The action of vanadium oxytrifluoride on N-arylbenzylamines - A route to some phenanthridines

Article abstract of DOI:10.1071/CH03177

The action of four equivalents of vanadium oxytrifluoride upon electron-rich N-arylbenzylamines provides a convenient synthesis of phenanthridines. Excess of oxidant can lead to selective hydroxylation of a methyl substituent. Benzylamines with a phosphonate substituent on the methylene group lead to 6-substituted phenanthridines.

Full text of DOI:10.1071/CH03177

Full Paper
CSIRO PUBLISHING
www.publish.csiro.au/journals/ajc
Aust. J. Chem. 2004, 57, 473–482
The Action of Vanadium Oxytrifluoride on
N-Arylbenzylamines—a Route to Some Phenanthridines
Andris J. Liepa,A,C Roland N. Nearn,A and Denis M. J. WrightA,B
A CSIRO Division of Molecular Science, Clayton VIC 3169, Australia.
B Present address: C/O Colours and Chemicals, West Footscray VIC 3012, Australia.
C Author to whom correspondence should be addressed (e-mail: andy.liepa@csiro.au).
The action of four equivalents of vanadium oxytrifluoride upon electron-rich N-arylbenzylamines provides a con-
venient synthesis of phenanthridines. Excess of oxidant can lead to selective hydroxylation of a methyl substituent.
Benzylamines with a phosphonate substituent on the methylene group lead to 6-substituted phenanthridines.
Manuscript received: 4 July 2003.
Final version: 21 October 2003.
Introduction
In order to dissipate the potentially deactivating effect of
the azomethine linkage, 1a was reduced with dimethylamine
borane[8] to the benzylamine 2a. Reaction with four equiva-
lents of vanadium oxytrifluoride readily effected cyclization
with concomitant dehydrogenation to generate the phenan-
thridine 3a in 41% yield. In addition, a trace of a more
polar phenanthridine was isolated. Although the latter was
Following the introduction of vanadium oxytrifluoride as a
reagent for coupling monophenolic[1] and non-phenolic[2]
electron-rich aromatic nuclei, it has found utility in the syn-
thesis of several natural products[3,4] as well as in the conver-
sion of substituted stilbenes[5,6] into phenanthrenes.
The phenanthridine ring system[7] represents an aza-
analogue of the phenanthrenes, and we envisaged a synthesis
based upon an oxidative coupling process starting from read-
ily available imines (Schiff’s bases) in place of stilbenes.
1
obtained only in small quantity, the H NMR spectrum of
this product suggested a phenanthridine in which one of
the methyl groups had been selectively converted into a
hydroxymethyl group. An attempt was made to convert a
purified sample of the phenanthridine 3a into this putative
hydroxymethyl product by further treatment with additional
vanadium oxytrifluoride. Negligible reaction occurred and
the phenanthridine was recovered unchanged, which sug-
gested that the hydroxylation step occurs with some inter-
mediate species, not the final phenanthridine product. As
a result of some cyclizations (see 3j in the experimental
section) carried out during the later stages of this investi-
gation, interest in hydroxymethylation was rekindled, and
some variations to the standard experimental procedure were
investigated. In these experiments a reversed order of addi-
tion was explored, wherein the substrate 2a was added to
more than six equivalents of vanadium oxytrifluoride which
was either suspended in dichloromethane/trifluoroacetic acid
or dissolved by incorporation of ethyl acetate. Although
neither modification enhanced the formation of the pre-
sumed hydroxymethylphenanthridine, the yield of the parent
phenanthridine was markedly improved from the original
Results and Discussion
Additionofvanadiumoxytrifluorideasasolutioninamixture
of trifluoroacetic acid, dichloromethane, and ethyl acetate∗ to
a solution of the Schiff’s base 1a (Scheme 1), obtained from
piperonaldehyde and 2,4-dimethylaniline, resulted merely
in a moderate darkening of the original yellowish† solution.
Little further change was noted until dilution with water,
which caused formation of deeply coloured mixtures.
When the reaction was quenched, piperonaldehyde was
recovered accompanied by a complex mixture of coloured
oxidation products. Evidently, little reaction had transpired
until the mixture was diluted with water, whereupon the
Schiff’s base hydrolyzed to the precursor aldehyde (inert
under these conditions) together with the (susceptible) ani-
line. The aniline then reacted further to produce a cascade
of oxidation products, presumably through the action of
vanadium pentoxide or related hydrolyzed VV species.
∗ Vanadium oxytrifluoride has low solubility in solvents with which it does not react, such as trifluoroacetic acid or dichloromethane; the addition of 1–2
moles of ethyl acetate causes a marked increase in solubility, apparently without deleterious effects upon the potency of the reagent.
† An unfavourable portent; successful coupling reactions require initial formation of radical cations whose existence is often indicated by formation of green,
blue, or violet species at some stage during the reaction.
© CSIRO 2004
10.1071/CH03177
0004-9425/04/050473

474
A. J. Liepa, R. N. Nearn and D. M. J. Wright
R4
R4
R4
H
N
R3
R2
R7
R3
R2
R3
R2
R7
N
N
R1
R1
R1
R5
R5
R5
R6
R6
R6
1
2
3
R1
R2
R3
R4
R5
R6
–OCH2O–
R7
H
H
Me
H
Me
1a
H
H
H
Me
CF3
Me
Me
H
H
OMe
OMe
OMe
OMe
H
H
H
1b
1c
2a
H
H
Me
–OCH2O–
H
H
H
H
H
Me
CF3
Cl
Me
H
H
OMe
OMe
OMe
OMe
H
H
H
H
H
2b
2c
2d
2e
2f
H
H
Cl
Cl
Cl
–OCH2O–
H
Cl
H
OMe
OMe
OMe
OMe
Cl
H
H
H
H
Cl
H
H
H
H
Cl
–OCH2O–
P(O)(OEt)2
P(O)(OEt)2
2g
2h
2i
Me
Me
Me
Me
Me
Me
–OCH2O–
–OCH2O–
–OCH2O–
P(O)(OH)(OEt)
H
3a
H
Me
Me
Me
H
H
H
OMe
OMe
OMe
OMe
H
H
3b
3c
Me
OMe
OMe
H
H
CF3
Cl
H
H
H
H
H
3d
3e
Cl
–OCH2O–
H
H
Cl
Cl
OMe
OMe
OMe
OMe
H
3f
H
H
Cl
Cl
H
H
Cl
Cl
H
3g
3h
–OCH2O–
P(O)(OEt)2
H
H
Me
H
H
Me
Me
–OCH2O–
–OCH2O–
P(O)(OEt)2
P(O)(OEt)2
3i
3j
CH2OH
Scheme 1.
41% to 80% or more. It seems likely that the yields from some
of the cyclizations described below which were only carried
out by the original protocol would have been significantly
increased had they been revisited using the methodology of
reversed order of addition.
A similar absence of cyclization was observed with
the Schiff’s base 1b obtained from the reaction between
veratraldehyde and 3,4-dimethylaniline. Once again, prior
reduction (with sodium borohydride[9]) to the benzylamine
2b enabled the cyclization to be carried out success-
fully. Although a combined yield of approximately 68% of
phenanthridine-containing material was obtained, it was dis-
tributed between several products. In each of the compounds
produced, the site of reaction was consistent with an elec-
trophilic substitution directed by substituent groups on the
rings. Thus, coupling of the methoxylated ring of 2b took
place para- to a methoxyl group and ortho- to the amino
substituent in the other ring. In this substrate, the aniline
has two ortho-positions free to provide potential coupling
sites. It is noteworthy that while a majority of the product
arose from reaction at the relatively less hindered ortho-
position to give 3b (40% yield), a substantial proportion

Action of Vanadium Oxytrifluoride on N-Arylbenzylamines
475
OMe
OMe
MeO
MeO
ϩ
VOF3
NH
NH
Me
Me
Me
Me
2b
OMe
MeO
MeO
MeO
ϩ
ϩ
NH
NH
Me
Me
Me
Me
MeO
MeO
OMe
Me
MeO
Me
MeO
OMe
Nϩ
H
dimerization
ϩN
H
H
Nϩ
H
Me
H
Nϩ
H
Me
Me
OMe
Me
OMe
A
Me
Me
3 VOF3
3 VOF3
ϩ
ϩ
6 VOF3
Ϫ4 H
Ϫ2 H
ϩ
Ϫ4 H
Me
MeO
MeO
OMe
Me
MeO
MeO
OMe
N
N
N
Me
N
Me
OMe
Me
Me
MeO
Me
3c
Me
3b
4
Scheme 2.
of the coupling nevertheless occurred at the more hindered
ortho-position, despite two flanking substituents, to give the
phenanthridine 3c in 21% yield. In addition to these isomeric
phenanthridines a modest quantity (7%) of an apparently
dimeric product (4, Scheme 2) was also formed. The small
4 arises merely from dimerization of the phenanthridine prod-
uct 3b. Rather, it seems more likely that the benzylamine 1a
forms a mono-cation radical (A, Scheme 2) which dimerizes
to an appreciable extent before further conversion into the
dication radical can take place.
The synthesis of phenanthridines by cyclization of Schiff’s
bases appears to be inhibited by the presence of the electron-
withdrawing imine bond linking the two rings. This has the
effect of depleting the aromatic rings of electron density, and
this effect is enhanced by extensive protonation within the
highly acidic reaction medium. Consequently, prior oxidation
1
number of peaks observed in the H NMR spectrum of 4
argued for formation of a symmetrically coupled product,
and the site at which the linkage occurs was assigned on
the basis of NOE experiments. Once formed, the phenanthri-
dine nucleus appears to be resistant to further transformation
by vanadium oxytrifluoride. Therefore, it is improbable that

476
A. J. Liepa, R. N. Nearn and D. M. J. Wright
to a Schiff’s base is not likely to be an enabling step on an
oxidative path to phenanthridines from N-arylbenzylamines.
Even so, this unproductive oxidation may still occur as a com-
peting pathway during an otherwise successful cyclization.
For example, the trifluoromethyl-substituted benzylamine
2c gave the phenanthridine 3d together with substantial
quantities of veratraldehyde and 4-trifluoromethylaniline.
Presumably these products arise from partial oxidation of
2c to the imine 1c, followed by hydrolytic cleavage of the
imine to its components during the subsequent aqueous acidic
workup. In contrast with the indeterminate products observed
with the Schiff’s base 1a, in this instance the regenerated
aniline is sufficiently robust to survive the aqueous oxidative
medium relatively unscathed.
Vanadium oxytrichloride has electron-abstracting proper-
ties similar to the trifluoride, and has also been used to effect
coupling between aromatic rings.[12] A brief investigation
with N-arylbenzylamines which had already been cyclized
successfully with the trifluoride usually showed that inferior
results were obtained.
other hand, the diester 2h cyclized readily in the presence
of a little more than four equivalents of vanadium oxytri-
fluoride, with retention of the phosphorus substituent, to give
the phosphorylated product 3i in 59% yield. A small amount
(8%) of the analogous dephosphorylated phenanthridine 3a
was also recovered.
During chromatographic purification of 3i, traces of what
appeared to be a closely related material were isolated. This
minor constituent had very similar spectroscopic properties
except that one of the original methyl substituents was no
longer apparent in the 1H NMR spectrum but was replaced
by a methylene group at δ 4.83, apparently as the result of
further reaction. Acting on the assumption that this mate-
rial was most likely to be the result of over-oxidation, we
repeated the cyclization using six equivalents of vanadium
oxytrifluoride instead of four. In addition to the 2,4-dimethyl
product 3i (22%), a major phenanthridine product 3j (52%)
was obtained in which the 2-methyl group had been selec-
tively hydroxylated. Presumably, during the course of the
reaction, in the presence of abundant oxidant, selective triflu-
oroacetoxylation of the 2-methyl group occurs (see Scheme 3
and related discussion), and the hydroxymethyl product 3j is
the final outcome from hydrolysis of a trifluoroacetate ester
during workup in a basic medium.
Formation of 6-Substituted Phenanthridines
Following a series of successful phenanthridine cyclizations,
it was of additional interest to determine whether 6-
substituted phenanthridines might be prepared by this proce-
dure since they are less accessible by classic methodology.[7]
It was decided that a phosphoryl substituent would offer the
challenge of keeping this substituent intact during the vigor-
ous reaction conditions. It had the added attraction that no
6-phosphorylated phenanthridines have been reported and
would thus be attractive candidates for biological testing.
It is known[10] that phosphites add readily to Schiff’s bases
and it was expected that, with judicious selection of ring
substituents, the resulting benzylamine would be a suitable
substrate to test the procedure.
Warming a mixture of piperonaldehyde, 2,4-dichloro-
aniline, and two equivalents of diethyl phosphite at 85◦C for
8 haffordedthephosphonate2gasacandidateforcyclization.
Gratifyingly, this substituent survived the conditions required
for cyclization to give the first example of a 6-phosphono-
substituted phenanthridine 3h, albeit in low yield (16%, based
on reacted starting material). The rate-retarding effect of
the phosphonate substituent was initially underestimated and
under the standard reaction conditions much of the starting
material (57%) was recovered. By a similar procedure, fusion
of piperonaldehyde, 2,4-dimethylaniline, and two equivalents
of diethyl phosphite gave the corresponding diethyl phos-
phonate 2h. While phosphonic esters are usually relatively
resistant to hydrolysis, it was found that even under these
mild reaction conditions a significant quantity of the corre-
sponding monoethyl ester 2i was isolated, presumably from
the action of water generated during the initial condensation.
This partially hydrolyzed material was easily separated from
themainproduct 2hbyextractionofthemixturewithaqueous
sodium carbonate. However, the monoester 2i failed to give
a phosphorylated phenanthridine with vanadium oxytrifluo-
ride and produced only a low yield of the dephosphorylated
material 3a, previously obtained by cyclization of 2a. On the
It is interesting to note that the benzylisoquinoline alkaloid
laudanosine has been cyclized with two molar equivalents of
vanadium oxytrifluoride to give 4-hydroxyglaucine[11] (40%
yield), possibly by a mechanistically related hydroxylation at
a benzylic position.
Mechanism and Scope
In the current study, it is unlikely that oxidation to the imine
(Schiff’s base) is the first step, since attempts to oxidize
either the imine 1a or 1b failed to produce any phenan-
thridine product. By contrast, it is noteworthy that some
success has been achieved in a vanadium oxytrifluoride
mediated synthesis of a benzophenanthridine from the cor-
responding 1-naphthylamine derived Schiff’s base, albeit in
‘extremely variable’yields.[13] On the other hand, anodic oxi-
dation, which sometimes gives[14] products resembling those
obtained with electron-abstracting inorganic oxidants, failed
to give any benzophenanthridine. Interestingly, reduction
to the N-naphthylbenzylamine followed by anodic oxida-
tion also failed to produce any cyclized material. The effect
of vanadium oxytrifluoride on the benzylamine was not
reported.[13]
It is generally agreed[15] that cation radicals are formed
as reactive intermediates during coupling between aromatic
rings during reactions of this type as well as within related
electrochemical processes. Despite this knowledge it is usu-
ally not possible to decide whether a given coupling has
occurred from an initial reaction between an electrophilic
cation radical and an aromatic ring or, alternatively, as a
result of pairing between two radical cations followed by
proton expulsion. As an example, one can speculate upon
the processes which may take place during the cyclization of
2a to give the phenanthridine 3a. It appears[16] that oxida-
tive coupling of non-phenolic aromatics, either by action of

Action of Vanadium Oxytrifluoride on N-Arylbenzylamines
477
O
O
O
O
O
O
ϩ
ϩ
R
R
R
H
Ϫ2e
Ϫ2Hϩ
NH
NH
N
H3C
CH3
H3C
CH3
CH3
H3C
2a
A
ϩ
O
ϩ
O
path a
O
O
O
O
H
R
R
R
H
path a
ϪHϩ
Ϫe
Ϫe
N
6
H
Nϩ
Nϩ
H
CH3
4
H3C
2
H
CH3
CH3
C
H3C
H
VOF3
H
3a R ϭ H
2h R ϭ –P(O)(OEt)2
B
path b
ϪHϩ
path b
O
O
O
O
O
H
O
R
R
N
R
Ϫ2e Ϫ2Hϩ
Nϩ
H2O
H
NH
CH3
HO
CH3
O
O
CH3
CF3COOϪ
CF3
C
D
3j
Rϭ –P(O)(OEt)2
Scheme 3.
a chemical agent or by an electric current is initiated by
removalofanelectronfromthearomaticsextetofanelectron-
rich aromatic ring. The ring in which the cation radical
has formed (possibly stabilized by complexation with a
vanadyl species) may then undergo nucleophilic attack by
an unchanged aromatic ring followed by proton expulsion.
Oxidation of the resultant radical to a cation followed by
another proton loss gives the final product by an ECE (elec-
tron abstraction–coupling–electron abstraction) mechanism
(for example 2b to 3b, Scheme 2). Alternatively, each aro-
matic nucleus may be converted into a cation radical followed
by radical coupling and expulsion of two protons in an
EEC process (2a to 3a, Scheme 3). Usually it is difficult
to distinguish between these pathways, although the electro-
chemically induced ECE mechanism may favour intermolec-
ular coupling.[17] Following formation of the electron-rich
tetrahydrophenanthridine (A; R = H, Scheme 3), sequential
removal of two electrons to generate the dicationic species
(B; R = H, or an equivalent canonical form) seems unexcep-
tional. Elimination of the proton at C6 (B, path a) would then
lead to the phenanthridine salt (3a; R = H).
follows. A minor pathway may be present wherein a pro-
ton is abstracted from the intermediate dication (B; R = H)
at the 2-methyl group (path b, Scheme 3) rather than C6
(path a, Scheme 3) to give C. This could then add a trifluoro-
acetate anion to give the dihydrophenanthridine D, which is
readily oxidized further to a phenanthridine and then finally
hydrolyzed to a benzyl alcohol during the alkaline workup.
Notably, cyclization of the phosphonate 2h led to substan-
tial amounts of a hydroxymethylphenanthridine product 3j.
Previously, it had been found that the addition of vanadium
oxytrifluoride in excess of the four equivalents required to
form the phenanthridine 3a did little to affect the trace of the
accompanying hydroxymethyl compound. On the other hand,
while the phosphonate starting material and four equivalents
of oxidant readily gave the phenanthridine 3i and some (8%)
of the 2-hydroxymethyl product 3j, the addition of six equiva-
lents raised the yield of 3j to 52%. It may be that the presence
of the bulky phosphonate at C6 (Scheme 3) makes deproto-
nation via path a (B, R = P(O)(OEt)2) relatively less ready,
allowing path b (B, R = P(O)(OEt)2) to assume a dominant
role in this instance.
During some of these cyclizations, small quantities of
2-hydroxymethyl products apparently arise by transforma-
tion of an aromatic methyl substituent. This may occur as
An attempt was made to verify the intervention of a
mechanism where a potentially reversible C–H dissociation
such as the one implied in Scheme 3, path b, might occur.

478
A. J. Liepa, R. N. Nearn and D. M. J. Wright
Thus, the cyclization of 2a was reinvestigated but using a
solution in deuterated trifluoroacetic acid rather than trifluo-
roacetic acid. However, no appreciable loss or diminution of
requires C 75.8, H 7.1, N 5.2%). δH (CDCl3) 2.27, 2.29 (each 3H, each
s, 2 Me), 3.95, 3.99 (each 3H, each s, 2 OMe), 6.92 (1H, d, J 8.0,
ArH), 7.0–7.4 (4H, m, 4 ArH), 7.63 (br s, ArH), 8.38 (1H, s, ArH). This
Schiff’s base failed to give any phenanthridine product when treated
with vanadium oxytrifluoride.
1
any of the previously observed H NMR signals indicating
incorporation of deuterium in the product, 3a, was seen.
As successful cyclization is dependent upon removal of
an electron from an aromatic sextet, the synthesis is limited
to aromatic nuclei which are relatively electron rich in order
to achieve a necessary minimum ionization potential, a value
probably[16] in the order of +1.2V. This requirement can be
readily accommodated by the presence of two alkoxy groups
or by an amino substituent on one ring. In the latter instance,
some mild electron-withdrawing substituents may then be
tolerated on the same ring as shown by the cyclization of
2c–2f to form 3d–3g.
(Benzo[1,3]dioxol-5-ylmethyl)(2,4-dimethylphenyl)amine 2a
Method A
Dimethylamine borane (1 g, 17.0 mmol) was added to a solution of
piperonaldehyde (3.0 g, 20.0 mmol) and 2,4-dimethylaniline (2.4 g,
19.8 mmol) in acetic acid (20 mL) with cooling to maintain the tem-
perature at less than 25◦C. The solution was stirred until it became
colourless, heated on a steam bath (2 min), and diluted with water to a
faint turbidity. When the mixture had cooled, the crystalline precipitate
was collected by filtration and recrystallized from isopropyl alcohol to
give the product (4.1 g, 80%) as colourless blades, mp 98–99◦C (Found:
C 75.1, H 6.7, N 5.6. C16H17NO2 requires C 75.3, H 6.7, N 5.5%).
δH (CDCl3) 2.14, 2.23 (each 3H, each s, 2 Me), 4.26 (2H, s, CH2), 5.9
(2H, s, OCH2O), 6.52 (1H, d, J 8.8, ArH), 6.76–6.91 (5H, m, 5 ArH).
Experimental
Melting points were determined on a Reichert Kofler hot-stage micro-
melting point apparatus and are uncorrected. Microanalyses were per-
formed by Campbell Microanalytical Laboratory, University of Otago,
New Zealand. Infrared spectra were recorded on a Perkin Elmer 842
spectrophotometer using KBr disks. 1H and 13C NMR spectra were
recorded at 200 and 50.3 MHz respectively on a Bruker AC-200 spec-
trometer, or at 250 and 62.9 MHz on a Bruker AC250 instrument.
Phosphorus NMR spectra were recorded relative to 85% phosphoric
acid as an external standard. Chemical shifts (δ) are measured in ppm.
High-resolution chemical ionization mass spectra were obtained on a
Jeol JMS-DX303 mass spectrometer. Low-resolution mass spectra were
recorded on a Fisons Instruments VG Platform quadrupole using either
atmospheric pressure chemical ionization (APCI) or electrospray ion-
ization (ESI) in the positive and/or negative ion modewith a cone voltage
of 30 eV for both APCI and ESI, with either 1 : 1 acetonitrile/water or
methanol as solvent. Radial thin-layer chromatography was performed
on a Harrison Research Chromatotron (7924T) using 4-mm thick silica
plates (silica gel 60 PF254, Merck No. 7749). Light petroleum refers to
the fraction with a bp of 40–60◦C. Trifluoroacetic acid, when used for
NMR, was in a 10% concentration v/v in CDCl3.
Method B
A mixture of piperonaldehyde (16.5 g, 0.11 mol) and 2,4-dimethyl-
aniline (12.1 g, 0.10 mol) was heated at 100◦C for 3 h in an open flask.
Thecooledmixturewasdissolvedinmethanol(180 mL)at40◦C, sodium
borohydride (4.0 g, 0.11 mol) was added in portions, and the tempera-
ture of the mixture raised to 60◦C for 2 h. The mixture was cooled,
water (300 mL) added, and the precipitate collected by filtration. The
crude product was stirred with a mixture of ether (100 mL) and aqueous
hydrochloric acid (2 M, 100 mL). The aqueous solution and the ethereal
layer were separated from an oily material at the interface and the
ether solution was re-extracted with hydrochloric acid (2 M, 2 × 50 mL).
The oil was dissolved in ethyl acetate (100 mL), which was further
extracted with hydrochloric acid (2 M, 100 mL). The combined aque-
ous extracts were neutralized by the addition of sodium bicarbonate, and
the precipitate was collected and recrystallized from isopropyl alcohol
to give colourless needles identical with the product obtained above
(14.9 g, 53%).
The following benzylamines were obtained by in-situ preparation of
the Schiff’s bases followed by reduction (method B).
(3,4-Dimethoxybenzyl)(3,4-dimethylphenyl)amine 2b
(Benzo[1,3]dioxol-5-ylmethylene)(2,4-dimethylphenyl)amine 1a
Veratraldehyde (3.3 g, 0.02 mol) and 3,4-dimethylaniline (2.4 g,
0.02 mol) were heated together at 100◦C for 4 h. Addition of ethanol
(80 mL) followed by sodium borohydride (1 g, 0.026 mol) gave the
product (4.1 g, 76%) as colourless needles, mp 115–116◦C, from iso-
propylalcohol(Found:C75.3, H7.9, N5.2. C17H21NO2 requiresC75.3,
H 7.8, N 5.2%). δH (CDCl3) 2.18, 2.21 (each 3H, each s, 2 Me), 3.79
(1H, m, NHCH2), 3.89 (each 3H, s, 2 OMe), 4.2 (2H, d, J 5.4, NHCH2),
6.6–7.0 (6H, m, 6 ArH).
Piperonaldehyde and 2,4-dimethylaniline in equimolar quantities were
heated under reflux in benzene for 4 h and the solution was evaporated
under reduced pressure. Recrystallization of the residue from isopropyl
alcohol gave the product as pale yellow prisms, mp 67–68◦C (Found:
C 76.0, H 6.3, N 5.6. C16H15NO2 requires C 75.8, H 6.0, N 5.5%). δH
(CDCl3) 2.34 (6H, s, 2 Me), 6.04 (2H, s, CH2), 6.8–7.3 (5H, m, 5ArH),
7.59 (1H, s, ArH) 8.25 (1H, s, ArH).
Reaction of 1a with Vanadium Oxytrifluoride
(3,4-Dimethoxybenzyl)(4-trifluoromethylphenyl)amine 2c
The Schiff’s base 1a (1.3 g, 5.1 mmol) was dissolved in a mixture of
trifluoroacetic acid (4 mL) and dichloromethane (6 mL) at 0◦C and
treated with a solution of vanadium oxytrifluoride (1.3 g, 10.5 mmol)
dissolved in a mixture of ethyl acetate (3 mL) and trifluoroacetic acid
(7 mL). The orange solution was stirred at 0◦C for 30 min and then
at room temperature for 30 min without any significant change in
colour. It was then stirred into a mixture of 5% aqueous citric acid
(50 mL) and dichloromethane (10 mL) at 0◦C. An orange-yellow mix-
ture was observed briefly which rapidly changed to red then purple,
particularly within the dichloromethane layer. After 5 min, examination
of the dichloromethane phase by TLC showed no significant amount
of phenanthridine; only piperonaldehyde and a highly coloured polar
material were evident.
This was recrystallized from isopropyl alcohol to give the product as
colourless prisms (58%), mp 99–101◦C (Found: C 61.9, H 5.3, N 4.6.
C16H16F3NO2 requires C 61.7, H 5.2, N 4.5%). δH (CDCl3) 3.86, 3.87
(each 3H, each s, 2 OMe), 4.29 (2H, s, CH2), 4.45 (1H, br s, NH),
6.64 (2H, d, J 8.8, 2 ArH), 6.82–6.94 (3H, m, 3 ArH), 7.39 (2H, d,
J 8.8, 2 ArH).
(Benzo[1,3]dioxol-5-ylmethyl)(2,4-dichlorophenyl)amine 2d
This was obtained by heating piperonaldehyde (4.5 g, 0.03 mol) with
2,4-dichloroaniline (4.9 g, 0.03 mol) followed by reduction with sodium
borohydride (2 g, 0.053 mol) in ethanol to afford the product (5.4 g,
61%)ascolourlessneedlesfromisopropylalcohol, mp63–64◦C(Found:
C 56.7, H 3.6, N 4.6%. C14H11Cl2NO2 requires C 56.8, H 3.7, N 4.7%).
δH (CDCl3) 4.28 (2H, s, CH2N), 5.96 (2H, s, OCH2O), 6.56 (1H, d,
J 8.8, ArH), 6.78–6.82 (3H, m, 3 ArH), 7.04 (1H, dd, J 2.2, ArH), 7.26
(1H, d, J 2.2, ArH).
(3,4-Dimethoxybenzylidene)(3,4-dimethylphenyl)amine 1b
This was recrystallized from ethanol to give the product as pale yellow
needles, mp 123–124◦C (Found: C 75.6, H 7.0, N 5.5. C17H19NO2

Action of Vanadium Oxytrifluoride on N-Arylbenzylamines
479
By Method A
45%) as colourless prisms, mp 81–82◦C (Found: C 61.5, H 6.6, N 3.6.
C20H26NO5P requires C 61.4, H 6.7, N 3.5%). δH (CDCl3) 1.18, 1.29
(each 3H, each t, J 7.3, 2 CH2Me), 2.18, 2.23 (each 3H, each s, 2 Me),
3.6–4.2 (4H, m, 2 CH2Me), 4.65 (1H, d, J 24.1, CH), 5.93 (2H, dd,
J 1.5, 4.4, OCH2O), 6.41 (1H, d, J 8.4, ArH), 6.7–7.0 (5H, m, 5 ArH).
Dimethylamine borane (1.3 g, 0.022 mol) was added in portions (0.2 g)
over 1 h to a solution of piperonaldehyde (6.0 g, 0.04 mol) and 2,4-
dichloroaniline (6.5 g, 0.04 mol) in acetic acid (25 mL) maintained at
20◦C. After standing the solution for 2 h, colourless needles began to
separate and the whole was left overnight. The next day, the mixture was
diluted slowly with water (50 mL), and the solid collected by filtration
and recrystallized from ethanol to give colourless needles (8.7 g, 72%)
identical with the compound prepared above.
2,4-Dimethyl-[1,3]dioxolo[4,5-j]phenanthridine 3a
A solution of the benzylamine 2a (4.74 g, 0.018 mol) in a mixture of tri-
fluoroacetic acid/dichloromethane (1 : 1, 40 mL) was cooled to −20◦C
(internal temperature) and treated with a solution of vanadium oxytri-
fluoride (10.3 g, 0.083 mol) in a mixture of dichloromethane (20 mL),
trifluoroacetic acid (20 mL), and ethyl acetate (10 mL). After 5 min,
TLC showed a partial reaction, and stirring was continued at −10◦C
for 15 min. The reaction mixture was poured into a mixture of aque-
ous citric acid (10%, 100 mL), aqueous sodium metabisulfite (10%,
100 mL), and ice (100 g). After stirring for 15 min, the mixture was
chilled and adjusted to pH 8 by the addition of concentrated aque-
ous ammonia. The organic solvents were allowed to evaporate, and
the solid was collected by filtration and stirred with dichloromethane
(200 mL), leaving behind some insoluble residue. The solution was
filtered, the solvent was removed by evaporation, and the residue was
chromatographed upon silica gel using dichloromethane as the initial
eluant and progressing to dichloromethane/ethyl acetate (1 : 1). Early
fractions returned unchanged benzylamine (0.93 g, 0.004 mol), while
crude phenanthridine was obtained by combining the more polar frac-
tions. Evaporation followed by recrystallization of the residual material
from ethyl acetate/light petroleum gave the title compound as colour-
less needles (1.96 g, 41%), mp 186–188◦C with prior sublimation from
165◦C (Found: C 76.6, H 5.2, N 5.6. C16H13NO2 requires C 76.5,
H 5.2, N 5.6%). δH (CDCl3) 2.57, 2.83 (each 3H, each s, 2 Me), 6.16
(2H, s, CH2), 7.32, 7.39, 7.89, 8.01 (each 1H, each s, 4 ArH), 9.08 (1H,
s, CH=N). δC (CDCl3) 18.6, 21.8, 99.8, 101.7, 105.0, 119.3, 122.8,
123.9, 130.0, 130.5, 135.8, 137.1, 141.2, 147.5, 149.4, 150.9.
(2,3-Dichlorophenyl)(3,4-dimethoxybenzyl)amine 2e
This was recrystallized from cyclohexane to give the product as colour-
less prisms (17.5 g, 56%), mp 110–111◦C (Found: C 57.5, H 4.9, N 4.5.
C15H15Cl2NO2 requires C 57.7, H 4.8, N 4.5%). δH (CDCl3) 3.88 (6H,
s, 2 OMe), 4.33 (2H, s, CH2), 6.54 (1H, dd, J 1.5, 8.1, ArH), 6.79 (1H,
dd, J 2.4, 8.1, ArH), 6.86–7.06 (4H, m, 4 ArH).
(2,4-Dichlorophenyl)(3,4-dimethoxybenzyl)amine 2f
This was recrystallized from light petroleum to give the product as
colourless prisms (29%), mp 62–64◦C (Found: C 57.7, H 5.0, N 4.4.
C15H15Cl2NO2 requires C 57.7, H 4.8, N 4.5%). δH (CDCl3) 3.87 (6H,
s, 2 OMe), 4.31 (2H, s, CH2), 6.56 (1H, d, J 8.8, ArH), 6.84–6.92 (3H,
m, 3 ArH), 7.05 (1H, dd, J 2.5, 8.8, ArH), 7.27 (1H, d, J 2.5, ArH).
Diethyl [Benzo[1,3]dioxol-5-yl-
(2,4-dichlorophenylamino)methyl]phosphonate 2g
A mixture of piperonaldehyde (1.5 g, 0.01 mol), 2,4-dichloroaniline
(1.6 g, 0.01 mol), and diethyl phosphite (2.8 g, 0.02 mol) was heated
at 80◦C for 8 h, and then cooled, dissolved in ether (60 mL), and washed
with water (3 × 50 mL).The ether solution was evaporated to give a light
brown oil which began to crystallize after several hours. The material
was collected and recrystallized from benzene to give the product (2.7 g,
62%) as fawn needles, mp 110–111◦C (Found: C 50.2, H 4.6, N 3.6.
C18H20Cl2NO5P requires C 50.0, H 4.7, N 3.3%). δH (CDCl3) 1.21,
1.29 (each 3H, each t, J 7.3, 2 CH2Me), 3.7–4.2 (4H, m, 2 CH2Me),
4.64 (1H, d, J 24.2, CH), 5.24 (1H, br s, NH), 5.94 (2H, dd, J 1.4, 2.6,
OCH2O), 6.37 (1H, d, J 8.8, ArH), 6.74 (1H, d, J 8.8, ArH), 6.75–7.0
(3H, m, 3 ArH), 7.25 (1H, d, J 2.2, ArH).
A later crude fraction (15 mg) had a 1H NMR spectrum suggestive
of a monohydroxylated product. δH (CDCl3) 2.20 (1H, br, CH2OH),
2.83 (3H, s, Me), 4.89 (2H, s, CH2OH), 6.15 (2H, s, OCH2O), 7.29
(1H, s, ArH), 7.51, 7.82 (each 1H, br s, 2 ArH), 9.05 (1H, s, CH=N).
An attempt to generate the hydroxymethyl compound from the
phenanthridine 3a by treatment with additional vanadium oxytrifluoride
returned unchanged phenanthridine.
Diethyl [Benzo[1,3]dioxol-5-yl-
(2,4-dimethylphenylamino)methyl]phosphonate 2h
and Ethyl [Benzo[1,3]dioxol-5-yl-
(2,4-dimethylphenylamino)methyl]phosphonate 2i
Preparation of 3a by Reverse Addition—to Vanadium
Oxytrifluoride in Suspension
A solution of the benzylamine 2a (1.0 g, 0.004 mol) in a mixture of
dichloromethane (5 mL) and trifluoroacetic acid (5 mL) was stirred
into a suspension of vanadium oxytrifluoride (3.9 g, 0.31 mol) in a
mixture of dichloromethane (5 mL) and trifluoroacetic acid (5 mL) at
0◦C. After 15 min, the yellow-green suspension was stirred into a mix-
ture of d-tartaric acid (10 g), sodium metabisulfite (5 g), and ice/water
(100 g), and basified after 10 min to pH 9–10 by addition of concentrated
ammonium hydroxide. The product was extracted into dichloromethane
(2 × 100 mL), and the extract was washed with water and evaporated to
dryness to afford a solid which was recrystallized from ethyl acetate
to give the phenanthridine (0.79 g, 80%) as colourless needles, mp
187–188◦C, identical with the material 3a prepared above.
A mixture of piperonaldehyde (6.5 g, 0.04 mol) and 2,4-dimethylaniline
(4.8 g, 0.04 mol) in diethyl phosphite (11.4 g, 0.082 mol) was heated at
80◦C for 10 h and then stirred into water (100 mL). The mixture was
allowed to cool and the supernatant liquid was decanted from a tarry
residue that was dissolved in isopropyl alcohol (35 mL). The solution
was treated dropwise with water until a faint turbidity appeared, and then
stirred at room temperature for 48 h to afford a colourless precipitate
which was collected to yield the crude phosphonate diethyl ester (5.3 g).
The filtrate was diluted with water (200 mL) and extracted with ether
(100 mL), which was then extracted with aqueous sodium carbonate
(7%, 2 × 40 mL). The aqueous extract was acidified with concentrated
hydrochloric acid. The precipitated oil was collected by extraction with
ether (2 × 50 mL), which was then removed by evaporation to afford the
phosphonic acid monoethyl ester 2i as a red-brown oil (5.5 g, 38%) that
hardened to a glass (Found: m/z 364.1318. C18H22NO5P · H+ requires
364.1308). δH (CDCl3) 1.16 (3H, t, J 7.3, CH2Me), 2.20, 2.24 (each
3H, each s, 2 ArMe), 3.37–3.39 (2H, m, CH2Me), 4.56 (1H, d, J 22.6,
CHP) 6.43 (2H, br s, OCH2O), 6.3–6.9 (6H, m, 6 ArH), 9.05 (2H, br,
NH and OH). δP (CDCl3) 20.5 (d, J 0.22).
Preparation of 3a by Reverse Addition—to Vanadium
Oxytrifluoride in Solution
The reaction was carried out with the benzylamine 2a (1.0 g, 0.004 mol)
as in the previous experiment, except that complete dissolution of the
vanadium oxytrifluoride (4.0 g, 0.032 mol) was effected by prior addi-
tion of ethyl acetate (4 mL) to the mixture of dichloromethane (5 mL)
and trifluoroacetic acid (5 mL). The reaction gave a homogeneous deep
green-brown solution which was worked up in the usual way. Recrys-
tallization of the residue from aqueous ethanol gave the phenanthridine
as colourless needles (0.83 g, 83%), mp 186–188◦C, identical with the
material 3a prepared above.
The ether solution remaining after the sodium carbonate extraction
was evaporated and the residue stirred with aqueous isopropyl alco-
hol to afford a further quantity of the phosphonate diethyl ester (3.4 g)
which was combined with the first crop obtained above and recrystal-
lized from benzene to afford the phosphonic acid diethyl ester 2h (7.1 g,

480
A. J. Liepa, R. N. Nearn and D. M. J. Wright
8,9-Dimethoxy-2,3-dimethylphenanthridine 3b,
8,9-Dimethoxy-1,2-dimethylphenanthridine hydrochloride 3c,
and 8,9,8ꢀ,9ꢀ-Tetramethoxy-2,3,2ꢀ,3ꢀ-tetramethyl-
[10,10ꢀ]biphenanthridine 4
location of the substituents in 3c was confirmed by the following NOE
interactions. Irradiation of the aromatic singlet at δ 7.33 resulted in
an interaction with the CH adjacent to the N (δ 9.02) and one of the
methoxyl groups (δ 4.04). Irradiation of the other aromatic singlet (at
δ 8.13) gave an interaction with the other OMe (δ 4.06) and a smaller
interaction with one of the methyl groups (δ 2.92) from the other ring.
Irradiation of one of the methyls (δ 2.54) showed an interaction with
one of the aromatic ab pairs (δ 7.49). Irradiation of the other methyl
(δ 2.92) showed an interaction with the other methyl and one of the
proton singlets (δ 8.13) from the other ring but not with the aromatic ab
doublet.
A solution of the benzylamine 2b (4.6 g, 0.017 mol) in a mixture of
dichloromethane (20 mL) and trifluoroacetic acid (20 mL) was cooled
to −20◦C while a solution of vanadium oxytrifluoride (9.3 g, 0.075 mol)
in a mixture of dichloromethane (5 mL), trifluoroacetic acid (20 mL),
and ethyl acetate (10 mL) was added in a thin stream. Following com-
pletion of the addition, the cooling bath was removed and the mixture
was warmed to 20◦C over 15 min and then stirred into a mixture of aque-
ous citric acid (20%, 100 mL) and ice (100 g). After 10 min, the stirred
mixture was kept at a temperature of 10◦C and made slightly alkaline
by the addition of concentrated ammonia. The mixture was extracted
with dichloromethane (2 × 200 mL) and the combined extracts were
evaporated under reduced pressure to give a light brown solid (4.6 g).
The solid was boiled with methanol (200 mL) for 10 min, cooled, and
the product 4 was collected as a colourless powder by filtration (0.36 g,
7%), mp > 270◦C (Found: C 76.1, H 6.1, N 5.1. C34H32N2O4 · 0.25H2O
requires C 76.0, H 6.1, N 5.2%). δH (CDCl3) 2.54 (6H, s, 2 Me),
2.96 (6H, s, 2 Me), 3.95, 4.06 (each 6H, each s, 4 OMe), 7.18, 7.53,
8.16 (each 2H, each s, 6 ArH), 8.82 (1H, s, CH=N). δC (CDCl3)
21.3, 21.8, 55.9, 56.0, 107.7, 108.4, 123.0, 124.4, 128.8, 131.3, 132.3,
135.3, 138.4, 142.7, 148.6, 150.2, 150.8. m/z (APCI+) 533 (M + 1).The
assigned structure was supported by NOE experiments, which revealed
the following interactions.
Irradiation of both methoxyls resulted in an interaction with each of
the aromatic singlets but was without any effect upon the ab pair.
8,9-Dimethoxy-2-trifluoromethylphenanthridine 3d
A solution of the benzylamine 1c (1.2 g, 3.8 mmol) in dichloromethane/
trifluoroacetic acid (1 : 1, 10 mL) at −30◦C was treated with a solu-
tion of vanadium oxytrifluoride (1.9 g, 15.3 mmol) in ethyl acetate/
trifluoroacetic acid (1 : 2, 12 mL). After 10 min, the mixture was
worked up as in 3a and the residue chromatographed over silica gel.
Elution with dichloromethane/light petroleum (1 : 1) progressing to
dichloromethane/ethyl acetate (1 : 1) successively eluted 4-trifluoro-
methyl aniline (75 mg) and veratraldehyde (220 mg) followed by crude
phenanthridine which was recrystallized from ethanol to give the
product as colourless needles (0.62 g, 52%), mp 164–166◦C (Found:
C 62.5, H 3.9, N 4.5. C16H12F3NO2 requires C 62.5, H 3.9, N 4.6%).
δH (CDCl3) 4.07, 4.16 (each 3H, each s, 2 OMe), 7.34 (1H, s, ArH),
7.79 (1H, s, ArH), 7.83 (1H, dd, J 1.1, 8.0, ArH), 8.20 (1H, d, J 8.0,
ArH), 8.62 (1H, br s,ArH), 9.18 (1H, s, CH=N). δC (CDCl3) 56.0, 56.3,
101.4, 107.7, 119.3, 121.8, 123.4, 124.8 (q, J 61), 127.6, 128.2, 130.8,
130.9, 145.1, 150.4, 153.2, 153.5. m/z (APCI+) 308 (M + 1).
Irradiation of each methyl (at δ 2.54 and 2.96) independently resulted
in an equal response from two aromatic protons (δ 7.53 and 8.16 respec-
tively). Irradiation of one of the aromatic protons (δ 7.18) showed an
interaction with the CH adjacent to the N (δ 8.82), as well as one of
the methoxyls (δ 3.95). Irradiation of the CH adjacent to the N (δ 8.82)
resulted in a single interaction with one aromatic H (δ 7.18), which had
been previously demonstrated to be adjacent to one of the methoxyls
(δ 3.95).
2,4-Dichloro-8,9-methylenedioxyphenanthridine 3e
The benzylamine 2d (4.4 g, 0.015 mol) in dichloromethane (20 mL) and
trifluoroacetic acid (20 mL) was cooledto −20◦C and a solution of vana-
dium oxytrifluoride (9.1 g, 0.073 mol) in a mixture of trifluoroacetic
acid (20 mL) and ethyl acetate (10 mL) was added over 5 min. The mix-
ture was allowed to attain room temperature during the next 20 min and
then stirred into aqueous citric acid (20%, 100 mL) and ice (100 g). The
mixture was stirred and kept at <15◦C during the addition of concen-
trated ammonium hydroxide to pH 8. Dichloromethane (100 mL) was
added to the mixture, which was then stirred overnight and filtered.
The solid was washed on the filter with water and dichloromethane
to give the product 3e (2.5 g, 58%), and a portion was obtained as
needles from N,N-dimethylformamide, mp > 280◦C (Found: C 57.4,
H 2.3, N 4.9. C14H7Cl2NO2 requires C 57.6, H 2.4, N 4.8%). δH
(CDCl3/CF3COOH) 6.44 (2H, s, CH2), 7.73 (1H, s, ArH), 8.01 (1H,
d, J 2.2, ArH), 8.05 (1H, s, ArH), 8.51 (1H, d, J 2.2, ArH), 9.45
(1H, s, CH=NH+). δC (CDCl3/CF3COOH) 101.4, 104.8, 108.0, 121.6,
121.9, 123.1, 126.6, 126.8, 127.5, 131.8, 135.0, 136.5, 146.8, 152.0.
m/z (APCI+) 292 (M + 1).
The filtrate was evaporated, the residue was dissolved in a mixture
of dichloromethane (40 mL) and methanol (10 mL), diluted with ethyl
acetate (15 mL), and the temperature raised to boiling point. Solvent was
allowed to evaporate until a volume of 50 mL was reached, and evapora-
tion by boiling was continued with a constant volume being maintained
by the periodic addition of ethyl acetate. After 1 h, the mixture was
allowed to cool, was filtered, and the precipitate was washed lightly
with ethyl acetate to give a fawn powder which was recrystallized from
ethanol to afford the product 3b as cream needles (1.87 g, 40%), mp
222–224◦C (Found: C 76.2, H 6.4, N 5.2. C17H17NO2 requires C 76.4,
H 6.4, N 5.2%). δH (CDCl3/CF3COOH) 2.42 (3H, s, ArMe), 2.53 (3H,
s, ArMe), 4.02 (3H, s, OMe), 4.24 (3H, s, OMe), 7.30, 7.80, 7.89, 8.14
(each 1H, each s, 4 ArH), 9.31 (1H, s, CH=N). δC (CDCl3) 19.9, 20.0,
55.8, 55.9, 101.2, 107.4, 121.2, 121.4, 121.6, 127.6, 129.6, 135.8, 137.1,
142.5, 149.2, 150.5, 152.4.
The mother liquors were evaporated, the residue was dissolved in hot
methanol (40 mL), and concentrated hydrochloric acid (1.4 mL) was
added dropwise to give a pale yellow precipitate. Water (10 mL) was
added, the mixture was simmered for 2 h, and left to cool. The next
day, the precipitate (1.44 g) was collected as a pale yellow crystalline
solid (still containing approximately 15% of the other isomer). The
hydrochloride was recrystallized from formic acid/methanol (1 : 4) to
give pale yellow needles of 8,9-dimethoxy-1,2-dimethylphenanthridine
hydrochloride 3c (1.09 g, 21%), mp 238–241◦C (Found: C 66.9, H 6.1,
N 4.7. C17H18ClNO2 requires C 67.2, H 6.0, N 4.6%). δH (CDCl3/
CF3COOH) 2.66 (3H, s, ArMe), 3.06 (3H, s, ArMe), 4.15 (3H, s, OMe),
4.24 (3H, s, OMe), 7.26 (1H, s, ArH), 7.78 (1H, d, J 8.1, ArH) 8.08 (1H,
d, J 8.1, ArH), 8.35 (1H, s, ArH), 9.45 (1H, d, J 1.9, CH=NH+). δC
(CDCl3/CF3COOH) 20.8, 21.7, 56.4, 56.6, 108.1, 110.7, 111.6, 117.2,
118.9, 120.5, 132.0, 133.4, 133.9, 140.8, 144.6, 150.5, 157.1. For NOE
studies, a portion of the hydrochloride salt was converted into the free
base by shaking it with a mixture of aqueous sodium carbonate and
deuterated chloroform. δH (CDCl3) 2.54, 2.92, 4.04, 4.06 (each 3H,
each s, 2 ArMe, 2 OMe), 7.33 (1H, s, ArH), 7.49 (1H, d, J 8.2, ArH),
7.93 (1H, d, J 8.2, ArH), 8.13 (1H, s, ArH), 9.02 (1H, CH=N). The
3,4-Dichloro-8,9-dimethoxyphenanthridine 3f
Vanadium oxytrifluoride (1.6 g, 0.013 mol) dissolved in a mixture of tri-
fluoroacetic acid (10 mL) and ethyl acetate (5 mL) was added to the ben-
zylamine 2e (1.0 g, 0.0032 mol) in trifluoroacetic acid/dichloromethane
(1 : 1, 10 mL) maintained at 0◦C. After 30 min, the mixture was worked
up as in 3a. The residue was stirred with ethanol (50 mL) to recover
starting material (300 mg was obtained from the ethanol solution) and
the residue was crystallized from dichloromethane to yield the product
3f as fawn needles (450 mg, 69%), mp 251–252◦C (with prior sub-
limation from 230◦C) (Found: C 58.4, H 3.6, N 4.6. C15H11Cl2NO2
requires C 58.5, H 3.6, N 4.6%). δH (CDCl3/CF3COOH) 4.17 (3H, s,
Me), 4.33 (3H, s, Me), 7.83 (1H, s, ArH), 8.05 (1H, d, J 9.14, ArH),
8.09 (1H, s, ArH), 8.65 (1H, d, J 9.14, ArH), 9.62 (1H, s, CH=NH+).
δC (CDCl3/CF3COOH) 56.4, 57.1, 102.6, 110.1, 119.6, 122.3, 122.5,
123.8, 124.2, 129.7, 131.2, 133.6, 136.7, 147.0, 152.7. m/z (APCI+)
308 (M + 1).

Action of Vanadium Oxytrifluoride on N-Arylbenzylamines
2,4-Dichloro-8,9-dimethoxyphenanthridine 3g
481
keep the internal temperature at −25 to −30◦C. Workup of an aliquot
showed negligible reaction, the reaction mixture was allowed to warm
to 0◦C over 30 min when examination of a further aliquot indicated
no remaining starting material. The mixture was worked up in the
usual way and extracted with dichloromethane (2 × 50 mL). The sol-
vent was removed under reduced pressure and the residue was stirred
with ether (40 mL), leaving a colourless solid (1.65 g). The ether was
removed and the residue was chromatographed over silica progress-
ing from dichloromethane to dichloromethane/ethyl acetate (1 : 1). The
fractions containing less polar material were combined, evaporated, and
recrystallized from ethyl acetate to afford the dephosphorylated phenan-
thridine 3a (0.13 g, 8%), identical with the sample described previously.
Amorepolarmaterialwascontainedinthenextfewfractionswhichwere
combined with the solid obtained above by filtration and the material
remaining after removal of the solvent was recrystallized from methanol
to give colourless woolly needles of the diethyl ester 3i (1.52 g, 59%),
mp 200–202◦C (Found: C 61.7, H 5.6, N 3.6. C20H22NO3P requires
C 62.0, H 5.7, N 3.6%). δH (CDCl3) 1.42 (6H, t, J 6.2, 2 CH2Me),
2.51 (3H, s, ArMe), 2.78 (3H, s, ArMe), 4.2–4.4 (4H, m, 2 CH2Me),
6.09 (2H, s, OCH2O), 7.33 (1H, br s, ArH), 7.80 (1H, d, J 2.1, ArH),
7.89 (1H, br s, ArH), 8.28 (1H, s, ArH). δC (CDCl3) 16.4 (d, J 6.3),
18.4, 22.1, 63.5 (d, J 6.9), 100.0 (d, J 2.3), 101.9, 105.1, 119.2, 123
(d, J 31.3), 124.6 (J 3.5), 130.6, 130.8, 136.1, 136.4, 140.1 (d, J 27.1),
148.2, 149.7 (d, J 224.6), 150.9. m/z (APCI+) 388 (M + 1).
The benzylamine 2f (0.81 g, 2.6 mmol) in trifluoroacetic acid/ethyl
acetate (2 : 1, 15 mL) at 0◦C was treated with vanadium oxytri-
fluoride (1.42 g, 11.4 mmol) dissolved in trifluoroacetic acid/ethyl
acetate (1 : 1, 10 mL) After 15 min, the mixture was worked up in
the usual way and the mixture was extracted with dichloromethane.
Following evaporation of the solvent, the residue was recrystallized
from ethanol/dichloromethane to afford the product 3g as colourless
needles (0.38 g, 51%), mp 227–228◦C (with prior sublimation) fol-
lowing crystallization from ethanol/dichloromethane (Found: C 58.4,
H 3.6, N 4.6. C15H11Cl2NO2 requires C 58.5.0, H 3.6, N 4.6%). δH
(CDCl3/CF3COOH) 4.09 (3H, s, ArMe), 4.15 (3H, s, ArMe), 7.36 (1H,
s, ArH), 7.71 (1H, s, ArH), 7.75 (1H, d, J 2.2, ArH), 8.26 (1H, d, J
2.2, ArH), 9.21 (1H, s, CH=NH+). δC (CDCl3/CF3COOH) 56.6, 57.3,
102.8, 110.6, 111.9, 117.6, 120.1, 121.7, 126.2, 127.1, 127.5, 131.5,
132.1, 136.2, 147.3. m/z (APCI+) 308 (M + 1).
Reaction of 2b with Vanadium Oxytrichloride
Reactionof3,4-dimethoxybenzyl-(3,4-dimethylphenyl)amine2b(4.6 g,
14.7 mmol) with vanadium oxytrichloride (12.9 g, 0.104 mmol) instead
of the trifluoride in the manner described above gave 8,9-dimethoxy-
2,3-dimethylphenanthridine (1.60 g, 35%), mp 222–224◦C, identical
with the product 3b obtained in the earlier experiment. Neither of the
other two products, 3c and 4, obtained previously were found in isolable
quantities.
Further elution yielded a more polar compound (210 mg, 8%),
1H NMR of which suggested it was the hydroxymethyl analogue 3j
(see below).
Diethyl 2,4-dichloro-[1,3]dioxolo[4,5-j]phenanthridin-6-yl)-
phosphonate 3h
(b) With Six Equivalents of Vanadium Oxytrifluoride
Thephosphonate2g(4.0 g, 9.2 mmol)wasdissolvedindichloromethane/
trifluoroacetic acid (1 : 1, 40 mL), cooled to −30◦C, and a solution of
vanadium oxytrifluoride (5.4 g, 43.6 mmol) dissolved in a mixture of
trifluoroacetic acid (15 mL) and ethyl acetate (7 mL) was added in a
thin stream over 2 min. After 10 min, the mixture was worked up in the
usual way. Extraction with dichloromethane (2 × 50 mL), followed by
evaporation of solvents gave a reddish gum (4.1 g) which was stirred
with ether (40 mL). The precipitate was collected and recrystallized as
needles from methanol to afford the product 3h (0.65 g, 16%), based on
unrecovered starting material, mp 222–224◦C (Found: C 50.6, H 3.6,
N 3.2. C18H16Cl2NO5P requires C 50.5, H 3.8, N 3.3%). δH (CDCl3)
1.45 (6H, t, J 7.7, 2 CH2Me), 4.4–4.6 (4H, m, 2 CH2Me), 6.21 (2H, s,
OCH2O), 7.77 (1H, d, J 1.8, PCC=CH), 7.81 (1H, d, J 2.2, ArH), 8.25
(1H, d, J 2.2, ArH), 8.36 (1H, s, ArH). δC (CDCl3) 16.4 (d, J 5.5 Hz),
64.1 (d, J 7.2), 100.1, 102.5, 105.5, 120.5, 124.7 (d, J 30.1, CCP), 126.8
(d, J 2.9), 128.8, 129.7 (d, J 10.2), 133.7, 136.5, 137.6 (d, J 26.8,
PC=NC), 149.4, 151.9, 152.7 (d, J 222.7, N=CP). (The principal
phosphorus–carbon coupling values are assigned on the basis of proxim-
ity to the phosphorus atom; minor couplings are unassigned.)The filtrate
was evaporated and chromatographed over silica to recover starting
material (2.3 g).
The benzylamine 2h (2.38 g, 6.1 mmol) in trifluoroacetic acid/
dichloromethane (1 : 1, 20 mL) at 0◦C was treated with a solution
of vanadium oxytrifluoride (4.54 g, 0.036 mol) in trifluoroacetic acid/
dichloromethane (1 : 1, 20 mL). After 10 min, the reaction was worked
up as described above and extracted with dichloromethane (2 × 50 mL).
Theresidueremainingafterremovalofthesolventwaschromatographed
over silica, commencing with dichloromethane as eluent and progress-
ing to dichloromethane/ethyl acetate (1 : 1), successively yielded the
following: dephosphorylated phenanthridine 3a (75 mg), dialkoxyphos-
phorylated phenanthridine 3i (0.52 g, 22%; identical with the compound
prepared above), and diethyl ester 3j (1.31 g, 52%), mp 201–202◦C
(Found: C 59.6, H 5.5, N 3.5. C20H22NO6P requires C 59.8, H 5.6, N
3.4%). δH (CDCl3) 1.43 (6H, t, J 6.9, 2 CH2Me), 2.66 (3H, s, ArMe),
4.2–4.5 (4H, m, 2 CH2Me), 4.83 (2H, s, CH2OH), 6.07 (2H, s, OCH2O),
7.26 (1H, s, ArH), 7.33 (1H, br s, ArH), 7.80 (1H, br s, ArH), 7.90 (1H,
s, ArH). Irradiation of the methylene of the CH2OH (δ 4.83) caused
enhancement of two one-proton singlets (δ 7.26 and 7.80). Irradiation
of the aromatic methyl (δ 2.66) caused enhancement of a signal of only
one aromatic proton (δ 7.26). δC (CDCl3) 16.4 (d, J 6.7), 18.4, 63.7 (d,
J 6.9), 64.5, 99.4, 101.9, 104.2, 116.3, 122.6 (d, J 31.4), 123.9, 126.8,
130.4 (d, J 10.7), 137.8, 140.2 (d, J 26.7), 141.9, 147.6, 148.5 (d, J
218.9), 150.5.
Reaction of Benzo[1,3]dioxol-5-yl-(2,4-dimethylphenylamino)-
methyl]phosphonic Acid Monoethyl Ester 2i with Vanadium
Oxytrifluoride
Acknowledgments
Reaction with four equivalents of vanadium oxytrifluoride at −25 to
−30◦C in the usual way showed complete consumption of the starting
material, but only 290 mg of dephosphorylated phenanthridine 3a was
isolated from the reaction mixture after workup.
We thank E. I. DuPont de Nemours and Co. Agricultural
Products Department for the biological screening of these
compounds. We also thank Mr R. I. Willing for measurement
of NMR spectra and carrying out NOE determinations.
Diethyl (2,4-Dimethyl-[1,3]dioxolo[4,5-j]phenanthridin-6-yl)-
phosphonate 3i
and (2-Diethyl Hydroxymethyl-4-methyl-[1,3]dioxolo[4,5-j]-
phenanthridin-6-yl)phosphonate 3j
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