Reactions of a new family of amide derivatives of phenanthridinium azomethine ylides with dipolarophiles

Article abstract of DOI:10.1135/cccc19991993

Reaction of a series of N-alkyl- and N,N-dialkylbromoacetamides 1a-1e with phenanthridine afforded quaternary phenanthridinium salts 2a-2e. These compounds treated with triethylamine form azomethine ylides which undergo a cycloaddition reaction with activated C=C bond, giving 3-(N-alkylcarbamoyl)-1,2,3,12b-tetrahydropyrrolo[1,2-f]phenanthridines 3a-3e, 4c, 5c, 6c or 3-(N-alkylcarbamoyl)-2,3-dihydropyrrolo[1,2-f]phenanthridine 7c. Their stereochemistry was studied by NMR spectroscopy. The best results were obtained with fumaronitrile as a dipolarophile. It has been found that the ylides react in syn conformations but if 1-adamantyl moiety is bound to the ylide, it reacts in anti conformation, too. The azomethine ylides show a very poor reactivity towards dimethyl fumarate or dimethyl maleate. Yet we could prepare products for ylide bearing 1-adamantyl group.

Full text of DOI:10.1135/cccc19991993

Reactionsof New Family of Amide Derivatives
1993
REACTIONS OF A NEW FAMILY OF AMIDE DERIVATIVES
OF PHENANTHRIDINIUM AZOMETHINE YLIDES
WITH DIPOLAROPHILES
1
2,
Martin TRÁVNÍČEK , Jiří POSPÍŠIL and Milan POTÁČEK *
Department of Organic Chemistry, Faculty of Sciences, Masaryk University, Kotlářská 2,
1
2
611 37 Brno, Czech Republic; e-mail: martint@chemi.muni.cz, potacek@chemi.muni.cz
Received July 13, 1999
Accepted Septem ber 29, 1999
Dedicated to Professor Milan Kratochvíl on the occasion of his 75th birthday.
Reaction of a series of N-alkyl- an d N,N-dialkylbrom oacetam ides 1a–1e with ph en an th ridin e
afforded quatern ary ph en an th ridin ium salts 2a –2e. Th ese com poun ds treated with
trieth ylam in e form azom eth in e ylides wh ich un dergo a cycloaddition reaction with activated
C=C bon d, givin g 3-(N-alkylcarbam oyl)-1,2,3,12b-tetrah ydropyrrolo[1,2-f]ph en an th ridin es
3a–3e, 4c, 5c, 6c or 3-(N-alkylcarbam oyl)-2,3-dih ydropyrrolo[1,2-f]ph en an th ridin e 7c. Th eir
stereoch em istry was studied by NMR spectroscopy. Th e best results were obtain ed with
fum aron itrile as a dipolaroph ile. It h as been foun d th at th e ylides react in syn con form a-
tion s but if 1-adam an tyl m oiety is boun d to th e ylide, it reacts in anti con form ation , too.
Th e azom eth in e ylides sh ow a very poor reactivity towards dim eth yl fum arate or dim eth yl
m aleate. Yet we could prepare products for ylide bearin g 1-adam an tyl group.
Key w ord s: 1,3-Dipolar cycloaddition s; Stereoch em istry; NMR spectroscopy; Azom eth in e
ylides; Ph en an th ridin ium salts; Fum aron itrile; Dim eth yl fum arate; Dim eth yl m aleate;
5-Substituted 6-ph en an th ridon es.
Azom eth in e ylides derived from quatern ary ph en an th ridin ium salts h ave
been foun d to exh ibit versatility in 1,3-dipolar cycloaddition s actin g as
1,3-dipole with a series of activated alken es (dim eth yl fum arate, dim eth yl
m aleate an d fum aron itrile) affordin g pyrrolidin o[1,2-f]ph en an th ridin es1–6
.
Such cycloaddition s h ave been observed to proceed stereoselectively ac-
cordin gly to th e con certed tran sition structure.
In our laboratory a great effort h as been m ade to study stereoselectivity of
1,3-dipolar cycloaddition s of th ose azom eth in e ylides1–6
. Each of
1,3-dipoles un der exam in ation possessed a stabilisin g carbon yl group of an
ester attach ed to th e n egatively ch arged dipole part. In addition , literature
brin gs reports on a wide fam ily of sulfon ylacetam ide derivatives7–9. Never-
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

1994
Trávníček, Pospíšil, Potáček:
th eless, to th e best of our kn owledge, th ere is n on e paper con cern in g car-
bon yl stabilised ph en an th ridin ium based azom eth in e ylides with a sim ple
am ide group alth ough som e exam ples con cern in g oth er type of ylides h ave
been reported10. Th erefore, we were in terested in th eir preparation an d re-
activity with com m on dipolaroph iles, m ain ly from th e stereoselectivity
poin t of view. We wish ed to com pare th eir beh aviour with related com -
poun ds from our previous studies.
Th ere are dozen s of papers con cern in g preparation of N-alkyl- or
N,N-dialkyl brom oacetam ides. Cen tral to alm ost all of th em are classic
works by Weaver11 an d Drake12 th at were used or im proved by m an y oth er
auth ors13–22. N-Alkyl- or N,N-dialkylbrom oacetam ides are available th rough
a reaction of brom oacetyl brom ide or brom oacetyl ch loride an d appropriate
prim ary or secon dary am in es or am in e h ydroch lorides in in ert solven ts
(1,2-dich loroeth an e, CH2Cl2, ben zen e) at tem peratures ran gin g from –50 to
10 °C. In our work we used classic Weaver’s procedure. Brom oacetyl bro-
m ide reacts readily an d selectively on th e carbon yl carbon with a series of
prim ary an d secon dary aliph atic am in es in CH2Cl2 at –20 °C to form
N-alkyl- or N,N-dialkylbrom oacetam ides 1a–1e in acceptable yields
45–75%. Th e obtain ed N,N-dialkylbrom oacetam ides 1a, 1b an d N-alkyl-
O
R1
Br
O
O
N
N
R1
N
Ad
R2
N
N
H
Br
R2
MeOOC
COOMe
1a - 1e
2a - 2e
7c
R1
R2
O
cyclohexyl
i-Pr
1-adamantyl
benzyl
cyclohexyl
i-Pr
H
H
H
a
b
c
d
e
N
R1
N
R2
O
8b - 8e
(_)-1-(1-adamantyl)ethyl
+
brom oacetam ides 1c, 1d sh ow in FTIR spectra a very stron g ban d at
1 635–1 651 cm –1 correspon din g to th e am ide carbon yl stretch in g vibration
(am ide I). In addition , com poun ds 1c–1e exh ibit stron g ban ds at 3 300 cm –1
(N–H stretch in g vibration , am ide III) an d aroun d 1 500 cm –1 (am ide II). In
m ass spectra of com poun ds 1a–1e, m olecular ion s are always detectable;
th e paren t peaks are form ed from M+ peaks by loss of HBr (M+ – 80).
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Reactionsof New Family of Amide Derivatives
1995
Th e prepared brom oacetam ides un dergo a n ucleoph ilic substitution reac-
tion with ph en an th ridin e n itrogen . Such reaction s are described on ly in
our previous papers1–6. Reaction con dition s given in works dealin g with al-
kylation s of im in es23 or dih ydroisoch in olin es24–26 can be also used. With
ph en an th ridin e, wh en CH2Cl2 is used as a solven t, th e reaction at am bien t
tem perature takes several weeks up to m on th s, probably due to th e poor n i-
trogen n ucleoph ilicity. Yet by em ployin g a polar aprotic solven t aceto-
n itrile, we can sh orten reaction tim e up to th ree days at reflux tem pera-
ture5,6. Usin g th is procedure, quatern ary ph en an th ridin ium salts 2a–2e
were obtain ed in yields above 80%. Bein g often in soluble in th e reaction
m edium , th ey can be easily isolated. In IR spectra, th e quatern ary
ph en an th ridin ium salts 2a–2e sh ow a typical ban d 1 627 cm –1 belon gin g to
th e stretch in g vibration of CH=N+ group. In 13C NMR spectra th is group
with its ch em ical sh ift δ 157 ppm is difficult to detect due to bad relaxation
1
properties of CH=N+ carbon . H NMR ch em ical sh ifts of CH=N+ lie at very
low fields at 10.5 ppm , wh ich can be caused by th e presen ce of a full posi-
tive ch arge on th e n itrogen atom an d by th e used solven t. In m ass spectra,
we can fin d peaks M+ – 79, wh ich correspon d to th e cation ic part of th e
salts.
Wh en quatern ary ph en an th ridin ium salts 2a–2e are treated with a base
(trieth ylam in e), proton is abstracted from th e m eth ylen e attach ed to car-
bon yl, form in g a 1,3-dipole (azom eth in e ylide) (Sch em e 1). Th is species can
base
O
O
R1
N
R1
N
N
N
R2
Br
2a - 2e
R2
O
N
R1
N
O
N
R2
R2
1,3-dipole
N
syn-ylide
anti-ylide
R1
SCHEME 1
react in a cycloaddition reaction addin g on to an activated m ultiple bon d to
form a five-m em bered rin g (Sch em e 2). Such reaction s could proceed via
two extrem e m ech an ism s27,28, a con certed on e with reten tion of th e di-
polaroph ile con figuration or a two-step zwitterion ic m ech an ism wh ere th e
obtain ed products lose previous dipolaroph ile con figuration . Moreover,
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

1996
Trávníček, Pospíšil, Potáček:
ph en an th ridin e-based azom eth in e ylides can un dergo a con form ation
ch an ge th rough an equilibrium between syn an d anti form s by a possible
rotation on th e partial double bon d (Sch em e 1).
We were in terested in stereoch em istry of cycloadducts 3a–3e, 4c, 5c, 6c
(Sch em e 2) as a source of th e in form ation on th e tran sition structure ar-
ran gem en t. It also allows to m ake som e con clusion s about th e ylide con for-
m ation .
O
N
R2
N
R1
O
Y
Y
Y
N
R1
Et3N
+
3a - 3e, 5c
N
R2
Y
Br
2a - 2e
Y
O
3, 4
5, 6
CN
CO2Me
N
Ad
N
H
Y
Y
4c, 6c
Ad = 1-adamantyl
SCHEME 2
In situ gen erated azom eth in e ylides react with fum aron itrile to form
1,2,3,12b-tetrah ydropyrrolo[1,2-f]ph en an th ridin es 3a–3e, 4c, 5c, 6c. After
two-day h eatin g in argon atm osph ere, th e reaction is com pleted (TLC) an d
products are triturated with ben zen e (see Experim en tal). Th e products were
th en separated on a silica colum n by flash in g with an appropriate solven t
m ixture. Alth ough we h ave foun d in all th e reaction s th at two spots ap-
peared in TLC, th e m ore polar spot belon gs to an un iden tified decom posi-
tion product (accordin g to th e NMR an alysis) with th e on ly exception of
th e reaction of 2c wh en two diastereoisom ers 3c an d 4c could be isolated.
Relative con figuration s of h ydrogen atom s on C2–C3 an d C1–C12b atom s
were solved by com parin g couplin g con stan ts of th e com poun ds with th e
previous results1–6,29. It was foun d th at th e trans couplin g con stan t ran ges
from 3 to 5 Hz an d th e cis con stan t from 8 to 11 Hz. We assum e th at
1,3-dipolar cycloaddition s on azom eth in e ylides proceed via a con certed
m ech an ism with reten tion of th e dipolaroph ile con figuration . Th is could
3
be proved by th e J(1,2) couplin g con stan t provided th ey are sim ilar for ar-
3
bitrary con figuration s on C2–C3 an d C1–C12b atom s. Th e J(1,2) couplin g
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Reactionsof New Family of Amide Derivatives
1997
con stan t for com poun ds 3a–3e ran ges from 8 to 10 Hz an d for com poun d
4c is 8.2 Hz.
Th us, 1,3-dipolar cycloaddition s of azom eth in e ylides gen erated from
quatern ary ph en an th ridin ium salts 2a–2e yield pyrrolo[1,2-f]ph en an -
th ridin es 3a–3e, 4c, 5c an d 6c with preserved con figuration 1,2-trans. Th e
con figuration in com poun ds 3a–3e an d 5c was 1,12b-trans an d 2,3-cis an d
in com poun ds 4c an d 6c 1,12b-trans an d 2,3-trans. With com poun ds 2a,
2b, 2d an d 2e as a result of th e ylide addition in syn con form ation , on ly
on e product of addition was isolated in about 25% yields. However, th e
azom eth in e ylide from 2c adds on fum aron itrile both in syn an d anti form
as could be in ferred from th e product stereoch em istry. Th e reaction of 2c
gave excellen t yield of 95% related to sum of both products 3c an d 4c.
Besides fum aron itrile, we also tried to exam in e som e oth er types of di-
polaroph iles, particularly dim eth yl fum arate an d dim eth yl m aleate. Yet, to
our great surprise, th ese react with ylides m uch worse th an fum aron itrile,
givin g yields below 10%. Th e cycloadducts are con tam in ated with startin g
dipolaroph iles, wh ich im pedes furth er effort in th is field. On ly th e azo-
m eth in e ylide gen erated from quatern ary salt 2c an d dim eth yl fum arate us-
in g th e stan dard procedure gives two products 5c an d 6c in th e ratio 7 : 3,
h en ce in lower yields th an with 3c an d 4c. Wh en dim eth yl m aleate was
treated with th e ylide from 2c, we were on ly able to isolate 7c, th e oxida-
tion product on th e C1–C12b bon d wh ere th e stereoch em ical in form ation
about th e additon was lost. Th us we can n ot m ake an y con clusion s about
th e ylide con figuration .
Wh en azom eth in e ylides were gen erated from quatern ary salts 2b–2e by
treatin g with trieth ylam in e in th e absen ce of an y dipolaroph ile but in pres-
en ce of water (wet THF solution ), 5-substituted 6-ph en an th ridon es 8b–8e
were isolated as th e sole products in yields above 80%. Such com poun ds
were detected as by-products3,5, h en ce th is approach fully proved th eir for-
m ation as a con sequen ce of th e presen ce of water in th e reaction m edium .
5-Substituted 6-ph en an th ridon es 8b–8e are easily available by alkylation
of 6-phenanthridone with the appropriate halomethylcarbonyl compounds30–35
in th e presen ce of a base. Our procedure is an oth er con ven ien t way of th eir
preparation .
In NMR spectra of 5-substituted 6-ph en an th ridon es 8b–8d , two carbon yl
sign als can be foun d, first at 161–162 ppm correspon din g to th e lactam car-
bon yl (at C-6) an d th e oth er in th e ran ge of 164–168 ppm , wh ich corre-
spon ds to th e aliph atic am ide carbon yl. Neverth eless, in FTIR spectra, th e
sole ban d at 1 650 cm –1 can be foun d. In m ass spectra, th e m ost in ten sive
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1998
Trávníček, Pospíšil, Potáček:
peaks are th ose form ed from th e m olecular ion s by th e lost of NR1R2 or
O=CNR1R2 groups. Molecular ion s are also detectable.
We can con clude th at wh en th e ylide is gen erated by trieth ylam in e in
th e presen ce of dipolaroph ile th e 1,3-dipolar cycloaddition reaction pro-
ceeds in a way th at dipolaroph ile preserves its con figuration an d th e ylide
reacts in syn con form ation . Exception is th e reaction with th e ylide con -
tain in g adam an tyl skeleton boun d directly to th e am ide n itrogen atom . In
th at case, alth ough th e con figuration of th e dipolaroph ile is again pre-
served, th e relatively bulky group is push in g th e m olecule of th e ylide to
possess en ergetically m ore stable anti con form ation . Th e fact is reflected in
th e con figuration of th e products 3c, 4c or 5c an d 6c. Wh en th ere is a
spacer between th e am ide n itrogen atom an d th e adam an tyl group, as it is
in case of ylide form ed from ph en an th ridin ium 2e, th e form ed product
sh ows th at th e ylide reacts in syn con form ation . Th e sam e results were ob-
served irrespective of th e dipolaroph ile.
EXPERIMENTAL
Meltin g poin ts were m easured on a Kofler h ot stage (VEB Wagetech n ik Rapido 79/2106) an d
are in corrected. IR spectra were recorded on an FTIR Ati Mattson spectroph otom eter in KBr
pellets (ν in cm –1). NMR spectra were recorded on a Bruker Avan ce 500 Apparatus with
workin g frequen cy 500 MHz for 1H an d 125 MHz for 13C in CDCl3 (un less given oth erwise)
with TMS as an in tern al stan dard. Ch em ical sh ifts are given in ppm (δ-scale), couplin g con -
stan ts J in Hz. Mass spectra were recorded on a Fison s In strum en ts Trio 1000 spectrom eter in
positive m ode with EI ion isation . TLC was carried out on com m ercial silica foils (Silufol
Kavalier, Czech Republic). Colum n ch rom atograph y was carried out on Merck silica
(63–100 µm ). CH2Cl2 (On ex, Czech Republic) was dried over CaH2 an d distilled from it.
Trieth ylam in e was dried over KOH an d rectified on to
a colum n with BaO. Dicyclo-
h exylam in e, diisopropylam in e (Fluka) an d ben zylam in e (Reach im , Russia) were dried over
KOH an d distilled. Brom oacetyl brom ide (Fluka) was distilled un der reduced pressure (b.p.
35–37 °C/2 m m Hg) prior to use. Ph en an th ridin e, dim eth yl fum arate, dim eth yl m aleate an d
fum aron itrile (Aldrich ) were used as received.
Brom oacetam ides 1a–1e. Gen eral Procedure
Brom oacetyl brom ide (10.0 g, 50.0 m m ol) was added dropwise to a stirred solution of am in e
(100.0 m m ol) in dry CH2Cl2 cooled to tem peratures from –20 to –30 °C. A stron g exoth er-
m ic reaction occurred an d a wh ite solid precipitated. Reaction tem perature durin g th e addi-
tion of brom oacetyl brom ide sh ould n ot exceed –10 °C. After th e wh ole am oun t of
brom oacetyl brom ide was added, stirrin g at th e sam e tem perature con tin ued for addition al
20 m in . Fin ally, th e reaction m ixture was allowed to h eat to am bien t tem perature an d
ice-cold dilute h ydroch loric acid (1 : 1) was added. Th e organ ic layer was dried over an h y-
drous Na2SO4, evaporated in vacuo an d th e residue (sticky or solid) was crystallised from an
appropriate solven t.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Reactionsof New Family of Amide Derivatives
1999
N,N-Dicyclohexylbromoacetamide (1a). Yield 7.54 g (50%), colourless n eedles (cycloh exan e);
m .p. 121–122 °C. FTIR: 2 931, 2 858, 1 635 (C=O), 1 459, 1 371, 1 319, 1 114, 1 056, 1 000,
894. 1H NMR: 1.07–1.82 m , 20 H (10 × CH2); 2.90 m , 1 H (CH); 3.40 m , 1 H (CH); 3.77 s,
2 H (CH2Br). 13C NMR: 24.97; 25.05; 25.65; 26.25; 28.83; 29.24; 30.91 (7 × CH2); 56.21 (2 × CH);
165.30 (C=O). EI MS: 304 (M+ + 2, 5), 302 (M+, 5), 224 (5), 223 (19), 222 (100), 180 (5), 178 (8),
176 (7), 141 (9), 140 (74), 138 (15), 99 (5), 98 (22), 81(20), 84 (7), 83 (22), 81 (21), 56 (19), 56 (9),
55 (19).
N,N-Diisopropylbromoacetamide (1b). Yield 10.0 g (45%), colourless leaflets (ligroin ); m .p.
57–59 °C. FTIR: 2 967, 2 934, 2 873, 1 634 (C=O), 1 476, 1 373, 1 343, 1 212, 1 138, 1 098,
1 043, 912. 1H NMR: 1.23 d, 6 H, J = 4.5 (CH3); 1.36 d, 6 H, J = 4.5 (CH3); 3.42 m , 1 H (CH);
3.79 s, 2 H (CH2Br); 3.94 m , 1 H (CH). 13C NMR: 19.97; 20.53 (2 × CH3); 28.45 (CH2Br);
46.11; 50.21 (2 × CH); 165.17 (C=O). EI MS: 224 (M+ + 2, 3), 222 (M+, 3), 208 (32), 206 (30),
166 (43), 164 (45), 143 (7), 142 (100), 87 (4), 86 (95), 72 (3), 70 (12), 58 (22), 57 (18), 44 (16),
43 (18).
N-(1-Adamantyl)bromoacetamide (1c). Yield 8.2 g (63%), colourless n eedles (ben zen e); m .p.
124–126 °C. FTIR: 3 266 (NH, am ide III), 3 081, 2 904, 2 856, 1 656 (C=O), 1 563 (am ide II),
1 454, 1 402, 1 305, 1 211, 1 093, 998, 914, 750, 696. 1H NMR: 1.69 s, 6 H (3 × CH2); 2.02 s,
6 H (3 × CH2); 2.10 s, 3 H (3 × CH); 3.77 s, 2 H (CH2Br); 6.15 bs, 1 H (NH). 13C NMR: 30.01
(CH); 36.35 (CH2); 41.31 (CH2); 52.68 (Cq); 164.24 (C=O). EI MS: 273 (M+ + 2, 23), 271 (M+, 22),
216 (38), 214 (41), 194 (5), 193 (18), 192 (100), 151 (3), 150 (15), 137 (3), 136 (18), 135
(97), 123 (10), 121 (13), 119 (7), 107 (16), 105 (12), 95 (14), 94 (36), 93 (43), 92 (38), 91
(39), 81 (16), 79 (32), 77 (29).
N-Benzylbromacetamide (1d). Yield 8.4 g (75%), colourless n eedles (toluen e); m .p. 105–107 °C.
FTIR: 3 278 (NH, am ide III), 3 071, 3 017, 2 952, 1 646 (C=O), 1 553 (am ide II), 1 453,
1 421, 1 321, 1 210, 1 006, 749, 698. 1H NMR: 3.88 s, 2 H (CH2Br); 4.45 d, 2 H, J = 5.8
(CH2Ph ); 6.80 br s, 1 H (NH); 7.25–7.35 m , 5 H (CHar). 13C NMR: 28.87 (CH2Br); 44.09
(CH2Ph); 127.58; 127.63; 128.68 (3 × CHar); 137.24 (Cq ar); 165.28 (C=O). EI MS: 230 (M+ + 2, 5),
228 (M+, 5), 150 (3), 149 (8), 148 (100), 108 (5), 107 (58), 106 (45), 92 (8), 91 (71), 79 (32),
77 (27), 44 (8), 42 (16).
(±)-N-[1-(1-Adamantyl)ethyl]bromoacetamide (1e). Yield 9.48 g (60%), colourless n eedles
(toluene); m.p. 128–129 °C. FTIR: 3 294 (NH, amide III), 3 044, 2 902, 2 847, 1 647 (NH, amide I),
1 559 (am ide II), 1 449, 1 386, 1 340, 1 212, 1 160, 1 125, 1 023, 722. 1H NMR: 1.04 d, 3 H,
J = 6.9 (CHCH3); 1.36 d, 1 H, J = 6.9 (CHCH3); 1.53 dd, 6 H, J = 34.7, J = 12.0 (3 × CH2);
1.62 t, 6 H, J = 11.1 (3 × CH2); 1.99 s, 3 H (3 × CH); 3.63 m , 1 H (NH); 3.89 s, 2 H (CH2Br).
13C NMR: 14.12 (CH3); 28.13 (3 × CH); 34.70 (CH2Br); 35.74 (Cq); 36.86 (CH2); 38.21 (CH2);
53.90 (CH); 164.46 (C=O). EI MS: 302 (M+ + 2, 9), 300 (M+, 9), 223 (3), 221 (16), 220 (91),
179 (3), 178 (23), 137 (3), 136 (23), 135 (100), 123 (7), 121 (9), 119 (7), 107 (42), 105 (12),
94 (8), 93 (75), 91 (31), 85 (46), 81 (31), 79 (78), 77 (28), 69 (26), 67 (33), 57 (29), 55 (23),
44 (58).
Syn th esis of Quatern ary Ph en an th ridin ium Salts 2a–2d . Gen eral Procedure
A ch loroform solution of ph en an th ridin e (3.0 g, 16.7 m m ol) was added to a h ot solution of
appropriate brom acetam ide 1a–1e (16.7 m m ol) in aceton itrile (50 m l) an d th e solution was
refluxed for 5 days. Durin g th e h eatin g, a yellowish solid precipitated an d th e solution
turn ed oran ge. Th e reaction m ixture was con cen trated un der reduced pressure, th e residue
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

2000
Trávníček, Pospíšil, Potáček:
was collected, wash ed con secutively with ch loroform an d dieth yl eth er, an d dried at room
tem perature.
5-[(N,N-Dicyclohexylcarbamoyl)methyl]phenanthridinium bromide (2a). Yield 0.43 g (85%),
yellowish n eedles; n ot m eltin g up to 300 °C. FTIR: 2 958, 2 929, 2 852, 1 654 (C=O), 1 629
(CH=N+), 1 448, 1 305, 1 267, 1 240, 1 155, 995, 800, 763. 1H NMR (DMSO-d6): 1.00–2.21 m ,
22 H (cycloh exyl); 6.39 s, 2 H (CH2C=O); 8.22–9.25 m , 8 H (CHar); 10.37 s, 1 H (CH=N+).
13C NMR (DMSO-d6): 24.78; 25.16; 25.56; 28.82; 29.63; 30.73 (6 × CH2); 55.73; 57.24 (2 × CH);
59.83 (CH2C=O); 119.97; 123.51; 125.67; 130.45; 132.10; 133.16; 138.81 (8 × CHar); 124.97;
130.71; 134.49; 134.95 (4 × Cq ar). EI MS: 402 (M+ – 79, 1), 401 (2), 223 (6), 222 (38), 194
(17), 193 (13), 180 (42), 179 (100), 178 (38), 152 (14), 151 (16), 150 (9), 140 (31), 138 (17),
98 (22), 83 (18), 81 (18), 56 (15), 55 (39), 41 (29).
5-[(N,N-Diisopropylcarbamoyl)methyl]phenanthridinium bromide (2b). Yield 5.37 g (80%), yel-
lowish n eedles; n ot m eltin g up to 300 °C. FTIR: 2 994, 2 966, 2 926, 1 651 (C=O), 1 629
(CH=N+), 1 534, 1 448, 1 352, 1 317, 1 264, 1 208, 1 156, 1 039, 803, 760. 1H NMR
(DMSO-d6): 1.26 d, 6 H, J = 6.6 (2 × CH3); 1.39 d, 6 H, J = 6.5 (2 × CH3); 3.64 septet, 1 H, J =
6.6 (CH); 4.20 septet, 1 H, J = 6.5 (CH); 6.27 s, 2 H (CH2C=O); 8.11–9.21 m , 8 H (CHar);
10.31 s, 1 H (CH=N+). 13C NMR (DMSO-d6): 20.62; 20.95 (2 × CH3); 46.08; 48.84 (2 × CH);
59.80 (CH2C=O); 120.12; 123.45; 125.25; 130.71; 130.99; 132.44; 133.42; 139.07 (8 × CH);
123.70; 125.86; 134.63; 135.11 (4 × Cq ar); 157.64 (CH=N+); 162.61 (C=O). EI MS: 322 (M+
–
79, 5), 321 (15), 194 (18), 193 (38), 180 (42), 179 (100), 178 (23), 165 (18), 164 (11), 152
(14), 151 (18), 150 (9), 142 (15), 141 (12), 99 (11), 98 (17), 86 (28), 84 (26), 58 (21), 57 (12),
44 (42), 43 (49).
5-{[N-(1-Adamantyl)carbamoyl]methyl}phenanthridinium bromide (2c). Yield 6.0 g (80%), yel-
lowish crystals; m .p. 228–230 °C. FTIR: 3 187 (N–H, am ide III), 3 037, 2 904, 2 848, 1 683
(C=O, am ide I), 1 625 (CH=N+), 1 552 (am ide II), 1 450, 1 359, 1 259, 1 220, 1 089, 746,
695. 1H NMR (DMSO-d6): 1.61 s, 6 H (3 × CH2); 2.01 d, 6 H, J = 8.75 (3 × CH2); 3.30 s, 3 H
(3 × CH); 5.93 s, 2 H (CH2C=O); 8.11–9.19 m , 8 H (CHar); 10.40 s, 1 H (CH=N+). 13C NMR
(DMSO-d6): 30.72 (CH); 37.79 (CH2); 42.75 (CH2); 54.03 (Cq ); 120.96; 125.25; 127.00;
132.33; 132.50; 134.12; 134.92; 140.47 (8 × CHar); 125.14; 124.41; 135.61; 136.42 (4 ×
CHq ar); 155.36 (CH=N+); 164.52 (C=O). EI MS: 372 (M+ – 79, 2), 370 (2), 273 (5), 271 (5),
216 (7), 214 (7), 194 (18), 193 (100), 192 (29), 180 (17), 179 (50), 178 (16), 167 (2), 166 (5),
165 (18), 135 (22), 94 (7), 93 (10), 92 (7), 91 (9), 79 (13), 77 (8), 41 (6).
5-[(N-Benzylcarbamoyl)methyl]phenanthridinium bromide (2d ). Yield 6.0 g (88%), beige n ee-
dles; m .p. 293–295 °C. FTIR: 3 202 (N–H, am ide III), 3 047, 2 959, 1 683 (C=O, am ide I),
1 627 (CH=N+), 1 547 (am ide II), 1 452, 1 421, 1 352, 1 262, 1 222, 1 150, 1 066, 1 005, 939,
758, 708. 1H NMR (DMSO-d6): 4.39 d, 2 H, J = 5.7 (CH2Ph); 6.05 s, 2 H (CH2C=O); 7.26–7.36 m ,
5 H (CHar); 8.09–8.15 m , 3 H (CHar + NH); 8.39–9.44 m , 6 H (CHar); 10.47 s, 1 H (CH=N+).
13C NMR (DMSO-d6): 43.11 (CH2Ph ); 59.58 (CH2C=O); 119.64; 123.75; 125.47; 127.48;
127.78; 128.75; 130.81; 131.00; 132.56; 133.47; 139.04 (11 × CHar); 123.68; 125.90; 134.09;
134.98; 138.73 (5 × Cq ar); 157.68 (CH=N+); 164.50 (C=0). EI MS: 328 (M+ – 79, 3), 326 (4),
235 (28), 234 (13), 194 (25), 193 (52), 180 (83), 179 (100), 166 (18), 165 (34), 152 (19), 151
(27), 148 (48), 107 (21), 105 (15), 91 (82), 65 (13), 63 (12), 51 (11), 50 (8).
(±)-5-({N-[1-(1-Adamantyl)ethyl]carbamoyl}phenanthridinium bromide (2e). Yield 5.84
g
(73%), yellowish n eedles; m .p. 175–177 °C. FTIR: 3 206 (NH, am ide III), 3 054, 2 901, 2 847,
1 683 (C=O, am ide I), 1 626 (CH=N+), 1 600 (C=C), 1 552 (am ide II), 1 505, 1 451, 1 384,
1 261, 1 219, 1 137, 1 079, 758. 1H NMR (DMSO-d6): 1.18 d, 3 H, J = 6.9 (CH3); 1.64 m , 9 H
(3 × CH2 + 3 × CH); 2.03 d, 6 H, J = 15.9 (3 × CH2); 3.59 m , 1 H (CHCH3); (5.98 an d 6.10)
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Reactionsof New Family of Amide Derivatives
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ABq, 2 H, J = 16 (CH2C=O); 8.19–9.28 m , 9 H (8 × CHar + NH); 10.42 (CH=N+). 13C NMR
(DMSO-d6): 13.07 (CH3); 27.81 (3 × CH); 34.45 (Cq); 36.07 (3 × CH2); 36.93 (3 × CH2); 53.93
(CHCH3); 59.72 (CH2C=O); 119.45; 123.75; 125.53; 130.84; 131.11; 132.40; 133.44; 138.99
(8 × CHar); 123.64; 125.91; 133.97; 134.89 (4 × Cq ar); 163.58 (C=O). EI MS: 400 (M+ – 79, 1),
399 (1), 263 (17), 261 (4), 222(1), 221 (6), 220 (39), 180 (18), 179 (98), 178 (22), 153 (4),
152 (11), 151 (18), 136 (12), 135 (100), 107 (12), 105 (5), 93 (24), 85 (15), 79 (25), 44 (24).
Preparation of Cycloadducts 3a–3e, 4c, 5c, 6c, an d 7c. Gen eral Procedure
To a suspen sion of 1.0 g of appropriate quatern ary salt 2a–2d in dry CH2Cl2, an equivalen t
of fum aron itrile, dim eth yl fum arate or dim eth yl m aleate was added an d argon was in tro-
duced un der stirrin g at am bien t tem perature for 5 m in . Th en an equivalen t of dry trieth yl-
am in e was added un der argon an d th e reaction m ixture was refluxed for 2 days. Th e solven t
was rem oved in vacuo an d th e residue was triturated with ben zen e. Ben zen e was evaporated
an d th e residue was an alysed by TLC an d 1H NMR. Products were separated by colum n ch ro-
m atograph y on silica.
(1R*,2S*,3R*,12bS*)-1,2-Dicyano-N,N-dicyclohexyl-1,2,3,12b-tetrahydropyrrolo[1,2-f]phenanthri-
dine-3-carboxamide (3a ). Yield 0.28
g (25%), eluted with Et2O, yellow powder; m .p.
160–163 °C. FTIR: 3 069, 2 929, 2 856, 2 244 (CN), 1 643 (C=O, am ide I), 1 494, 1 446,
1 368, 1 299, 1 270, 1 120, 1 017, 893, 754. 1H NMR: 1.21–1.97 m , 20 H (10 × CH2); 3.03 m ,
1 H (CH); 3.35 dd, 1 H, J(2,3) = 9.7, J(1,2) = 8.2 (H-2); 3.73 m , 1 H (CH); 4.01 dd, 1 H, J(1,2) =
8.2, J(1,12b) = 3.4 (H-1); 5.10 d, 1 H, J(2,3) = 9.7 (H-3); 5.18 d, 1 H, J(1,12b) = 3.4 (H-12b);
6.63–7.83 m , 8 H (8 × CHar). 13C NMR: 25.06; 25.17; 25.61; 25.69; 26.41; 26.46; 29.41;
29.72; 31.18; 31.56 (10 × CH2); 33.98 (C-2); 39.49 (C-1); 57.18; 58.36 (2 × CH); 63.53 (C-3);
63.94 (C-12b); 117.24; 118.52 (2 × CN); 112.26; 119.11; 122.84; 124.21; 125.73; 128.23;
129.36; 129.62 (8 × CHar); 113.95; 129.92; 130.05; 140.00 (4 × Cq ar); 166.40 (C=O). EI MS:
479 (M+ + 1, 1), 478 (M+, 2), 450 (2), 449 (6), 271 (5), 270 (18), 269 (11), 268 (10), 267 (8),
244 (3), 243 (10), 242 (16), 220 (4), 219 (15), 218 (100), 180 (7), 179 (24), 178 (6), 165 (9),
83 (21), 81 (6), 56 (7), 55 (54), 54 (7). For C31H34N4O (478.6) calculated: 77.79% C, 7.16% H,
13.85% N; foun d: 78.03% C, 7.56% H, 13.95% N.
(1R*,2S*,3R*,12bS*)-1,2-Dicyano-N,N-diisopropyl-1,2,3,12b-tetrahydropyrrolo[1,2-f]phenanthri-
dine-3-carboxamide (3b). Yield 0.27 g (27%), eluted with CHCl3–Et2O (4 : 1), yellowish powder
(dieth yl eth er); m .p. 213–215 °C. FTIR: 3 065, 2 970, 2 932, 2 247 (CN), 1 641 (C=O, am ide I),
1 603 (C=C), 1 495, 1 445, 1 379, 1 302, 1 209, 1 122, 1 040, 751. 1H NMR: 1.25 d, 3 H, J = 6.6
(CH3); 1.36 d, 3 H, J = 6.6 (CH3); 1.41 d, 3 H, J = 6.7 (CH3); 1.46 d, 3 H, J = 6.7 (CH3); 3.34 dd,
J(2,3) = 9.6, J(1,2) = 8.2 (H-2); 3.51 septet, 1 H, J = 6.7 (CH); 4.05 dd, 1 H, J(1,2) = 8.2,
J(1,12b) = 3.5 (H-1); 4.21 septet, 1 H, J = 6.7 (CH); 5.08 d, 1 H, J(2,3) = 9.6 (H-3); 5.20 d,
1 H, J(1,12b) = 3.5 (H-12b); 6.61–7.43 m , 8 H (CHar). 13C NMR: 20.12; 20.25; 20.51; 21.07 (4 ×
CH3); 33.84 (C-2); 39.36 (C-1); 46.92; 49.41 (2 × CH); 63.56 (C-3); 63.89 (C-12b); 117.04;
118.30 (2 × CN); 112.01; 120.91; 122.75; 124.16; 125.72; 128.13; 129.30; 129.64 (8 × CHar);
128.95; 129.92; 140.01 (3 × Cq ar); 166.14 (C=O). EI MS: 398 (M+, 2), 270 (17), 268 (7), 244 (3),
243 (6), 242 (5), 219 (18), 218 (100), 180 (8), 179 (9), 165 (7), 99 (4), 98 (4), 86 (8), 44 (42),
43 (49). For C25H26N4O (398.5) calculated: 75.35% C, 6.58% H, 14.06% N; foun d: 75.61% C,
6.35% H, 13.87% N.
(1R*,2S*,3R*,12bS*)-N-(1-Ada m a ntyl)-1,2-dicya no-1,2,3,12b-tetra hydropyrrolo[1,2-f]-
phenanthridine-3-carboxamide (3c). Yield 0.62 g (60%), less polar com poun d eluted with
CH2Cl2–Et2O (4 : 1), yellow crystals; m .p. 133–135 °C. FTIR: 3 342 (NH, am ide III), 3 061,
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2002
Trávníček, Pospíšil, Potáček:
2 909, 2 851, 2 247 (CN), 1 678 (C=O, am ide I), 1 602 (C=C), 1 518 (am ide II), 1 444, 1 263,
1 094, 755. 1H NMR: 1.66 d, 6 H, J = 2.9 (CH2); 1.97 d, 6 H, J = 3.1 (CH2); 2.07 br s, 3 H
(CH); 3.19 t, 1 H, J(2,3) = J(1,2) = 9.7 (H-2); 3.93 dd, 1 H, J(1,2) = 9.7, J(1,12b) = 4.7 (H-1);
4.63 d, 1 H, J(2,3) = 9.7 (H-3); 4.85 d, 1 H, J(1,12b) = 4.7 (H-12b); 6.40 br s, 1 H (NH);
6.79–7.87 m , 8 H, (8 × CHar). 13C NMR: 29.25 (CH); 33.54 (C-2); 36.01 (CH2); 41.05 (C-1);
41.33 (CH2); 52.56 (Cq); 64.20 (C-3); 69.53 (C-12b); 117.87; 119.69 (2 × CN); 113.31; 121.97;
122.73; 123.87; 127.05; 128.37; 129.94; 130.36 (8 × CHar); 116.28; 126.58; 129.19; 140.74
(4 × Cq ar); 166.70 (C=O). EI MS: 449 (M+ + 1, 1), 448 (M+, 2), 421 (1), 419 (1), 371 (1), 370 (1),
369 (1), 271 (2), 270 (9), 220 (3), 219 (16), 218 (100), 194 (1), 193 (3), 180 (9), 179 (2), 150 (2),
149 (2), 136 (2), 135 (13), 120 (2), 93 (2), 79 (2). For C29H28N4O (448.6) calculated: 77.65% C,
6.29% H, 12.49% N; foun d: 77.35% C, 6.45% H, 12.61% N.
(1R*,2S*,3R*,12bS*)-N-Benzyl-1,2-dicyano-1,2,3,12b-tetrahydropyrrolo[1,2-f]phenanthridine-
3-carboxamide (3d ). Yield 0.25 g (25%), eluted with CHCl3–Et2O (4 : 1), yellowish powder
(dieth yl eth er); m .p. 171–173 °C. FTIR: 3 292 (NH, am ide III), 3 064, 2 932, 2 864, 2 246
(CN), 1 667 (C=O, am ide I), 1 602 (C=C), 1 522 (am ide II), 1 494.9, 1 445, 1 387, 1 294,
1 213, 1 171, 1 066, 1 028, 950, 756, 700. 1H NMR: 3.20 dd, 1 H, J(2,3) = 10.05, J(1,2) = 9.5
(H-2); 3.97 dd, 1 H, J(1,2) = 9.5, J(1,12b) = 4.6 (H-1); 4.49 m , 2 H (CH2NH); 4.63 d, 1 H,
J(2,3) = 10.05 (H-3); 5.01 d, 1 H, J(1,12b) = 4.6 (H-12b); 6.79 d, 1 H, J = 8.1 (CHar); 7.03 t,
1 H, J = 7.6 (CHar); 7.17 br t, 1 H, J = 5.8 (NH); 7.24–7.86 m , 11 H (CHar). 13C NMR: 33.68
(C-1); 40.89 (C-2); 43.88 (CH2NH); 64.32 (C-3); 68.96 (C-12b); 117.75; 119.70 (2 × CN);
113.27; 122.07; 122.72; 123.91; 127.04; 127.68; 127.87; 128.39; 128.83; 129.98; 130.35 (11 ×
CHar); 116.14; 126.35; 129.11; 136.97; 140.49 (5 × Cq ar); 168.11 (C=O). EI MS: 406 (M+ + 2, 2),
405 (M+ + 1, 6), 404 (M+, 6), 314 (2), 313 (6), 243 (16), 242 (14), 219 (6), 218 (27), 217 (8),
188 (11), 187 (38), 180 (100), 179 (25), 166 (3), 165 (11), 164 (3), 92 (7), 91 (85). For
C
26H20N4O (404.5) calculated: 77.21% C, 4.98% H, 13.85% N; foun d: 77.38% C, 4.92% H,
13.56% N.
(1R*,2S*,3R*,12bS*)-N-[1-(1-Ada ma ntyl)ethyl]-1,2-dicya no-1,2,3,12b-tetra hydropyrrolo-
[1,2-f]phenanthridine-3-carboxamide (3e). Yield 0.15 g (26%), elution with eth yl acetate, ligh t
yellow crystals; m .p. 195–197 °C. FTIR: 3 299 (NH, am ide III), 3 061, 2 903, 2 847, 2 247
(CN), 1 674 (C=O, am ide I), 1 603 (C=C), 1 522 (am ide II), 1 495, 1 444 , 1 383, 1 297,
1 260, 1 212, 1 159, 1 093, 1 023, 946, 750. 1H NMR: 1.04 d, 3 H, J = 6.9 (CHCH3); 1.36 d,
1 H, J = 6.9 (CHCH3); 1.53 dd, 6 H, J = 34.7, J = 12.0 (3 × CH2); 1.62 t, 6 H, J = 11.1 (3 ×
CH2); 1.99 s, 3 H (3 × CH); 3.25 m , 1 H (H-2); 3.68 d(dd), 1 H, J = 32.9, J(1,2) = 9.95,
J(1,12b) = 4.6 (H-1); 4.72 dd, 1 H, J = 13.3, J(2,3) = 9.95 (H-3); 4.97 dd, 1 H, J = 22.03,
J(1,12b) = 4.6 (H-12b); 6.48 br s, 1 H (NH); 6.82–7.90 m , 8 H (8 × CHar). 13C NMR: 14.45
(CH3); 28.13 (3 × CH); 33.89 (C-2); 35.85 (Cq); 36.72 (3 × CH2); 38.28 (3 × CH2); 41.07 (C-1);
53.54 (CH); 63.90 (C-3); 69.05 (C-12b); 1117.79; 119.53 (2 × CN); 113.22; 121.74; 122.71;
123.75; 126.73; 128.34; 129.78; 130.21 (8 × CHar); 113.61; 126.65; 129.05; 140.38 (4 × Cq ar);
167.07 (C=O). EI MS: 478 (M+ + 2, 1), 477 (M+ + 1, 1), 476 (M+, 3), 270 (21), 245 (10), 243
(12), 242 (8), 220 (5), 219 (21), 218 (100), 193 (16), 180 (27), 179 (18), 165 (13), 163 (8),
135 (11), 79(11). For C31H32N4O (476.6) calculated: 78.12% C, 6.77% H, 11.75% N; foun d:
78.07% C, 6.63% H, 11.81% N.
(1R*,2R*,3R*,12bR*)-N-(1-Ada ma ntyl)-1,2-dicya no-1,2,3,12b-tetra hydropyrrolo[1,2-f]-
phenanthridine-3-carboxamide (4c). Yield 0.49 g (35%), m ore polar com poun d eluted with
CH2Cl2–Et2O (4 : 1), yellow crystals; m .p. 157–159 °C. FTIR: 3 361 (NH, am ide III), 3 064,
2 907, 2 851, 2 247 (CN), 1 674 (C=O, am ide I), 1 603 (C=C), 1 522 (am ide II), 1 446, 1 263,
1 094, 746. 1H NMR: 1.68 br s, 6 H (CH2); 2.06 d, 6 H, J = 2.7 (CH2); 2.09 br s, 3 H (CH);
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Reactionsof New Family of Amide Derivatives
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3.67 d, 1 H, J(2,3) = 4.1 (H-3); 3.99 dd, 1 H, J(1,2) = 8.3, J(1,12b) = 4.1 (H-1); 4.57 d, 1 H,
J(1,2) = 8.3, J(2,3) = 4.1 (H-2); 5.54 d, 1 H, J(1,12b) = 4.1 (H-12b); 6.48 br s, 1 H (NH);
6.50–7.92 m , 8 H (8 × CHar). 13C NMR: 29.28 (CH); 36.65 (C-2); 36.06 (CH2); 41.26 (CH2);
42.96 (C-1); 52.59 (Cq); 62.94 (C-3); 68.81 (C-12b); 114.99; 115.98 (2 × CN); 113.01; 121.04;
122.66; 123.14; 126.60; 128.34; 129.66; 130.03 (8 × CHar); 118.89; 126.01; 130.00; 142.09
(4 × Cq ar); 166.08 (C=O). EI MS: 449 (M+ + 1, 1), 448 (M+, 2), 421 (1), 419 (1), 371 (1), 370
(1), 369 (1), 271 (2), 270 (9), 220 (3), 219 (16), 218 (100), 194 (1), 193 (3), 180 (9), 179 (2),
150 (2), 149 (2), 136 (2), 135 (13), 120 (2), 93 (2), 79 (2). For C29H28N4O (448.6) calculated:
77.65% C, 6.29% H, 12.49% N; foun d: 77.71% C, 6.34% H, 12.52% N.
(1R*,2S*,3R*,12bS*)-Dimethyl 3-[N-(1-adamantyl)]carbamoyl-1,2,3,12b-tetrahydropyrrolo[1,2-f]-
phenanthridine-1,2-dicarboxylate (5c). Yield 0.46 g (35%), less polar com poun d eluted with
CH2Cl2–Et2O (5 : 1), yellowish crystals; m .p. 191–193 °C. FTIR: 3 300 (NH, am ide III), 3 035,
2 908, 2 849, 1 730 (C=O ester), 1 675 (C=O, am ide I), 1 603 (C=C), 1 519 (am ide II), 1 497,
1 449, 1 358, 1 306, 1 233, 1 167 (C–O), 1 102, 1 026, 806, 741. 1H NMR: 1.67 s, 6 H (3 × CH2);
1.97 d, 6 H, J = 2.9 (3 × CH2); 2.07 s, 3 H (3 × CH); 3.38 t, 1 H, J = 9.4 (H-2); 3.68 s, 3 H
(OCH3); 3.73 s, 3 H (OCH3); 3.75 dd, 1 H, J(1,2) = 9.4, J(1,12b) = 5.1 (H-1); 4.79 d, 1 H,
J(2,3) = 9.4 (H-3); 4.97 d, 1 H, J(1,12b) = 5.1 (H-12b); 6.44 br s, 1 H (N-H); 6.69–8.65 m , 8 H
(8 × CHar). 13C NMR: 29.32 (CH); 36.17 (CH2); 41.41 (CH2); 50.37 (C-2); 51.87 (Cq); 52.17
(OCH3); 52.27 (OCH3); 55.18 (C-1); 64.02 (C-3); 68.53 (C-12b); 113.50; 119.98; 122.23;
123.15; 126.03; 127.47; 128.56; 129.72 (8 × CHar); 119.82; 130.19; 133.28; 142.98 (4 × Cq ar);
169.54 (C=O, am ide); 171.81; 172.05 (2 × C=O, ester). EI MS: 516 (M+ + 2, 1), 515 (M+ + 1, 1),
514 (M+, 2), 336 (3), 334 (3), 302 (11), 277 (8), 276 (35), 275 (8), 253 (2), 252 (17), 251
(100), 244 (18), 220 (5), 219 (36), 217 (18), 136 (2), 135 (19), 93 (10), 79(8).
(1R*,2R*,3R*,12bR*)-Dimethyl 3-[N-(1-adamantyl)]carbamoyl-1,2,3,12b-tetrahydropyrrolo[1,2-f]-
phenanthridine-1,2-dicarboxylate (6c). Yield 0.36 g (27%), m ore polar com poun d eluted with
CH2Cl2–Et2O (5 : 1), yellowish crystals; m .p. 208–210 °C. FTIR: 3 399 (NH, am ide III), 3 035,
2 909, 2 855, 1 729 (C=O ester), 1 647 (C=O, am ide I), 1 608 (C=C), 1 547 (am ide II), 1 497,
1 450, 1 358, 1 306, 1 233, 1 168 (C–O), 1 102, 1 026, 806, 741. 1H NMR: 1.68 s, 6 H (3 × CH2);
1.99 d, 6 H, J = 2.9 (3 × CH2); 2.06 s, 3 H (3 × CH); 3.10 s, 3 H (OCH3); 3.37 d, 1 H, J(1,2) =
5.5 (H-2); 3.74 m , 1 H (H-1); 3.76 s, 3 H (OCH3); 4.72 d, 1 H, J(2,3) = 5.5 (H-3); 5.69 d, 1 H,
J(1,12b) = 5.7 (H-12b); 6.55 br s, 1 H (N-H); 6.81–8.64 m , 8 H (8 × CHar). 13C NMR: 29.45
(CH); 36.32 (CH2); 41.38 (CH2); 46.17 (C-2); 52.38 (Cq); 52.41 (OCH3); 52.56 (OCH3); 55.79
(C-1); 63.31 (C-3); 71.36 (C-12b); 112.75; 119.48; 121.76; 122.04; 127.45; 127.57; 128.48;
129.81 (8 × CHar); 118.77; 128.87; 129.92; 144.42 (4 × Cq ar); 169.02 (C=O, am ide); 171.22;
172.90 (2 × C=O, ester). EI MS: 516 (M+ + 2, 1), 515 (M+ + 1, 1), 514 (M+, 2), 336 (3), 334 (3),
302 (11), 277 (8), 276 (35), 275 (8), 253 (2), 252 (17), 251 (100), 244 (18), 220 (5), 219 (36),
217 (18), 136 (2), 135 (19), 93 (10), 79 (8).
(2R*,3R*)-Dimethyl 3-[N-(1-adamantyl)carbamoyl]-1,2-dihydropyrrolo[1,2-f]phenanthridine-
1,2-dicarboxylate (7c). Yield 0.45 g (34%), eluted with CH2Cl2–Et2O (2 : 1), yellowish crystals;
m .p. 189–192 °C. FTIR: 3 342 (NH, am ide III), 3 061, 2 908, 2 851, 1 748 (C=O ester), 1 654
(C=O, am ide I), 1 607 (C=C), 1 532 (am ide II), 1 440, 1 363, 1 260, 1 212, 1 169, 1 098
(C–O), 1 026, 803, 750. 1H NMR: 1.60 d, 6 H, J = 3 (3 × CH2); 1.88 d, 6 H, J = 2.9 (3 × CH2);
1.99 s, 3 H (3 × CH); 3.73 s, 3 H (OCH3); 3.76 s, 3 H (OCH3); 4.21 d, 1 H, J(2,3) = 5.0 (H-2);
4.79 d, 1 H, J(2,3) = 5.0 (H-3); 6.15 br s, 1 H (N-H); 6.82–8.53 m , 8 H (8 × CHar). 13C NMR:
29.22 (CH); 36.13 (CH2); 41.25 (CH2); 49.17 (Cq); 52.00 (OCH3); 52.32 (C-2); 52.58 (OCH3);
65.53 (C-3); 95.28; 119.31; 120.65; 124.92; 136.20; 137.20 (6 × Cq ar); 113.06; 115.94;
121.86; 123.14; 128.10; 128.85; 129.79; 132.92 (8 × CHar); 166.92 (C=O, am ide); 167.42
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Trávníček, Pospíšil, Potáček:
(C=O, ester, con jug.); 173.50 (C=O, ester, free). EI MS: 514 (M+ + 2, 1), 513 (M+ + 1, 2), 512
(M+, 3), 387 (8), 302 (10), 236 (7), 235 (5), 211 (1), 210 (17), 209 (100), 195 (3), 180 (9), 178
(28), 152 (8), 135 (17), 93 (8), 79 (8), 67 (4).
Preparation of 5-Substituted 6-Ph en an th ridon es 8b–8e. Gen eral Procedure
To a suspen sion of 1.0 g of quatern ary salt 2b–2e in THF, an equivalen t of TEA an d 1.0 m l
of water were added. Th e m ixture was refluxed for 4–6 h . Th e ph en an th ridin ium salt gradu-
ally dissolved durin g th e h eatin g an d trieth ylam m on ium brom ide precipitated upon cool-
in g. THF was rem oved un der reduced pressure, th e residue was triturated with water. Th e
solid was sucked off, dried at 100 °C an d crystallised from an appropriate solven t.
N,N-Diisopropyl-2-[6(5H)-oxophenanthridin-5-yl]acetamide (8b). Yield 0.57 g (85%), yellow
powder (cycloh exan e); m .p. 203–205 °C. FTIR: 3 073, 2 994, 2 965, 2 931, 1 648 (C=O),
1 448, 1 353, 1 312, 1 212, 1 131, 1 042, 802, 750, 720. 1H NMR: 1.43 d, 6 H, J = 6.3 (CH3);
1.48 d, 6 H, J = 6.6 (CH3); 3.63 septet, 1 H, J = 6.3 (CH); 4.27 septet, 1 H, J = 6.6 (CH); 5.31 s,
2 H (CH2C=O); 7.24–8.62 m , 8 H (CHar). 13C NMR: 20.51 (CH3); 20.93 (CH3); 45.51
(CH2C=O); 46.25 (CH); 48.05 (CH); 115.09; 121.53; 122.53; 123.23; 127.68; 128.89; 129.33;
132.47 (8 × CHar); 119.97; 125.17; 133.86; 137.75 (4 × Cq ar); 161.50 (C=O, lactam ); 164.93
(C=O). EI MS: 338 (M+ + 2, 3), 336 (M+, 8), 237 (9), 236 (43), 235 (9), 210 (4), 209 (22), 208
(48), 180 (16), 179 (23), 178 (88), 153 (7), 152 (28), 151 (12), 129 (4), 128 (42), 101 (8), 100
(100), 98 (10), 87 (7), 86 (98), 44 (7), 43 (81).
N-(1-Adamantyl)-2-[6(5H)-oxophenanthridin-5-yl]acetamide (8c). Yield 0.69 g (81%), yellow-
ish powder (m eth an ol–eth an ol, 1 : 1); m .p. 205–207 °C. FTIR: 3 276 (NH, am ide III), 3 070,
2 904, 2 848, 1 648 (C=O), 1 604 (C=C), 1 548 (am ide II), 1 434, 1 363, 1 257, 1 162, 1 064,
1 007, 796, 719. 1H NMR: 1.54 t, 6 H, J = 2.8 (3 × CH2); 1.85 d, 6 H, J = 2.8 (3 × CH2); 1.93 m ,
3 H (3 × CH); 4.82 s, 2 H (CH2C=O); 6.08 br s, 1 H (NH); 7.28–8.46 m , 8 H (8 × CHar). 13C
NMR: 29.25 (CH); 36.13 (CH2); 41.25 (CH2); 49.17 (Cq); 52.00 (CH2C=O); 115.93; 121.73;
123.13; 127.97; 128.85; 129.96; 132.91 (7 × CHar); 119.90; 124.92; 133.87; 137.21 (4 × Cq ar);
161.98 (C=O, lactam ); 166.99 (C=O). EI MS: 385 (M+, 5), 237 (2), 123 (9), 235 (8), 211 (4),
210 (18), 209 (100), 196 (3), 195 (7), 181 (6), 180 (15), 179 (15), 178 (25), 153 (5), 152 (21),
151 (11), 135 (18), 94 (6), 93 (18), 91 (8), 79 (19), 77 (10). For C25H26N2O2 (385.5) calcu-
lated: 77.69% C, 6.78% H, 7.25% N; foun d: 77.73% C, 6.81% H, 7.24% N.
N-Benzyl-2-[6(5H)-oxophenanthridin-5-yl]acetamide (8d ). Yield 0.82 g (82%), yellow powder
(m eth an ol–eth an ol, 1 : 1); m .p. 204–206 °C. FTIR: 3 284 (NH, am ide III), 3 071, 3 032,
2 954, 2 929, 1 652 (C=O), 1 608 (C=C), 1 549 (am ide II), 1 433, 1 364, 1 240, 1 169, 1 078,
1 009, 751, 723. 1H NMR: 4.42 d, 2 H, J = 5.9 (CH2Ph ); 5.07 s, 2 H (CH2C=O); 6.82 br s, 1 H
(NH); 7.13–7.25 m , 5 H (CHar); 7.37–8.49 m , 8 H (CHar). 13C NMR: 43.26 (CH2Ph ); 48.05
(CH2C=O); 115.58; 121.77; 123.27; 123.31; 127.24; 127.28; 128.08; 128.47; 130.03; 133.04
(10 × CHar); 119.40; 124.80; 137.03; 137.67 (4 × CHq ar); 162.12 (C=O, lactam ); 168.09
(C=O). EI MS: 342 (M+, 18), 238 (3), 237 (16), 236 (82), 210 (13), 209 (76), 208 (62), 196
(45), 195 (10), 194 (5), 181 (8), 180 (28), 179 (26), 178 (100), 153 (11), 152 (45), 151 (31),
107 (5), 106 (28), 91 (31), 77 (12), 65 (11).
(±)-N-[1-(1-Adamantyl)ethyl]-2-[6(5H)-oxophenanthridin-5-yl]acetamide (8e). Yield 0.43 g
(87%), yellowish powder (methanol–ethanol, 1 : 1); m.p. 214–216 °C. FTIR: 3 309 (NH, amide III),
3 047, 2 974, 2 901, 2 845, 1 657 (C=O, am ide I), 1 609 (C=C), 1 587, 1 553 (am ide II), 1 492,
1 438, 1 364, 1 316, 1 254, 1 163, 1 095 , 998, 753, 724. 1H NMR: 0.92 d, 3 H, J = 10
(CHCH3); 1.26 an d 1.33 AB quartet, 6 H, J = 10 (3 × CH2); 1.38 an d 1.55 AB quartet, 6 H, J =
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Reactionsof New Family of Amide Derivatives
2005
10 (3 × CH2); 1.79 s, 3 H (3 × CH); 3.63 m , 1 H (CHCH3); (4.83 an d 5.19) AB quartet, 2 H, J =
15 (CH2C=O); 6.34 d, 1 H, J = 10 (NH); 7.35–8.55 m , 8 H (8 × CHar). 13C NMR: 14.29
(CHCH3); 28.14 (3 × CH); 35.82 (Cq); 36.87 (3 × CH2); 38.15 (3 × CH2); 48.34 (CH2C=O);
53.15 (CHCH3); 116.19; 121.89; 123.28; 128.18; 128.95; 130.08; 133.13 (7 × CHar); 119.38;
124.93; 133.94; 137.09 (4 × Cq ar); 162.21 (C=O, lactam ); 167.54 (C=O). EI MS: 416 (M+ + 2, 2),
414 (M+, 4), 238 (1), 237 (9), 236 (100), 209 (58), 208 (33), 195 (10), 180 (12), 178 (43), 153 (1),
152 (7), 151 (2), 135 (13), 93 (5), 81 (4), 79 (5), 57 (4), 55 (4), 44 (1), 43 (3).
This work was supported by the Grant of Ministry of Education (CEZ:J07/98:143100011)
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