Synthesis of tetrahydrophthalazine and phthalamide (phthalimide) derivatives via palladium-catalysed carbonylation of iodoarenes

Article abstract of DOI:10.1016/j.tet.2011.09.095

1,2,3,4-Tetrahydrophthalazin-1-one and 1,2,3,4-tetrahydrophthalazin-1,4- dione derivatives were synthesised in high (up to 85%) and low yields using 2-iodobenzyl bromide and 1,2-diiodobenzene as bifunctional substrates, respectively. Iodoarenes, carbon monoxide and various hydrazine derivatives as N-nucleophiles were used in a three-component palladium-catalysed cascade hydrazinocarbonylation. A similar palladium-catalysed reaction, the aminocarbonylation of 1,2-diiodobenzene, resulted mainly in the formation of two types of major products depending on the amine N-nucleophiles: the use of primary amines yielded N-substituted phthalimides in double carbonylation, while secondary amines react with one of the iodoarene functionalities affording the corresponding 2-iodobenzamides. Due to double carbon monoxide insertion at one or both iodoarene functionalities, ketocarboxamide-carboxamide or bis-ketocarboxamide derivatives could be isolated by the modification of the reaction conditions. Some mechanistic details of the ring-closure reactions and the conditions leading to side-products are also discussed.

Full text of DOI:10.1016/j.tet.2011.09.095

Tetrahedron 67 (2011) 9122e9128
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of tetrahydrophthalazine and phthalamide (phthalimide) derivatives
via palladium-catalysed carbonylation of iodoarenes
*
ꢀ
€
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
Diana Marosvolgyi-Hasko, Andrea Petz, Attila Takacs, Laszlo Kollar
ꢀ
ꢀ
Department of Inorganic Chemistry, University of Pecs, H-7624 Pecs, PO Box 266, Hungary
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 10 June 2011
Received in revised form 29 August 2011
Accepted 20 September 2011
Available online 25 September 2011
1,2,3,4-Tetrahydrophthalazin-1-one and 1,2,3,4-tetrahydrophthalazin-1,4-dione derivatives were syn-
thesised in high (up to 85%) and low yields using 2-iodobenzyl bromide and 1,2-diiodobenzene as bi-
functional substrates, respectively. Iodoarenes, carbon monoxide and various hydrazine derivatives as N-
nucleophiles were used in a three-component palladium-catalysed cascade hydrazinocarbonylation. A
similar palladium-catalysed reaction, the aminocarbonylation of 1,2-diiodobenzene, resulted mainly in
the formation of two types of major products depending on the amine N-nucleophiles: the use of pri-
mary amines yielded N-substituted phthalimides in double carbonylation, while secondary amines react
with one of the iodoarene functionalities affording the corresponding 2-iodobenzamides. Due to double
carbon monoxide insertion at one or both iodoarene functionalities, ketocarboxamide-carboxamide or
bis-ketocarboxamide derivatives could be isolated by the modification of the reaction conditions. Some
mechanistic details of the ring-closure reactions and the conditions leading to side-products are also
discussed.
Keywords:
Aminocarbonylation
Hydrazinocarbonylation
Carbon monoxide
Palladium
Tetrahydrophthalazine
Amino acid
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
The synthesis of N-aryl-substituted phthalimides in palladium-
catalysed aminocarbonylation was described using 1,2-
Phthalazine and tetrahydrophthalazine skeletons, containing
a hydrazine moiety in the ring system, are incorporated in com-
pounds of biological importance, such as pseudopeptides1 and C-
nucleosides.2 A recent method uses microwave irradiation for the
synthesis of phthalazine-1,4-diones based on phthalic anhydride.3
The protonated forms of 1-hydrazinophthalazine and phthala-
zone hydrazone derivatives were also studied.4
The transition metal-catalysed processes, containing a key-step
of carbonylation of iodoarenes in the presence of hydrazine de-
rivatives, provide an excellent route to the above N-heterocycles.
The efficient synthesis of N-aminoisoindolone and phthalazone
derivatives from iodoarenes were reported recently, depending on
whether monosubstituted hydrazine or 1,2-disubstituted hydra-
zine was used,5 via a cascade process, involving the carbonylation
of an aryl iodide/Michael acceptor to give an acylpalladium species,
which is intercepted by a hydrazine nucleophile.
diiodobenzene and a range of 4-substituted anilines as N-nucleo-
philes.10 Substituted indenones were synthesised from the same
substratewith alkynes and carbon monoxide in the presence of nickel
carbonyl.11 Recently, high-yielding palladium-catalysed double car-
bonylation of ortho-dihaloarenes were carried out in phosphonium
salt ionic liquids resulting in N-substituted phthalimides.12
It should be noted, that 1,2-diiodobenzene, one of the substrates
used in our present study as well, is a building block in conven-
tional synthesis13,14 and a ligand in iridium-catalysed Nazarov cy-
clization.15,16 Its isomer, 1,4-diiodobenzene is widely used in
various homogeneous catalytic reactions, e.g., in Sonogashira cou-
pling,17 in a three-component domino Heck DielseAlder reaction,18
in homocoupling reaction19 and in single and double Suzu-
kieMiyaura coupling.20
Although it is well-known since the early discovery of Heck,21
that amides and esters could be obtained in high yields from aro-
matic iodides, nucleophiles (amines or alcohols, respectively) and
carbon monoxide in the presence of Pd(0) and Pd(II) catalysts, the
functionalization of bifunctional substrates still provide challenging
routes for the synthesis of derivatives of practical importance. In this
paper we describe the systematic investigation of the cyclo-
aminocarbonylation of bifunctional 2-iodobenzyl bromide and 1,2-
diiodobenzene substrates towards tetrahydrophthalazinone (tetra-
hydrophthalazindione) and phthalimide derivatives, respectively.
The palladium-catalysed hydrazinocarbonylation of steroidal
iodoalkenes, leading to cyclized derivatives, was studied also in our
group6e8 and reviewed recently.9
ꢀ
* Corresponding author. E-mail address: kollar@ttk.pte.hu (L. Kollar).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.09.095

€
ꢀ
D. Marosvolgyi-Hasko et al. / Tetrahedron 67 (2011) 9122e9128
9123
2. Results and discussion
O
I
CO, H2NNMe2 (e)
NH
2.1. Hydrazinocarbonylation of 2-iodobenzyl bromide leading
to 1,2,3,4-tetrahydrophthalazine-1-one
Br
NMe
Pd(OAc)2 / PPh3
2-Iodobenzyl bromide (1) was reacted with hydrazine de-
rivatives, such as methylhydrazine (a), phenylhydrazine (b), hy-
drazine (c), 1,2-dimethylhydrazine (d) and 1,1-dimethylhydrazine
(e) under atmospheric carbon monoxide pressure in DMF in the
presence palladium(0) catalysts generated in situ from palladiu-
m(II) acetate catalytic precursor (Schemes 1 and 3). It is worth
noting that although the reduction of Pd(II) precursors to Pd(0)
species has been proved in the presence of various phosphines
while they have been oxidised to P(V) derivatives (monophosphine
oxides or diphosphine oxide/hemioxide),22e25 the exact mecha-
nism of reduction under reductive conditions (carbon monoxide,
hydrazine or amine derivatives) is still not known.
1
2a
Pd(0)
- NEt3HI
+ CO
+ H2NNMe2
I
+ NEt3
I
- MeBr
Br-
NH2
NMe
NMe+2
NH2
Scheme 3. The hydrazinocarbonylation of 2-iodobenzyl bromide (1) with 1,1-
dimethylhydrazine (e).
O
O
used as the N-nucleophile, 2b and 3b was obtained in a ratio
of 25/75.
I
CO, RHNNH2
NH
NR
NR
NH
+
The formation of the tetrahydrophthalazinones can be inter-
preted by a simplified mechanism depicted in Scheme 2. The
hydrazines are benzylated by 1. In case of a the alkylation takes
place selectively on the more nucleophilic nitrogen bearing the
methyl substituent. A facile alkylation is observed also with d.
Unexpectedly, the benzylation of b with 1 occurs on both nitrogen
atoms. The (2-iodobenzyl)hydrazine derivatives react with the
coordinatively unsaturated palladium(0) complex, formed in situ,
resulting in arylepalladium intermediates (A, A0) in oxidative
addition. It is followed by carbon monoxide activation leading to
carbonyl complexes (B, B0) and the insertion of carbon monoxide
into the palladium(II)earyl bond. The formed palladium-acyl
derivatives (C, C0) are intercepted by the NH2 (a, b) or NHR (b,
d) fragment in intramolecular hydrazinocarbonylation yielding
the products (2, 3). The abstraction of HI with base (triethyl-
amine) provides the palladium(0) complex via reductive elimi-
nation step.
Br
Pd(OAc)2 / PPh3
1
2
3
a
b
R = Me
R = Ph
O
I
I
RHNNHR
CO
NR
NR
NRNHR
Br
Pd(OAc)2 / PPh3
4
1
1'
c
R = H
d
R = Me
Scheme 1. The synthesis of substituted 1,2,3,4-tetrahydrophthalazin-1-one derivatives
in the hydrazinocarbonylation of 2-iodobenzyl bromide with mono- and 1,2-
disubstituted hydrazines.
Highly selective reactions were observed with methylhydrazine
(a) and 1,2-dimethylhydrazine (d) resulting in the major formation
of 2a and 4d, respectively. Accordingly, both compounds were
isolated in high yields. However, when phenylhydrazine (b) was
The hydrazinocarbonylation with 1,1-dimethylhydrazine (e)
yielded the same product (2a) as methylhydrazine (a) (Scheme 3).
With the above reaction mechanism in hand, it means that the
I
1
Br
Et3N
H2NNHR
Et3N
H2NNHR
Et3NHBr
Et3NHBr
O
O
I
I
R
H
H
N
N
N
N
3
2
NRNH2
NHNHR
R
Et3NHI
Et3NHI
PdLn
PdLn
Et3N
2 L
2 L
2 L
Et3N
2 L
O
O
PdILn-2
NHNHR
PdILn-2
NRNH2
PdILn-2
NRNH2
PdILn-2
A'
A
C
NHNHR
C'
CO
CO
PdI(CO)Ln-2
NRNH2
PdI(CO)Ln-2
NHNHR
B
B'
Scheme 2. The simplified reaction mechanism of cyclo-hydrazinocarbonylation of 1 leading to tetrahydrophthalazinones.

€ ꢀ
D. Marosvolgyi-Hasko et al. / Tetrahedron 67 (2011) 9122e9128
9124
benzylation step occurred exclusively on the more nucleophilic
NMe2 nitrogen forming a quaternary salt. The loss of methyl iodide
yielded 1-(2-iodobenzyl)-1-methylhydrazine, which reacted as N-
nucleophile in carbonylative cyclization.
synthetic interest, the following points are worth to be addressed
from a catalytic point of view. (i) The reactivity of the two hydrazine
nucleophile is strikingly different: a is more reactive providing
carbonylated products even under atmospheric carbon monoxide
pressure, while d is unreactive under similar conditions (entries 1
and 3). (ii) The formation of hydrazinocarbonylated products is
accompanied by the formation of anthraquinone (8). (iii) Instead of
the complete formation of the ring-closure product (6d), a double
carbonylation resulting in ketohydrazide (70d) under higher carbon
monoxide pressure was observed (entries 4 and 5). (iv) Surpris-
ingly, the slight excess of methylhydrazine (a) could serve as methyl
source resulting in dimethylhydrazide (7d), which is the expected
product with d (entry 2).
Primary amines, such as tert-butylamine (f), methyl glycinate (g)
and methyl alaninate (h) were used in aminocarbonylation of 5
under atmospheric carbon monoxide pressure using the same
catalytic system as above (Scheme 5). N-Substituted phthalimides
(9feh) were obtained in moderate yields (Table 3). The isolated
yields are definitely lower than expected on the basis of previous
investigations carried out with aniline derivatives.9 A further
compound was isolated in all cases: while the formation of 9f was
accompanied with that of 11f (entry 1), the amino acid derivatives
(g and h) provided the iodobenzamide intermediates, 10g and 10h,
respectively (entries 2 and 3).
As shown in Table 1, excellent isolated yields were obtained with
hydrazines a and e due to the complete conversion resulting in
a sole product (entries 1 and 6). The less nucleophilic b led to two
isomers (2b and 3b) and much lower isolated yields (entry 2). The
ring-closure derivative of expected structure (4c) could not be
isolated when the parent hydrazine (c) was used as N-nucleophile
(entry 3). (Waxy polymeric material was obtained, except for 1,2-
bis(2-iodophenyl)ethane, the coupled product of 1.) Using 1,2-
dimethylhydrazine (d) and short reaction time, the benzylated in-
termediate (10d) could also be detected in addition to the final
phthalazinone product (4d) (entry 4). Interestingly, the double
demethylation of the hydrazine moiety was observed when in-
creased reaction times (168 h) were used, leading to 4c as minor
product (entry 5). Thus, 4c can be synthesised although in low
yields in a roundabout way by using d, but not in a direct pathway
in the presence of c as N-nucleophile.
Table 1
Palladium-catalysed hydrazinocarbonylation of 1 with hydrazine N-nucleophilesa
Entry
Hydrazine
R. timeb
[h]
Composition of the
r. mixturec [%]
Isolated yieldd
(amide) [%]
Three products were detected and isolated using secondary
amines, such as piperidine (i) and morpholine (j) in the amino-
carbonylation of 5 (Scheme 6). 2-Iodobenzamides (12) and the
ketocarboxamide-carboxamide derivatives (13) were formed and
isolated with both amines (Table 3, entries 4 and 5). The formation
of the latter compound can be rationalised via mono and double
carbon monoxide insertion into the palladiumearyl bond in
position-1 and position-2, respectively. Furthermore, bis(keto-
carboxamide) (14j) was also formed when j was used as the nu-
1
2
3
4
5
6
a
b
c
d
d
e
24
120
120
24
168
24
100 (2a)
85 (2a)
52 (3b)
d
25 (2b); 75 (3b)
0 (4c)
80 (4d), 20 (10d)
83 (4d), 17 (4c)
100 (2a)
66 (4d)
70 (4d)
82 (2a)
a
Reaction conditions: 0.025 mmol Pd(OAc)2, 0.05 mmol PPh3, 1 mmol substrate
(1), 1.2 mmol hydrazine derivative (aee), 0.5 mL triethylamine, 10 mL DMF; tem-
perature: 50 ꢀC, p(CO)¼1 bar.
b
Practically complete conversion (>99%) determined by GCeMS was obtained in
cleophile under higher pressure of CO (entries
6 and 7).
all cases.
c
Surprisingly, the presence of 1,2-bis-carboxamides was not ob-
served under the reaction conditions investigated.
Determined by GCeMS.
Based on the amount of the substrate (1) used.
d
2.2. Hydrazino- and aminocarbonylation of 1,2-
diiodobenzene
3. Conclusions
It has been shown that 2-iodobenzyl bromide can be transformed
via a palladium-catalysed intramolecular hydrazinocarbonylation to
give 1,2,3,4-tetrahydrophthalazine-1-one derivatives. The same re-
action with 1,2-diiodobenzene as substrate resulted in complicated
1,2-Diiodobenzene (5) was reacted with hydrazines (a, d) (Scheme
4), as well as primary (Scheme 5) and secondary amines (Scheme 6).
The three types of N-nucleophilesledtocompletelydifferentproducts.
I
O
O
NR'NHR''
R'
I
CO, R'HNNR"H
Pd(OAc)2 / PPh3
N
N
O
+
+
7
R"
I
o
NEt3, DMF, 50
C
I
O
O
8
5
6
O
R', R"
NR'NHR"
a
d
CH3, H
CH3, CH3
O
7'
Scheme 4. Hydrazinocarbonylation of 5.
The cyclo-hydrazinocarbonylation of 5 with hydrazine de-
rivatives (a and d) provided the expected phthalazindione de-
rivatives, 2-methyl-1,2,3,4-tetrahydrophthalazin-1,4-dione (6a)
and 2,3-dimethyl-1,2,3,4-tetrahydrophthalazin-1,4-dione (6d), re-
spectively. However, due to the formation of side-products, such as
monohydrazide (7), 2-ketohydrazide (70) and anthraquinone (8), as
well as to the low conversions, very low isolated yields were ob-
tained for 6a and 6d (Scheme 4, Table 2). In spite of the limited
reaction mixtures containing various hydrazides in addition to the
targeted 1,2,3,4-tetrahydrophthalazin-1,4-dione derivatives. The
aminocarbonylation of 1,2-diiodobenzene in the presence of primary
amines brought about the expected phthalimide, as well as iodo-
carboxamide and dicarboxamide. The same reaction in the presence
of secondary amines yielded iodocarboxamides and ketocarbox-
amides. Theappropriate choiceof the reaction conditionsenabled the
isolation of all above mentioned aminocarbonylated compounds.

€
ꢀ
D. Marosvolgyi-Hasko et al. / Tetrahedron 67 (2011) 9122e9128
9125
O
O
O
I
I
I
CO, H2NR
Pd(OAc)2 / PPh3
NHR
NHR
NR
+
+
NHR
o
NEt3, DMF, 50
C
O
O
10
5
9
11
R
f
t-Bu
g
CH2COOCH3
h
CH(CH3)COOCH3
Scheme 5. Aminocarbonylation of 5 using primary amines.
NR'R"
O
O
O
I
I
CO, HNR'R"
O
O
NR'R"
+
+
NR'R"
O
Pd(OAc)2 / PPh3
I
o
NEt3, DMF, 50
C
O
12
13
14
5
O
NR'R"
NR'R"
R', R"
i
j
-(CH2)5-
-(CH2)2O(CH2)2-
Scheme 6. Aminocarbonylation of 5 using secondary amines.
Table 2
Palladium-catalysed intramolecular hydrazinocarbonylation of 5 with hydrazine N-nucleophilesa
Entry
Hydrazine
p(CO) [bar]
R. time [h]
Composition of the r. mixtureb,c [%]
Isolated yieldd [%]
1
2
3
4
5
a
a
d
d
d
1
40
1
40
60
96
96
70
72
96
12 (6a), 88 (8)
6a (n.d.)
6a (15), 7a (40), 7d (20)
22 (6a), 50 (7a), 28 (7d)
0 (6d), 0 (7d), 0 (8)
16 (6d), 21 (7d), 7 (70d), 11 (8)
27 (6d), 25 (7d), 4 (70d), 13 (8)
6d (n.d.), 7d (18)
6d (n.d.), 7d (21)
a
Reaction conditions: 0.025 mmol Pd(OAc)2, 0.05 mmol PPh3, 1 mmol substrate (5), 1.2 mmol hydrazine derivative (a, d), 0.5 mL triethylamine, 10 mL DMF; temperature:
50 ꢀC.
b
c
The amounts of the products are indicated in the table, the rest is unconverted substrate.
Determined by GCeMS.
Based on the amount of the substrate (5) used.
d
Table 3
Palladium-catalysed aminocarbonylation of 5 with primary (f, g, h) and secondary (i, j) amines as N-nucleophilesa
Entry
Amine
p(CO) [bar]
R. time [h]
1/amine ratio
Composition of the r. mixtureb,c [%]
Isolated yieldd [%]
1
2
3
4
5
6
7
f
g
h
i
j
j
1
1
1
1
1
72
72
96
72
96
24
96
1/6
38 (9f), 62 (11f)
30 (9f), 51 (11f)
1/2.2
1/2.2
1/3
1/3
1/3
39 (9g), 53 (10g)
38 (9h), 49 (10h)
54 (12i), 40 (13i)
34 (12j), 57 (13j)
4 (12j), 31 (13j), 65 (14j)
47 (13j), 53 (14j)
31 (9g), 48 (10g)
32 (9h), 40 (10h)
46 (12i), 30 (13i)
30 (12j), 51 (13j)
n.d.(12j), n.d.(13j), 60(14j)
40 (13j), 48 (14j)
40
40
j
1/3
n.d.¼not determined (i.e., the target compound was not isolated as a pure substance).
a
Reaction conditions: 0.025 mmol Pd(OAc)2; 0.05 mmol PPh3, 1 mmol substrate (5); 0.5 mL triethylamine; 10 mL DMF; temperature: 50 ꢀC.
Determined by GCeMS.
The amounts of the products are indicated in the table, the rest is unconverted substrate.
Based on the amount of the substrate (5) used.
b
c
d
4. Experimental
coated with OV-1. The FT-IR spectra were taken in KBr pellets using
an IMPACT 400 spectrometer (Nicolet) applying a DTGS detector in
the region of 400e4000 cmꢁ1, the resolution was 4 cmꢁ1. The
amount of the samples was ca. 0.5 mg.
2-Iodobenzyl bromide (1), 1,2-diiodobenzene (5), hydrazine
derivatives (aee), amines (f, i, j), amino acid esters (g, h) were
purchased from SigmaeAldrich. The products of known structure
(2a,26 6d27 and 9f28) gave identical spectra with those given in the
literature. However, where further analytical data for the target
compounds are available, the isolated compounds with full char-
acterisation are given below.
4.1. General procedures
1H and 13C NMR spectra were recorded in CDCl3 on a Varian
Inova 400 spectrometer at 400.13 MHz and 100.62 MHz, re-
spectively. Chemical shifts
d are reported in parts per million rela-
tive to CHCl3 (7.26 and 77.00 ppm for 1H and 13C, respectively).
Elemental analyses were measured on an 1108 Carlo Erba appara-
tus. Samples of the catalytic reactions were analysed with a Hewlett
Packard 5830A gas chromatograph fitted with a capillary column

€ ꢀ
D. Marosvolgyi-Hasko et al. / Tetrahedron 67 (2011) 9122e9128
9126
4.2. Hydrazinocarbonylation of 2-iodobenzyl bromide (1)
under atmospheric carbon monoxide pressure
4.6. Characterisation of the products
4.6.1. 3-Methyl-1,2,3,4-tetrahydrophthalazin-1-one (2a). 1H NMR
In a typical experiment Pd(OAc)2 (5.6 mg, 0.025 mmol), PPh3
(13.1 mg, 0.05 mmol), 2-iodobenzyl bromide (297 mg, 1 mmol),
1.2 mmol of hydrazine derivative (aed) and 0.5 mL triethylamine
were dissolved in DMF (10 mL) under argon in a 100 mL three-
necked flask equipped with a gas inlet and a reflux condenser
with a balloon at the top. The atmosphere was changed to carbon
monoxide. The reaction was conducted for the given reaction time
upon stirring at 50 ꢀC and analysed by GCeMS. The mixture was
then concentrated and evaporated to dryness. The residue was
dissolved in chloroform (20 mL) and washed with water (3ꢂ20 mL).
The organic phase was dried over Na2SO4 and evaporated to
a crystalline material or to a waxy residue. All compounds were
subjected to column chromatography using the solvent mixture
indicated for the Rf values in Section 4.6.
(CDCl3)
t, J¼7.5 Hz, AreH), 7.42 (1H, t, J¼7.5 Hz, AreH), 7.20 (1H, d, J¼7.5 Hz,
AreH); 4.21 (2H, s, CH2), 2.61 (3H, s, Me). 13C NMR (CDCl3)
: 164.4,
(cmꢁ1)):
d
: 8.05 (1H, d, J¼7.5 Hz, AreH), 7.67 (1H, br s, NH), 7.53 (1H,
d
135.2, 133.0, 127.9, 127.1, 126.9, 126.1, 55.8, 45.0. IR (KBr,
n
3420 (v br, NH), 1670 (CON). MS m/z (rel int.): 162 (32, Mþ), 161
(100), 118 (20), 90 (46). Analysis calculated for C9H10N2O (162.19):
C, 66.65; H, 6.21; N, 17.27. Found: C, 66.47; H, 6.43; N, 17.48. Rf (4%
EtOH/CHCl3) 0.56. Beige crystals, mp 111 ꢀC. Yield: 130 mg (85%).
4.6.2. 3-Phenyl-1,2,3,4-tetrahydrophthalazin-1-one (2b). 1H NMR
(CDCl3)
d
: 8.03 (1H, d, J¼7.6 Hz, AreH), 7.60e7.40 (3H, m,
AreHþNH), 7.30e7.10 (3H, m, AreHþPh(meta)), 6.91 (1H, t,
J¼7.6 Hz, Ph(para)), 6.72 (2H, d, J¼7.6 Hz, Ph(ortho)), 4.62 (2H, s,
CH2). 13C NMR (CDCl3)
d: 167.6, 146.4, 135.9, 132.0, 129.0 (double
intensity), 128.2, 127.9, 124.1, 123.0, 116.6, 113.3 (double intensity),
51.1. IR (KBr,
n
(cmꢁ1)): 3254 (v br, NH), 1662 (CON). MS m/z (rel
4.3. Hydrazinocarbonylation of 1,2-diiodobenzene (5) under
atmospheric carbon monoxide pressure
int.): 224 (100, Mþ), 223 (34), 132 (25), 118 (9), 93 (29). Analysis
calculated for C14H12N2O (224.26): C, 74.98; H, 5.39; N, 12.49.
Found: C, 74.77; H, 5.53; N, 12.20. Rf (4% EtOH/CHCl3) 0.65. Orange
crystals, mp 152 ꢀC. Yield: 116 mg (52%).
In a typical experiment Pd(OAc)2 (5.6 mg, 0.025 mmol), PPh3
(13.1 mg, 0.05 mmol), 1,2-diiodobenzene (330 mg, 1 mmol),
1.2 mmol of hydrazine derivative (aed) and 0.5 mL triethylamine
were dissolved in DMF (10 mL) under argon in a 100 mL three-
necked flask equipped with a gas inlet, reflux condenser with
a balloon at the top. The atmosphere was changed to carbon
monoxide. The mixture was then concentrated and evaporated to
dryness. The residue was dissolved in chloroform (20 mL) and
washed with water (20 mL). The organic phase was thoroughly
washed twice with 5% aq HCl (20 mL), satd aq NaHCO3 (20 mL), satd
aq brine (20 mL), and dried over Na2SO4 and evaporated to a crys-
talline material or to a waxy residue. All compounds were subjected
to column chromatography using the solvent mixture indicated for
the Rf values in Section 4.6.
4 . 6 . 3 . 2 - P h e n yl - 1, 2 , 3 , 4 - t e t ra hy d r o p h t h a l a z i n - 1 - o n e
(3b). Compound 3b (characterised in a 60/40 mixture of 2b/3b): 1H
NMR (CDCl3):
d
: 7.91 (1H, d, J¼7.6 Hz, AreH), 7.62e7.40 (3H, m,
AreHþNH), 7.08e7.25 (3H, m, AreHþPh(meta)), 7.02 (2H, d,
J¼7.6 Hz, Ph(ortho)), 6.90 (1H, t, J¼7.6 Hz, Ph(para)), 4.86 (2H, s,
CH2). MS m/z (rel int.): 224 (77, Mþ), 223 (100), 118 (25), 90 (36).
4.6.4. 2,3-Dimethyl-1,2,3,4-tetrahydrophthalazin-1-one
NMR (CDCl3)
(4d). 1H
d
: 8.04 (1H, d, J¼7.5 Hz, AreH), 7.49 (1H, t, J¼7.5 Hz,
AreH), 7.40 (1H, t, J¼7.5 Hz, AreH), 7.17 (1H, d, J¼7.5 Hz, AreH),
4.21 (2H, s, CH2), 3.25 (3H, s, Me), 2.52 (3H, s, Me). 13C NMR (CDCl3)
d
: 163.1, 134.6, 132.4, 127.8, 127.4, 127.2, 125.8, 55.1, 40.5, 33.5. IR
(KBr,
n
(cmꢁ1)): 1643 (CON). MS m/z (rel int.): 176 (100, Mþ), 161
(29), 132 (13), 118 (79), 90 (60). Analysis calculated for C10H12N2O
(176.22): C, 68.16; H, 6.86; N, 15.90. Found: C, 68.07; H, 6.95; N,
15.66. Rf (50% EtOAc/CHCl3) 0.62. Pale-yellow crystals, mp 79 ꢀC.
Yield: 124 mg (70%).
4.4. Aminocarbonylation of 1,2-diiodobenzene (5) in the
presence of primary and secondary amines under
atmospheric carbon monoxide pressure
In a typical experiment Pd(OAc)2 (5.6 mg, 0.025 mmol), PPh3
(13.1 mg, 0.05 mmol),1,2-diiodobenzene (330 mg,1 mmol), 6 mmol
of tert-butylamine (f) (or 2.2 mmol of amino acid methyl ester
hydrochloride (g, h) or 3 mmol of secondary amine (i, j)) and 0.5 mL
triethylamine were dissolved in DMF (10 mL) under argon in
a 100 mL three-necked flask equipped with a gas inlet, reflux
condenser with a balloon at the top. The atmosphere was changed
to carbon monoxide. The reaction was conducted for the given
reaction time upon stirring at 50 ꢀC and analysed by GCeMS. The
work-up procedure was identical with those described in Section
4.3.
4.6.5. 2-Methyl-1,2,3,4-tetrahydrophthalazin-1,4-dione
NMR (CDCl3) : 8.10e7.78 (4H, m, AreH), 7.67 (1H, br s, NH), 3.12
(3H, s, Me). 13C NMR (CDCl3)
(6a). 1H
d
d
: 170.7, 169.2, 139.1, 135.1, 134.9, 128.4,
34.7. MS m/z (rel int.): 176 (19, Mþ), 148 (90), 130 (100), 104 (45), 76
(48). Rf (50% EtOAc/CHCl3) 0.56. Brown-yellow viscous material.
Yield: 27 mg (15%).
4.6.6. N-Methyl-2-iodobenzhydrazide (7a). 1H NMR (CDCl3)
d: 7.81
(1H, d, J¼7.8 Hz, AreH), 7.39 (1H, t, J¼7.8 Hz, AreH), 7.21 (1H, d,
J¼7.8 Hz, AreH), 7.05 (1H, t, J¼7.8 Hz, AreH), 2.82, 3.15 (3H, s, CH3)
(two singlets due to C(O)N hindered rotation), 1.62 (2H, br s, NH2).
13C NMR (CDCl3)
d: 170.7, 142.8, 139.1, 130.0, 128.4, 127.0, 92.4, 38.4,
34.7 (two methyl signals due to C(O)N hindered rotation). MS m/z
(rel int.): 276 (4, Mþ) 275 (51), 274 (70), 231 (100), 203 (32). Rf (50%
EtOAc/CHCl3) 0.72. Yellow viscous material. Yield: 117 mg (40%).
4.5. Aminocarbonylation of 1,2-diiodobenzene (5) in the
presence of primary and secondary amines under high carbon
monoxide pressure
4.6.7. 2,3-Dimethyl-1,2,3,4-tetrahydrophthalazin-1,4-dione
(6d). Compound 6d (characterised in a 1/2 mixture of 6d/7d): MS
m/z (rel int.): 190(Mþ)/60, 162/21, 132/12, 104/100, 76/51.
The above amounts of catalyst, substrate and amines were dis-
solved in DMF (10 mL) under argon in a 100 mL autoclave. The
atmosphere was changed to carbon monoxide and the autoclave
was pressurized to 40 bar with carbon monoxide. The reaction was
conducted for the given reaction time upon stirring at 50 ꢀC and
analysed by GCeMS. The work-up procedure was identical with
those described in Section 4.3.
4.6.8. N,N0-Dimethyl-2-iodobenzhydrazide (7d). 1H NMR (CDCl3)
d:
7.82e7.75 (2H, m, AreHþNH), 7.40 (1H, t, J¼7.4 Hz, AreH), 7.23 (1H,
d, J¼7.4 Hz, AreH), 7.07 (1H, d, J¼7.4 Hz, AreH), 3.01 (3H, s, CH3),
2.77 (3H, s, CH3). 13C NMR (CDCl3)
d: 168.1, 139.2, 133.3, 130.8, 127.2,

€
ꢀ
D. Marosvolgyi-Hasko et al. / Tetrahedron 67 (2011) 9122e9128
9127
123.6, 92.3, 36.1, 35.5. IR (KBr,
n
(cmꢁ1)): 1652 (CON). MS m/z (rel
EtOAc/CHCl3) 0.73. Pale-yellow powderlike crystals, mp 127 ꢀC.
Yield: 133 mg (40%).
int.): 290 (14, Mþ), 261 (41), 231 (100), 203 (30). Rf (50% EtOAc/
CHCl3) 0.40. Brown-yellow viscous material. Yield: 58 mg (21%).
4.6.16. N,N-(Pentan-1,5-diyl)-2-iodobenzamide
(CDCl3)
(12i). 1H
NMR
4 . 6 . 9 . N , N 0- D i m e t h yl - 2 - i o d o p h e n yl g l y o x y l h y d ra z i d e
(70d). Compound 70d (identified in the catalytic mixture obtained
in the hydrazinocarbonylation of 5 (Table 2, entry 4)) MS m/z (rel
int.): 318 (12, Mþ), 261 (19), 231 (100), 203 (32).
d
: 7.79 (1H, d, J¼7.5 Hz, AreH), 7.35 (1H, t, J¼7.5 Hz, AreH),
7.15 (1H, d, J¼7.5 Hz, AreH), 7.03 (1H, t, J¼7.5 Hz, AreH), 3.80e3.60
(2H, m, N(CH2)), 3.12e3.05 (2H, m, NCH2), 1.72e1.40 (6H, m,
(CH2)3). 13C NMR(CDCl3)
92.4, 47.9, 42.4, 26.2, 25.3, 24.4. IR (KBr,
d
: 169.1, 142.7, 139.1, 129.9, 128.2, 126.8,
(cmꢁ1)): 1636 (CON). MS
n
4.6.10. N-(tert-Butyl)phthalimide (9f). 1H NMR (CDCl3)
d, J¼3.5 Hz, AreH), 7.65 (2H, d, J¼3.5 Hz, AreH), 1.68 (9H, s, t-Bu).
d: 7.75 (2H,
m/z (rel int.): 315 (37, Mþ) 314 (100), 231 (65), 188 (24). Analysis
calculated for C12H14INO (315.15): C, 45.73; H, 4.48; N, 4.44. Found:
C, 45.57; H, 4.60; N, 4.18. Rf (50% EtOAc/CHCl3) 0.78. Brown viscous
material. Yield: 126 mg (40%).
13C NMR (CDCl3)
d: 169.6, 133.6, 132.1, 122.5, 57.8, 29.1. IR (KBr, n
(cmꢁ1)): 1637 (CON). MS m/z (rel int.): 203 (22, Mþ), 188 (100), 148
(66), 130 (73). Analysis calculated for C12H13NO2 (203.24): C, 70.92;
H, 6.45; N, 6.89. Found: C, 70.87; H, 6.65; N, 6.68. Rf (50% EtOAc/
CHCl3) 0.85. White needle-like crystals, mp 203 ꢀC. Yield: 61 mg
(30%).
4.6.17. 2-(N,N-Pentan-1,5-diylcarboxamido)-N,N-(pentan-1,5-diyl)-
phenylglyoxylamide (13i). 1H NMR (CDCl3)
d
: 7.88 (1H, d, J¼7.7 Hz,
AreH), 7.57 (1H, t, J¼7.7 Hz, AreH), 7.45 (1H, t, J¼7.7 Hz, AreH), 7.29
(1H, d, J¼7.7 Hz, AreH), 3.70 (2H, br s, N(CH2)), 3.61 (2H, br s,
NCH2), 3.33 (2H, t, J¼5.5 Hz, NCH2), 3.19 (2H, t, J¼5.5 Hz, NCH2),
4.6.11. N,N0-Bis(tert-butyl)-phthalamide (11f). 1H NMR (CDCl3)
7.54 (2H, d, J¼3.2 Hz, AreH), 7.42 (2H, d, J¼3.2 Hz, AreH), 6.63 (2H,
br s, NH), 1.45 (9H, s, t-Bu). 13C NMR (CDCl3)
: 168.6, 135.1, 129.7,
128.2, 51.9, 28.6. IR (KBr,
(cmꢁ1)): 3291 (br, NH), 1636 (CON). MS
d:
1.70e1.42 (12H, m, 2ꢂ (CH2)3). 13C NMR (CDCl3)
d: 191.2, 168.8,
d
164.8, 138.6, 133.7, 131.9, 131.7, 128.9, 127.2, 48.1, 47.0, 42.5, 42.2,
n
25.9, 25.7, 25.3, 25.2, 24.5, 24.3. IR (KBr, n
(cmꢁ1)): 1768 (CO), 1642
m/z (rel int.): 276 (5, Mþ) 204 (18), 148 (100), 130 (19). Analysis
calculated for C16H24N2O2 (276.38): C, 69.53; H, 8.75; N, 10.14.
Found: C, 69.37; H, 8.92; N, 9.92. Rf (50% EtOAc/CHCl3) 0.77. Yellow
powder, mp 224 ꢀC. Yield: 140 mg (51%).
(v br, CON). MS m/z (rel int.): 328 (2, Mþ), 245 (8), 216 (100), 160
(40). Analysis calculated for C19H24N2O3 (328.41): C, 69.49; H, 7.37;
N, 8.53. Found: C, 69.17; H, 7.55; N, 8.27. Rf (50% EtOAc/CHCl3) 0.56.
Yellow viscous material. Yield: 98 mg (30%).
4.6.12. N-(Methoxycarbonylmethyl)phthalimide
(CDCl3)
4.42 (2H, s, NCH2), 3.73 (3H, s, OCH3). 13C NMR (CDCl3)
(9g). 1H
NMR
4.6.18. N,N-(3-Oxa-pentan-1,5-diyl)-2-iodobenzamide
NMR (CDCl3)
(12j). 1H
d
: 7.85 (2H, d, J¼3.5 Hz, AreH), 7.74 (2H, d, J¼3.5 Hz, AreH),
d
: 7.82 (1H, d, J¼8.1 Hz, AreH), 7.39 (1H, t, J¼7.4 Hz,
d
: 167.6,
AreH), 7.19 (1H, d, J¼7.4 Hz, AreH), 7.08 (1H, t, J¼7.4 Hz, AreH),
3.90e3.70 (5H, m, O(CH2)2þNCH), 3.62e3.56 (1H, m, NCH), 3.26
167.4, 134.2, 131.9, 123.5, 52.6, 38.7. IR (KBr,
n
(cmꢁ1)): 1732 (COO),
1644 (CON). MS m/z (rel int.): 219 (9, Mþ), 160 (100), 133 (5), 104
(10). Analysis calculated for C11H9NO4 (219.20): C, 60.28; H, 4.14; N,
6.39. Found: C, 60.07; H, 4.33; N, 6.17. Rf (50% EtOAc/CHCl3) 0.83.
Yellow crystals, mp 96 ꢀC. Yield: 68 mg (31%).
(1H, br s, NCH), 3.18 (1H, br s, NCH). 13C NMR (CDCl3)
d: 169.3, 141.8,
139.2, 130.3, 128.4, 127.0, 92.4, 66.7, 66.6, 47.2, 41.9. IR (KBr,
n
(cmꢁ1)): 1623 (CON). MS m/z (rel int.): 317 (40, Mþ), 231 (100), 203
(28), 190 (9). Analysis calculated for C11H12INO2 (317.43): C, 41.66;
H, 3.81; N, 4.42. Found: C, 41.56; H, 3.93; N, 4.20. Rf (50% EtOAc/
CHCl3) 0.58. Yellow crystals, mp 82e83 ꢀC. Yield: 95 mg (30%).
4.6.13. N-(Methoxycarbonylmethyl)-2-iodobenzamide
NMR (CDCl3)
: 7.83 (1H, d, J¼8.2 Hz, AreH), 7.41e7.30 (2H, m,
AreH), 7.08 (1H, t, J¼7.6 Hz, AreH), 6.48 (1H, br s, NH), 4.18 (1H, s,
NCH2), 3.73 (3H, s, OCH3). 13C NMR (CDCl3)
: 169.9, 169.2, 141.2,
139.9, 131.3, 128.4, 128.1, 92.3, 52.4, 41.6. IR (KBr,
(cmꢁ1)): 3254
(10g). 1H
d
4.6.19. 2-(N,N-(3-Oxa-pentan-1,5-diylcarboxamido))-N,N-(3-oxa-
d
pentan-1,5-diyl)-phenylglyoxylamide (13j). 1H NMR (CDCl3)
d: 7.95
n
(1H, d, J¼7.7 Hz, AreH), 7.60 (1H, t, J¼7.7 Hz, AreH), 7.52 (1H, t,
J¼7.7 Hz, AreH), 7.29 (1H, d, J¼7.7 Hz, AreH), 3.65e3.80 (12H, m,
OCH2þNCH2), 3.50 (2H, br s, N(CH2)), 3.32 (2H, br s, NCH2). 13C NMR
(NH), 1732 (COO), 1646 (CON). MS m/z (rel int.): 319 (51, Mþ), 260
(27), 231 (100), 203 (26), 104 (6). Analysis calculated for C10H10INO3
(319.10): C, 37.64; H, 3.16; N, 4.39. Found: C, 37.57; H, 3.26; N, 4.18.
Rf (50% EtOAc/CHCl3) 0.72. Yellow crystals, mp 104 ꢀC. Yield: 153 mg
(48%).
(CDCl3)d:190.1,169.1,164.7,137.4,133.5,132.4,131.6,129.6,127.0, 66.6
(double intensity); 66.4 (double intensity); 47.8, 46.3, 42.2, 41.7. IR
(KBr, n
(cmꢁ1)): 1679 (CO),1635 (v br, CON). MS m/z (rel int.): 332 (2,
Mþ), 247 (5), 218 (100), 174 (9). Analysis calculated for C17H20N2O5
(332.36): C, 61.44; H, 6.07; N, 8.43. Found: C, 61.55; H, 6.23; N, 8.19. Rf
(6%EtOH/CHCl3)0.45. Yellowcrystals,mp129ꢀC.Yield:170mg(51%).
4.6.14. N-(1-(Methoxycarbonyl)-ethyl)phthalimide (9h). 1H NMR
(CDCl3)
d
: 7.84 (2H, d, J¼3.3 Hz, AreH), 7.73 (2H, d, J¼3.3 Hz, AreH),
4.97 (1H, q, J¼7.2 Hz, CHCH3), 3.72 (3H, s, OCH3), 1.68 (3H, d,
J¼7.2 Hz, CHCH3). 13C NMR (CDCl3)
d
: 170.1, 167.3, 134.1, 131.9, 123.5,
4.6.20. 2,20-(1,2-Phenylene)bis(1-morpholinoethane-1,2-dione)
52.7, 47.4, 15.2. IR (KBr,
n
(cmꢁ1)): 1747 (COO). MS m/z (rel int.): 233
(14j). 1H NMR (CDCl3)
d
: 7.81 (2H, d, AreH), 7.68 (2H, d, AreH), 3.70
(8H, br s, OCH2), 3.63 (8H, br s, NCH2).13C NMR (CDCl3)
: 191.7,163.6,
(cmꢁ1)): 1768 (CO),
(5, Mþ), 174 (100), 147 (25), 130 (30), 104 (12). Analysis calculated
for C12H11NO4 (233.22): C, 61.80; H, 4.75; N, 6.01. Found: C, 61.57; H,
4.83; N, 5.88. Rf (20% EtOAc/CHCl3) 0.85. Pale-yellow viscous ma-
terial. Yield: 75 mg (32%).
d
135.8,133.3, 131.3, 66.7, 66.5, 46.2, 42.1. IR (KBr,
n
1643 (v br, CON). MS m/z (rel int.): 360 (3, Mþ), 246 (60), 218 (41),147
(14); 114 (100). Analysis calculated for C18H20N2O6 (360.77): C, 59.99;
H, 5.59; N, 7.77. Found: C, 59.87; H, 5.73; N, 7.58. Rf (6% EtOH/CHCl3)
0.70. Brown viscous material. Yield: 216 mg (60%).
4.6.15. N-(1-(Methoxycarbonyl)-ethyl)-2-iodobenzamide (10h). 1H
NMR (CDCl3)
d
: 7.86 (1H, d, J¼8.1 Hz, AreH), 7.32e7.41 (2H, m,
AreH), 7.09 (1H, d, J¼7.5 Hz, AreH), 6.43 (1H, br s, NH), 4.78 (1H,
Acknowledgements
qi, J¼7.1 Hz, CHCH3), 3.78 (3H, s, OCH3), 1.55 (3H, d, J¼7.1 Hz,
CHCH3). 13C NMR (CDCl3)
d
: 173.1, 168.5, 141.4, 139.9, 131.3, 128.3,
The authors thank the Hungarian Research Fund (CK78553) and
Developing Competitiveness of Universities in the South Trans-
danubian Region (SROP-4.2.1.B-10/2/KONV-2010-0002) for the fi-
nancial support and Johnson Matthey for the generous gift of
palladium(II) acetate.
128.1, 92.3, 52.6, 48.5, 18.4. IR (KBr,
n
(cmꢁ1)): 3270 (v br, NH),
1739 (COO), 1648 (CON). MS m/z (rel int.): 333 (19, Mþ), 274 (73),
231 (100), 203 (23). Analysis calculated for C11H12INO (301.13): C,
43.88; H, 4.02; N, 4.65. Found: C, 43.67; H, 4.25; N, 4.58. Rf (20%

€
ꢀ
9128
D. Marosvolgyi-Hasko et al. / Tetrahedron 67 (2011) 9122e9128
14. Zhou, L. S.; Nakajima, K.; Kanno, K.; Tzakahashi, T. Tetrahedron Lett. 2009, 50,
References and notes
2722e2726.
15. Janka, M.; He, W.; Frontier, A. J.; Eisenberg, R. J. Am. Chem. Soc. 2004, 126,
6864e6865.
16. Janka, M.; He, W.; Frontier, A. J.; Flaschenriem, C.; Eisenberg, R. Tetrahedron
2005, 61, 6193e6206.
17. Terao, J.; Wadahama, A.; Fujihara, T.; Tsuji, Y. Chem. Lett. 2010, 39, 518e519.
18. Nuske, H.; Brase, S.; Kozhuskov, S. I.; Noltemeyer, M.; Es-Sayed, M.; de Mejiere,
A. Chem.dEur. J. 2002, 8, 2350e2369.
19. Luo, F. T.; Jeevanandam, A.; Basu, M. K. Tetrahedron Lett. 1998, 39, 7939e7942.
20. Sinclair, D. J.; Sherburn, M. S. J. Org. Chem. 2005, 70, 3730e3733.
21. Schoenberg, A.; Heck, R. F. J. Org. Chem. 1974, 39, 3327e3331.
22. Amatore, C.; Jutand, A.; M’Barki, M. A. Organometallics 1992, 11, 3009e3013.
23. Amatore, C.; Jutand, A.; Khalil, F.; M’Barki, M. A.; Mottier, L. Organometallics
1993, 12, 3168e3178.
1. Kline, T.; Mueller, L.; SieberMcMaster, E.; Lau, W. F.; Meyers, C. A. Int. J. Pept.
Protein Res. 1996, 47, 142e147.
2. Maeba, I.; Ishikawa, T.; Furukawa, H. Carbohydr. Res. 1985, 140, 332e335.
3. Mogilaiah, K.; Rani, J. U.; Babu, H. S. Indian J. Chem., Sect. B 2007, 46, 1361e1363.
4. Buzykin, B. I.; Stolyarov, A. P.; Bystrykh, N. N. Tetrahedron Lett. 1980, 21,
209e210.
5. Grigg, R.; Sridharan, V.; Shah, M.; Mutton, S.; Kilner, C.; MacPherson, D.; Milner,
P. J. Org. Chem. 2008, 73, 8352e8356.
ꢀ
ꢀ
6. Kollar, L.; Szarka, Z.; Horvath, J.; Tuba, Z. Tetrahedron Lett. 1997, 38, 4467e4468.
€
ꢀ
ꢀ
7. Skoda-Foldes, R.; Szarka, Z.; Kollar, L.; Dinya, Z.; Horvath, J.; Tuba, Z. J. Org. Chem.
1999, 64, 2134e2136.
8. Szarka, Z.; Skoda-Foldes, R.; Horvath, J.; Tuba, Z.; Kollar, L. Steroids 2002, 67,
581e586.
€
ꢀ
ꢀ
24. Amatore, C.; Carre, E.; Jutand, A.; M’Barki, M. A.; Meyer, G. Organometallics
1995, 14, 5605e5614.
9. Licandro, E.; Perdicchia, D. Eur. J. Org. Chem. 2004, 665e675.
10. Perry, R. J.; Turner, S. R. J. Org. Chem. 1991, 56, 6573e6579.
11. Liebeskind, L. S.; South, M. S. J. Org. Chem. 1980, 45, 5426e5429.
12. Cao, H.; Alper, H. Org. Lett. 2010, 12, 4126e4129.
13. Baumgartner, M. T.; Jimenez, L. B.; Pierini, A. B.; Rossi, R. A. J. Chem. Soc., Perkin
Trans. 2 2002, 1092e1097.
ꢀ
€
ꢀ
25. Csakai, Z.; Skoda-Foldes, R.; Kollar, L. Inorg. Chim. Acta 1999, 286, 93e97.
26. Kost, A. N.; Grabliauskas, K.; Vinokurov, V. G.; Zhakun, A. M. J. Prakt. Chem. 1970,
312, 542e544.
27. Nematollahi, J. J. Heterocyclic Chem. 1972, 9, 963e965.
28. Smith, L.; Emerson, O. H. J. Am. Chem. Soc. 1945, 67, 1862.