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Organic & Biomolecular Chemistry
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differed from that described by Miltojević and Radulović:1 Only
minor amounts (ca. 25%, GC-FID peak area) of a dimeric
compound (m/z 328 at 11.85 min) were detected, which was
different from the dimer 2a, while the major thermolysis
product was anthranilate 3a (m/z 165). A sharp peak at 7.05 min
(10%) and an additional broad peak (7.50-7.80 min, 54%) were
observed, indicating that 3a was formed in the injector and on
the column, respectively.1 Another difference was the
appearance of an additional signal at 8.27 min with m/z of 163,
which is 2 units less than that of 3a. At that point we could not
ascertain the exact structure of this compound.
DOI: 10.1039/D0OB01946A
To gain more information on the decomposition of 1a, a
differential scanning calorimetry (DSC) measurement of methyl
N-nitroso-N-methylanthranilate (1a) was performed before
moving to the gas-phase thermolysis using FVP. The DSC
analysis indicated a thermal decomposition at 219 °C (see Fig.
S3 in the ESI†), which is in good agreement with the
experimental decomposition data reported by Miltojević and
Radulović.1 Therefore, with sublimation temperatures set to
≤110 °C in the FVP experiments, degradation of 1a should not
occur in the sublimation flask.
As initial conditions for flash vacuum pyrolysis of 1a an oven
temperature of 450 °C and 100-110 °C sublimation temperature
were chosen (Table 1, entry 1). A mixture of 3a and the same
compound with m/z of 163 that was also observed under GC
thermolysis was obtained. This compound could be isolated by
chromatography and its structure elucidated by a combination
of 1D and 2D NMR analyses (see Figs. S4‒S7 in the ESI†). HSQC
and HMBC experiments allowed us to unambiguously identify
this compound as 7-(methylamino)phthalide (4a), which has
never been reported before. The HMBC correlations of the H-3
signal (5.20 ppm) with C-1 (173.1 ppm) and C-3a (148.1 ppm)
confirmed the presence of a lactone ring, and a 3-bond HMBC
cross peak between the N-CH3 protons (2.93 ppm) and C-7
(149.1 ppm) confirmed the substitution pattern. In contrast to
the GC thermolysis, compounds 3a and 4a were obtained in a
ca 1:1 ratio (Table 1, entry 1), implying the pyrolysis to be a
disproportionation reaction. To further investigate that
Fig. 1 The pressure of the FVP system changes because of NO gas being released. Higher
sublimation temperatures lead to shorter total sublimation times. The three curves
correspond to entries 2 (green), 4 (blue) and 5 (red) from Table 1.
observation, additional FVP experiments were performed
varying the temperatures of sublimation (Tpre) and reaction
(Toven, Tzone2), respectively, (Table 1). The ratio 3a/4a did not
change significantly under the tested reaction conditions and
was between 0.97 and 1.20. The total qNMR yield of products
ranged from 66 to 76%, and isolated yields of
chromatographically purified material correlated well with the
qNMR yields (Table 1, entry 4).
GC-MS and GC-FID analyses of the mixture that was
collected in the cold trap revealed the additional presence of o-
toluidine, N-methyl-o-toluidine and methyl anthranilate (in
total up to 5%). Non-transformed 1a was also detected and
quantified by NMR (1‒3% with respect to 1a in the sublimation
flask). We assume that the rest of 1a was lost either by
decomposition to volatile compounds and/or complete
degradation inside of the quartz tube.
An interesting observation was the increase in pressure
during the FVP experiments, which can be attributed to the
liberated NO. Once the starting nitroso compound was
consumed, the pressure dropped to the initial 4‒5 × 10-3 mbar
(Fig. 1). This allowed us to monitor the progress of the
thermolysis: Depending on Tpre and Toven, complete sublimation
of 1a through the tube was achieved within 25‒50 min (Fig. 1).
For mechanistic insights toward the disproportionation
pathway in the thermolysis of 1a, the deuterated methyl ester
derivate 1b was subjected to FVP experiments employing the
conditions from entry 2 in Table 1 (Scheme 2). In the initial step
‒ the homolysis of the N-NO bond ‒ a nitrogen radical
(intermediate ib) is formed which abstracts the deuterium from
the methyl ester (intermediate ii) and subsequently cyclizes to
intermediate iii. The second equivalent of intermediate ib
quenches iii by abstraction of the C-3a hydrogen and
anthranilate 3b is generated. The deuteration degree at the CD3
group in 3b was 100%, which implies that the proton and
deuterium abstraction step, respectively, occurred from the N-
atom of intermediate ib. The alternative mechanism (radical
transfer from N to C in intermediate ib and proton abstraction
by the C-centered radical ib’, Scheme 2)8 could not be observed,
because a deuteration degree of 0% was detected at the NMe
group in the phthalide product.
Table 1 Reaction condition screening for the flash vacuum pyrolysis of methyl N-
methyl-N-nitrosoanthranilate (1a).a
3a/4a
Tpre
Toven
Tzone2
Entry
(%)c
(°C) b
(°C) b
(°C)b
34/32d
1
2
3
4
5
6
100-110
80-90
70-80
60-70
70-80
50-70
450
450
450
400
350
300
+20
+20
+20
0
33/34
37/36
40/36 (39/35)d
37/33
+20
+20
36/30
a Conditions: 0.5 mmol of 1a, vacuum: 4-5 × 10-3 mbar, quartz tube (QT): 3.5
cm inner diameter and 60 cm length. b see Figure S1 in the ESI
details. c 1H NMR yield. d Isolated yields.
† for further
2 | J. Name., 2012, 00, 1-3
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