Reductive one batch synthesis of N-substituted pyrrolidines from primary amines and 2,5-dimethoxytetrahydrofuran

Article abstract of DOI:10.1055/s-1999-3685

The construction of the pyrrolidine ring about a nitrogen of a primary amine by a reductive condensation reaction using 2,5- dimethoxytetrahydrofuran and sodium borohydride in acidic water medium is described. The reaction is fast, affords good to excellent yields and appears insensitive to electron effects and severe steric hindrance; it is found to be compatible with a large variety of aryl substituents, including nitro and oxo groups. The reaction allows the introduction of two deuterium atoms, with label conservation, in both the α-positions of the pyrrolidine ring by the use of sodium borodeuteride instead of sodium borohydride.

Full text of DOI:10.1055/s-1999-3685

74
PAPER
Reductive One Batch Synthesis of N-Substituted Pyrrolidines from Primary
Amines and 2,5-Dimethoxytetrahydrofuran
Giancarlo Verardo,* Anna Dolce, Nicoletta Toniutti
Department of Chemical Sciences and Technologies, University of Udine, I-33100 Udine, Italy
Fax: +039(0432)558803; E-mail: gverardo@tin.dstc.uniud.it
Received 30 April 1998; revised 13 June 1998
ification of the two hydroxyl groups with sulfonic acids
Abstract: The construction of the pyrrolidine ring about a nitrogen
derivatives8 allowed milder reaction conditions.
of a primary amine by a reductive condensation reaction using 2,5-
dimethoxytetrahydrofuran and sodium borohydride in acidic water
medium is described. The reaction is fast, affords good to excellent
yields and appears insensitive to electron effects and severe steric
hindrance; it is found to be compatible with a large variety of aryl
substituents, including nitro and oxo groups. The reaction allows
the introduction of two deuterium atoms, with label conservation, in
both the a-positions of the pyrrolidine ring by the use of sodium
borodeuteride instead of sodium borohydride.
Of particular synthetic value are reactions which permit
selective functionalization of otherwise unactivated at-
oms. The oldest representative of such a process is the
HofmannÐLšfflerÐFreytag reaction.9 In this reaction sec-
ondary N-haloamines, in which one alkyl group has a hy-
drogen in the 4-position, are heated with H2SO4 to give N-
alkylpyrrolidines.
Key words: pyrrolidine, 2,5-dimethoxytetrahydrofuran, sodium
borohydride, sodium borodeuteride, reductive alkylation
Reported procedures to make N-arylpyrrolidines from
pyrrolidine require either the presence of activated halo-
gens (ar-SN2)10 or the activation of the nucleophile as an
alkali salt (ar-SN2 and/or benzyne reactions).11
Examples of reduction of N-substituted 2,5-dioxopyrro-
lidines with LiAlH412 and 2-oxopyrrolidines with catalytic
hydrogenation13 or NaBH4 in presence of POCl314 are re-
ported in the literature. The catalytic hydrogenation has
been extensively used for the reduction of N-substituted
pyrroles15 with some limitations for N-aryl pyrroles be-
cause of concomitant hydrogenation of the aromatic ring.
In principle, the methods to build up cyclic amines can be
distinguished by the type and size of the fragments to be
joined and by the type of reactions employed to perform
the cyclization.
The synthesis of N-substituted pyrrolidines, an important
endeavour in many synthetic fields, has been studied ex-
tensively and a number of procedures are available.1 A
versatile synthetic way, also for a large scale utilisation, is
the reaction between tetrahydrofuran and the appropriate
primary amine in the presence of water-splitting catalysts
Little attention, however, has been paid to the reductive
alkylation of amines using succinaldehyde derivatives.
We applied our reductive N-alkylation procedure16 using
a primary amine (1) and 2,5-dimethoxytetrahydrofuran
(2). We used NaBH4 in H2SO4ÐwaterÐmethanol as the re-
ducing agent for the intermediate condensation products
(Scheme 1). R groups are listed in Table 1.
such as Al2O3 or other oxides3 (i.e. TiO2, ThO2, Fe2O3,
2
MoO3) at elevated temperatures (300Ð500¡C). This meth-
od has been utilised both with aromatic and aliphatic
amines, but it is not suitable for medium scale or labora-
tory preparation due to the need of special equipment.
Previous methods applying the reductive 2,5-dimeth-
oxytetrahydrofuran (2) condensation-reaction approach
were a procedure using tetracarbonylhydroferrate under
carbon monoxide atmosphere17 and another employing
sodium cyanoborohydride to convert N-aminopiperidine
to N-piperidylpyrrolidine.18
The pyrrolidine skeleton may be also obtained by the
4C+1N scheme from a reactive C4 molecule suitably
functionalized at both ends and a primary amine via a dis-
placement reaction.
The method described here is very simple, fast and cheap,
both in handling and equipment. We have successfully ap-
plied our procedure not only to aromatic amines bearing
substituents of widely different electronic effect and very
severe steric hindrance, i.e. 1e and 1n, but also to aliphatic
ones, i.e. 1t and 1u (see Table 1).
The reactive C4 molecule may be a 1,4-dihalide4 (X = Cl
or Br) or 1,4-diol.5 This route, even if particularly conve-
nient, suffers from some disadvantages: with the former
substrate the reaction is very sensitive to steric hindrance6
and to the basicity of the amine: in some cases, a catalyst
(ZnCl2, AlCl3)7 or long reaction times are needed. With
the latter, a catalyst [RuCl2(PPh3)3, Al2O3 or aluminosili-
cate] and very high temperatures are requested. The ester-
GCMS analysis of the crude reaction mixtures after neu-
tralisation showed the presence ca. 5Ð6% of the corre-
sponding N-substituted pyrrole (4) as the only side
product (Scheme 1). We confirmed the structures of 4aÐu
by the comparison of their GC retention times and mass
spectra with those of authentic samples prepared accord-
ing to a known procedure.19
Synthesis 1999, No. 1, 74Ð79 ISSN 0039-7881 © Thieme Stuttgart á New York

PAPER
Reductive One Batch Synthesis of N-Substituted Pyrrolidines
75
Scheme 1
The amount and the concentration of H2SO4 are important
in order to reduce the formation of 4 and the proper con-
ditions depend on the nature of the amine 1. In general, we
used a lesser amount of acid and a greater amount of water
than in the previously reported reductive alkylation proce-
dure.16
We noticed that also the form of the NaBH4 used was very
important for the good proceeding of the reaction. NaBH4
as pellets (diameter 11 mm) or half-broken caplets have to
be preferred to NaBH4 powder that favours the formation
of the alcohol 9 as a side product.
(11, δ = 126.1 ppm).20 This observation can be taken as an
indication of the lack of conjugation between the nitrogen
lone pair and the ring, as a consequence of the mutual Òor-
thogonalÓ position of the two rings as we already saw in
11.20 This conformational situation in 3e may explain its
resistance to iodination, in fact, while it was easy to syn-
thesise 4-iodo-2,6-diisopropylbenzenamine (1n) from 1e,
the same reaction proved to be ineffective on 3e in order
to synthesise 3n.
When NaBD4 was used instead of NaBH4, two deuterium
atoms were introduced to the 2- and 5-position of the pyr-
rolidine ring: the procedure applied on 4-methylben-
zenamine (1d) gave 2,5-dideuterio-1-(4'-methyl-phenyl)-
pyrrolidine (3d-d2) in high yield.
There was some consideration on the 13C NMR spectrum
of 1-(2,6-diisopropylphenyl)pyrrolidine (3e): it can be
seen that the ArÐC1 chemical shift is located in the usual
region for benzenamines, whereas ArÐC4 appears to be
deshielded (δ = 126.2 ppm) in comparison with ben-
zenamine (δ = 119.0 ppm) and N,N-dimethylbenzenamine
(δ = 116.7 ppm), showing a value quite close to that of tol-
uene and isopropylbenzene (δ = 125.6 and δ = 126.0 ppm,
respectively) and 1-(2',6'-diisopropylphenyl)piperidine
Data pertinent to the synthesised 1-substituted pyrro-
lidines (3) are collected on Table 2.
With the exception of 4-iodo-2,6-diisopropylbenzenamine (1n),
which was prepared as described,21 the other amines 1aÐm and 1oÐ
u used in this work, 2,5-dimethoxytetrahydrofuran (2), NaBH4 pel-
lets (11 mm diameter) and NaBD4 powder (96 atom% D) were pur-
chased from Aldrich, Italy, Milan. NaBH4 (Venpure) caplets were
kindly offered by Morton International S.p.A. (Mozzate, Como).
Synthesis 1999, No. 1, 74–79 ISSN 0039-7881 © Thieme Stuttgart · New York

76
G. Verardo et al.
PAPER
Table 1 Yields and Some Properties of 1-Substituted Pyrrolidines (3)
Prod-
uct
R
Separated mpa (°C)
yield (%) or bpa (°C)/ or bp (°C)/
Lit. mp (°C) Formula
Elemental analysis
Calcd.
mbar
mbar
Found
3a
3b
C6H5
87
80
58/0.30f
100/7.98,8b
37-8/0.13,13a
70/0.7717a
2-MeC6H4
60/0.60f
114/14.6,6a
55/0.5117a
3c
3-MeC6H4
4-MeC4H4
83
83
60/0.40f
69/0.42f
70/0.8517a
3d
120/10.6,15b
64/0.1917a
3d-d2
3e
72
71/0.42f
70/0.15f
85/0.42g
41c
C11H13D2N C: 80.53, H: 7.38, N: 9.40
C: 80.06, H: 7.33, N: 9.23
2,6-i-Pr2C6H3
3-MeOC6H4
4-MeOC6H4
2,3,4-F3C6H2
3-CF3C6H4
2-ClC6H4
58; 80b
78
C16H25N
C: 83.06, H: 10.89, N: 6.05 C: 83.15, H: 10.84, N: 6.12
3f
174/26.66a
86/0.4317a
3g
3h
3i
81
79
74/1.0f
73/0.41f
78/0.80f
119/0.70f
86d
C10H10F3N C: 59.70, H: 5.01, N: 6.96
C: 59.62, H: 4.93, N: 6.87
C: 66.08, H: 6.72, N: 7.65
82
60-2/0.365e
54/0.2717a
3j
85
3k
3l
3-ClC6H4
83
C10H12ClN C: 66.12, H: 6.66, N: 7.71
C10H12BrN C: 53.12, H: 5.35, N: 6.19
4-ClC6H4
86
85-617a
3m
3n
3o
3p
3q
3r
3-BrC6H4
79
95/0.20f
121d
C: 53.17, H. 5.42, N: 6.23
C: 53.72, H: 6.72, N: 4.02
C: 70.15, H: 7.43, N: 6.88
C: 76.02, H: 7.92; N: 7.34
2,6-i-Pr2-4-I-C6H2 43; 72b
C16H24lN
C: 53.79, H: 6.77, N: 3.92
2-MeO2CC6H4
4-MeOCC6H4
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
77b
87
105/0.30f
126d
C12H15NO2 C: 70.22, H: 7.37, N: 6.82
C12H15NO C: 76.16, H: 7.99, N: 7.40
32; 65b
87
34h
105–7/0.1310c
98–10010e
100e
3s
89
177c
167–8,10b
169-71,10d
178-910e
3t
C6H5CH2
40
36
42/0.38f
40/0.22f
95/7.98,2b
82/6.65,8b
44/0.4317a
3u
C6H11
200-10/10135a
a Uncorrected.
e Recrystallized from Et2O.
f Purified by distillation.
b Yield obtained after a second treatment on the reaction mixture.
c Recrystallized from MeOH/H2O.
g Purified by absorption chromatography on alumina (eluent: hexane).
d Recrystallized from MeOH.
Purified by absorption chromatography on alumina (eluent: hex-
h
ane-Et2O 90:10).
Alumina (active neutral, Brokmann Grade I) was obtained from
BDH (Milan, Italy). Thin layer chromatography was performed on
alumina (Aluminiumoxid 60 F254 neutral, Merck, Darmstadt, Ger-
many) and hexaneÐEt2O (60:40) were used as eluents. Solvents
were used as received. GCMS analyses were performed with a
Fisons TRIO 2000 gas chromatographÐmass spectrometer, working
in the positive ion 70 eV electron impact mode. Spectra were re-
corded in the range 35Ð450 u. Injector temperature was kept at
250¡C and the column (Supelco SPBTM-5, 30 m long, 0.25 mm I.D.)
temperature was programmed from 60¡C to 300¡C with a gradient
of 10¡C/min. IR spectra were obtained with a Nicolet FT-IR Magna
550 spectrophotometer using KBr technique for solids and recorded
in the range 4000Ð400 cmÐ1. 1H and 13C NMR spectra were recorded
in CDCl3 at r.t. on a Bruker AC-F 200 spectrometer at 200 and
50 MHz, respectively. NMR peak locations are reported as δ-values
from TMS (1H NMR) and the central peak of CDCl3 (13C NMR).
Synthesis 1999, No. 1, 74–79 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Reductive One Batch Synthesis of N-Substituted Pyrrolidines
77
Table 2 Infrared, 1H and 13C NMR Spectra and Electron Impact Mass Spectra of 1-Substituted Pyrrolidines (3)
Product
IR (Kbr or neat)
(cm–1)
1H NMR (CDCl3/TMS)
d, J (Hz)
13C NMR (CDCl3); d
MS (70 eV)
m/z (%)
3d-d2
3019, 2980, 2868, 1.90–1.97 (m, 4H, CH2), 2.24 (s, 3H, 20.2, 25.2, 47.4 (t, J = 163(M+, 89), 162(100), 161(63),
1619, 1522, 1365, CH3), 3.16–3.24 (m, 2H, N-CHD), 6.47 20.76), 111.7, 124.3, 160(9), 159(4), 135(5), 120(5),
1189, 1169, 801
(app d, 2H, Harom, J = 8.5), 7.02 (app d, 129.5, 146.0
2H, Harom, J = 8.5)
119(10), 118(11), 106(37),
91(13)
3e
3f
2960, 2867, 1653, 1.21 (d, 12H, CH3), 1.95–2.05 (m, 4H, 24.5, 26.6, 28.0, 52.7, 231(M+, 74), 230(53), 216(20),
1622, 1447, 1383, CH2), 3.12–3.35 (m, 6H, N-CH2+CH), 123.8, 126.2, 142.8, 150.0 190(100), 188(22), 146(27),
1286, 1174, 1102
7.03–7.15 (m, 3H, Harom
)
144(8), 132(15), 130(8), 91(7)
2964, 1608, 1573, 1.92–2.00 (m, 4H, CH2), 3.22–3.30 (m, 25.3, 47.5, 55.0, 97.8, 177(M+, 75), 176(100), 174(4),
1502, 1487, 1373, 4H, N-CH2), 3.78 (s, 3H, CH3O), 6.00– 100.4, 104.8, 129.7, 149.2, 149(6), 148(6), 134(8), 121(21),
1220, 1166, 1082, 6.27 (m, 3H, Harom), 7.05–7.27 (m, 1H, 160.6
1052 Harom
107(5), 92(7), 77(5)
)
3h
2973, 2877, 1519, 1.90–2.05 (m, 4H, CH2), 3.30–3.45 (m, 25.0, 49.6 (d, J = 4.2), 201(M+, 80), 200(100), 199(12),
1498, 1463, 1358, 4H, N-CH2), 6.22–6.36 (m, 1H, Harom), 107.5 (m), 110.6 (dd, J1 = 198(11), 197(7), 169(6),
1280, 1000
6.70–6.86 (m, 1H, Harom
)
18.3, J2 = 3.1), 135.1 (m), 159(13), 158(72), 145(76),
138.5 (app t, J = 14.8), 138(10), 138(10), 131(26)
140.7 (app dd, J1 = 10.4, J2
= 3.2), 143.4 (app t, J =
14.8), 145.5 (app dd, J1 =
10.2, J2 = 2.2)
3k
2968, 2873, 1591, 1.95–2.05 (m, 4H, CH2), 3.18–3.32 (m, 4H, 25.4, 47.5, 109.8, 111.4, 183(M+, 25), 182(32), 181 (M+,
1480, 1354, 1297, N-CH2), 6.41 (ddd, 1H, Harom, J1 = 6.0, J2 = 115.0, 130.0, 135.0, 148.8 54), 180(87), 146(24), 140(18),
1146, 1111, 1037, 2.4, J3 = 0.8), 6.51 (t, 1H, Harom, J = 2.2),
139(10), 138(47), 127(38),
125(100), 117(12), 113(11),
111(29), 77(12), 75(17)
743
6.61 (ddd, 1H, Harom, J1 = 5.0, J2 = 1.1, J3 =
0.8), 7.1 (app t, 1H, Harom, J = 8.0)
3m
2969, 2843, 1653, 1.90–2.02 (m, 4H, CH2), 3.15–3.25 (m, 25.3, 47.5, 110.2, 114.2, 227(M+, 68), 226(95), 225(M+,
1622, 1593, 1552, 4H, N-CH2), 6.42 (ddd, 1H, Harom, J1 = 8.3, 117.9, 123.2, 130.2, 148.9 70), 224(100), 199(4), 197(4),
1495,
1458s, J2 = 2.4, J3 = 0.9), 6.64 (t, 1H, Harom, J =
184(8),
182(8),
171(17),
1371, 1246, 1170, 2.0), 6.73 (app ddd, 1H, Harom, J1 = 8.0, J2
169(17), 157(8), 155(8), 117(7),
91(4), 90(5)
1090, 982
= 2.0, J3 = 0.9), 7.02 (app t, 1H, Harom, J =
8.0)
3n
3o
2973, 2874, 2821, 1.18 (d, 12H, CH3), 1.95–2.05 (m, 4H, 24.3, 26.5, 28.0, 52.6, 357(M+, 91), 356 (54), 342(19),
1568, 1455, 1368, CH2), 3.05–3.25 (m, 6H, N-CH2+CH), 92.2, 133.4, 142.9, 152.9
1330, 1170, 1061 7.38 (s, 2H, Harom
316(100), 314(25), 301(16),
187(48), 173(17), 172(26),
158(15), 144(15), 139(10),
115(10), 43(8)
)
2975, 2875, 1712, 1.85–1.95 (m, 4H, CH2), 3.15–3.25 (m, 25.5, 50.5, 51.6, 113.6, 205(M+, 55), 201(10), 190(100),
1600, 1500, 1450, 4H, N-CH2), 3.84 (s, 3H, CH3), 6.67 (app 115.3, 116.7, 130.7, 131.4, 177(40), 174(24), 172(15),
1369, 1299, 1229, dt, 1H, Harom, J1 = 8.0, J2 = 1.0), 6.74 (app 147.6, 169.2
170(12), 154(44), 146(17),
145(40), 117(13), 105(28),
91(14), 77(34)
1130, 1084
dd, 1H, Harom, J1 = 8.5, J2 = 0.7), 7.21–7.32
(m, 1H, Harom), 7.55 (dd, 1H, Harom, J1 =
7.8, J2 = 1.7)
3p
3q
3r
2966, 1656, 1603, 1.95–2.05 (m, 4H, CH2), 2.50 (s, 3H, 25.3, 47.4, 110.5, 124.7, 189(M+, 52), 188(25), 174(100),
1524, 1466, 1405, CH3), 3.28–3.38 (m, 4H, N-CH2), 6.48 130.5, 150.8, 196.1
146(20),
133(17),
117(10),
145(8),
132(9),
105(10),
144(8),
118(10),
104(9),
1286vs, 1186
(app d, 2H, Harom, J = 8.8), 7.84 (app d,
2H, Harom, 2H, Harom, J = 8.8)
91(11), 77(8)
2976, 1602, 1573, 1.90–2.05 (m, 4H, CH2), 3.13–3.25 (m, 25.6, 50.2, 115.3, 115.8, 192(M+, 34), 175(55), 158(5),
1522, 1464, 1405, 4H, N-CH2), 6.65–6.75 (m, 1H, Harom), 126.6, 132.8, 136.9, 142.6 157(9), 145(94), 144(100),
1344, 1292, 1252, 6.89 (dd, 1H, Harom, J1 = 8.8, J2 = 1.2),
1158, 1109 7.31–7.41 (m, 1H, Harom), 7.72 (dd, 1H,
arom, J1 = 8.3, J2 = 1.7)
131(9),
104(42), 91(13), 77(18)
119(17),
117(23),
H
2979, 1627, 1614, 1.95–2.10 (m, 4H, CH2), 3.22–3.35 (m, 25.4, 47.7, 105.5, 109.6, 192(M+, 82), 191(100), 164(7),
1522, 1481, 1381, 4H, N-CH2), 6.74 (ddd, 1H, Harom, J1 = 8.3, 117.2, 129.4, 148.1, 149.2 146(21),
1345, 1312, 1250, J2 = 2.4, J3 = 0.8), 7.20–7.30 (m, 2H, 136(36),
1150 arom), 7.40 (ddd, 1H, Harom, J1 = 8.1, J2 =
2.1, J3 = 0.9)
145(30),
130(5),
104(11), 91(8), 90(10), 77(9)
144(8),
117(7),
H
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G. Verardo et al.
PAPER
Table 2 (continued)
Product
IR (Kbr or neat)
(cm–1)
1H NMR (CDCl3/TMS)
d, J (Hz)
13C NMR (CDCl3); d
MS (70 eV)
m/z (%)
3s
2976, 1602, 1573, 2.00–2.12 (m, 4H, CH2), 3.30–3.42 (m, 25.4, 47.9, 110.4, 126.2, 192(M+, 95), 191(100), 176(5),
1522, 1464, 1405, 4H, N-CH2), 6.44 (app d, 2H, Harom, J = 136.4, 151.8
1362, 1292, 1194, 9.3), 8.07 (app d, 2H, Harom, J = 9.3)
1109, 1044
164(11), 162(18), 146(20),
145(50), 144(10), 136(31),
130(6), 120(5), 117(7), 106(9),
90(5)
3u
2936, 2850, 1620, 1.10–1.30 (m, 6H, CH2), 1.55–2.05 (m, 23.0, 25.0, 25.9, 32.0, 153(M+, 76), 152(15), 124(11),
1454, 1388, 1137, 8H, CH2), 2.50–2.63 (m, 5H, N-CH2+N- 51.3, 63.6
1077 CH)
111(37), 110(100), 108(6),
97(30), 96(31), 84(13), 70(20),
69(13), 68(8), 55(7)
1
Some H multiplets are characterised by the term app (apparent):
this refers only to their appearance and may be an oversimplifica-
tion. Elemental analysis were performed with a Carlo Erba Mod.
1106 elemental analyser and were in satisfactory agreement with
calculated values. Mps were determined with an automatic Mettler
(Mod. FP61) and are not corrected. Boiling points refer to the cen-
tral cut of small distillations and are uncorrected.
Bird, C. W.; Cheeseman, G. W. H.; Synthesis of Five-mem-
bered Rings with One Heteroatom. In Comprehensive Hetero-
cyclic Chemistry; Katritzky, A. R.; Rees, C.W., Eds.;
Pergamon: Oxford, 1984; Vol. 3, p 89.
(2) (a) Farbenind, I. G. Ger. Pat. 637730/1936 (Chem. Abstr.
1937, 31, 26161).
(b) YurÕev, Yu. K.; Tronova, V. A.; LÕvova, N. A.; Bukshpan,
Z. Ya. J. Gen. Chem. 1941, 11, 1128.
(c) Walkup, R. E.; Searles, S. Jr. Tetrahedron 1985, 41, 101.
(3) Farbenind, I. G. Fr. Pat. 851178/1940 (Chem. Abstr. 1942, 36,
19572).
N-Substituted Pyrrolidines (3); General Procedure
A THF (25 mL) solution of 2,5-dimethoxytetrahydrofuran (2,
2.99 mL, 23.1 mmol) and 2.5M H2SO4 (17.80 mL, 44.5 mmol) was
added dropwise (ca. 20 min) to an open vessel containing a solution
of the appropriate amine 1 (17.8 mmol) in MeOH/THF (40 mL; 1:1)
and some NaBH4 pellets or half-broken caplets (one every ca.
4 min, to a total of approximately 2.70 g, 71 mmol) were added un-
der vigorous magnetic stirring at ca. 10¡C. The mixture, under stir-
ring, was then allowed to warm up to r.t. over 90 min, then it was
diluted with H2O (30 mL), made strongly alkaline (cooling) with
NaOH pellets (3.0 g) and extracted with Et2O (3 × 30 mL). Prelim-
inary acid-base treatment of the residue removed pyrrole 4: the
combined extracts were treated with a 6M aq HCl (30 mL). The
aqueous phase, containing the hydrochloride of 3, was washed with
Et2O (2 × 15 mL), basified and extracted with Et2O (3 × 20 mL)
from which the product 3 was recovered after washing with brine
(30 mL) and drying (Na2SO4). Final purification yielded products
as specified in Table 1.
YurÕev, Yu. K.; Levi, I. S. Vestnik Moskov. Univ., Ser. Mat.
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In the case of alkyl amines 1t and 1u, the procedure was the same,
but the amount and concentration of the acid were varied: 3M
H2SO4 (11.9 mL, 35.6 mmol) was used.
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NaBD4 pellets (prepared by us from the powder using the same pro-
cedure as for KBr pellets in IR analysis) instead of NaBH4 were
used in the synthesis of 2,5-dideuterio-1-(4'-methylphenyl)pyrroli-
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Acknowledgement
Financial support was obtained from the Italian Ministry of Uni-
versity, Sciences and Technology (MURST 40% 1996 and
MURST 60% 1992Ð95 to GV). The authors are grateful to Dr. P.
Martinuzzi for recording 1H and 13C NMR spectra and Mr P. Pado-
vani for expert instrumental maintenance.
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