Electron Impact Induced Fragmentation of Aromatic Alkoxyimines II [5]. Formation and Transformation of Heterocyclic Radical Cations in the Gas Phase

Article abstract of DOI:10.1007/s00706-002-0485-8

The molecular ion 1 of N-(n-propoxy)benzaldimine I rearranges by an 1,5-H-shift to the δ-distonic ion 2 which subsequently cyclizes to the α-distonic ion 3. Homolytic cleavage of the N-O bond in 3 results in the δ-distonic ion 4 which expels CH₂

Full text of DOI:10.1007/s00706-002-0485-8

Monatshefte fur Chemie 134, 343±354 ꢀ2003)
DOI 10.1007/s00706-002-0485-8
Electron Impact Induced Fragmentation
of Aromatic Alkoxyimines II [5]. Formation
and Transformation of Heterocyclic Radical
Cations in the Gas Phasea
Alexander Kaiser, Klaus K. Mayer, Andreas Sellmer,
Ã
and Wolfgang Wiegrebe
Faculty of Chemistry and Pharmacy, University of Regensburg, D-93040 Regensburg, Germany
Received February 12, 2002; accepted ꢀrevised) April 9, 2002
Published online December 18, 2002 # Springer-Verlag 2002
Summary. The molecular ion 1 of N-ꢀn-propoxy)benzaldimine I rearranges by an 1,5-H-shift to the
ꢀ-distonic ion 2 which subsequently cyclizes to the ꢁ-distonic ion 3. Homolytic cleavage of the N±O
bond in 3 results in the ꢀ-distonic ion 4 which expels CH2O leading to the ꢂ-distonic ion 5. Ion 5 is also
‡ꢀ
formed from the molecular ions of tetrahydrooxazines II and III and from M of phenylazetidine
IVa. In a subsequent step, ion 5 cyclizes to the N-protonated 3,4-dihydroisoquinolinium ion 6. The
syntheses of II±IV and their derivatives are described.
Keywords. Alkoxybenzaldimines; Tetrahydrooxazines; 2-Phenylazetidines; Mass spectrometry;
Longevialle migration.
Introduction
Many N-alkoxyimines are pharmacologically active. Fluvoxamine, a selective se-
rotonin reuptake inhibitor ꢀsee e.g. Ref. [1a]), comprises a CˆN±O±ꢀCH2)2±NH2
increment, and the antibacterial cephalosporins cefuroxime, cefotaxime, ceftizox-
ime, e.g. [1a, 1b] are N-methoxyimines. In 1971, Cooks et al. [2] studied the
fragmentations of alkoxybenzaldimine radical cations. Methoxy derivatives lose
‡ꢀ
27 mu ꢀHCN) after migration of OCH3 and 31 mu ꢀꢀOCH3) directly from M ,
whereas in the homologous ethyl ether, a neutral loss of C2H4 occurs. More impor-
tant, the authors discovered that M‡ꢀ ꢀ1) of N-ꢀn-propoxy)benzaldimine ꢀI) shows a
1,5-H-shift of one of the ꢃ-CH3 hydrogen atoms, thus affording the ꢀ-distonic ion1 2
a

Dedicated to Prof. Dr. J. Knabe, Saarbrucken, Germany
Corresponding author. E-mail: wolfgang.wiegrebe@chemie.uni-regensburg.de
Ã
1
Distonic radical ions are ions with separated radical and charge sites ꢀRadom L, Bouma WJ, Nobes
RH, Yates BF ꢀ1984) Pure Appl Chem 56: 1831)

344
A. Kaiser et al.
which expels formaldehyde ꢀ30 mu) and furnishes the ꢂ-distonic ion 5, presumably
via a four-membered transition state or intermediate. Grutzmacher et al. [3] have
shown that Longevialle migration [4] along the propoxy chain of the benzaldimine
moiety within ion 2 takes place, thus affording the ꢀ-distonic ion 4 which in turn
leads to the ꢂ-distonic ion 5 by loss of CH2O. Ion 5 was veri®ed by ab initio
calculations of the stationary points of the minimum energy reaction path [3]
and proved to be the corner stone of subsequent reactions leading to the fragment
‡
‡ꢀ
[M ±CH2O±Hꢀ] , which in contrast to Cooks [2] was identi®ed by us as the N-
‡
protonated 3,4-dihydroisoquinolinium ion 6 [5]. The [M±CH2O±Hꢀ] ion does
not arise by loss of Hꢀ from the ꢃ-CH2 increment [2, 5] of ion 5, but by elimination
of Hꢀ from the aromatic ring. If this aromatic group is deuterated or halogenated
ꢀCl, Br, I), deuterium or halogen atoms are lost [5].
Results and Discussion
Cooks' proposal [2] includes the connection of the outside parts of 2 after loss of
CH2O, affording the ꢂ-distonic ion 5. This interesting mechanistic concept moti-
vated us to consider whether transformation of ion 2 into 4 could start by attack of
‡
the terminal CHꢀ2 group of 2 onto its CˆNH double bond in the course of an
endo-trig radical cyclization leading to 3-phenyl-3,4,5,6-tetrahydro-1,2-oxazine
Scheme 1. Isomerization and reaction of the molecular ions 1, 7, 8, and 9

EI-MS of Aromatic Alkoxyimines
345
radical cation 7. Formation of the isomeric 2-phenyl-3,4,5,6-tetrahydro-1,3-oxa-
zine radical cation 8, however, might proceed stepwise, starting with an exo-trig
‡
attack of the terminal CHꢀ2 group of 2 onto the CˆNH increment creating the
ꢁ-distonic ion 3 [3], followed by N±O cleavage to ion 4. At this stage, the terminal
‡
CH2±Oꢀ group of 4 attacks the C-atom of its CˆNH increment affording 8. As
stated by Vainiotalo et al. [6], 8 and its open chain tautomer N-ꢀ3-hydroxypropyl)-
benzaldimine radical cation 80 equilibrate in the gas phase. Therefore, we compared
Scheme 2. Synthesis of 3-phenyl-tetrahydro-1,2-oxazines

346
A. Kaiser et al.
the EI mass spectra of 8 ꢀas a source of 80) and 7 and that of the azetidine radical
cation 9, because these ions are potential sources of ion 5.
For this purpose, the tetrahydro-1,2-oxazine II, its pentadeuterophenyl and its
2-chlorophenyl derivatives, the 1,3-oxazine III, the azetidine IVa, and its deuter-
ated and chlorinated derivatives were synthesized.
Syntheses of tetrahydrooxazines
3-Phenyl-5,6-dihydro-4H-1,2-oxazine was prepared according to Ellames et al. [7]
and reduced to 3-phenyl-3,4,5,6-tetrahydro-1,2-oxazine ꢀII) by NaBH3CN follow-
ing a method of Reissig [8]. For the synthesis of 2-phenyl-3,4,5,6-tetrahydro-1,3-
oxazine ꢀIII), see Ref. [6] and the literature cited there.
Pentadeuterobenzaldehyde was converted to its dithiane derivative V for umpol-
ung, which gave dithiane VI with 3-chloropropyl-1-iodide after deprotonation.
This dithiane was cleaved with HgꢀClO4)2 [9], and the resulting butyroketone
VII was converted into its oxime VIII. Ring closure afforded the corresponding
dihydro-1,2-oxazine IX which was reduced to X ꢀvide supra). For the synthesis
of 3-ꢀ2-chlorophenyl)-3,4,5,6-tetrahydro-1,2-oxazine ꢀXV), 3-ꢀ2-chlorobenzoyl)-
2,3,4,5-tetrahydrofuran-2-one ꢀXI) [10] was converted to 4-chloro-1-ꢀ2-chloro-
phenyl)butan-1-one ꢀXII) [11] by heating with HCl. For the further steps to product
XV, see above.
Syntheses of 2-phenylazetidines
2-Phenylazetidine ꢀIVa), its pentadeuterophenyl ꢀIVb), its 2-chlorophenyl ꢀIVc),
and its 4-chlorophenyl derivative ꢀIVd) were synthesized according to Scheme 3.
Benzaldehyde, pentadeuterobenzaldehyde ꢀobtained according to Schlosser [12]),
Scheme 3. Synthesis of 2-phenylazetidines

EI-MS of Aromatic Alkoxyimines
347
1
Fig. 1. 1H, H±NOE NMR spectrum of 4-ꢀ2-chlorophenyl)-2-azetidone ꢀXVIIIc)
2-chloro, and 4-chlorobenzaldehyde, were converted to the corresponding racemic
ꢂ-phenyl-ꢂ-aminopropionic acids XVI. Carboxyl-and N-trimethylsilylation ꢀcf.
XVII) [13], deprotonation by EtMgBr, and cyclization to the corresponding 4-
phenyl-2-azetidinones XVIII were performed using Birkofer's procedure [13].
The structure of XVIIIc was additionally ascertained by 1H, 1H NOE spectroscopy
1
ꢀFig. 1), because the analytical data ± especially H NMR ± signi®cantly differ
from those described in Ref. [14]. The lactams XVIII were reduced to the azeti-
dines IV by BH3 Á THF according to Wells [15].
Mass spectrometry
As expected, the isomeric phenyltetrahydrooxazines II and III ꢀScheme 1) gave
different EI mass spectra, indicating that there is no ꢀor only partial) isomerization
in the ion source prior to fragmentation. On the other hand, both isomers lose
CH2O upon electron impact, and ± more conclusive ± the MIKE and the CAD
‡ꢀ
spectra of the ꢀM±CH2O) ions of 7 and 8 and the pertinent spectra of fragment
ion 5 are virtually identical [3]. Moreover, the 3,4-dihydroisoquinolinium ion 6 is
generated from both phenyloxazines by radical attack within ion 5 and subsequent
‡ꢀ
Fig. 2. CAD MS of ꢀM±CH2O) ions from N-ꢀn-propoxy)benzaldimine ꢀ1) and of 2-phenylazeti-
dine ꢀ9) radical cations

348
A. Kaiser et al.
loss of Hꢀ ꢀor Dꢀ, Clꢀ, respectively, if the phenyl increment of 5 carries these sub-
stituents) [5] as has been shown for the oxime ether I [5].
In the EI-MS ꢀ70 eV) of oxime ether I, a small but reproducible part of the ions
at m=z ˆ 104 was identi®ed as C8H8 ꢀstyrene) by HRMS. This can be explained by
cyclization of ion 5 to the 2-phenylazetidine radical cation 9 and subsequent 2 ‡ 2-
cycloreversion, forming a styrene radical cation and methyleneimine [16]. How-
ever, as indicated by computational data [3], only high energy species of ions 5 are
able to cyclize to 9.
In competition with 2 ‡ 2-cycloreversion, the molecular ions 9 of IVa and those
of its derivatives ꢀScheme 3) isomerize by ring cleavage to the ꢀanalogously sub-
stituted) distonic ions 5 ꢀScheme 1), which eliminate a Hꢀ atom ꢀor Dꢀ, Clꢀ, respec-
tively, if appropriately substituted), thus forming 6. Furthermore, the CAD spectra
of the molecular ion 9 and of the ꢀM±CH2O)ꢀ‡ ion from propoxybenzaldimine
radical cation 1 are identical and verify an identical structure ꢀor identical mixture
of structures) of these ions shown as 5 ꢀFig. 2).
Experimental
Melting points were determined with a Reichert Thermovar melting point table and are not corrected.
1
IR spectra were recorded with a Nicolet 510 FT-IR Spectrometer ꢀKBr; ®lms for liquids). H NMR
spectroscopy was performed with a Bruker NMR spectrometer WM 250 ꢀ250MHz), using TMS as an
internal standard. The ꢀ-values of AB-systems were determined according to the rules of zero order
spectra. Mass spectra were taken with a Varian MAT 95 MS ꢀ70 eV). Chromatography was performed
on SiO2 Merck No. 7734 Kieselgel 60 ꢀ70±230 mesh ASTM). The results of elemental analyses agreed
favourably with the calculated values.
3-Phenyl-3,4,5,6-tetrahydro-2H-1,2-oxazine ꢀII; C10H13NO)
To a solution of 3-phenyl-5,6-dihydro-4H-1,2-oxazine ꢀ[7]; 0.806 g, 5 mmol) in 15cm3 of AcOH,
NaBH3CN ꢀ1.0g, 15.9mmol) was added with stirring. Stirring was continued for 6 h at room tem-
perature. Then, 130 cm3 of saturated Na2CO3 solution were added, and the mixture was extracted with
EtOAc ꢀ2Â 100 cm3). The combined organic phases were washed with saturated NaCl solution
ꢀ2Â 50cm3), dried, and evaporated in vacuo. Kugelrohr distillation ꢀoven temperature 70ꢁC, 3.5 torr)
afforded II ꢀ0.59 g, 72%) as a colourless oil.
EI-MS ꢀ70 eV) m=z ꢀ%) ˆ 163 ꢀ57), 162 ꢀ9), 145 ꢀ8), 133 ꢀ11), 132 ꢀ41), 131 ꢀ13), 121 ꢀ10), 120
ꢀ15), 118 ꢀ14), 117 ꢀ25), 116 ꢀ9), 115 ꢀ14), 105 ꢀ33), 104 ꢀ100), 91 ꢀ30), 84 ꢀ24), 78 ꢀ23), 77 ꢀ34); EI-
MS ꢀ12 eV): m=z ꢀ%) ˆ 163 ꢀ100), 162 ꢀ12), 145 ꢀ9), 133 ꢀ21), 132 ꢀ52), 121 ꢀ9), 120 ꢀ7), 118 ꢀ11),
st
117 ꢀ8), 105 ꢀ22), 104 ꢀ49), 91 ꢀ4); HRMS: m=z ˆ 133 ꢀC9H11N); B=E ꢀM ˆ 163, 1 ffr2): m=z
‡ꢀ
ꢀ%) ˆ 162 ꢀ51), 133 ꢀ100), 132 ꢀ70), 121 ꢀ4), 120 ꢀ5), 119 ꢀ6), 118 ꢀ7), 105 ꢀ1), 104 ꢀ8); B=E ꢀꢀM±
À 1
‡ꢀ
CH2O) ˆ 133): m=z ꢀ%) ˆ 132 ꢀ100), 118 ꢀ1), 105 ꢀ1), 104 ꢀ6); IR ꢀ®lm): ꢄ ˆ 3280 ꢀN±H) cm
;
1H NMR ꢀCDCl3): ꢀ ˆ 7.23±7.40 ꢀm, 5H, aromat.), 5.34 ꢀs, 1H, NH, exch.), 4.00±4.15 and 3.80±3.92
ꢀ2m, 3H, CHN and CH2O), 1.70±2.00 ꢀm, 4H, CH±CH2±CH2) ppm.
2
1st ffr: ®rst ®eld free region; B: magnetic ®eld strength; E: electrostatic sector voltage; B=E linked
scan gives all daugther cations from a selected cation ꢀChapman JR ꢀ1985) Practical Organic Mass
Spectrometry, John Wiley & Sons, Chichester, p 145)

EI-MS of Aromatic Alkoxyimines
349
2-Pentadeuterophenyl-1,3-dithiane ꢀV; C10H7D5S2)
Benzaldehyde-d5 ꢀ[12]; 0.55 g, 5 mmol) was stirred with 1,3-propanedithiol ꢀ0.54 g, 5 mmol) and
CaCO3 ꢀ0.5g, 5 mmol) in 5 cm3 of CHCl3 for 1 h in an ice=NaCl bath. BF3 Á Et2O ꢀ0.2 cm3, 1.6mmol)
was added, and stirring was continued for 15min in the ice=NaCl bath and for 4 h at room temperature.
Addition of BF3 Á Et2O ꢀ0.2cm3, 1.6 mmol) and stirring at room temperature for 9 h were repeated. The
mixture was diluted with 5 cm3 of CHCl3 and washed with H2O ꢀ3Â 5 cm3), 10% NaOH ꢀ3Â 5 cm3),
and again with H2O ꢀ3Â 5 cm3). After drying ꢀK2CO3) and removing the solvent in vacuo, colourless
crystals ꢀ0.86 g, 85%) were obtained.
M.p.: 72ꢁC; IR ꢀ®lm): ꢄ ˆ 2275 ꢀˆC±D) cmÀ 1; 1H NMR ꢀCDCl3): ꢀ ˆ 5.17 ꢀs, 1H, S2CH), 2.88±
3.15 ꢀm, 4H, 2 SCH2), 2.13±2.25 ꢀm, 1H, CH2±CHH±CH2), 1.85±2.05 ꢀm, 1H, CH2±CHH±CH2)
ppm.
2-23-Chloropropyl)-2-2pentadeuterophenyl)-1,3-dithiane ꢀVI; C13H12ClD5S2)
To the solution of V ꢀ0.81 g, 4 mmol) in 20 cm3 of absolute THF, n-BuLi ꢀ3.8cm3 of a 1.6 M solution
in hexane) was added dropwise under N2 at À 78ꢁC. After 1 h, a solution of 3-chloropropyl-1-iodide
ꢀ0.82 g, 4 mmol) in 8 cm3 of absolute THF was added. The cooling bath was allowed to reach 0ꢁC, half
saturated NH4Cl solution ꢀ8cm3) was added, the organic phase was separated, and the aqueous phase
was extracted with EtOAc ꢀ2Â 20cm3). The combined organic phases were washed with saturated
NaCl solution ꢀ2Â 20cm3), dried ꢀNa2SO4), and evaporated in vacuo. Column chromatography ꢀCC;
SiO2; Et2O:petroleum ether 40±60ꢁC ˆ 1:4) afforded VI ꢀ0.63 g, 56%) as a weakly yellow oil.
1
3
IR ꢀ®lm): ꢄ ˆ 2275 ꢀˆC±D) cmÀ 1; H NMR ꢀCDCl3): ꢀ ˆ 3.40 ꢀt, J ˆ 6.5 Hz, 2H, CH2Cl),
2.65±2.78 ꢀm, 4H, 2 SCH2), 2.13±2.23 ꢀm, 2H, CH2), 1.90±2.02 ꢀm, 2H, CH2), 1.69±1.84 ꢀm, 2H,
CH2±CH2±CH2) ppm.
4-Chloro-1-2pentadeuterophenyl)butan-1-one ꢀVII; C10H6ClD5O)
A suspension of VI ꢀ0.60 g, 2.16 mmol) and CaCO3 ꢀ1.1g, 11 mmol) in 9 cm3 of THF and 1.2cm3 of
H2O was stirred with HgꢀClO4)2 ꢀ1.30 g, 3.25mmol) for 5 min. Stirring was continued with additional
HgꢀClO4)2 ꢀ0.20 g, 0.5 mmol) for 5 min. After addition of Et2O ꢀ35 cm3), the suspension was ®ltered
through celite, the ®lter cake was washed thoroughly with Et2O, the combined ®ltrates were washed
with a saturated solution of NaHCO3 ꢀ20 cm3), H2O ꢀ2Â 20cm3), and saturated NaCl solution ꢀ10cm3),
dried ꢀNa2SO4), and evaporated in vacuo. CC ꢀSiO2; Et2O:petroleum ether 40±60ꢁC ˆ 1:1) afforded
VII ꢀ0.3g, 75%) as a colourless oil.
IR ꢀ®lm): ꢄ ˆ 2279 ꢀˆC±D), 1684 ꢀCˆO) cmÀ 1; 1H NMR ꢀCDCl3): ꢀ ˆ 3.69 ꢀt, 3J ˆ 6.2Hz, 2H,
3
CH2Cl) 3.19 ꢀt, J ˆ 7.0 Hz, 2H, OˆC±CH2), 2.19±2.30 ꢀm, 2H, CH2±CH2±CH2) ppm.
4-Chloro-1-2pentadeuterophenyl)butan-1-one oxime ꢀVIII; C10H7ClD5NO)
VIII was prepared from VII ꢀ0.28 g, 1.5mmol) analogously to the non-deuterated compound [7] and
further processed without puri®cation.
3-2Pentadeuterophenyl)-5,6-dihydro-4H-1,2-oxazine ꢀIX; C10H6D5NO)
IX was prepared from crude VIII analogously to the non-deuterated compound [7]. Recrystallization
from diisopropyl ether afforded IX ꢀ0.18 g, 72%) as colourless crystals.
M.p.: 71ꢁC; IR ꢀKBr): 2362, 2271 ꢀˆC±D) cmÀ 1; 1H NMR ꢀCDCl3): ꢀ ˆ 4.07 ꢀt, 3J ˆ 5.0Hz, 2H,
3
OCH2), 2.60 ꢀt, J ˆ 6.8 Hz, 2H, NˆCCH2), 2.07±2.18 ꢀm, 2H, CH2±CH2±CH2) ppm.

350
A. Kaiser et al.
3-2Pentadeuterophenyl)-3,4,5,6-tetrahydro-2H-1,2-oxazine ꢀX; C10H8D5NO)
X was prepared analogously to the non-deuterated compound II starting from IX ꢀ0.166g, 1.0mmol).
CC ꢀSiO2; CH2Cl2:EtOAc ˆ 95:5) afforded X ꢀ0.081 g, 48%) as a colourless oil.
EI-MS ꢀ70 eV): m=z ꢀ%) ˆ 168 ꢀ52), 167 ꢀ8), 150 ꢀ7), 138 ꢀ6), 137 ꢀ8), 136 ꢀ36), 126 ꢀ7), 124 ꢀ11),
122 ꢀ24), 121 ꢀ7), 120 ꢀ6), 119 ꢀ7), 110 ꢀ29), 109 ꢀ100), 96 ꢀ16), 86 ꢀ11), 83 ꢀ19), 82 ꢀ30); EI-MS
ꢀ12 eV): m=z ꢀ%) ˆ 168 ꢀ100), 150 ꢀ5), 138 ꢀ9), 137 ꢀ6), 136 ꢀ31), 126 ꢀ4), 124 ꢀ2), 123 ꢀ4), 122 ꢀ4),
st
‡ꢀ
110 ꢀ11), 109 ꢀ31); B=E ꢀM ˆ 168, 1 ffr): m=z ꢀ%) ˆ 167 ꢀ63), 138 ꢀ100), 137 ꢀ3), 136 ꢀ24), 126 ꢀ2),
‡ꢀ
125 ꢀ4), 124 ꢀ6), 123 ꢀ7), 110 ꢀ1), 109 ꢀ6); B=E ꢀꢀM±CH2O) ˆ 138): m=z ꢀ%) ˆ 137 ꢀ11), 136
ꢀ100), 123 ꢀ1), 110 ꢀ1), 109 ꢀ19); IR ꢀ®lm): ꢄ ˆ 3278, 3115 ꢀN±H), 2400, 2254 ꢀˆC±D) cmÀ 1
;
1H NMR ꢀCDCl3): ꢀ ˆ 4.45 ꢀbr s, 1H, NH, exch.), 4.02±4.18 ꢀm, 2H, OCHH and NCH), 3.80±3.94
ꢀm, 1H, OCHH), 1.73±2.05 ꢀm, 4H, OCH2±CH2±CH2) ppm.
4-Chloro-1-22-chlorophenyl)butan-1-one ꢀXII; C10H10Cl2O)
A solution of 3-ꢀ2-chlorobenzoyl)-2,3,4,5-tetrahydrofuran-2-one ꢀXI [10]; 0.9g, 4 mmol) in 4 cm3 of
dioxane was mixed with 8 cm3 of concentrated HCl and re¯uxed for 1 h. The solution was diluted with
H2O ꢀ50 cm3), extracted with Et2O ꢀ4Â 20cm3), and the organic phase was washed with saturated
NaHCO3 solution ꢀ2 Â 15 cm3) and saturated NaCl solution ꢀ2Â 15cm3), dried, and evaporated
in vacuo. CC ꢀSiO2; CH2Cl2) afforded XII ꢀ[11]; 0.73g, 84%) as a colourless oil.
1H NMR ꢀCDCl3): ꢀ ˆ 7.30±7.52 ꢀm, 4H, aromat.), 3.66 ꢀt, 3J ˆ 6.3 Hz, 2H, CH2Cl), 3.14 ꢀt, 3J ˆ
7.0 Hz, 2H, OˆCCH2), 2.17±2.30 ꢀm, 2H, CH2±CH2±CH2) ppm.
4-Chloro-1-22-chlorophenyl)butane-1-one oxime 2XIII; C10H11Cl2NO)
XIII was prepared analogously to compound VIII from 0.54g ꢀ2.5mmol) XII and 0.52 g ꢀ7.5mmol)
hydroxylammonium chloride ꢀreaction time: 24 h) and further used without puri®cation.
3-22-Chlorophenyl)-5,6-dihydro-4H-1,2-oxazine ꢀXIV; C10H10ClNO)
XIV was prepared from crude XIII analogously to compound IX ꢀreaction time: 50min). CC ꢀSiO2;
CH2Cl2:Et2O ˆ 9:1) led to 0.30g ꢀ62%) of XIV as yellowish crystals.
1
M.p.: 69ꢁC; IR ꢀKBr): 1594 ꢀCˆN) cmÀ 1; H NMR ꢀCDCl3): ꢀ ˆ 7.25±7.45 ꢀm, 4H, aromat.),
4.13 ꢀt, 3J ˆ 5.3 Hz, 2H, OCH2), 2.54 ꢀt, 3J ˆ 6.8 Hz, 2H, NˆC±CH2), 2.05±2.17 ꢀm, 2H, CH2±CH2±
CH2) ppm.
3-22-Chlorophenyl)-3,4,5,6-tetrahydro-2H-1,2-oxazine ꢀXV; C10H12ClNO)
XV was prepared analogously to compound X from 0.195g ꢀ1mmol) of XIV. CC ꢀSiO2; CH2Cl2:
Et2O ˆ 9:1) afforded XV ꢀ0.090 g, 45%) as a colourless oil.
EI-MS ꢀ70 eV): m=z ꢀ%) ˆ 199 ꢀ16), 198 ꢀ9), 197 ꢀ53), 196 ꢀ10), 181 ꢀ1), 179 ꢀ2), 169 ꢀ5), 168 ꢀ9),
167 ꢀ16), 166 ꢀ23), 157 ꢀ2), 156 ꢀ3), 155 ꢀ6), 154 ꢀ7), 153 ꢀ3), 152 ꢀ8), 151 ꢀ5), 140 ꢀ35), 139 ꢀ38), 138
ꢀ100), 132 ꢀ16), 131 ꢀ3), 130 ꢀ14), 129 ꢀ9), 128 ꢀ6), 127 ꢀ8), 125 ꢀ15), 114 ꢀ4), 113 ꢀ3), 112 ꢀ11), 111
ꢀ5); EI-MS ꢀ12 eV): m=z ꢀ%) ˆ 199 ꢀ32), 198 ꢀ14), 197 ꢀ100), 196 ꢀ12), 181 ꢀ1), 179 ꢀ3), 169 ꢀ8), 168
ꢀ11), 167 ꢀ26), 166 ꢀ28), 157 ꢀ1), 155 ꢀ5), 154 ꢀ3), 152 ꢀ6), 141 ꢀ9), 140 ꢀ21), 139 ꢀ30), 138 ꢀ56), 132
ꢀ21); B=E ꢀM‡ꢀ ꢀ35Cl) ˆ 197, 1st ffr): m=z ꢀ%) ˆ 196 ꢀ14), 167 ꢀ100), 166 ꢀ6), 156 ꢀ2), 155 ꢀ1), 154 ꢀ6),
35Cl ˆ 167): m=z ꢀ%) ˆ 166 ꢀ100), 152 ꢀ1), 139
‡ꢀ
153 ꢀ3), 140 ꢀ1), 138 ꢀ3), 132 ꢀ2); B=E ꢀꢀM±CH2O)
,
ꢀ1), 138 ꢀ24), 132 ꢀ28); IR ꢀ®lm): ꢄ ˆ 3276 ꢀNH) cmÀ 1; H NMR ꢀCDCl3): ꢀ ˆ 7.17±7.50 ꢀm, 4H,
aromat.), 5.55 ꢀs, 1H, NH, exch.), 4.52±4.63 ꢀm, 1H, NCH), 4.02±4.13 ꢀm, 1H, OCHH), 3.83±3.96
ꢀm, 1H, OCHH), 1.70±2.10 ꢀm, 4H, OCH2±CH2±CH2) ppm.
1

EI-MS of Aromatic Alkoxyimines
351
2 Æ )-ꢂ-Phenyl-ꢂ-aminopropionic acid ꢀXVIa): Ref. [17]
2 Æ )-ꢂ-Pentadeuterophenyl-ꢂ-aminopropionic acid ꢀXVIb; C9H6D5NO2)
A solution of pentadeuterobenzaldehyde ꢀ[12]; 2.3 g, 15.4mmol), malonic acid ꢀ1.63 g, 15.4mmol),
and ammonium acetate ꢀ1.18 g, 15.4mmol) in EtOH ꢀ4.0cm3) was re¯uxed for 5 h. After 1 h, XVIb
began to precipitate as white crystals. It was ®ltered off from the cold solution and washed with a small
amount of ice-cold EtOH.
Yield: 1.13g ꢀ43%); m.p.: 242±243ꢁC ꢀdecomp.); IR ꢀKBr): ꢄ ˆ 3431 ꢀN±H), 3000±2500 ꢀO±H),
2273 ꢀˆC±D), 2205 ꢀˆC±D), 1625 ꢀCˆO Á Á Á HN) cmÀ 1; 1H NMR ꢀD2O): ꢀ ˆ 4.52 ꢀdd, 3J ˆ 6.7 Hz,
3
2
3
3J ˆ 7.9 Hz, 1H, CH-phen), 2.78 ꢀdd, J ˆ 7.9 Hz, J ˆ 16.2Hz, 1H, CHH), 2.68 ꢀdd, J ˆ 6.7 Hz,
2J ˆ 16.2Hz, 1H, CHH) ppm.
2 Æ )-ꢂ-Phenyl-ꢂ-aminopropionic acids XVIc and XVId: Ref. [18]
2 Æ )-Trimethylsilyl ꢂ-2N-trimethylsilylamino)-ꢂ-phenylpropionates XVII;
general procedure according to Birkofer [13]
To 25 mmol of the corresponding ꢂ-aminopropionic acid XVI suspended in dry benzene ꢀ25 cm3), a
solution of trimethylsilyl chloride ꢀ50 mmol) was added under N2. After stirring at room temperature
ꢀ30 min), the mixture was heated for 15min, and a solution of triethylamine ꢀ52 mmol) in benzene
ꢀ20 cm3) was added. The solution was heated on a steam bath for 2 h, cooled to room temperature, and
triethylammonium chloride was ®ltered off. The solvent was removed under reduced pressure, and the
colourless product was distilled in vacuo. The known compound ꢀ Æ )-trimethylsilyl ꢂ-ꢀN-trimethyl-
silylamino)-ꢂ-phenylpropionate ꢀXVIIa) was prepared from XVIa according to this procedure [13].
2 Æ )-Trimethylsilyl ꢂ-2N-trimethylsilylamino)-ꢂ-2pentadeuterophenyl)propionate
ꢀXVIIb; C15H22D5NO2Si2)
Preparation from XVIb ꢀ1.34 g, 7.87mmol); yield: 1.52 g ꢀ63%); b.p. ꢀ0.4torr): 102ꢁC; IR: ꢄ ˆ 3381
ꢀN±H), 2954 ꢀC±H), 2897 ꢀC±H), 2271 ꢀˆC±D), 1717 ꢀCˆO) cmÀ 1
.
2 Æ )-Trimethylsilyl ꢂ-2N-trimethylsilylamino)-ꢂ-22-chlorophenyl)propionate
ꢀXVIIc; C15H26ClNO2Si2)
Preparation from XVIc ꢀ4.80 g, 24.04 mmol); yield: 7.17g ꢀ87%); b.p. ꢀ0.1torr): 108±109ꢁC; IR:
ꢄ ˆ 3394 ꢀN±H), 2958 ꢀC±H), 2902 ꢀC±H), 1717 ꢀCˆO) cmÀ 1
.
2 Æ )-Trimethylsilyl ꢂ-2N-trimethylsilylamino)-ꢂ-24-chlorophenyl)propionate
ꢀXVIId; C15H26ClNO2Si2)
Preparation from XVId ꢀ5.00 g, 25.0mmol); yield: 5.25g ꢀ61%); b.p. ꢀ0.1torr): 99ꢁC; IR: ꢄ ˆ 3381
ꢀN±H), 2954 ꢀC±H), 1709 ꢀCˆO) cmÀ 1
.
4-Phenyl-2-azetidinones XVIII; general procedure according to Birkofer [13]
To 20mmol of the corresponding trimethylsilyl ꢂ-ꢀtrimethylsilylamino)-ꢂ-phenylpropionate XVII in
Et2O ꢀ20 cm3), 1.2 equivalents of EtMgBr in Et2O ꢀ20 cm3) were added at 0ꢁC under N2. Vigorous
development of ethane occured. After 2 h, the mixture was allowed to reach room temperature and
then stirred for 12h. The solution was cooled to À 18ꢁC, hydrolyzed with 2N HCl, and saturated with
NH4Cl to reach pH 3±4. The mixture was extracted with Et2O ꢀ5Â 50cm3), the combined organic

352
A. Kaiser et al.
layers were dried ꢀNa2SO4), and the solvent was removed under reduced pressure. CC ꢀSiO2;
CH2Cl2:Et2O ˆ 2:1) and recrystallization from Et2O afforded colourless crystals. The known com-
pound 4-phenyl-2-azetidinone ꢀXVIIIa) was prepared according to this procedure [13].
2 Æ )-4-2Pentadeuterophenyl)-2-azetidinone ꢀXVIIIb; C9H4D5NO)
Preparation from XVIIb ꢀ1.52 g, 4.93 mmol). The mixture was hydrolyzed with saturated NH4Cl
1
solution without addition of HCl; yield: 0.31g ꢀ41%); degree of deuteration according to H NMR:
>96%; m.p.: 105ꢁC; EI-MS ꢀ70 eV): m=z ˆ 152 ꢀM‡ꢀ, 9), 109 ꢀ[M±HNCO]‡ꢀ, 100); IR ꢀKBr):
ꢄ ˆ 3210 ꢀN±H), 2947 ꢀC±H), 2278 ꢀˆC±D), 1745 ꢀCˆO) cmÀ 1; 1H NMR ꢀCDCl3): ꢀ ˆ 6.52 ꢀbr s,
1H, NH, exch.), 4.71 ꢀdd, 3J ˆ 5.3 Hz, 3J ˆ 2.5 Hz, 1H, CH-phen), 3.42 ꢀddd, 3J ˆ 5.3 Hz, 2J ˆ 14.9Hz,
3
2
4
4JNH ˆ 2.4 Hz, 1H, CHH); 2.85 ꢀddd, J ˆ 2.5 Hz, J ˆ 14.9 Hz, JNH ˆ 1.0Hz, 1H, CHH) ppm.
2 Æ )-4-22-Chlorophenyl)-2-azetidinone ꢀXVIIIc; C9H8ClNO)
Preparation from XVIIc ꢀ6.59 g; 19.2 mmol); yield: 1.23 g ꢀ35%); m.p.: 121±122ꢁC ꢀdecomp.; Ref.
[14]: 110ꢁC); EI-MS ꢀ70 eV): m=z ˆ 183 ꢀM‡ꢀ, 2), 181 ꢀM‡ꢀ, 7), 146 ꢀ[M±Cl]‡ꢀ, 0.5), 140 ꢀ[M±
‡
HNCO]‡ꢀ, 35), 138 ꢀ[M±HNCO]‡ꢀ, 100), 103 ꢀ[138±Clꢀ] , 27); IR ꢀKBr): ꢄ ˆ 3456 ꢀN±H), 3166
ꢀC±H), 1798 ꢀCˆO) cmÀ 1; 1H NMR ꢀCDCl3): ꢀ ˆ 7.49±7.23 ꢀm, 4H, aromat.), 6.46 ꢀbr s, 1H, NH),
5.06 ꢀdd, 3J ˆ 5.4 Hz, 3J ˆ 2.7 Hz, 1H, CH-phen), 3.55 ꢀddd, 3J ˆ 5.4 Hz, 2J ˆ 15.0Hz, 4JNH ˆ 2.9 Hz,
3
2
4
1H, CHH), 2.83 ꢀddd, J ˆ 2.7 Hz, J ˆ 15.0Hz, JNH ˆ 0.6 Hz, 1H, CHH) ppm.
2 Æ )-4-24-Chlorophenyl)-2-azetidinone ꢀXVIIId; C9H8ClNO)
Preparation from XVIId ꢀ5.00 g, 15.5mmol); yield: 1.02g ꢀ36%); m.p.: 95ꢁC ꢀRef. [19]: 98±99ꢁC
‡
ꢀMeOH=H2O)); EI-MS ꢀ70 eV): m=z ˆ 183 ꢀM‡ꢀ,7), 181 ꢀM‡ꢀ,19), 146 ꢀ[M±Clꢀ] , 8), 140 ꢀ[M±
‡
HNCO]‡ꢀ, 37), 138 ꢀ[M±HNCO]‡ꢀ, 100), 103 ꢀ[138±Clꢀ] , 20); IR ꢀKBr): ꢄ ˆ 3438 ꢀN±H), 3218
ꢀN±H), 2919 ꢀC±H), 1787 ꢀCˆO) cmÀ 1; 1H NMR ꢀCDCl3): ꢀ ˆ 7.36±7.27 ꢀm, 4H, aromat.), 6.19 ꢀbr
3
3
3
2
s, 1H, NH), 4.64 ꢀdd, J ˆ 5.3 Hz, J ˆ 2.5 Hz, 1H, CH-phen), 3.39 ꢀddd, J ˆ 5.3 Hz, J ˆ 14.9Hz,
4JNH ˆ 2.6 Hz, 1H, CHH), 2.78 ꢀddd, J ˆ 2.5 Hz, J ˆ 14.9Hz, JNH ˆ 0.9 Hz, 1H, CHH) ppm.
3
2
4
Phenylazetidines IV; general procedure according to Wells [15]
To 3.3 mmol of the corresponding lactam in THF ꢀ10.0 cm3), BH3 Á THF ꢀ1.0M in THF, 5.5 equiva-
lents) was added under N2 at 0ꢁC. The mixture was allowed to reach room temperature and then
re¯uxed for 16h, followed by cooling to 0ꢁC and addition of 6 N HCl ꢀ30 cm3). The mixture was
re¯uxed ꢀ30 min) to complete hydrolysis, and the solvent was removed under reduced pressure. The
solution was rendered basic with 6 N NaOH ꢀpH ˆ 9), and the aqueous phase was extracted with Et2O
ꢀ3Â 30cm3). The combined organic layers were dried ꢀNa2SO4), the solvent was removed under
reduced pressure, and the product was distilled in vacuo yielding colourless oils.
2-Phenylazetidine ꢀIVa)
IVa was prepared according to Testa [20]. EI-MS ꢀ70 eV) m=z ꢀ%) ˆ 133 ꢀ14), 132 ꢀ26), 118 ꢀ1), 105
ꢀ8), 104 ꢀ100), 103 ꢀ17), 78 ꢀ19), 77 ꢀ16), 51 ꢀ8); EI-MS ꢀ12 eV): m=z ꢀ%) ˆ 133 ꢀ7), 132 ꢀ100), 118
st
‡ꢀ
ꢀ1), 105 ꢀ13), 104 ꢀ71); B=E ꢀM ˆ 133, 1 ffr): m=z ꢀ%) ˆ 132 ꢀ100), 118 ꢀ1), 105 ꢀ1), 104 ꢀ8).
2 Æ )-2-2Pentadeuterophenyl)azetidine ꢀIVb; C9H6D5N)
Preparation from XVIIIb ꢀ0.17 g, 1.12 mmol). Hydrolysis of the borane adduct was performed with
6 N NaOH ꢀnot HCl !) by heating to re¯ux for 30min. IVb was distilled from a water bath at 50±80ꢁC
bath temperature ꢀ0.3torr).

EI-MS of Aromatic Alkoxyimines
353
Yield: 0.098 g ꢀ63%); degree of deuteration: >95% ꢀ1H NMR); EI-MS ꢀ70 eV): m=z ꢀ%) ˆ 138
ꢀ15), 137 ꢀ6), 136 ꢀ17), 123 ꢀ1), 110 ꢀ16), 109 ꢀ100), 83 ꢀ10), 82 ꢀ13), 54 ꢀ7); EI-MS ꢀ12 eV): m=z
st
‡ꢀ
ꢀ%) ˆ 138 ꢀ74), 137 ꢀ20), 136 ꢀ73), 123 ꢀ1), 110 ꢀ26), 109 ꢀ100); B=E ꢀM ˆ 138, 1 ffr): m=z
ꢀ%) ˆ 137 ꢀ18), 136 ꢀ100), 123 ꢀ1), 110 ꢀ1), 109 ꢀ19); IR ꢀ®lm): ꢄ ˆ 3274 ꢀN±H), 2869 ꢀC±H),
2271 ꢀC±D, aromat.) cmÀ 1; 1H NMR ꢀCDCl3): ꢀ ˆ 4.93 ꢀdd, 3J ˆ 7.8 Hz, 3J ˆ 8.3Hz, 1H, CH-phen),
3.72 ꢀddd, 3J ˆ 7.9 Hz, 3J ˆ 8.9 Hz, 2J ˆ 7.1 Hz, 1H, NH±CHH), 3.35 ꢀdddd, 3J ˆ 3.4 Hz, 3J ˆ 8.7 Hz,
3
2
3
3
2J ˆ 7.1 Hz, JNH ˆ 0.7 Hz, 1H, NH±CHH), 2.53 ꢀdddd, J ˆ 10.7Hz, J ˆ 7.9 Hz, JCH-phen ˆ 7.8 Hz,
3J ˆ 3.4 Hz, 1H, CH±CHH), 2.35 ꢀdddd, J ˆ 10.7 Hz, J ˆ 8.9 Hz, JCH-phen ˆ 8.3 Hz, J ˆ 8.7 Hz,
2
3
3
3
1H, CH±CHH), 2.35 ꢀbr s, 1H, NH) ppm.
2 Æ )-2-22-Chlorophenyl)azetidine ꢀIVc; C9H10ClN)
Preparation from XVIIIc ꢀ0.60 g, 3.31mmol); yield: 0.37 g ꢀ69%); b.p. ꢀ0.07 torr): 49ꢁC; EI-MS
ꢀ70 eV): m=z ꢀ%) ˆ 169 ꢀ5), 168 ꢀ8), 167 ꢀ17), 166 ꢀ19), 141 ꢀ6), 140 ꢀ33), 139 ꢀ22), 138 ꢀ100),
132 ꢀ19), 114 ꢀ3), 112 ꢀ9), 103 ꢀ31), 102 ꢀ17), 77 ꢀ16), 51 ꢀ7); EI-MS ꢀ12 eV): m=z ꢀ%) ˆ 169 ꢀ27), 168
‡ꢀ
ꢀ19), 167 ꢀ95), 166 ꢀ37), 141 ꢀ7), 140 ꢀ32), 139 ꢀ26), 138 ꢀ100), 132 ꢀ33), 112 ꢀ2); B=E ꢀM
ꢀ35Cl) ˆ 167, 1st ffr): m=z ꢀ%) ˆ 166 ꢀ100), 152 ꢀ1), 138 ꢀ13), 139 ꢀ1), 132 ꢀ45); IR ꢀ®lm):
ꢄ ˆ 3324 ꢀN±H), 3274 ꢀN±H), 2865 ꢀC±H) cmÀ 1; 1H NMR ꢀCDCl3): ꢀ ˆ 7.73±7.13 ꢀm, 4H, aromat.),
5.22 ꢀdd, 3J ˆ 7.9 Hz, 3J ˆ 8.5 Hz, 1H, CH-phen), 3.80 ꢀddd, 3J ˆ 7.9 Hz, 3J ˆ 9.2 Hz, 2J ˆ 6.9 Hz, 1H,
3
3
2
3
NH±CHH), 3.32 ꢀdddd, J ˆ 3.0 Hz, J ˆ 8.7 Hz, J ˆ 6.9 Hz, JNH ˆ 0.8Hz, 1H, NH±CHH), 2.68
3
ꢀdddd, 2J ˆ 10.7 Hz, 3J ˆ 7.9 Hz, JCH-phen ˆ 7.9 Hz, 3J ˆ 3.0 Hz, 1H, CH±CHH), 2.28 ꢀdddd,
3
3
3
2J ˆ 10.7Hz, J ˆ 9.2 Hz, JCH-phen ˆ 8.5 Hz, J ˆ 8.7 Hz, 1H, CH±CHH), 2.20 ꢀs, 1H, NH) ppm.
2 Æ )-2-24-Chlorophenyl)azetidine ꢀIVd; C9H10ClN)
Preparation from XVIIId ꢀ0.35 g; 1.93 mmol); yield: 0.17 g ꢀ53%); b.p. ꢀ0.3torr): 62ꢁC; EI-MS
ꢀ70 eV): m=z ꢀ%) ˆ 169 ꢀ4), 168 ꢀ6), 167 ꢀ14), 166 ꢀ15), 141 ꢀ7), 140 ꢀ32), 139 ꢀ24), 138 ꢀ100),
132 ꢀ8), 114 ꢀ3), 113 ꢀ2), 112 ꢀ9), 111 ꢀ5), 103 ꢀ29), 77 ꢀ17); EI-MS ꢀ12 eV): m=z ꢀ%) ˆ 169 ꢀ20), 168
ꢀ19), 167 ꢀ64), 166 ꢀ44), 141 ꢀ7), 140 ꢀ33), 139 ꢀ24), 138 ꢀ100), 132 ꢀ24); B=E ꢀM ꢀ35Cl) ˆ 167, 1st
‡ꢀ
ffr): m=z ꢀ%) ˆ 166 ꢀ100), 152 ꢀ1), 139 ꢀ1), 138 ꢀ12), 132 ꢀ23); IR ꢀ®lm): ꢄ ˆ 3320 ꢀN±H), 3280
ꢀN±H), 2869 ꢀC±H) cmÀ 1
;
1H NMR ꢀCDCl3): ꢀ ˆ 7.46±7.26 ꢀm, 4H, aromat.), 4.86 ꢀdd, 3J ˆ
3
3
3
2
7.9 Hz, J ˆ 8.5 Hz, 1H, CH-phen), 3.68 ꢀddd, J ˆ 7.9 Hz, J ˆ 9.1 Hz, J ˆ 7.0Hz, 1H, NH±CHH),
3
3
2
3
2
3.29 ꢀdddd, J ˆ 3.2 Hz, J ˆ 8.7 Hz, J ˆ 7.0 Hz, JNH ˆ 0.8 Hz, 1H, NH±CHH), 2.48 ꢀdddd, J ˆ
3
3
3
2
10.7Hz, J ˆ 7.9 Hz, JCH-phen ˆ 7.9 Hz, J ˆ 3.2 Hz, 1H, CH-phen±CHH), 2.25 ꢀdddd, J ˆ 10.7Hz,
3
3
3J ˆ 9.1 Hz, JCH-phen ˆ 8.5 Hz, J ˆ 8.7Hz, 1H, CH±CHH), 2.06 ꢀs, 1H, NH) ppm.
Acknowledgements
We thank the Fonds der Chemischen Industrie, Frankfurt=Main ꢀFRG) for ®nancial support.
References

[1a] Mutschler E, Geisslinger G, Kroemer HK, Schafer-Korting M ꢀ2001) Arzneimittelwirkungen,
8th ed. Wissenschaftl. Verlagsges., Stuttgart, p 178, 794, 795
[1b] Mandel GL, Petri WA Jr ꢀ1996) In: Goodman & Gilman's The Pharmacological Basis of
Therapeutics, 9th ed. McGraw-Hill, New York, p 1090, 1091
[2] Cooks RG, Varvoglis AG ꢀ1971) Org Mass Spectrom 5: 687
[3] Letzel MC, Grutzmacher H-F, Furst T, Mayer KK, Wiegrebe W ꢀ2002) Intern J Mass Spectrom
217: 153
[4] Vidavsky I, Chorush RA, Longevialle P, McLafferty FW ꢀ1994) J Amer Chem Soc 116: 5865

354
A. Kaiser et al.: EI-MS of Aromatic Alkoxyimines
[5] Pongratz H, Mayer KK, Wiegrebe W ꢀ1997) Monatsh Chemie 128: 659
 
Mattinen J, Bernath G ꢀ1987) J Org Chem 52: 3821
 
[6] Vainiotalo P, Fulop FK, Pihlaja K ꢀ1991) Org Mass Spectrom 26: 438; Fulop F, Pihlaja K,
[7] Ellames GJ, Hewkin CT, Jackson RFW, Smith DI, Standen SP ꢀ1989) Tetrahedron Lett 30: 3471
[8] Zimmer R, Arnold T, Homann K, Reissig H-U ꢀ1994) Synthesis 1050
[9] Mahboobi S, Wiegrebe W ꢀ1991) Arch Pharm ꢀWeinheim) 324: 275 and lit. cited therein
[10] Balani RA, Kulkarni KD ꢀ1963) Indian J Chem 254
[11] Seth-Paul WA, Vermylen-De Winter J ꢀ1969) J Mol Struct 4: 303 and lit. cited therein
[12] Schlosser M, Choi JH, Takagishi S ꢀ1990) Tetrahedron 46: 5633
[13] Birkofer L, Schramm J ꢀ1975) Liebigs Ann Chem 2195
[14] Hollywood F, Suschitzky H ꢀ1982) Synthesis 662
[15] Wells JN, Tarwater OR ꢀ1971) J Pharm Sci 60: 156
[16] Jackson MB, Spotswood TM, Bowie JH ꢀ1968) Org Mass Spectrom 1: 857
[17] Rodionow WW, Malewinskaja ET ꢀ1926) Ber Dtsch Chem Ges 59: 2952
[18] Richtmyer NK ꢀ1946) J Amer Chem Soc 68: 1137
[19] Graf R ꢀ1963) Liebigs Ann Chem 661: 111, cf. also p 156
[20] Testa E, Fontanella L, Aresi V ꢀ1962) Liebigs Ann Chem 656: 114