid, oth erwise n eat, was added. Th e m ixture was stirred for 2 h , th en rem oved from th e
coolin g bath an d allowed to warm to room tem perature, diluted with eth yl acetate (20 m l)
an d quen ch ed with aqueous saturated am m on ium ch loride solution (20 m l). Th e organ ic
layer was wash ed with water (2 × 20 m l), dried (MgSO4) an d evaporated un der reduced pres-
sure. Th e products were recrystallized from m eth an ol to give th e yields quoted in Table I.
2-Ethyl-4(3H)-quinazolinone (2): m .p. 236 °C (ref.20 gives m .p. 235 °C).
2-Monodeuteriomethyl-4(3H)-quinazolinone (5): m .p. 238–239 °C. EIMS, m/z: 161. 1H NMR
(DMSO-d6): 12.21 s, exch ., 1 H (NH); 8.07 d, 1 H, J = 7.9 (H-5); 7.74 t, 1 H, J = 7.9 (H-7);
7.54 d, 1 H, J = 7.9 (H-8); 7.42 t, 1 H, J = 7.9 (H-6); 2.34 1 : 1 : 1 t, 2 H, J = 2.2 (CH2D).
13C NMR (DMSO-d6): 161.63 s (C-4), 154.03 s (C-2), 148.80 s (C-8a), 133.96 d (C-7), 126.35 d
(C-5), 125.58 d (C-6), 125.53 d (C-8), 120.62 s (C-4a), 21.31, 21.26, 20.87 1 : 1 : 1 t (CH2D).
HRMS: for C9H7N2OD calculated: 161.0699; foun d: 161.0699. An alysis: for C9H7N2OD
(161.2) calculated: 67.07% C 5.63% H, 17.38% N; foun d: 67.00% C, 5.54% H, 17.33% N.
2-[(Phenylamino)carbonylmethyl]-4(3H)-quinazolinone (6): m .p. >250 °C. EIMS, m/z: 279.
1H NMR (DMSO-d6): 12.33 s, exch ., 1 H (NH); 10.27 s, exch ., 1 H (Ph NH); 8.11 d, 1 H, J =
7.9 (H-5); 7.76 t, 1 H, J = 7.9 (H-7); 7.60 m , 3 H (H-8 an d H-2 of Ph ); 7.47 t, 1 H, J = 7.9
(H-6); 7.30 t, 2 H, J = 7.5 (H-3 of Ph ); 7.04 t, 1 H, J = 7.5 (H-4 of Ph ); 3.78 s, 2 H (CH2).
13C NMR (DMSO-d6): 165.58 s (Ph NHCO), 161.45 s (C-4), 152.01 s (C-2), 148.57 s (C-8a),
138.86 s (C-1 of Ph ), 134.07 d (C-7), 128.56 d (C-3 of Ph ), 126.62 d (C-5), 126.07 d (C-6),
125.67 d (C-8), 123.20 d (C-4 of Ph ), 120.94 s (C-4a), 118.97 d (C-2 of Ph ), 42.97 t (CH2).
HRMS: for C16H13N3O2 calculated: 279.1008; foun d: 279.1008. An alysis: for C16H13N3O2
(279.3) calculated: 68.81% C, 4.69% H, 15.04% N; foun d: 69.00% C, 4.47% H, 15.22% N.
2-(2-Hydroxy-2-phenylethyl)-4(3H)-quinazolinone (7): m .p. 204 °C. EIMS, m/z: 266. 1H NMR
(DMSO-d6): 12.19 s, exch ., 1 H (NH); 8.09 d, 1 H, J = 8.0 (H-5); 7.76 t, 1 H, J = 8.0 (H-7);
7.61 d, 1 H, J = 8.0 (H-8); 7.35 t, 1 H, J = 7.5 (H-2 of Ph ); 7.27–7.22 m , 4 H (H-6, H-3 an d
H-4 of Ph ); 5.54 s, exch ., 1 H (OH); 5.19 m , 1 H (CH); 2.90 m , 2 H (CH2). 13C NMR
(DMSO-d6): 161.65 s (C-4), 155.22 s (C-2), 148.80 s (C-8a), 144.89 s (C-1 of Ph ), 134.03 d
(C-7), 127.95 d (C-3 of Ph ), 126.87 d (C-4 of Ph ), 126.63 d (C-5), 125.74 d (C-6), 125.70 d
(C-8), 125.85 d (C-2 of Ph ), 120.87 s (C-4a), 70.69 d (CH-OH), 44.77 t (CH2). HRMS: for
C16H15N2O2 calculated: 267.1134; foun d: 267.1134. An alysis: for C16H14N2O2 (266.3) calcu-
lated: 72.17% C, 5.30% H, 10.52% N; foun d: 72.25% C, 5.46% H, 15.52% N.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Convenient Synthesis of Quinazolinones
521
2-(2,2-Diphenyl-2-hydroxyethyl)-4(3H)-quinazolinone (8): m .p. 178 °C (ref.19 gives 163–164 °C).
EIMS, m/z: 342. 1H NMR (DMSO-d6): 12.15 s, exch ., 1 H (NH); 8.01 d, 1 H, J = 7.9 (H-5); 7.70 t,
1 H, J = 7.9 (H-7); 7.53–7.11 m , 13 H (H-6, H-8, OH an d 2 Ph ); 3.64 s, 2 H (CH2). 13C NMR
(DMSO-d6): 166.85 s (C-4), 155.61 s (C-2), 147.36 s (C-8a), 146.59 s (C-1 of Ph ), 134.34 d
(C-7), 127.86 d (C-3 of Ph ), 126.54 d (C-4 of Ph ), 126.34 d (C-5), 126.20 d (C-6), 125.60 d
(C-8), 125.48 d (C-2 of Ph ), 120.59 s (C-4a), 76.84 s (C-OH), 43.76 t (CH2). HRMS: for
C22 H19N2O2 calculated: 343.1425; foun d: 343.1425. An alysis: for C22H18N2O2 (342.4) calcu-
lated: 77.16% C, 5.30% H, 8.19% N; foun d: 76.95% C, 5.28% H, 8.09% N.
2-[(1-Hydroxycyclopentyl)methyl]-4(3H)-quinazolinone (9): m .p. 158–159 °C. EIMS, m/z: 244.
1H NMR (CDCl3): 11.81 s, exch ., 1 H (NH); 8.26 d, 1 H, J = 8.0 (H-5); 7.76 t, 1 H, J = 8.0
(H-7); 7.67 d, 1 H, J = 8.0 (H-8); 7.49 t, 1 H, J = 8.0 (H-6); 4.74 s, exch ., 1 H (OH); 3.06 s, 2 H
(CH2); 1.88–1.71 m , 8 H ((CH2)4). 13C NMR (CDCl3): 163.43 s (C-4), 155.36 s (C-2), 148.67 s
(C-8a), 134.85 d (C-7), 127.12 d (C-5), 126.62 d (C-6), 126.27 d (C-8), 120.37 s (C-4a), 81.08 s
(C-OH), 44.95
t (CH2), 39.88, 23.73 2 t ((CH2)4). HRMS: for C14H17N2O2 calculated:
245.1290; foun d: 245.1290. An alysis: for C14H16N2O2 (244.3) calculated: 68.83% C, 6.60% H,
11.47% N; foun d: 68.69% C, 6.69% H, 11.60% N.
2-(2-Hydroxy-2-methylbutyl)-4(3H)-quinazolinone (10): m .p. 150–151 °C. EIMS, m/z: 232.
1H NMR (DMSO-d6): 11.77 s, exch ., 1 H (NH); 8.09 d, 1 H, J = 8.0 (H-5); 7.77 t, 1 H, J = 8.0
(H-7); 7.60 d, 1 H, J = 8.0 (H-8); 7.46 t, 1 H, J = 8.0 (H-6); 4.84 s, exch ., 1 H (OH); 2.75, 2.71
2 d, 2 H, J = 13.7 (CH2COH); 1.50 (2 overlappin g dq’s, 2 H, J = 7.5 an d 15.5 (CH2CH3); 1.16 s,
3 H, (CH3COH); 0.90 t, 3 H, J = 7.5 (CH3CH2). 13C NMR (DMSO-d6): 161.24 s (C-4), 155.46 s
(C-2), 148.35 s (C-8a), 134.11 d (C-7), 126.59 d (C-5), 125.88 d (C-6), 125.60 d (C-8), 120.77 s
(C-4a), 77.52 s (C-OH), 45.12 t (CH2COH), 34.39 t (CH2CH3), 25.95 q (CH3COH), 8.16 q
(CH3CH2). HRMS: for C13H17N2O2 calculated: 233.1290; foun d: 233.1290. An alysis: for
C13H16N2O2 (232.3) calculated: 67.22% C, 6.94% H, 12.06% N; foun d: 67.09% C, 7.02% H,
11.92% N.
2-[(1-Hydroxy-5-isopropenyl-2-methylcyclohex-2-en-1-yl)methyl]-4(3H)-quinazolinone (11): m .p.
65–67 °C. EIMS, m/z: 310. Com poun d 11 appears in its NMR spectra as a m ixture of two iso-
m ers, a an d b, in a ratio of 1 : 4. 1H NMR (CDCl3): 11a, 11.36 s, exch ., 1 H (NH); 8.27 d,
1 H, J = 7.9 (H-5); 7.77 t, 1 H, J = 7.9 (H-7); 7.68 d, 1 H, J = 7.9 (H-8); 7.47 t, 1 H, J = 7.9
(H-6); 5.69 m , 1 H (H-3′); 4.62 m , 2 H (CH2=C); 4.42 s, exch ., 1 H (OH); 3.40, 2.68 2 d, 2 H,
J = 14.6 (CH2); 2.40 m , 1 H (H-5′); 2.13 m , 1 H (1 H of H-4′); 2.03 m , 2 H (H-6′); 1.88 s, 3 H
(CH3); 1.68 m , 4 H (1 H of H-4′ an d CH3C=CH2); 11b, 11.67 s, exch ., 1 H (NH); 8.27 d, 1 H,
J = 7.9 (H-5); 7.77 t, 1 H, J = 7.9 (H-7); 7.68 d, 1 H, J = 7.9 (H-8); 7.47 t, 1 H, J = 7.9 (H-6);
5.57 m , 1 H (H-3′); 4.62 m , 2 H (CH2=C); 4.42 s, exch ., 1 H (OH); 3.26, 2.98 2 d, 2 H, J =
14.8 (CH2); 2.51 m , 1 H (H-5′); 2.17 m , 1 H (1 H of H-4′); 2.00 m , 2 H (H-6′); 1.84 s, 3 H
(CH3); 1.61 m , 4 H (1 H of H-4′ an d CH3C=CH2). 13C NMR (CDCl3): 11a, 163.07 s (C-4),
155.13 s (C-2), 148.59 s (C-8a), 148.44 s (C=CH2), 137.08 s (C-2′), 135.17 d (C-7), 127.15 d
(C-5), 126.68 d (C-6), 126.31 d (C-8), 124.99 d (C-3′), 120.75 s (C-4a), 109.48 t (CH2=C),
72.34 s (C-1′), 44.70
t (CH2), 40.60 t (C-6′), 36.97 d (C-5′), 30.93 t (C-4′), 20.65 q
(CH3C=CH2), 17.88 q (CH3); 11b, 163.12 s (C-4), 154.71 s (C-2), 148.71 s (C-8a), 148.33 s
(C=CH2), 137.08 s (C-2′), 134.85 d (C-7), 127.15 d (C-5), 126.68 d (C-6), 126.36 d (C-8),
124.99 d (C-3′), 120.75 s (C-4a), 109.33 t (CH2=C), 74.27 s (C-1′), 42.69 t (CH2), 40.66 t
(C-6′), 39.29 d (C-5′), 30.80 t (C-4′), 20.57 q (CH3C=CH2), 17.24 q (CH3). HRMS: for
C19H23N2O2 calculated: 311.1760; foun d: 311.1760. An alysis: for C19H22N2O2 (310.4) calcu-
lated: 73.52% C, 7.14% H, 9.03% N; foun d: 73.74% C, 7.39% H, 8.94% N.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

522
Smith, El-Hiti, Abdel-Megeed, Abdo:
2-(2-Iminopropylidene)-1,2-dihydro-4(3H)-quinazolinone (12): yield 72%; m .p. >250 °C.
EIMS, m/z: 201. 1H NMR (DMSO-d6): 11.40 s, exch ., 1 H (NHCO); 9.60 br s, exch ., 1 H (NH);
9.26 s, exch ., 1 H (NH=CH); 7.94 d, 1 H, J = 8.0 (H-5); 7.60 t, 1 H, J = 8.0 (H-7); 7.42 d, 1 H,
J = 8.0 (H-8); 7.19 t, 1 H, J = 8.0 (H-6); 4.62 s, 1 H (CH); 1.94 s, 3 H (CH3). 13C NMR
(DMSO-d6): 161.68 s (C-4), 157.19 s (C=NH), 155.22 s (C-2), 149.78 s (C-8a), 133.66 d (C-7),
125.51 d (C-5), 125.12 d (C-6), 122.87 d (C-8), 118.86 s (C-4a), 83.42 d (CH), 22.19 q (CH3).
HRMS: for C11H11N3O calculated: 201.0900; foun d: 201.0900. An alysis: for C11H11N3O
(201.2) calculated: 65.66% C, 5.51% H, 20.88% N; foun d: 65.53% C, 5.45% H, 20.83% N.
2-Substituted 4(3H)-Quin azolin on es 15–26. Gen eral Procedure
A 1.6 M solution of LDA in h eptan e (2.75 m l, 4.4 m m ol) was added in a dropwise m an n er to
a stirred solution of 2 or 3 (2.0 m m ol) in an h ydrous THF (40 m l) m ain tain ed at –78 °C un -
der n itrogen . Form ation of th e dian ion was observed as a very deep red solution . Th e m ix-
ture was stirred at –78 °C for 2 h , after wh ich an electroph ile (2.2 m m ol), as a solution in
THF (8 m l) if solid, was added. Th e m ixture was stirred for 4 h , th en rem oved from th e cool-
in g bath an d allowed to warm to room tem perature, diluted with eth yl acetate (30 m l) an d
quen ch ed with aqueous saturated am m on ium ch loride solution (25 m l). Th e organ ic layer
was wash ed with water (2 × 25 m l), dried (MgSO4) an d evaporated un der reduced pressure.
Th e products were recrystallised from m eth an ol to give th e yields recorded in Table II.
2-(1-Methylethyl)-4(3H)-quinazolinone (15): m .p. 229–231 °C. EIMS, m/z: 188. 1H NMR
(DMSO-d6): 12.13 s, exch ., 1 H (NH); 8.09 d, 1 H, J = 8.0 (H-5); 7.75 t, 1 H, J = 8.0 (H-7);
7.60 d, 1 H, J = 8.0 (H-8); 7.44 t, 1 H, J = 8.0 (H-6); 2.90 sept, 1 H, J = 6.9 (CH(CH3)2); 1.28 d,
6 H, J = 6.9 (CH(CH3)2). 13C NMR (DMSO-d6): 161.88 s (C-4), 161.38 s (C-2), 148.87 s (C-8a),
133.98 d (C-7), 126.87 d (C-5), 125.70 d (C-6), 125.57 d (C-8), 120.94 s (C-4a), 33.24 d
(CH(CH3)2), 20.31
q (CH(CH3)2). HRMS: for C11H12N2O calculated: 188.0949; foun d:
188.0949. An alysis: for C11H12N2O (188.2) calculated: 70.19% C, 6.43% H, 14.88% N; foun d:
70.21% C, 6.26% H, 15.00% N.
2-(1-Methylpropyl)-4(3H)-quinazolinone (16): m .p. 176–177 °C. EIMS, m/z: 202. 1H NMR
(DMSO-d6): 12.16 s, exch ., 1 H (NH); 8.11 d, 1 H, J = 8.0 (H-5); 7.77 t, 1 H, J = 8.0 (H-7);
7.62 d, 1 H, J = 8.0 (H-8), 7.46 t, 1 H, J = 8.0 (H-6); 2.69 sext, 1 H, J = 6.9 (CH); 1.82, 15.9 2
overlappin g m ′s, 2 H (CH2); 1.27 d, 3 H, J = 6.9 (CH3CH); 0.87 t, 3 H, J = 7.4 (CH3CH2).
13C NMR (DMSO-d6): 161.94 s (C-4), 160.87 s (C-2), 148.93 s (C-8a), 134.12 d (C-7), 126.91 d
(C-5), 125.79 d (C-6), 125.63 d (C-8), 120.91 s (C-4a), 40.34 d (CH), 27.49 t (CH2), 18.21 q
(CH3CH), 11.65 q (CH3CH2). HRMS: for C12H14N2O calculated: 202.1106; foun d: 202.1106.
An alysis: for C12H14N2O (202.3) calculated: 71.26% C, 6.98% H, 13.85% N; foun d: 71.09% C,
6.95% H, 13.66% N.
2-(1-Monodeuterioethyl)-4(3H)-quinazolinone (17): m .p. 235 °C. EIMS, m/z: 175. 1H NMR
(DMSO-d6): 12.15 s, exch ., 1 H (NH); 8.08 d, 1 H, J = 8.1 (H-5); 7.75 t, 1 H, J = 8.1 (H-7);
7.58 d, 1 H, J = 8.1 (H-8); 7.43 t, 1 H, J = 8.1 (H-6); 2.63 m , 1 H (CHD); 1.27 m , 3 H (CH3).
13C NMR (DMSO-d6): 161.74 s (C-4), 158.10 s (C-2), 148.95 s (C-8a), 133.96 d (C-7), 126.71 d
(C-5), 125.63 d (C-6), 125.59 d (C-8), 120.78 s (C-4a), 27.72, 27.52, 27.33 1 : 1 : 1 d (CH),
11.21 q (CH3). HRMS: for C10H9N2OD calculated: 175.0871; foun d: 175.0856. An alysis: for
C10H9N2OD (175.2) calculated: 68.54% C, 6.33% H, 16.00% N; foun d: 68.37% C, 6.21% H,
15.95% N.
2-(1-Monodeuteriopropyl)-4(3H)-quinazolinone (18): m .p. 207 °C. EIMS, m/z: 189. 1H NMR
(DMSO-d6): 12.16 s, exch ., 1 H, (NH); 8.07 d, 1 H, J = 8.0 (H-5); 7.74 t, 1 H, J = 8.0 (H-7);
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Convenient Synthesis of Quinazolinones
523
7.58 d, 1 H, J = 8.0 (H-8); 7.44 t, 1 H, J = 8.0 (H-6); 2.57 m , 1 H (CHD); 1.75 m , 2 H (CH2);
0.94 t, 3 H, J = 7.3 (CH3). 13C NMR (DMSO-d6): 161.76 s (C-4), 157.16 s (C-2), 148.91 s
(C-8a), 134.08 d (C-7), 126.90 d (C-5), 125.74 d (C-6), 125.59 d (C-8), 120.76 s (C-4a), 36.30,
35.97, 35.77 1 : 1 : 1 d (CH), 120.18 t (CH2), 13.54 q (CH3). HRMS: for C11H11N2OD calcu-
lated: 189.1012; foun d: 189.1012. An alysis: for C11H11N2OD (189.2) calculated: 69.80% C,
6.93% H, 14.81% N; foun d: 69.77% C, 6.88% H, 14.77% N.
2-[1-(Diphenylhydroxymethyl)ethyl]-4(3H)-quinazolinone (19): m .p. 181–182 °C. EIMS, m/z:
356. 1H NMR (DMSO-d6): 12.01 s, exch ., 1 H (NH); 8.08 d, 1 H, J = 8.0 (H-5), 7.70–7.00 m ,
14 H (H-6, H-7, H-8, OH an d 2 Ph ); 4.10 q, 1 H, J = 6.9 (CH); 1.29 d, 3 H, J = 6.9 (CH3).
13C NMR (DMSO-d6): 161.85 s (C-4), 161.12 s (C-2), 148.01, 147.52 2 s (C-1 of Ph ), 145.27 s
(C-8a), 134.08 d (C-7), 127.94, 127.82 2 d (C-3 of Ph ), 126.36 d (C-5), 126.18, 125.98 2 d
(C-4 of Ph ), 125.70 d (C-6), 125.68 d (C-8), 125.22, 125.06 2 d (C-2 of Ph ), 120.78 s (C-4a),
78.80 s (C-OH), 44.35 d (CH), 15.43 q (CH3). HRMS: for C23H21N2O2 calculated: 357.1603;
foun d: 357.1603. An alysis: for C23H20N2O2 (356.4) calculated: 77.49% C, 5.66% H, 7.86% N;
foun d: 77.45% C, 5.65% H, 7.82% N.
2-[1-(Diphenylhydroxymethyl)propyl]-4(3H)-quinazolinone (20): m .p. 17–175 °C. EIMS, m/z:
370. 1H NMR (CDCl3): 12.66 s, exch ., 1 H (NH); 8.34 d, 1 H, J = 8.0 (H-5); 7.80 t, 1 H, J = 8.0
(H-7); 7.78–6.88 m , 12 H (H-6, H-8 an d 2 Ph ); 6.69 s, exch ., 1 H (OH); 3.89 dd, 1 H, J = 3.0
an d 11.0 (CH); 2.14, 1.80 2 m , 2 H (CH2); 0.87 t, 3 H, J = 7.5 (CH3). 13C NMR (CDCl3):
163.91 s (C-4), 159.56 s (C-2), 148.26, 147.34 2 s (C-1 of Ph ), 145.12 s (C-8a), 135.11 d
(C-7), 128.36, 128.04 2 d (C-3 of Ph ), 127.10 d (C-5), 126.83 d (C-6), 126.62 d (C-8), 126.47,
126.16 2 d (C-4 of Ph ), 125.19, 125.16 2 d (C-2 of Ph ), 120.17 s (C-4a), 79.56 s (C-OH),
53.82 d (CH), 23.49 t (CH2), 12.30 q (CH3). HRMS: for C24H23N2O2 calculated: 371.1760;
foun d: 371.1760. An alysis: for C24H22N2O2 (370.4) calculated: 77.81% C, 5.99% H, 7.56% N;
foun d: 77.80% C, 5.99% H, 7.71% N.
2-(2-Hydroxy-1-methyl-2-phenylpropyl)-4(3H)-quinazolinone (21): m .p. 139–141 °C. EIMS,
m/z: 294. 1H NMR (CDCl3): 11.75 s, exch ., 1 H (NH), 8.33 d, 1 H, J = 8.0 (H-5); 7.82 t, 1 H, J =
8.0 (H-7); 7.75 d, 1 H, J = 8.0 (H-8); 7.58 d, 2 H, J = 8.4 (H-2 of Ph ); 7.52 t, 1 H, J = 8.0 (H-6);
7.42 t, 2 H, J = 8.4 (H-3 of Ph ); 7.31 t, 1 H, J = 8.4 (H-4 of Ph ); 5.18 s, exch ., 1 H (OH); 3.25 q,
1 H, J = 7.1 (CH); 1.61 s, 3 H (CH3COH), 1.17 d, 3 H, J = 7.1 (CH3CH). 13C NMR (CDCl3):
163.46 s (C-4), 159.72 s (C-2), 148.65 s (C-1 of Ph ), 145.92 s (C-8a), 135.04 d (C-7), 128.34 d
(C-3 of Ph ), 127.25 d (C-4 of Ph ), 126.87 d (C-5), 126.82 d (C-6), 126.39 d (C-8), 124.84 d
(C-2 of Ph ), 120.84 s (C-4a), 75.81 s (C-OH), 49.55 d (CH), 30.11 q (CH3COH), 14.92 q
(CH3CH). HRMS: for C18H19N2O2 calculated: 295.1447; foun d: 295.1447. An alysis: for
C18H18N2O2 (294.3) calculated: 73.45% C, 6.16% H, 9.52% N; foun d: 73.42% C, 5.99% H,
9.41% N.
2-(1-Ethyl-2-hydroxy-2-phenylpropyl)-4(3H)-quinazolinone (22): m .p. 139–141 °C. EIMS, m/z:
308. Com poun d 22 appears in its NMR spectra as a m ixture of two isom ers, a an d b, in a ra-
tio of 1 : 3. 1H NMR (CDCl3): 22a, 11.72 s, exch ., 1 H (NH); 8.20 d, 1 H, J = 8.0 (H-5);
7.87–7.29 m , 8 H (H-5, H-6, H-8 an d Ph ); 5.05 s, exch ., 1 H (OH); 3.12 dd, 1 H, J = 5.8 an d
9.2 (CH); 2.22 m , 1 H, 1 H (1 H of CH2); 1.66 s, 3 H (CH3); 1.11 m , 1 H (1 H of CH2); 0.95 t,
3 H, J = 7.4 (CH3CH2); 22b, 11.83 s, exch ., 1 H (NH); 8.36 d, 1 H, J = 8.0 (H-5); 7.87–7.29 m ,
8 H (H-5, H-6, H-8 an d Ph ); 5.05 s, exch ., 1 H (OH); 3.04 dd, 1 H, J = 3.5 an d 11.5 (CH);
1.92 m , 1 H, 1 H (1 H of CH2); 1.51 s, 3 H (CH3); 1.40 m , 1 H (1 H of CH2); 0.72 t, 3 H, J =
7.4 (CH3CH2). 13C NMR (CDCl3): 22a, 163.35 s (C-4), 158.90 s (C-2), 148.40 s (C-8a), 147.66 s
(C-1 of Ph ), 133.90 d (C-7), 128.33 d (C-3 of Ph ), 127.02 d (C-5), 126.57 d (C-6), 126.46 d
(C-8), 126.12 d (C-4 of Ph ), 124.49 d (C-2 of Ph ), 120.17 s (C-4a), 75.99 d (C-OH), 56.21 d
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

524
Smith, El-Hiti, Abdel-Megeed, Abdo:
(CH), 27.59 q (CH3), 22.17 t (CH2), 12.33 q (CH3CH2); 22b, 163.39 s (C-4), 158.81 s (C-2),
148.61 s (C-8a), 146.23 s (C-1 of Ph ), 135.05 d (C-7), 128.33 d (C-3 of Ph ), 127.84 d (C-5),
127.35 d (C-6), 126.82 d (C-8), 126.37 d (C-4 of Ph ), 124.81 d (C-2 of Ph ), 120.82 s (C-4a),
75.99 s (C-OH), 57.23 d (CH), 30.47 q (CH3), 22.33 t (CH2), 12.09 q (CH3CH2). HRMS: for
C19H21N2O2 calculated: 309.1603; foun d: 309.1603.
2-(2-Hydroxy-1-methyl-2-phenylethyl)-4(3H)-quinazolinone (23): m .p. 181–182 °C. EIMS, m/z:
280. Com poun d 23 appears in its NMR spectra as a m ixture of two isom ers, a an d b, in a ra-
tio of 1 : 2. 1H NMR (CDCl3): 23a, 12.05 s, exch ., 1 H (NH); 8.03 d, 1 H, J = 8.0 (H-5); 7.73 t,
1 H, J = 8.0 (H-7); 7.59 d, 1 H, J = 8.0 (H-8); 7.48–7.13 m , 6 H (H-6 an d Ph ); 5.49 d, exch .,
1 H, J = 4.6 (OH); 4.99 dd, 1 H, J = 4.6 an d 10.9 (CHOH); 3.00 dq, 1 H, J = 6.9 an d 10.9
(CHCH3); 1.25 d, 3 H, J = 6.9 (CH3); 23b, 12.12 s, exch ., 1 H (NH); 8.11 d, 1 H, J = 8.0 (H-5);
7.76 t, 1 H, J = 8.0 (H-7); 7.63 d, 1 H, J = 8.0 (H-8); 7.48–7.13 m , 6 H (H-6 an d Ph ); 5.46 d,
exch ., 1 H, J = 4.2 (OH); 4.80 dd, 1 H, J = 4.6 an d 9.4 (CHOH); 3.00 dq, 1 H, J = 7.0 an d 9.4
(CHCH3); 0.96 d, 3 H, J = 7.0 (CH3). 13C NMR (CDCl3): 23a, 161.58 s (C-4), 158.99 s (C-2),
148.60 s (C-8a), 143.69 s (C-1 of Ph ), 133.99 d (C-7), 127.54 d (C-3 of Ph ), 127.25 d (C-5),
126.84 d (C-6), 126.64 d (C-4 of Ph ), 125.74 d (C-8), 125.48 d (C-2 of Ph ), 120.79 s (C-4a),
74.06 d (CHOH), 46.13 d (CHCH3), 13.51 q (CH3); 23b, 161.69 s (C-4), 160.20 s (C-2),
149.01 s (C-8a), 143.78 s (C-1 of Ph ), 133.99 d (C-7), 127.96 d (C-3 of Ph ), 127.25 d (C-5),
126.84 d (C-6), 126.70 d (C-4 of Ph ), 125.74 d (C-8), 125.60 d (C-2 of Ph ), 121.03 s (C-4a),
76.07 d (CHOH), 46.84 d (CHCH3), 15.71 q (CH3). HRMS: for C17H17N2O2 calculated:
281.1290; foun d: 281.1290. An alysis: for C17H16N2O2 (280.3) calculated: 72.84% C, 5.75% H,
9.99% N; foun d: 72.88% C, 5.97% H, 10.06% N.
2-(1-Ethyl-2-hydroxy-2-phenylethyl)-4(3H)-quinazolinone (24): m .p. 72–74 °C. EIMS, m/z: 294.
Com poun d 24 appears in its NMR spectra as a m ixture of two isom ers, a an d b, in a ratio of
1 : 2. 1H NMR (CDCl3): 24a, 11.70 s, exch ., 1 H (NH); 8.29 d, 1 H, J = 8.0 (H-5); 7.79–7.13 m ,
8 H (H-6, H-7, H-8 an d Ph ); 5.11 br s, exch ., 1 H (OH); 4.85 br s, 1 H (CHOH); 3.02 m , 1 H
(CHCH2); 1.95 m , 1 H (1 H of CH2); 1.75 m , 1 H (1 H of CH2); 0.97 t, 1 H, J = 7.5 (CH3);
24b, 11.78 s, exch ., 1 H (NH); 8.24 d, 1 H, J = 8.0 (H-5); 7.79–7.13 m , 8 H (H-6, H-7, H-8
an d Ph ); 5.28 d, exch ., 1 H, J = 2.2 (OH); 4.78 d, 1 H, J = 7.2 (CHOH); 2.94 m , 1 H (CHCH2);
1.75 m , 1 H, (1 H of CH2); 1.25, 1.75 m , 1 H (1 H of CH2); 0.80 t, 1 H, J = 7.5 (CH3).
13C NMR (CDCl3): 24a, 163.53 s (C-4), 158.88 s (C-2), 148.69 s (C-8a), 142.76 s (C-1 of Ph ),
134.91 d (C-7), 128.36 d (C-3 of Ph ), 127.48 d (C-5), 127.78 d (C-4 of Ph ), 126.58 d (C-6),
126.26 d (C-8), 126.01 d (C-2 of Ph ), 120.67 s (C-4a), 75.05 d (CHOH), 54.00 d (CHCH2),
19.69 t (CH2), 11.90 q (CH3); 24b, 163.53 s (C-4), 157.96 s (C-2), 148.62 s (C-8a), 141.62 s
(C-1 of Ph ), 134.81 d (C-7), 128.26 d (C-3 of Ph ), 127.41 d (C-5), 127.20 d (C-4 of Ph ),
126.69 d (C-6), 126.33 d (C-8), 125.84 d (C-2 of Ph ), 120.80 s (C-4a), 74.20 d (CHOH), 53.43 d
(CHCH2), 24.94 t (CH2), 11.96 q (CH3). HRMS: for C18H19N2O2 calculated: 295.1447; foun d:
295.1442.
2-(1-Phenylaminocarbonylethyl)-4(3H)-quinazolinone (25): m .p. >250 °C. EIMS, m/z: 293.
1H NMR (DMSO-d6): 12.17 s, exch ., 1 H (NH); 10.11 s, exch ., 1 H (Ph NH); 8.09 d, 1 H, J =
8.0 (H-5); 7.76 t, 1 H, J = 8.0 (H-7); 7.61 m , 3 H (H-8 an d H-2 of Ph ); 7.47 t, 1 H, J = 8.0
(H-6); 7.28 t, 2 H, J = 7.6 (H-3 of Ph ); 7.03 t, 1 H, J = 7.6 (H-4 of Ph ); 3.90 q, 1 H, J = 7.1
(CH); 1.56 d, 3 H, J = 7.1 (CH3). 13C NMR (DMSO-d6): 168.81 s (CONHPh ), 161.54 s (C-4),
155.55 s (C-2), 148.47 s (C-8a), 139.02 s (C-1 of Ph ), 134.06 d (C-7), 128.48 d (C-3 of Ph ),
127.03 d (C-5), 126.13 d (C-6), 125.61 d (C-8), 123.13 d (C-4 of Ph ), 121.12 s (C-4a), 119.13 d
(C-2 of Ph ), 46.22 d (CH), 15.63 q (CH3). HRMS: for C17H16N3O2 calculated: 294.1243;
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Convenient Synthesis of Quinazolinones
525
foun d: 294.1243. An alysis: for C17H15N3O2 (293.3) calculated: 69.61% C, 5.15% H, 14.33% N;
foun d: 69.40% C, 5.10% H, 14.10% N.
2,2′-(2,3-Butanediyl)bis-4(3H)-quinazolinone (26): yield 60%, m .p. >250 °C. EIMS, m/z: 346.
1H NMR (DMSO-d6): 12.26 s, exch ., 2 H (2 NH); 8.02 d, 2 H, J = 8.0 (H-5 an d H-5′); 7.70 t,
2 H, J = 8.0 (H-7 an d H-7′); 7.51 d, 2 H, J = 8.0 (H-8 an d H-8′); 7.40 t, 2 H, J = 8.0 (H-6 an d
H-6′); 3.36 m , 2 H (2 CH); 1.30 d, 6 H, J = 6.4 (2 CH3). 13C NMR (DMSO-d6): 161.58 s (C-4
an d C-4′), 159.90 s (C-2 an d C-2′), 148.48 s (C-8a an d C-8a′), 134.10 d (C-7 an d C-7′),
126.69 d (C-5 an d C-5′), 125.87 d (C-6 an d C-6′), 125.54 d (C-8 an d C-8′), 120.67 s (C-4a
an d C-4a′), 41.20 d (CH), 15.40 q (CH3). HRMS: for C20H18N4O2 calculated: 346.1430; foun d:
346.1430. An alysis: for C20H18N4O2 (346.4) calculated: 69.34% C, 5.24% H, 16.18% N; foun d:
69.33% C, 5.03% H, 15.92% N.
We thank the EPSRC Mass Spectrometry Service, University of Wales Swansea, for recording mass
spectra for us. We also thank the EPSRC and the University of Wales for grants that enabled the pur-
chase of NMR equipment used in the course of this work. G. A. El-Hiti thanks the Egyptian Govern-
ment and the University of Wales Swansea for financial support and the Royal Society of Chemistry
for an international author grant.
REFERENCES
1. See, for example: a) Gschwend H. W., Rodriquez H. R.: Org. React. 1980, 26, 1; b) Slocum
D. W., Jennings C. A.: J. Org. Chem. 1976, 41, 3653; c) Beak P., Zajdel W. J., Reitz D. B.:
Chem. Rev. 1984, 84, 471; d) Snieckus V.: Chem. Rev. 1990, 90, 879; e) Führer W.,
Gschwend H. W.: J. Org. Chem. 1979, 44, 1133.
2. Strekowski L.: Rocz. Chem. 1974, 48, 2157.
3. Kauffmann T., Greving B., Köning J., Mitschker A., Woltermann A.: Angew. Chem., Int.
Ed. Engl. 1975, 14, 713.
4. Kress T. J.: J. Org. Chem. 1979, 44, 2081.
5. Kowalewski A., Strekowski L., Szajda M., Walenciak K., Brown D. J.: Aust. J. Chem. 1981,
34, 2629.
6. Radinov R., Haimova M., Simova E.: Synthesis 1986, 886.
7. Wada A., Yamamoto J., Kanatomo S.: Heterocycles 1987, 26, 585.
8. Plé N., Turck A., Heynderickx A., Quéguiner G.: J. Heterocycl. Chem. 1994, 31, 1311.
9. Turck A., Plé N., Mojovic L., Quéguiner G.: J. Heterocycl. Chem. 1990, 27, 1377.
10. Radinov R., Chanev C., Haimova M.: J. Org. Chem. 1991, 56, 4793.
11. Parkanyi C., Cho N. S., Yoo G. S.: J. Organomet. Chem. 1988, 1, 342.
12. Plé N., Turck A., Fiquet E., Quéguiner G.: J. Heterocycl. Chem. 1991, 28, 283.
13. Wada A., Yamamoto J., Hamoaka Y., Ohki K., Nagai S., Kanatomo S.: J. Heterocycl. Chem.
1990, 27, 1831.
14. See, for example: a) Smith K., Matthews I., Hulme N. M., Martin G. E.: J. Chem. Soc.,
Perkin Trans. 1 1986, 2075; b) Lindsay C. M., Smith K., Martin G. E.: J. Heterocycl. Chem.
1987, 24, 1357; c) Matthews I., Smith K., Martin G. E.: J. Chem. Soc., Perkin Trans. 1
1987, 2839; d) Smith K., Morris I. K., Owen P. G., Bass R. J.: J. Chem. Soc., Perkin Trans. 1
1988, 77; e) Smith K., James D. M., Mistry A. G., Bye M. R., Faulkner D. J.: Tetrahedron
1992, 48, 7479; f) El-Hiti G. A.: Bull. Chem. Soc. Jpn. 1997, 70, 2209; g) Abdel-Megeed M. F.,
Aly Y. L., Saleh M. A., Abdo I. M., El-Hiti G. A., Smith K.: Sulfur Lett. 1995, 19, 129.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

526
Smith, El-Hiti, Abdel-Megeed, Abdo:
15. See, for example: a) Smith K., Pitchard G. J.: Angew. Chem. 1990, 102, 298; b) Smith K.,
Pitchard G. J.: Angew. Chem., Int. Ed. Engl. 1990, 29, 282; c) Smith K., Lindsay C. M.,
Morris I. K., Matthews I., Pritchard G. J.: Sulfur Lett. 1994, 17, 197; d) Smith K., Lindsay C. M.,
Morris I. K: Chem. Ind. (London) 1988, 9302; e) Smith K., Anderson D. K., Matthews I.:
Sulfur Lett. 1995, 18, 79.
16. Smith K., El-Hiti G. A., Abdo M. A., Abdel-Megeed M. F.: J. Chem. Soc., Perkin Trans. 1
1995, 1029.
17. Smith K., El-Hiti G. A., Abdel-Megeed M. F., Abdo M. A.: J. Org. Chem. 1996, 61, 647.
18. Smith K., El-Hiti G. A., Abdel-Megeed M. F., Abdo M. A.: J. Org. Chem. 1996, 61, 656.
19. Murray T. P., Hay J. V., Protlock D. E., Wolfe J. F.: J. Org. Chem. 1974, 39, 595.
20. a) Bogert M. T., Gotthelf A. H.: J. Am. Chem. Soc. 1990, 26, 522; b) Patel V. S., Patel S. R.:
J. Indian Chem. Soc. 1965, 42, 531.
21. Watson S. C., Eastham J. F.: J. Organomet. Chem. 1967, 9, 165.
22. Vogel′s Textbook of Practical Organic Chemistry, 5th ed. Longman, Harlow 1989.
23. Perrin D. D., Armarego W. L. F.: Purification of Laboratory Chemicals, 3rd ed. Butterworth
Heinemann, Oxford 1988.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)