New Types of Very Efficient Photolabile Protecting Groups Based upon the [2-(2-Nitrophenyl)propoxy]carbonyl (NPPOC) Moiety

Article abstract of DOI:10.1002/hlca.200490060

Based upon the photolabile [2-(2-nitrophenyl)propoxy]carbonyl group (NPPOC), a large number of modified 2-(2-nitrophenyl)propanol derivatives substituted at the phenyl ring (see 23-34 and 57-76) as well as at the side-chain (see 85-92 and 95-98) were synthesized to improve the photoreactivity of this new type of photolabile entity. The phenyl moiety was also exchanged by the naphthalenyl group (see 102, 103, 105, 108, 110, 113, and 114), the thienyl substituent (see 115, 117, 118, and 120), and the benzothienyl substituent (see 121). The 2-(2-nitroaryl- and heteroaryl) propanols were converted with diphosgene into the corresponding carbonochloridates, which reacted subsequently with thymidine to the thymidine 5′-(protected carbonates) 123-178 as the main reaction products. In several cases, the corresponding 3′-carbonates and 3′,5′ -dicarbonates 179-212 were also isolated and characterized. Photolysis studies under standardized conditions (see Table) indicated that the rate of photocleavage varies in a broad range depending on the substituents. So far, the thymidine 5′-[2-(5-halo-2-nitrophenyl)propyl carbonates] 127-129, 5′-[2-(nitro[1,1′-biphenyl]3-yl)propyl carbonates] 136-139, 5′-{2-[2-nitro-5-(thianthren-1-yl)phenyl]propyl carbonate} (140), 5′-[2-(5-naphthalenyl-2-nitrophenyl)propyl carbonates] 141 and 142, and 5′-[2-(2-nitro-5-thienylphenyl)propyl carbonates] 143 and 144 showed the best properties regarding fast and uniform deprotection. Since the nucleobases of 213-215 do not influence the photocleavage features, in general, the new type of photolabile building blocks allows in form of their 3′ -phosphoramidites the photolithographic formation of high-quality biochips.

Full text of DOI:10.1002/hlca.200490060

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New Types of Very Efficient Photolabile Protecting Groups Based upon the
[2-(2-Nitrophenyl)propoxy]carbonyl (NPPOC) Moiety
by Sigrid B¸hlerb), Irene Lagojaa), Heiner Giegricha), Klaus-Peter Stengeleb) and Wolfgang Pfleiderera)*
a) Fachbereich Chemie, Universit‰t Konstanz, Postfach 5560, D-78457 Konstanz
b) Chemogenix, Beuthener Str. 2, D-84478 Waldkraiburg
Based upon the photolabile [2-(2-nitrophenyl)propoxy]carbonyl group (NPPOC), a large number of
modified 2-(2-nitrophenyl)propanol derivatives substituted at the phenyl ring (see 23 34 and 57 76) as well as
at the side-chain (see 85 92 and 95 98) were synthesized to improve the photoreactivity of this new type of
photolabile entity. The phenyl moiety was also exchanged by the naphthalenyl group (see 102, 103, 105, 108, 110,
113, and 114), the thienyl substituent (see 115, 117, 118, and 120), and the benzothienyl substituent (see 121).
The 2-(2-nitroaryl- and heteroaryl)propanols were converted with diphosgene into the corresponding
carbonochloridates, which reacted subsequently with thymidine to the thymidine 5'-(protected carbonates)
123 178 as the main reaction products. In several cases, the corresponding 3'-carbonates and 3',5'-dicarbonates
179 212 were also isolated and characterized. Photolysis studies under standardized conditions (see Table)
indicated that the rate of photocleavage varies in a broad range depending on the substituents. So far, the
thymidine 5'-[2-(5-halo-2-nitrophenyl)propyl carbonates] 127 129, 5'-[2-(nitro[1,1'-biphenyl]3-yl)propyl car-
bonates] 136 139, 5'-{2-[2-nitro-5-(thianthren-1-yl)phenyl]propyl carbonate} (140), 5'-[2-(5-naphthalenyl-2-
nitrophenyl)propyl carbonates] 141 and 142, and 5'-[2-(2-nitro-5-thienylphenyl)propyl carbonates] 143 and 144
showed the best properties regarding fast and uniform deprotection. Since the nucleobases of 213 215 do not
influence the photocleavage features, in general, the new type of photolabile building blocks allows in form of
their 3'-phosphoramidites the photolithographic formation of high-quality biochips.
1. Introduction. Photolabile protecting groups [1 3] are an interesting alternative
to extend normal blocking-group strategies in synthetic organic chemistry into an
orthogonal dimension. The most common representatives featuring the anticipated
photochemical lability are derived from o-nitrobenzyl alcohol (ˆ2-nitrobenzene-
methanol) [1] and its derivatives. It was shown that the quantum yield of photo-
deprotection is strongly influenced by substituents at the phenyl moiety [5] and the
CH2(a) group [6], which on substitution by a Me group at C(a) revealed a fivefold
increase in quantum yield of the photocleavage. The o-nitrobenzyl function has been
used since its discovery in 1901 [7] to protect hydroxy, amino, mercapto, carboxy, and
carbonyl functions [1 3][8] and is well established in nucleic acid [9 16], carbohy-
drate [17], and peptide [4][18 20] chemistry. More recently, photolabile protection of
the 5'-OH of 2'-deoxyribonucleoside 3'-phosphoramidites [5][21 23] and of the 3'-OH
of the isomeric 2'-deoxyribonucleoside 5'-phosphoramidites [24][25] has been em-
ployed in the solid-phase synthesis of DNA probe arrays [26][27]. For this purpose the
[(o-nitroveratryl)oxy]carbonyl (ˆ [(3,4-dimethoxy-2-nitrophenyl)methoxy]carbonyl;
NVOC) and the [(a-methyl-o-nitropiperonyl)oxy]carbonyl (ˆ [1-(1,3-benzodioxal-5-
yl)ethoxy]carbonyl; MeNPOC) groups have been considered as excellent candidates in
the biochip production of oligonucleotide arrays by the photolithographic technique

Helvetica Chimica Acta Vol. 87(2004)
621
[5]. This method has already revolutionized microelectronics to a large extent and is
now applied as another consequential technology in molecular biology to serve as
analytic and diagnostic tool for DNA analyses [5][28][29] and as an alternative
approach for DNA sequencing by hybridization (SBH) [30 32]. Besides the o-
nitrobenzyl group and its modified derivatives, other types of photolabile functions
have been found such as the benzoine (ˆ1,2-diphenyl-2'-hydroxyethanone) residue
[22][33][34], the pyrenylmethyl group [35], and the [(9,10-dihydro-9,10-dioxoanthra-
cen-2-yl)methoxy]carbonyl group and the cinnamyl esters [36][37]. Their use,
however, is limited to special applications, and the cleavage efficiences are only
moderate.
An improvement in the photolytic blocking-group strategy was achieved recently
with the introduction of the [2-(2-nitrophenyl)ethoxy]carbonyl (NPEOC) [38][39]
and the [2-(2-nitrophenyl)ethyl]sulfonyl (NPES) [39] group as new types of photo-
labile functions, especially prone for application in nucleoside and nucleotide
chemistry. In contrast to the cleavage mechanism of the 2-nitrobenzyl group, which
has been well studied [40][41], the photodecomposition of the NPEOC and NPES
functions follows a new pathway established as a photoinduced b-elimination process
[42]. Preliminary investigations have shown that the branching in a-position,
preferentially by a Me group, increases also the quantum yield of photocleavage in
this series by a factor of 10 [38]. It became obvious to modify in more detailed studies
the 2-(2-nitrophenyl)propan-1-ol molecule at the phenyl moiety and by synthesis of
structurally related 2-(2-nitroheteroaryl)propan-1-ols, to improve further the photo-
lytic features. In this paper, the results of these broad structural variations will be
reported and discussed comparatively.
2. Synthesis. Our initial investigations on modified 2-(2-nitrophenyl)propan-1-ol
derivatives [38] indicated that the most versatile approach to this group of compounds
should start from 1-ethyl-2-nitro-substituted benzenes allowing many direct variations
at the phenyl moiety. The 4-amino-substituted 1-ethyl-2-nitrobenzene 1 [43] was
converted by known procedures applying the Sandmeyer reaction into the 4-chloro-, 4-
bromo-, and 4-iodo-substituted 1-ethyl-2-nitrobenzenes 2 4. In a similar manner, the
3-amino-substituted 1-ethyl-2-nitrobenzenamine 5 [44] was converted into the
corresponding 3-chloro-, 3-bromo-, and 3-iodo-substituted 1-ethyl-2-nitrobenzenes
6 8. Analogously, the 5-amino-substituted 1-ethyl-2-nitrobenzene 9 [45] yielded the 5-
chloro-, 5-bromo-, and 5-iodo-substituted 1-ethyl-2-nitrobenzenes 10 12. The intro-
duction of the halogen atoms into 6-position afforded several steps to prepare first 1-
ethyl-2,6-dinitrobenzene (13) [46], which was then reduced in MeCN with HCOOH in
presence of Pd/C to give 6-amino-substituted 1-ethyl-2-nitrobenzene 14 [47] in 81%
yield. The Sandmeyer reaction worked very well with 14 and led in high yields to the 6-
bromo- and 6-iodo-substituted 1-ethyl-2-nitrobenzenes 15 and 16. Since another
interesting structural motif was seen in the 1-ethyl-dinitrobenzenes, the 2,3-, 2,4-, 2,5-
and 2,6-dinitro derivatives were synthesized. The 1-ethyl-2,3-dinitrobenzene (17) [46]
resulted from the 4-amino-substituted 1-ethyl-2,3-dinitrobenzene 18, 1-ethyl-2,5-
dinitrobenzene (19) [46] from the 4-amino-substituted 1-ethyl-2,5-dinitrobenzene 20,
and 1-ethyl-2,6-dinitrobenzene (13) from the 4-amino-substituted 1-ethyl-2,6-dinitro-
benzene 21, each by diazotation in conc. H2SO4 solution/AcOH and subsequent heating

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in EtOH. The 1-ethyl-2,4-dinitrobenzene (22) could not be obtained in pure form but
only as a 1:1 mixture with 1-ethyl-2,6-dinitrobenzene (13).
The interconversion of the Et group into the corresponding 2-substituted propan-1-
ol derivatives was achieved with paraformaldehyde under the catalysis of potassium
tert-butoxide (tBuOK) in aprotic dipolar solvents like DMSO, DMF, or hexamethyl-
phosphoric triamide (HMPA) [48 50]. Such solvents are essential since, for the aldol-
addition reaction, the activation of alkylbenzenes by only one NO2 group is relatively
weak and, therefore, needs more severe conditions [46]. The hydroxymethylation
reactions to the 2-(2-nitrophenyl)propan-1-ols worked well with the 4-halogeno- and 5-
halogeno-substituted 1-ethyl-2-nitrobenzenes 2 4 and 10 12, respectively, to 23 28
in yields of 66 85%, however, the 3-halogeno derivatives 6 8 did not react under
various modified reaction conditions. These findings are explained by the fact that the
2-NO2 group is forced by the adjacent halogen-atoms to adapt a perpendicular
conformation to the aromatic ring and thus can not activate the relevant H-atom of the
Et group. The steric interference is also seen in the NMR spectra of 6 8 (MeCH2
shifted up-field from d 2.82 2.90 to 2.60). Analogously, 1-ethyl-2,3-dinitrobenzene
(18) did not undergo the aldol-addition reaction. Problems were also encountered with
the 6-iodo-substituted 1-ethyl-2-nitrobenzene 16, which did not react with paraformal-
t
dehyde and BuOK neither in DMSO nor in DMF. Other bases like DBU (1,8-

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623
diazabicyclo[5.4.0]undec-7-ene) or NaH also showed no addition reaction, and the use
of NaOMe in DMSO caused a drastic structural change in the molecule leading to 1-(2-
nitrophenyl)ethanol (29) in 28% isolated yield. Analogous reactions with 6-bromo-
substituted 1-ethyl-2-nitrobenzene 15 again were not successful. However, the treat-
ment of 15 with paraformaldehyde in DMSO in presence of NaCN at room
temperature led in very low yield of 6% to the anticipated 2-(2-bromo-6-nitro-
phenyl)propan-1-ol (30) besides the isolation of 77% of educt. The same reaction
conditions were applied to 16, which gave finally 5% of isolated 2-(6-iodo-2-nitro-
phenyl)-propan-1-ol (31). For the synthesis of the 2-(2,4-dinitrophenyl)propan-1-ol
(32), a 1:1 mixture 13/22 was treated under the normal reaction conditions for 2 h at
808 leading to a mixture of 1-ethyl-2,6-dinitrobenzene (13), 34% of 2-(2,4-dinitrophe-
nyl)propan-1-ol (32), and 5% of 2-(2,6-dinitrophenyl)propan-1-ol (33). If pure 13 was
applied, the reaction was very slow, and even heating for 3 days was not satisfactory.
Exchange of DMSO against DMF, however, made a big difference since 28% of 33
besides 70% of educt was isolated after 3 h heating to 908. The same conditions were
successful with 19, which gave in DMF 25% of 2-(2,5-dinitrophenyl)propan-1-ol (34).
Since the photocleavage reactions are based on a n-p* transition of low extinction,
efforts were undertaken to extend the aromatic p-system by new conjugated
substituents in 4- and 5-position. First, 4- and 5-amino-substituted 1-ethyl-2-nitro-
benzenes 1 and 9 were phenylated under the conditions of the GombergÀBachmann
reaction [51] to 4-ethyl-3-nitro- and 3-ethyl-4-nitro-1,1'-biphenyls 35 and 36, respec-
tively (Scheme 1). A more universal approach was the Suzuki coupling, which gave
with 5-bromo-substituted 1-ethyl-2-nitrobenzene 11 and phenyl-, (4-methoxyphenyl)-,
(3,4-dimethoxyphenyl)-, (4-phenoxyphenyl)-, (thianthren-1-yl)-, (1-naphthyl)-, (2-
naphthyl)-, (2-thienyl)-, and (3-thienyl)boronic acid good yields of 36 44. The 5-
vinyl derivative 45 resulted from a Stille coupling [52] with tributyl(vinyl)stannane,
bis(dibenzylideneacetone)palladium(0), and triphenylphosphine in 83% yield. Fur-
thermore, 4-ethyl-3-nitrobenzoic acid (46) was esterified to the methyl and tert-butyl
benzoates 47 and 48. Furthermore, 46 was transformed into its acid chloride, which was
subsequently treated with diphenylamine, diisopropylamine, and N-methylaniline to
give the corresponding amides 50 52 and esterification of 46 with thiophenol gave 49.
Starting from 4- and 5-amino-substituted 1-ethyl-2-nitrobenzenes 1 and 9, the
Sandmeyer reaction with CuCN led to 4- and 5-cyano-substituted 1-ethyl-2-nitro-
benzenes 53 and 54. Hydrolysis of 54 to 3-ethyl-4-nitro-benzoic acid (55) and
t
subsequent esterification with dicyclohexylcarbodiimide (DCC) in BuOH under 4-
pyrrolidinopyridine catalysis [53] afforded the tert-butyl ester 56 in good yield.
The hydroxymethylation reactions of 35 45, 47 54, and 56 proceeded well, except
for 45 and 54, applying paraformaldehyde in DMSO and in presence of tBuOK to give
the corresponding 4- and 5-substituted 2-(2-nitrophenyl)propan-1-ols 57 76
(Scheme 1).
The next series of compounds are dealing with modifications in the side chain of 2-
(2-nitrophenyl)ethanol. The synthetic approach started from 1-(2-nitrophenyl)propan-
2-one (77) [54] and 2-(2-nitrophenyl)-1-phenylethanone (78) [55], which were
alkylated in the exocyclic 1-position with MeI, EtI, or allyl bromide to form in good
yields the corresponding ketones 79 84 (Scheme 2). NaBH4 reduction of 77 84 led to
the exocyclic 1-monosubstituted and 1,2-disubstituted 2-(2-nitrophenyl)ethanols

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Helvetica Chimica Acta Vol. 87(2004)
Scheme 1
85 92, which allowed studies regarding the influence of side-chain substituents on the
photocleavage reaction.
A formal exocyclic 1,2-disubstitution is also present in 4-(2-hydroxypentyl)- and 4-
(2-hydroxyhexyl)-substituted 1,3-dinitrobenzenes 95 and 96, which resulted from 2-
(2,4-dinitrophenyl)cyclopentanone (93) [56] and 2-(2,4-dinitrophenyl)cyclohexanone
(94) [56] by NaBH4 reduction in form of diastereoisomer (Scheme 2) mixtures. In the
case of 95, separation into the cis- and trans-racemates 97 and 98 could be achieved by
chromatography. Another formal exocyclic 1-substitution is also obvious in (1,2,3,4-
tetrahydro-8-nitro-1-naphthyl)methanol (99), synthesized according to [57].
The substitution of the benzene ring by the naphthalene skeleton was the next
challenge to synthesize new photolabile protecting groups. It was realized that the
chemistry involved was much more difficult and, therefore, only a few o-nitronaphthyl
alcohols were prepared. The synthesis of 2-(1-nitro-2-naphthyl)ethanol (102) and 2-(1-
nitro-2-naphthyl)propan-1-ol (103) was achieved from 2-methyl- and 2-ethyl-1-nitro-
naphthalene (100 and 101, respectively) by the aldol-addition reaction with para-
formaldehyde; however, the same reaction with 1-methyl-8-nitronaphthalene (104) to
2-(8-nitro-1-naphthyl)ethanol (105) was unsuccessful. Diborane reduction of (8-nitro-
1-naphthyl)acetic acid (106) [58] on the other hand led to 105. The isomeric 1-(8-nitro-
1-naphthyl)ethanol (108) resulted from the reduction of 8-nitro-1-acetonaphthone
(107) [59], and (8-nitro-1-naphthyl)methanol (110) [60] was synthesized from

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625
Scheme 2
8-nitro-naphthalene-1-carboxylic acid (109) by treatment with diborane. The (1-nitro-
2-naphthyl)methanol (113) was prepared from 2-methyl-1-nitronapthalene (100) by
monobromination to the 2-(bromomethyl) derivative 111, followed by substitution
with AcOK to give the 2-[(acetyloxy)methyl] compound 112 and subsequent
hydrolysis. The (3-nitro-2-naphthyl)methanol (114) was obtained according to [61].

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Finally, a few o-nitroheteroaryl alcohols based on the electronically similar
thiophene ring were added as a potential photoactive alternative group. The (3-
nitro-2-thienyl)methanol (115) was obtained in low yield according to [62]. The 2-
ethyl-3-nitrothiophene (116) [63] was the starting material for the synthesis of 1-(3-
nitro-2-thienyl)ethanol (117) [63], and the homologous 2-(3-nitro-2-thienyl)propan-1-
t
ol (118) [63] resulted from the aldol addition of paraformaldehyde with BuOK in
DMSO. Similarly, 2-methyl-3-nitrothiophene (119) [64] reacted to 2-(3-nitro-2-
thienyl)ethanol (120). In the benzothiophene series, only the 2-(2-nitrobenzo[b]-
thien-3-yl)ethanol (121) was synthesized from 3-methyl-2-nitrobenzo[b]thiophene
(122) [65] by reaction with paraformaldehyde since it turned out that 121 is
photostable.
3. Photoreactions.
To study the photoreactivity of the newly synthesized o-
nitrophenyl-, o-nitronaphthyl, and o-nitroheteroaryl alcohols as versatile photolabile
protecting groups in nucleoside and nucleotide chemistry, all the correspondingly
esterified thymidine 5'-carbonates were synthesized by reacting the alcohol with
phosgene or diphosgene to give the carbonochloridates, which were then further
coupled to thymidine. The reactions took place preferentially at the 5'-OH group giving
the thymidine 5'-monocarbonates 123 178 as the main reaction products.
As by-products also the 3'-monocarbonates, e.g., 179, and the 3',5'-dicarbonates,
e.g., 180, were formed in small amounts and could be isolated by column
chromatography. In several cases, these by-products 179 203 were purified and
characterized. To study the universal application of the NPPOC group in nucleic acid
chemistry, N4-benzoyl-2'-deoxycytidine, 2'-deoxy-N4-isobutyrylcytidine, 2'-deoxy-N6-
(phenoxyacetyl)adenosine, and 2'-deoxy-N2-(phenoxyacetyl)guanosine were coupled
with 2-(2-nitrophenyl)propyl carbonochloridate to the corresponding 5'-carbonates
213 216.
To compare the photolability of the various thymidine derivatives, we developed
standardized conditions for the photolysis experiments. The thymidine 5'-(protected-
carbonates) (100 mmol) were dissolved in MeOH/H2O 1:1. An aliquot (25 ml) of the
sample was analyzed by HPLC (RP-18 column Lichrosorb (Merck), linear gradient
MeCN/H2O, monitoring at 260 nm). The solution (3 ml) was transferred to a 1-cm
pathlength stoppered quartz cuvette and irradiated with a 200-W Hg arc lamp by using
the 365-nm band, which was separated by filter systems according to the schematic
apparatus shown in Fig. 1. The light is emitted from the light source (LQ) passing first

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627
an infrared filter (IF, H2O) followed by the electronic shutter (S), going through a
condensing lens (CL) and a broad band filter (BF; UGI from Schott) to avoid
overheating of the UV filter (UV-F; DAD-8-1 from Schott), before reaching the

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Helvetica Chimica Acta Vol. 87(2004)
629
Fig. 1. Schematic drawing of the photolysis apparatus
cuvette in the cuvette holder (CH). Six cuvettes per experiment were used, each of
which was irradiated in different time intervals and followed by HPLC-analysis for
decreasing educt concentration and increasing thymidine formation.
Since there is no simple mathematical function describing the experimentally
determined photolytic degradation of the thymidine 5'-(protected carbonates), the
half-life was calculated from the slope of the section including the 50% concentration
of the educt. A typical picture of this evaluation is seen in Fig. 2 for 129. The half-lifes
of the photolabile protection groups determined under the described standard reaction
conditions are listed in the Table.
The evaluation of the Table reveals several interesting effects of which a short half-
life (t1/2), a high thymidine concentration after cleavage (c(Thd)end), and an optimal
disappearance of the educt (c(educt)end) are the ruling factors. In many cases, the
photolysis of the educt was a very clean reaction leading to only thymidine without
formation of other by-products. Analysis by HPLC (Fig. 3), however, indicates that
also small amounts of the 2-nitroso derivatives such as 219 derived from the second
possible degradation mode 129 ! 217 ! 218 ! 219 (Scheme 3) were formed explaining
the difference between the complete disappearance of the thymidine 5'-(protected
carbonate) and the detection of thymidine concentrations < 100%.
Starting the discussion with thymidine 5'-[2-(2-nitrophenyl)propyl carbonate]
(123), it is noticed that the presence of a halogeno substituent at the 5-position of
the phenyl group (see 127 129), is associated with a fast cleavage rate and a high
recovery of thymidine. These results can be attributed to a heavy-atom effect, which
facilitates the intersystem-crossing mode. The best series of compounds so far are found
among 135 145 where the p-system of the parent 2-(2-nitrophenyl) moiety is
elongated in view of a biphenyl interaction. Thus, thymidine 5'-[2-(4-nitro[1,1'-
biphenyl]-3-yl)propyl carbonate] (136) (NBPPOC-T) offers the highest quality with
respect to the cleavage rate and purity of the photolysis products. Other functions like
ester or cyano groups (see 146 154) are also interesting since thymidine recovery is
almost quantitative. Additional substitutions in the propyl side chain (see 155 165 and
173) led to no improvement of the anticipated properties, and the exchange of the
phenyl against the naphthyl or thienyl moiety as in 166 172 and 174 178, respectively,
can not be recommended at all.
It is noteworthy to mention that the nucleobase has, as expected, no direct influence
on the rate of the photolysis, which is very similar for the corresponding thymidine 123,
2'-deoxycytidines 213 and 214, 2'-deoxyadenosine 215, and 2'-deoxyguanosine 216

Fig. 2. Time-dependent photolysis of 129 under standard cleavage conditions

Helvetica Chimica Acta Vol. 87(2004)
631
Table. Photolysis of Thymidine 5'-Protected Carbonates
t1/2 [s]
tend [min]
c(Thd)end
c(educt)end
t1/2 [s]
tend [min]
c(Thd)end
c(educt)end
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
48
62
60
53
38
32
25
90
150
85
7
44
30
11
23
20
16
25
32
23
22
25
33
77
7
10
10
10
10
5
88
82
85
80
95
95
85
980
85
90
90
75
90
90
90
75
98
85
85
90
90
95
80
97
98
90
85
85
90
0
0
0
0
0
1
0
0
0
4
1
0
1
0
1
0
0
0
1
1
0
0
2
3
1
0
0
0
0
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
213
214
215
216
90
60
56
720
780
52
5710
7
10
5
90
90
90
76
50
86
4
1
2
18
28
0
10
30
25
10
80
10
10
10
10
10
10
10
14
9
5
5
3
15
15
10
10
10
10
5
0
4
80
90
75
90
90
90
90
20
40
5
28
85
85
10
60
7
65
20
15
0
94
88
77
76
12
59
65
7
0
0
8
0
62
60
65
840
515
240
60
35
2
160
50
7
66
77
86
0
0
0
65
43
55
2
0
0
5
5
5
5
5
5
5
5
15
10
5
8
10
10
10
10
10
10
10
10
15
15
15
0
0
5
8
6
0
0
10
10
10
10
10
10
0
0
0
5
50
39
54
51
100
3
0
0
1
7
56
52
52
showing that these nucleic acid building blocks could be applied with the same
efficencies as their phosphoramidites in photolithographic processes.
Experimental Part
General. Products were dried under high vacuum. Irradiation equipment: Hg-high-pressure lamp (200 W)
and IR-filter (Oriel); electronic shutter (Prontor); broad-band filter UG1 and interference filter UV-DAD-8-1
(Schott). Melting point: B¸chi B545. TLC: precoated silica gel thin-layer sheets 60 F254 (Merck). Column
chromatography (CC): silica gel (Baker; 30 60 mm). Reversed-phase HPLC: L-6000 pump and AS-4000
autosampler (Merck-Hitachi); UV-detector Uvikon 730 SLC (Kontron); RP-18 column, LiChrosorb 125 Â
4 mm, 5 mm (Merck); gradient MeCN/H2O, flow rate 1 ml/min. UV/VIS: Perkin-Elmer Lambda 5; dmax in nm
(log e). 1H-NMR: Bruker AC-250; d in ppm rel. to SiMe4 or CDCl3 ((D6)DMSO) as internal standard. 31P-
NMR: Bruker DRX-600; d in ppm rel. to H3PO4.
1. 3-Ethyl-2-nitrobenzenamine (5) [44]. SnCl2 ¥ 2 H2O (52 g, 0.23 mol) in sat. HCl/MeOH (65 ml) was added
dropwise with stirring and cooling to a suspension of 1-ethyl-2,3-dinitrobenzene (17) (13.6 g, 69 mmol) in sat.
HCl/MeOH (110 ml) whereby the temp. was kept below 88. After stirring overnight at 88, the mixture was

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Helvetica Chimica Acta Vol. 87(2004)
Fig. 3. Time-dependent photocleavage of 129 followed by HPLC
evaporated. H2O (50 ml) was added, the mixture neutralized with 4n NaOH and extracted with Et2O, the Et2O
phase dried (Na2SO4) and evaporated, and the residue distilled in vacuo at 89 1028/0.2 mbar ([44]: b.p.
120 1308/4 mbar). The crude product was purified by CC (SiO2 (160 g), 6 Â 16 cm; hexanes/AcOEt 15 :1 !
1:2): 8.62 g (75%) of 5. Orange solid. M.p. 31 328 ([44] 32 338). TLC (hexanes/AcOEt 4 :1): Rf 0.41. UV
(MeOH): 203 (4.28), 235 (4.09), 255 (sh, 3.54), 277 (sh, 3.36), 402 (3.35). 1H-NMR ((D6)DMSO): 7.15 (t,

Helvetica Chimica Acta Vol. 87(2004)
633
Scheme 3
HÀC(5)); 6.76 (d, HÀC(6)); 6.50 (d, HÀC(4)); 6.05 (br., NH2); 2.58 (q, MeCH2); 1.15 (t, MeCH2). 13C-NMR
(600 MHz, (D6)DMSO): 142.77 (C(1)); 138.12 (C(3)); 135.68 (C(2)); 132.24 (C(5)); 116.75 (C(4)); 115.63
(C(6)); 25.37(CH 2); 14.96 (Me).
2. 3-Chloro-1-ethyl-2-nitrobenzene (6). Finely powdered 5 (2.7g, 16 mmol) was added to conc. HCl soln.
(20 ml) and H2O (40 ml) at 608, the soln. rapidly cooled to 08, and the resulting suspension diazotized at 0 58
with NaNO2 (1.24 g, 18 mmol) in H2O (15 ml). After stirring for 5 min at 08, the soln. was treated with urea and
stirred for another 10 min. The mixture was then added under stirring to a 808-warm suspension of CuCl (2.4 g,
24 mmol) in conc. HCl soln. (16 ml) and H2O (8 ml). After 30 min, the mixture was cooled to r.t. and extracted
with AcOEt. The org. phase was washed with 4n NaOH (50 ml), dried (Na2SO4), and evaporated. Purification
by CC (SiO2 (68 g), 4 Â 16 cm; hexanes) gave 1.09 g (37%) of 6. Yellow oil. TLC (hexanes/AcOEt 4 :1): Rf 0.59.
UV (MeOH): 202 (4.11), 208 (sh, 4.10), 238 (sh, 3.08), 342 (sh, 2.38). 1H-NMR (CDCl3): 7.34 (m, 2 arom. H);
7.24 (m, 1 arom. H); 2.60 (q, MeCH2); 1.23 (t, MeCH2). Anal. calc. for C8H8ClNO2 (185.6): C 51.77, H 4.34,
N 7.55; found: C 51.00, H 4.17, N 7.43.
3. 1-Bromo-3-ethyl-2-nitrobenzene (7) [44]. Finely powdered 5 (2 g, 12 mmol) was added to 48% HBr soln.
(15 ml) and H2O (9 ml) at 608, the soln. rapidly cooled to 08, and the resulting suspension diazotized at 5 108
with NaNO2 (0.91 g, 13 mmol) in H2O (10 ml). After stirring for 10 min at 08, the soln. was treated with urea, the
mixture stirred for another 5 min and filtered, and the filtrate added at r.t. to a stirred suspension of CuSO4 ¥ 5
H2O (1.8 g, 7mmol) and Cu powder (0.72 g, 11 mmol) in 48% HBr soln. (15 ml) and H 2O (9 ml). The mixture
was heated to 808 for 30 min and, after cooling, extracted with AcOEt. The org. phase was washed with 4n
NaOH (150 ml) and H2O, dried (Na2SO4), and evaporated. CC (SiO2 (61 g), 4 Â 15 cm; hexanes) gave 1.59 g
(58%) of 7. Yellow oil. TLC (hexanes/AcOEt 4 :1): Rf 0.61. UV (MeOH): 203 (4.35), 212 (sh, 4.25), 269 (3.66),
337(sh, 2.81). 1H-NMR (CDCl3): 7.48 (t, HÀC(5)); 7.27 (m, HÀC(4), HÀC(6)); 2.60 (q, MeCH2); 1.23 (t,
MeCH2).
4. 1-Ethyl-3-iodo-2-nitrobenzene (8). Finely powdered 5 (2 g, 12 mmol) was added to conc. H2SO4 soln.
(4.5 ml) and H2O (30 ml) at 508. The resulting soln. was rapidly cooled to 08 and then diazotized at 0 58 with
NaNO2 (0.91 g, 13 mmol) in H2O (10 ml). After stirring for 10 min at 08, the soln. was treated with urea, stirred
for another 5 min, and then added to a stirred KI soln. (3 g, 18 mmol) in H2O (20 ml). The mixture was stirred
for 1 h at r.t. and, after cooling, extracted with AcOEt. The org. phase was washed with 4n NaOH (60 ml) and
H2O, dried (Na2SO4), and evaporated. CC (SiO2 (62 g), 4 Â 15 cm; hexanes) gave 2.48 g (74%) of 8. Red oil.
TLC (hexanes/AcOEt 4 :1): Rf 0.60. UV (MeOH): 203 (4.36), 228 (4.00), 336 (sh, 2.35). 1H-NMR (CDCl3): 7.70

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Helvetica Chimica Acta Vol. 87(2004)
(d, 1 arom. H); 7.28 (d, 1 arom. H); 7.11 (t, 1 arom. H); 2.60 (q, MeCH2); 1.21 (t, MeCH2). Anal. calc. for
C8H8INO2 (277.1): C 34.68, H 2.91, N 5.06; found: C 35.05, H 2.96, N 5.03.
5. 3-Ethyl-4-nitrobenzenamine (9) [45]. Mechanical stirring is essential for this reaction! N-(3-Ethyl-
phenyl)acetamide [45] (33 g, 0.2 mol) was added slowly to conc. H2SO4 (100 ml). The resulting soln. was cooled
to À158 and then fuming HNO3 (9.5 g, 6.2 ml, 0.15 mol) added dropwise. The temp. was kept between À208 and
À108 for 75 min. The soln. was poured on ice, neutralized with solid Na2CO3, and extracted with Et2O (3 Â
250 ml). The org. phase was washed with H2O (600 ml), dried (Na2SO4), and evaporated. The crude dark yellow
oil (39 g) was heated with conc. HCl soln. (125 ml) under reflux for 2.5 h. After cooling, the precipitate was
filtered off, washed with H2O, suspended in 1n NaOH (300 ml), and extracted with Et2O (2 Â 150 ml). The org.
phase was dried (Na2SO4) and evaporated to give a brown solid (14.2 g). The combined filtrates and the NaOH
phase were neutralized and again extracted with Et2O. The org. phase yielded after drying (Na2SO4) and
evaporation 16 g of a dark oil. The crude product was purified by CC (each fraction: SiO2 (235 g), 7 Â 14 cm;
hexanes/AcOEt 20 :1 ! 2 :1): 18.09 g (54%) of 9. Yellow solid. M.p. 84 858 ([45]: 80 818).TLC (hexanes/
AcOEt 7:3): R f 0.27. UV (MeOH): 203 (4.21), 231 (3.82), 245 (sh, 3.69), 372 (sh, 4.09).1H-NMR (CDCl3): 7.96
(m, HÀC(5)); 6.47( m, HÀC(2), HÀC(4)); 4.23 (br., NH2); 2.93 (q, MeCH2); 1.24 (t, MeCH2). 13C-NMR
(CDCl3): 151.30 (C(1)); 143.25 (C(3)); 139.42 (C(4)); 128.35(C(5)); 115.35 (C(2)); 111.72 (C(6)); 27.48 (CH2);
14.67(Me).
6. 5-Chloro-1-ethyl-2-nitrobenzene (10). Finely powdered 9 (10 g, 60 mmol) was added to conc. HCl soln.
(90 ml) and H2O (200 ml) at 608. The resulting soln. was rapidly cooled to 08 and then diazotized at 0 38 with
NaNO2 (4.57g, 66 mmol) in H 2O (20 ml). After stirring for 5 min at 08, urea was added, the mixture stirred for
another 10 min, and then the soln. added with stirring to a warmed (808) suspension of CuCl (9.05 g) in conc.
HCl soln. (60 ml) and H2O (30 ml). After reaction for 2 h at 808, the mixture was cooled and extracted with
AcOEt. The org. phase was washed with 1n NaOH (100 ml) and H2O (200 ml), dried (Na2SO4), and evaporated.
CC (SiO2 (120 g), 4 Â 16 cm; hexanes) gave 7.2 g (64%) of 10. Yellow oil. TLC (hexanes/AcOEt 4 :1): Rf 0.77.
UV (MeOH): 206 (4.09), 216 (sh, 3.91), 263 (3.79), 334 (sh, 2.84). 1H-NMR (CDCl3): 7.85 (d, HÀC(3)); 7.34 (d,
HÀC(6)); 7.29 (dd, HÀC(4)); 2.90 (q, MeCH2); 1.27( t, MeCH2). Anal. calc. for C8H8ClNO2 (185.6): C 51.77,
H 4.34, N 7.55; found: C 51.65, H 4.34, N 7.63.
7. 5-Bromo-1-ethyl-2-nitrobenzene (11). Finely powdered 9 (16.6 g, 0.1 mol) was added to 48% HBr soln.
(95 ml) and H2O (155 ml) at 608. The resulting soln. was rapidly cooled to 08 and then diazotized at 0 38 with
NaNO2 (7.0 g, 0.1 mol) in H O (20 ml). After stirring for 5 min at 08, the soln. was treated with urea (1 g), the
2
mixture stirred for 10 min and filtered, and the filtrate added at r.t. to a stirred suspension of CuSO4 ¥ 5 H2O
(15 g, 60 mmol) and Cu powder (6 g, 94 mmol) in HBr (63 ml) and H2O (37ml). The mixture was heated to 75 8
for 1 h and, after cooling, extracted with AcOEt. The org. phase was washed with 1n NaOH (150 ml) and H2O
(200 ml), dried (Na2SO4), and evaporated. 18.3 g (80%) of 11. Yellow oil. B.p. 75 1038/0.005 bar. TLC
(hexanes/AcOEt 4 :1): Rf 0.76. UV (MeOH): 203 (4.19), 217 (sh, 3.98), 267 (3.91), 320 (sh, 3.21). 1H-NMR
(CDCl3): 7.76 (d, HÀC(3)); 7.50 (d, HÀC(6)); 7.45 (dd, HÀC(4)); 2.89 (q, MeCH2); 1.27( t, MeCH2). Anal. calc.
for C8H8BrNO2 (230.1): C 41.77, H 3.50, N 6.09; found: C 41.71, H 3.59, N 6.08.
8. 1-Ethyl-5-iodo-2-nitrobenzene (12). Finely powdered 9 (6.2 g, 37mmol) was added to conc. H 2SO4 soln.
(11.2 ml) and H2O (125 ml) at 608. The resulting soln. was rapidly cooled to 08 and then diazotized at 0 38 with
NaNO2 (2.84 g, 41 mmol) in H2O (15 ml). After stirring for 5 min at 08, the soln. was treated with urea and the
mixture stirred for 10 min and then added to a stirred soln. of KI (9.34 g) in H2O (35 ml). The mixture was
stirred for 2 h at r.t. and, after cooling, extracted with AcOEt. The org. phase was washed with 1n NaOH
(100 ml) and H2O (200 ml), dried (Na2SO4), and evaporated. Purification by CC (SiO2 (120 g), 4 Â 16 cm;
hexanes) gave 8.7g (84%) of 12. Red oil. TLC (hexanes/AcOEt 4 :1): Rf 0.78. UV (MeOH): 203 (4.22), 220 (sh,
3.88), 281 (3.87), 328 (sh, 3.22). 1H-NMR (CDCl3): 7.72 (d, HÀC(6)); 7.66 (dd, HÀC(4)); 7.58 (d, HÀC(3));
2.85 (q, MeCH2); 1.25 (t, MeCH2). Anal. calc. for C8H8INO2 (277.1): C 34.68, H 2.91, N 5.06; found: C 34.84,
H 2.92, N 4.90.
9. 2-Ethyl-1,3-dinitrobenzene (13) [46]. NaNO2 (1.38 g, 20 mmol) in H2O (10 ml) was added dropwise to a
suspension of 4-ethyl-3,5-dinitrobenzenamine (21; 3 g, 14 mmol) in AcOH (50 ml) and conc. H2SO4 soln. (8 ml)
at 20 258. The mixture was stirred for 1 h in an ice bath and then added to a suspension of Cu2O (4 g, 28 mmol)
in EtOH (35 ml). After stirring for 90 min at r.t., the mixture was filtered with suction, the filtrate evaporated,
the residue treated with sat. NaHCO3 soln. (100 ml) and then extracted with AcOEt (3 Â 50 ml), the org. phase
washed with sat. NaHCO3 soln. (100 ml), dried (Na2SO4), and evaporated, and the crude product purified by
CC (SiO2 (80 g), 3.5 Â 17cm; hexanes/AcOEt 8 :1): 2.08 g (76%) of 13. Yellow solid. M.p. 56 588 ([46]: 57.58).
TLC (hexanes/AcOEt 7:3): Rf 0.63. UV (MeOH): 203 (4.16), 231 (sh, 3.95), 280 (sh, 3.20), 324 (sh, 3.14).
1H-NMR (CDCl3): 7.93 (d, HÀC(4), HÀC(6)); 7.50 (t, HÀC(5)); 2.92 (q, MeCH2); 1.32 (t, MeCH2).

Helvetica Chimica Acta Vol. 87(2004)
635
10. 2-Ethyl-3-nitrobenzenamine (14) [47]. Formic acid (1.95 g, 42 mmol) in MeCN (5 ml) was added
dropwise into a mixture of 13 (2.2 g, 11 mmol), Pd/C (0.11 g), and Et3N (6 ml, 43 mmol) in MeCN (5 ml). The
mixture was refluxed for 25 min and then cooled, the catalyst removed by filtration, the filtrate evaporated, and
the crude product purified by CC (SiO2 (42 g), 3.5 Â 13 cm; hexanes/AcOEt 8 :1 ! 1:1): 1.21 g (81%) of 14.
Yellow solid. M.p. 84 868 ([47]: 85 85.58). TLC (hexanes/AcOEt 7:3): Rf 0.40. UV (MeOH): 203 (4.22), 237
(4.13), 269 (sh, 3.49), 347(3.12). 1H-NMR (CDCl3): 7.09 (m, 2 arom. H); 6.83 (dd, 1 arom. H); 3.91 (br., NH2);
2.60 (q, MeCH2); 1.27( t, MeCH2).
11. 1-Bromo-2-ethyl-3-nitrobenzene (15) [66]. Finely powdered 14 (2.28 g, 14 mmol) was added to 48% HBr
soln. (70 ml) and H2O (42 ml), at 908 and the soln. was rapidly cooled to 08 and then diazotized at 5 108 with
NaNO2 (1.06 g, 15 mmol) in H2O (20 ml). After stirring for 10 min at 08, the soln. was treated with urea, the
mixture stirred for another 5 min and filtered, and the filtrate added at r.t. to a stirred suspension of CuSO4 ¥ 5
H2O (2.04 g, 8 mmol) and Cu powder (0.84 g, 13 mmol) in 48% HBr soln. (40 ml) and H2O (24 ml). The mixture
was heated to 808 for 1 h and, after cooling, extracted with AcOEt. The org. phase was washed with 4n NaOH
(100 ml), dried (Na2SO4), and evaporated, and the residue purified by CC (SiO2 (61 g), 4 Â 15 cm; hexanes/
AcOEt): 2.73 g (87%) of 15. Yellow solid. M.p. 32 368 ([68]: 33 348). TLC (hexanes/AcOEt 7:3): Rf 0.84. UV
(MeOH): 205 (sh, 4.06), 211 (4.08), 219 (sh, 4.05), 249 (sh, 3.44), 287(sh, 3.03). 1H-NMR (CDCl3): 7.76 (dd, 1
arom. H); 7.67 (dd, 1 arom. H); 7.18 (t, HÀC(5)); 2.89 (q, MeCH2); 1.29 (t, MeCH2).
12. 2-Ethyl-1-iodo-3-nitrobenzene (16). Finely powdered 14 (1.8 g, 11 mmol) was added to conc. H2SO4
soln. (4.5 ml) and H2O (30 ml) at 508, the resulting soln. rapidly cooled to 08, and the resulting suspension
diazotized at 0 58 with NaNO2 (2.83 g, 12 mmol) in H2O (10 ml). After stirring for 10 min at 08, the soln. was
treated with urea. The mixture was stirred for another 5 min, then added to a stirred soln. of KI (2.73 g,
16.5 mmol) in H2O (20 ml), stirred 1 h at r.t., and, after cooling, extracted with AcOEt. The org. phase was
washed with 4n NaOH (100 ml), dried (Na2SO4), and evaporated. Purification by CC (SiO2 (36 g), 3.5 Â 11 cm;
hexanes) gave 2.62 g (86%) of 16. Yellow solid. M.p. 42 438. TLC (hexanes/AcOEt 4 :1): Rf 0.72. UV
1
(MeOH): 204 (4.16), 229 (4.12), 256 (sh, 3.50), 300 (sh, 2.99). H-NMR (CDCl3): 78.02 (dd, 1 arom. H); 7.66
(dd, 1 arom. H); 7.01 (t, HÀC(5)); 2.89 (q, MeCH2); 1.26 (t, MeCH2). Anal. calc. for C8H8INO2 (277.1): C 34.68,
H 2.91, N 5.06; found: C 34.77, H 2.93, N 4.84.
13. 1-Ethyl-2,3-dinitrobenzene (17) [46]. 4-Ethyl-2,3-dinitrobenzenamine (18; 23 g, 0.11 mol) was added
dropwise into a soln. of NaNO2 (8.65 g, 0.125 mol) in conc. H2SO4 soln. (70 ml). The temp. was kept below 308.
After stirring for 40 min at r.t., EtOH (350 ml) was added to the cooled mixture. After 1 h of reflux, the mixture
was cooled to r.t., poured into conc. H2SO4 soln. (400 ml) and H2O (200 ml) and then steam-distilled. The
distillate was extracted with Et2O and the org. phase neutralized with sat. NaHCO3 soln., dried (Na2SO4), and
evaporated: 11.2 g (52%) of 17. Recrystallization from EtOH/H2O 4 :1 gave yellow needles. M.p. 57 58 8 ([46]:
58.58). TLC (hexanes/AcOEt 4 :1): Rf 0.28. UV (MeOH): 205 (4.17), 213 (sh, 4.05), 255 (3.76), 287 (sh, 3.29),
333 (sh, 2.76). 1H-NMR (CDCl3): 8.02 (dd, 1 arom. H); 7.68 (dd, 1 arom. H); 7.59 (t, 1 arom. H); 2.68 (q,
MeCH2); 1.28 (t, MeCH2).
14. 4-Ethyl-2,3-dinitrobenzenamine (18) and 4-Ethyl-2,5-dinitrobenzenamine (20) [46]. N-(4-Ethyl-3-
nitrophenyl)acetamide [46] (20.3 g, 0.1 mol) was added to a mixture of 65% HNO3 soln. (80 ml) and conc.
H2SO4 soln. (80 ml). After stirring for 3 days at r.t., the mixture was poured on ice. The precipitate was dissolved
in CH2Cl2, H2O (100 ml) was added, and the mixture was neutralized with solid Na2CO3. The org. layer was
dried (Na2SO4) and evaporated. The crude product (20.6 g, 81%) was suspended in EtOH (200 ml) and heated
with solid NaOH (2 g) under reflux. After 40 min, the mixture was cooled, silica gel (28 g) added, and the
mixture evaporated. The resulting solid was put onto a silica-gel column and purified by CC (SiO2 (140 g), 6 Â
14 cm; hexanes/AcOEt 7:1 ! 2 :1): 1.75 g (8%) of 18 and 12.5 g (60%) of 20.
Data of 18: Red solid. M.p. 122 1238 ([46]: 1258). TLC (hexanes/AcOEt 1:1): Rf 0.50. UV (MeOH): 202
(4.18), 227(4.37), 265 (sh, 3.59), 411 (3.75). 1H-NMR (CDCl3): 7.26 (d, 1 arom. H); 6.90 (d, 1 arom. H); 6.03
(br., NH2); 2.45 (q, MeCH2); 1.18 (t, MeCH2).
Data of 20: Orange solid. M.p. 124 1258 ([46]: 121.68). TLC (hexanes/AcOEt 1:1): Rf 0.85. UV (MeOH):
226 (4.39), 243 (sh, 4.16), 266 (sh, 3.86), 422 (3.71). 1H-NMR (CDCl3): 8.11 (s, 1 arom. H); 7.27 (s, 1 arom. H);
6.07(br., NH 2); 2.75 (q, MeCH2); 1.24 (t, MeCH2).
15. 2-Ethyl-1,4-dinitrobenzene (19) [46]. A soln. of 4-ethyl-2,5-dinitrobenzenamine (20; 4 g, 19 mmol) in
conc. H2SO4 soln. (50 ml) was diluted under cooling with H2O (50 ml) and the resulting suspension diazotized at
0
108 with NaNO2 (1.45 g, 18 mmol) in H2O (15 ml). After stirring for 10 min at 08, the soln. was added to
boiling EtOH (100 ml). After 10 min of reflux, the mixture was cooled, poured on ice, and extracted with Et2O
(3 Â 100 ml). The org. phase was washed with sat. NaHCO3 soln. (200 ml), dried (Na2SO4), and evaporated.
Purification by CC (SiO2 (67g), 4 Â 12 cm; hexanes/AcOEt 8 :1) gave 2.64 g (71%) of 19. Orange solid: M.p.

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Helvetica Chimica Acta Vol. 87(2004)
57 60 8 ([46]: 57.4 59.98). TLC (hexanes/AcOEt 4 :1): Rf 0.60. UV (MeOH): 204 (4.26), 257(4.02), 298 (sh,
3.37), 332 (sh, 3.06). 1H-NMR (CDCl3): 8.24 (d, HÀC(3)); 8.16 (dd, HÀC(5)); 7.95 (d, HÀC(6)); 2.95 (q,
MeCH2); 1.34 (t, MeCH2).
16. 4-Ethyl-3,5-dinitrobenzenamine (21) [46][67]. Through a soln. of 2-ethyl-1,3,5-trinitrobenzene [68]
(59 g, 0.24 mol) in dioxane (170 ml) and 2 drops of 20% ammonia, H2S gas was passed. The exothermic reaction
started on careful warming to 358 and addition of some more drops of ammonia. The temp. was kept at 35 408
by cooling, and when the exothermic reaction stopped, the mixture was cooled and filtered from sulfur, which
was washed with little dioxane and Et2O. The filtrate was neutralized by a few drops of conc. HCl soln. and then
evaporated. The resulting oil was refluxed in the presence of conc. HCl soln. (750 ml) and KI (5 g) to transform
possible hydroxylamine into the amino derivative. The mixture was filtered hot and the cooled filtrate
neutralized with solid Na2CO3 and extracted with Et2O (3 Â 250 ml). The org. phase was dried (Na2SO4), and
evaporated. Recrystallization from EtOH (700 ml) yielded 24.1 g (48%) of 21. Yellow needles. M.p. 180 1818
([67]: 1758). TLC (hexanes/AcOEt 1:1): Rf 0.67. UV (MeOH): 202 (4.19), 243 (4.37 ), 369 (3.30).1H-NMR
(CDCl3): 7.24 (s, HÀC(2), HÀC(6)); 6.21 (br.), NH2); 2.56 (q, MeCH2); 1.22 (t, MeCH2).
17. 1-Ethyl-2,4-dinitrobenzene (22) [46]. As described in Exper. 9, with a 1 :1 mixture of 4-ethyl-3,5-
dinitrobenzenamine (21) and 2-ethyl-3,5-dinitrobenzenamine (1.9 g, 9 mmol) and NaNO2 (0.69 g, 10 mmol). CC
(SiO2 (60 g), 4 Â 14 cm; hexanes/AcOEt 9 :1 ! 4 :1) gave 1.28 g (72%) of 13/22 1:1. Yellow solid.
18. 2-(2-Nitrophenyl)propan-1-ol Derivatives: General Procedure. 18.1. A mixture of the ethylbenzene
t
derivative (5 mmol) and paraformaldehyde (5 mmol) in dry DMSO (10 ml) was treated with BuOK (0.05
0.5 mmol) in tBuOH (3 ml). After stirring for 15 min at r.t. and 2 h at 808, the mixture was neutralized, diluted
with sat. NaCl soln. (25 ml), and extracted with AcOEt. The org. phase was dried (Na2SO4), filtered, and
evaporated. The crude product was purified by CC (SiO2 (45 g), 4 Â 12 cm; toluene ! toluene/AcOEt 8 :1).
18.2. Analogously to Exper. 18.1 by using DMF as the solvent and increasing the reaction time to 3 h at 908.
19. 2-(4-Chloro-2-nitrophenyl)propan-1-ol (23). According to Exper. 18.1, with 4-chloro-1-ethyl-2-nitro-
t
benzene (2) [43] (3.56 g, 19 mmol), paraformaldehyde (575 mg, 19 mmol), DMSO (10 ml), BuOK (360 mg,
3.2 mmol), and tBuOH (4 ml): 2.70 g (66%) of 23. Yellow oil. TLC (hexanes/AcOEt 7:3): Rf 0.35. UV
(MeOH): 214 (4.23), 248 (sh, 3.48), 293 (3.13). 1H-NMR (CDCl3): 7.73 (d, HÀC(3)); 7.50 (dd, HÀC(5)); 7.42
(d, HÀC(6)); 3.72 (m, CH(Me)CH2); 3.46 (m, CH(Me)CH2); 1.82 (br., OH); 1.28 (d, CH(Me)CH2). Anal. calc.
for C9H10ClNO3 (215.6): C 50.13, H 4.67, N 6.50; found: C 50.24, H 4.68, N 6.28.
20. 2-(4-Bromo-2-nitrophenyl)propan-1-ol (24). According to Exper. 18.1, with 4-bromo-1-ethyl-2-nitro-
benzene (3) [43] (2.11 g, 9 mmol), paraformaldehyde (275 mg, 9 mmol), DMSO (10 ml), tBuOK (57mg,
0.5 mmol), and tBuOH (4 ml): 1.62 g (69%) of 24. Yellow oil. TLC (hexanes/AcOEt 7:3): Rf 0.38. UV
(MeOH): 204 (sh, 4.16), 216 (4.25), 251 (sh, 3.51), 288 (sh, 3.13). 1H-NMR (CDCl3): 7.87 (d, HÀC(3)); 7.66 (dd,
HÀC(5)); 7.36 (d, HÀC(6)); 3.74 (m, CH(Me)CH2); 3.45 (m, CH(Me)CH2); 1.66 (br., OH); 1.29 (d,
CH(Me)CH2). Anal. calc. for C9H10BrNO3 (260.1): C 41.56, H 3.88, N 5.39; found: C 41.73, H 4.01, N 5.36.
21. 2-(4-Iodo-2-nitrophenyl)propan-1-ol (25). According to Exper. 18.1, with 1-ethyl-4-iodo-2-nitrobenzene
t
(4) [43] (2.77 g, 10 mmol), paraformaldehyde (0.3 g, 10 mmol), DMSO (10 ml), BuOK (180 mg, 1.4 mmol),
t
and BuOH (4 ml): 2.53 g (82%) of 25. Yellow oil. TLC (hexanes/AcOEt 7:3): Rf 0.35. UV (MeOH): 203
(4.23), 229 (4.28), 247(sh, 3.84), 300 (sh, 3.12). 1H-NMR (CDCl3): 8.04 (d, HÀC(3)); 7.85 (dd, HÀC(5)); 7.23
(d, HÀC(6)); 3.75 (m, CH(Me)CH2); 3.45 (m, CH(Me)CH2); 1.52 (br., OH); 1.29 (d, CH(Me)CH2). Anal. calc.
for C9H10INO3 (307.1): C 35.17, H 3.28, N 4.56; found: C 35.73, H 3.12, N 4.56.
22. 2-(5-Chloro-2-nitrophenyl)propan-1-ol (26). According to Exper. 18.1, with 10 (895 mg, 4.8 mmol),
t
t
paraformaldehyde (160 mg, 5.3 mmol), DMSO (10 ml), BuOK (76 mg, 0.7 mmol), and BuOH (4 ml): 0.87g
(84%) of 26. Yellow oil. TLC (hexanes/AcOEt 7:3): Rf 0.27. UV (MeOH): 206 (4.17 ), 216 (4.06), 262 (3.76),
328 (sh, 2.95). 1H-NMR (CDCl3): 7.72 (d, HÀC(3)); 7.45 (d, HÀC(6)); 7.30 (dd, HÀC(4)); 3.74 (m,
CH(Me)CH2); 3.54 (sext., CH(Me)CH2); 1.71 (br., OH); 1.30 (d, CH(Me)CH2). Anal. calc. for C9H10ClNO3
(215.6): C 50.13, H 4.67, N 6.50; found: C 50.20, H 4.75, N 6.20.
23. 2-(5-Bromo-2-nitrophenyl)propan-1-ol (27). According to Exper. 18.1, with 11 (1.39 g, 6 mmol),
t
paraformaldehyde (210 mg, 7mmol), DMSO (10 ml), tBuOK (0.1 g, 0.89 mmol), and BuOH (4 ml): 1.32 g
(85%) of 27. Yellow oil. TLC (hexanes/AcOEt 7:3): Rf 0.57. UV (MeOH): 202 (4.16), 218 (sh, 3.95), 263 (3.76),
330 (sh, 2.96). 1H-NMR (CDCl3): 7.63 (m, HÀC(3), HÀC(6)); 7.47 (dd, HÀC(4)); 3.74 (m, CH(Me)CH2); 3.52
(sext., CH(Me)CH2); 1.68 (br., OH); 1.30 (d, CH(Me)CH2). Anal. calc. for C9H10BrNO3 (260.1): C 41.56,
H 3.88, N 5.39; found: C 41.74, H 3.95, N 5.27.
24. 2-(5-Iodo-2-nitrophenyl)propan-1-ol (28). According to Exper. 18.1, with 12 (1.45 g, 5 mmol),
t
paraformaldehyde (165 mg, 5.5 mmol), DMSO (10 ml), BuOK (80 mg, 0.7mmol), and tBuOH (4 ml): 1.36 g
(85%) of 28. Yellow oil. TLC (hexanes/AcOEt 4 :1): Rf 0.29. UV (MeOH): 204 (4.29), 222 (sh, 3.93), 274

Helvetica Chimica Acta Vol. 87(2004)
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(3.80), 335 (sh, 3.18). 1H-NMR (CDCl3): 7.81 (d, HÀC(6)); 7.69 (dd, HÀC(4)); 7.46 (d, HÀC(3)); 3.76 (m,
CH(Me)CH2); 3.48 (sext., CH(Me)CH2); 1.54 (br., OH); 1.29 (d, CH(Me)CH2). Anal. calc. for C9H10INO3
(307.1): C 35.17, H 3.28, N 4.56; found: C 35.18, H 3.27, N 4.06.
25. 2-(2-Bromo-6-nitrophenyl)propan-1-ol (30). A mixture of 15 (1.11 g, 4.8 mmol) and paraformaldehyde
(435 mg, 14.5 mmol) in dry DMSO (10 ml) was treated with NaCN (235 mg, 4.8 mmol). After stirring for 2 h at
r.t., the mixture was neutralized with HCl, diluted with sat. NaCl soln. (25 ml), and extracted with AcOEt. The
org. phase was dried (Na2SO4), filtered, and evaporated. The crude product was purified by CC (SiO2 (40 g),
3.5 Â 11 cm; toluene ! toluene/AcOEt 7 :1): 0.85 g (77%) of 15, 80 mg (6%) of 30, and 20 mg (2%) of 2-(2-
nitrophenyl)propan-1-ol.
Data of 30: Yellow oil. TLC (hexanes/AcOEt 7:3): Rf 0.47. UV (MeOH): 202 (4.32), 209 (sh, 4.17 ), 239
(sh, 3.53), 282 (sh, 3.04). 1H-NMR (CDCl3): 7.75 (dd, 1 arom. H); 7.44 (dd, 1 arom. H); 7.19 (t, HÀC(4)); 4.02
(m, CH(Me)CH2); 3.87( m, CH(Me)CH2); 3.58 (m, CH(Me)CH2); 1.65 (br., OH); 1.37( d, CH(Me)CH2).
Anal. calc. for C9H10BrNO3 (260.1): C 41.56, H 3.88, N 5.39; found: C 41.46, H 3.99, N 5.18.
26. 2-(2-Iodo-6-nitrophenyl)propan-1-ol (31). According to Exper. 25, with 16 (2.56 g, 9.2 mmol),
paraformaldehyde (555 mg, 18.5 mmol), DMSO (30 ml), and NaCN (230 mg, 4.7mmol): 2.18 g (86%) of 16
(yellow oil), 140 mg (5%) of 31, and 60 mg (3%) of 2-(2-nitrophenyl)propan-1-ol.
Data of 31: Yellow oil. TLC (hexanes/AcOEt 7:3): Rf 0.70. UV (MeOH): 203 (4.37), 230 (4.12), 287 (sh,
1
3.04), 336 (sh, 2.74). H-NMR (CDCl3): 8.07( d, 1 arom. H), 7.45 (d, 1 arom. H); 7.01 (t, HÀC(4)); 3.85 (m,
CH(Me)CH2); 3.54 (m, CH(Me)CH2); 1.62 (br., OH); 1.33 (d, CH(Me)CH2); Anal. calc. for C9H10INO3
(307.1): C 35.17, H 3.28, N 4.56; found: C 35.45, H 3.29, N 4.48.
27. 2-(2,4-Dinitrophenyl)propan-1-ol (32) and 2-(2,6-Dinitrophenyl)propan-1-ol (33). According to
Exper. 18.1, with 22/13 1:1 (1.27g, 6.5 mmol), paraformaldehyde (215 mg, 7.1 mmol), DMSO (7ml), tBuOK
t
(100 mg, 0.89 mmol), and BuOH (3 ml): 0.496 g (34%) of 32, 72 mg (5%) of 33, and 0.596 g (47%) of 13 as
yellow oils.
Data of 32: TLC (hexanes/AcOEt 7: 3): Rf 0.18. UV (MeOH): 204 (4.15), 242 (4.07), 257 (sh, 4.04), 333
(sh, 2.83). 1H-NMR (CDCl3): 8.60 (d, HÀC(3)); 8.39 (dd, HÀC(5)); 7.74 (d, HÀC(6)); 3.90 3.73 (m,
CH(Me)CH2); 3.61 (sext., CH(Me)CH2); 1.62 (br., OH); 1.36 (d, CH(Me)CH2). Anal. calc. for C9H10N2O5
(226.2): C 47.79, H 4.46, N 12.39; found: C 47.98, H 4.48, N 12.35.
28. 2-(2,6-Dinitrophenyl)propan-1-ol (33). According to Exper. 18.2, with 13 (2.19 g, 11 mmol), paraform-
t
t
aldehyde (670 mg, 22 mmol), DMF (10 ml), BuOK (200 mg, 1.8 mmol), and BuOH: 1.52 g (72%) of 33.
Yellow solid. M.p. 52 548. TLC (hexanes/AcOEt 7:3): Rf 0.37. UV (MeOH): 205 (4.16), 226 (sh, 3.88), 267 (sh,
3.17), 324 (sh, 2.77). 1H-NMR (CDCl3): 7.73 (d, 2 H, HÀC(3), HÀC(5)); 7.51 (t, HÀC(4)); 3.87( m,
CH(Me)CH2); 3.40 (sext., CH(Me)CH2); 1.69 (t, OH); 1.33 (d, CH(Me)CH2). Anal. calc. for C9H10N2O5
(226.2): C 47.79, H 4.46, N 12.39; found: C 47.98, H 4.48, N 12.25.
29. 2-(2,5-Dinitrophenyl)propan-1-ol (34). According to Exper. 18.2, with 19 (1.44 g, 7mmol), paraform-
t
t
aldehyde (662 mg, 22 mmol), DMF (10 ml), BuOK (200 mg, 1.8 mmol), and BuOH (4 ml): 0.394 g (25%) of
34. Yellow solid. M.p. 82 838. TLC (hexanes/AcOEt 7:3): Rf 0.45. UV (MeOH): 205 (4.24), 256 (4.00), 289 (sh,
3.41), 334 (sh, 3.04). 1H-NMR (CDCl3): 8.38 (d, HÀC(6)); 8.19 (dd, HÀC(4)); 7.84 (d, HÀC(3)); 3.90-3.72 (m,
CH(Me)CH2); 3.52 (sext., CH(Me)CH2); 1.55 (t, OH); 1.38 (d, CH(Me)CH2). Anal. calc. for C9H10N2O5
(226.2): C 47.79, H 4.46, N 12.39; found: C 48.01, H 4.42, N 12.33.
30. 4-Ethyl-3-nitro-1,1'-biphenyl (35). Finely powdered 4-ethyl-3-nitrobenzenamine (1; 4.2 g, 25 mmol) was
added to conc. HCl soln. (10 ml) and H2O (50 ml) at 608, the soln. rapidly cooled to 08, and the resulting
suspension diazotized at 0 48 with NaNO2 (1.9 g, 27.5 mmol) in H O (10 ml). After stirring for 20 min at 08,
2
benzene (50 ml, 0.56 mol) was added, and the temp. was increased to 108. After 10 min, AcOK (8.2 g, 83 mmol)
in H2O (10 ml ) was dropped into the soln., and the mixture was stirred for 4 h at 108 and overnight at r.t. The aq.
phase was extracted with toluene, the combined org. phase washed with 10% NaOH soln., dried (Na2SO4), and
evaporated, and the residue purified by CC (SiO2 (62 g), 3.5 Â 17cm; hexanes): 3.33 g (59%) of 35. Yellow oil.
TLC (hexanes/AcOEt 4 :1): Rf 0.74. UV (MeOH): 204 (4.48), 247 (4.38), 309 (sh, 3.16). 1H-NMR (CDCl3): 8.09
(d, HÀC(3)); 7.73 (d, HÀC(5)); 7.57 (m, 2 arom. H); 7.43 (m, 4 arom. H); 2.94 (q, MeCH2); 1.31 (t, MeCH2).
31. 3-Ethyl-4-nitro-1,1'-biphenyl (36). 31.1. Gomberg-Bachmann Reaction. According to Exper. 30, with
finely powdered 9 (4.2 g, 25 mmol): 2.6 g (46%) of 36. Yellow needles. M.p. 54 568.
31.2. Suzuki Reaction. As described for 37, with 11 (6 g, 26 mmol), toluene (40 ml), EtOH (10.5 ml), 2n
NaHCO3 (16 ml), phenylboronic acid (3.82 g, 31 mmol), and [Pd(Ph3P)4] (400 mg, 0.35 mmol): 5.43 g (92%) of
36. Yellow needles. M.p. 558. TLC (hexanes/AcOEt 9 :1): Rf 0.67. UV (MeOH): 205 (4.52), 225 (sh, 4.05), 391
1
(4.04). H-NMR (CDCl3): 7.99 (d, 1 arom. H); 7.61, 7.38 (m, 7arom. H); 2.99 ( q, MeCH2); 1.33 (t, MeCH2).
Anal. calc. for C14H13NO2 (227.3): C 73.99, H 5.75, N 6.16; found: C 73.84, H 5.68, N 5.81.

638
Helvetica Chimica Acta Vol. 87(2004)
32. 3-Ethyl-4'-methoxy-4-nitro-1,1'-biphenyl (37). A mixture of 11 (1.36 g, 5.9 mmol), toluene (15 ml),
EtOH (4 ml), 2n NaHCO3 (6 ml), (4-methoxyphenyl)boronic acid (1 g, 6.6 mmol), and [Pd(Ph3P)4] (0.2 g,
0.17mmol) was heated under reflux for 5 h. After cooling, the mixture was diluted with sat. aq. NaCl soln.
(20 ml) and extracted with AcOEt (2 Â 25 ml). The combined org. phase was dried and evaporated. Purification
by CC (SiO2 (42 g) 3 Â 20 cm; hexanes/AcOEt 9 :1 ! 6 :1) gave 1.41 g (93%) of 37. Yellow solid. M.p. 94 958.
TLC (hexanes/AcOEt 9 :1): Rf 0.42. UV (MeOH): 204 (4.52), 232 (4.13), 320 (4.07). 1H-NMR (CDCl3): 7.97 (d,
1 arom. H); 7.51 (m, 4 arom. H); 6.70 (dd, 2 arom. H); 3.85 (s, MeO); 2.99 (q, MeCH2); 1.32 (t, MeCH2). Anal.
calc. for C15H15NO3 (257.3): C 70.02, H 5.88, N 5.44; found: C 70.00, H 5.97, N 5.14.
33. 3-Ethyl-3',4'-dimethoxy-4-nitro-1,1'-biphenyl (38). According to Exper. 32, with 11 (1.5 g, 6.5 mmol),
toluene (15 ml), EtOH (4 ml), 2n NaHCO3 (6 ml), (3,4-dimethoxyphenyl)boronic acid (1.4 g, 7.8 mmol), and
[Pd(Ph3P)4] (200 mg, 0.17mmol). Purification by CC (SiO 2 (42 g), 3 Â 15 cm; hexane/AcOEt 20 :1 ! 5 :1) gave
1.71 g (92%) of 38. Yellow solid. M.p. 84 858. TLC (hexane/AcOEt 3 :1): Rf 0.40. UV (MeOH): 242 (4.03), 335
1
(4.03), 352 (3.92). H-NMR ((D6)DMSO): 7.98 (d, HÀC(5)); 7.79 (d, HÀC(2)); 7.72 (dd, HÀC(6)); 7.32 (m,
HÀC(6'), HÀC(2')); 7.06 (m, HÀC(5')); 3.86 (s, MeO); 3.80 (s, MeO); 2.91 (q, MeCH2); 1.25 (t, MeCH2). Anal.
calc. for C16H17NO4 (287.31): C 66.89, H 5.96, N 5.96; found: C 66.87, H 5.96, N 4.92.
34. 3-Ethyl-4-nitro-4'-phenoxy-1,1'-biphenyl (39). According to Exper. 32, with 11 (1.5 g, 6.5 mmol),
toluene (15 ml), EtOH (4 ml), 2n NaHCO3 (6 ml), (4-phenoxyphenyl)boronic acid (1.95 g, 9.1 mmol), and
[Pd(Ph3P)4] (200 mg, 0.17mmol). Purification by CC (SiO 2 (42 g), 3 Â 15 cm; hexane/AcOEt 20 :1 ! 5 :1) gave
1.47g (71%) of 39. Light yellow solid. M.p. 61 628. TLC (hexane/AcOEt 9 :1): Rf 0.57. UV (MeOH): 235
(3.82), 306 (4.11), 352 (sh, 3.82). 1H-NMR ((D6)DMSO): 7.98 (d, 1 arom. H); 7.77 (m, 3 arom. H); 7.68 (dd, 1
arom. H); 7.41 (m, 2 arom. H); 7.17 (m, 1 arom. H); 2.89 (q, MeCH2); 1.23 (t, MeCH2). Anal. calc. for C20H17NO3
(319.35): C 75.22, H 5.37, N 4.39; found: C 75.05, H 5.38, N 4.57.
35. 1-(3-Ethyl-4-nitrophenyl)thianthrene (40). According to Exper. 32, with 11 (1.5 g, 6.5 mmol), toluene
(15 ml), EtOH (4 ml), 2n NaHCO3 (6 ml), (thianthren-1-yl)boronic acid (2.4 g, 9.1 mmol), and [Pd(Ph3P)4]
(200 mg, 0.17mmol). Purification by CC (SiO 2 (42 g), 3 Â 15 cm; hexane/AcOEt 20 :1 ! 5 :1) gave 1.79 g
(76%) of 40. Light yellow solid. M.p. 143 1458. TLC (hexane/AcOEt 9 :1): Rf 0.47. UV (MeOH): 252 (4.31),
278 (sh, 3.99), 336 (sh, 3.39); 1H-NMR ((D6)DMSO): 8.04 (d, 1 arom. H); 7.68 (dd, 1 arom. H); 7.59 (m, 2 arom.
H); 7.52 7.24 (m, 6 arom. H); 2.90 (q, MeCH2); 1.26 (t, MeCH2). Anal. calc. for C20H15NO2S2 (365.47): C 65.73,
H 4.14, N 3.83; found: C 65.86, H 4.08, N 3.84.
36. 1-(3-Ethyl-4-nitrophenyl)naphthalene (41). According to Exper. 32, with 11 (1.36 g, 5.9 mmol), toluene
(15 ml), EtOH (4 ml), 2n NaHCO3 (6 ml), (1-naphthyl)boronic acid [69] (1.4 g, 8 mmol), and [Pd(Ph3P)4]
(200 mg, 0.17mmol). Purification by CC (SiO 2 (37g), 2.5 Â 16 cm; hexanes/AcOEt 20 :1 ! 10 :1) gave 1.59 g
(97%) of 41. Yellow oil. TLC (hexanes/AcOEt 9 :1): Rf 0.68. UV (MeOH): 218 (4.79), 259 (sh, 3.96), 302 (sh,
3.89). 1H-NMR (CDCl3): 8.02 (d, 1 arom. H); 7.93 (m, 2 arom. H); 7.79 (dd, 1 arom. H); 7.57 7.39 (m, 6 arom.
H); 3.00 (q, MeCH2); 1.33 (t, MeCH2). Anal. calc. for C18H15NO2 (277.3): C 77.96, H 5.45, N 5.05; found: C 77.98,
H 5.18, N 5.08.
37. 2-(3-Ethyl-4-nitrophenyl)naphthalene (42). According to Exper. 36, with 11 (1.36 g, 5.9 mmol) and (2-
naphthyl)boronic acid [76] (1.22 g, 7.1 mmol). Purification by CC (SiO2 (37g) 2.5 Â 16 cm; hexanes/AcOEt
20 :1 ! 10 :1) gave 1.52 g (93%) of 39. Yellow solid. M.p. 110.5 111.58. TLC (hexanes/AcOEt 9 :1): Rf 0.55.
UV (MeOH): 212 (4.61), 233 (4.59), 271 (sh, 4.15), 310 (4.14), 339 (sh, 3.96). 1H-NMR (CDCl3): 8.03 (m, 2
arom. H); 7.90 (m, 3 arom. H); 7.66 (m, 3 arom. H); 7.52 (m, 2 arom. H); 3.03 (q, MeCH2); 1.36 (t, MeCH2).
Anal. calc. for C18H15NO2 (277.3): C 77.96, H 5.45, N 5.05; found: C 77.79, H 5.25, N 4.76.
38. 2-(3-Ethyl-4-nitrophenyl)thiophene (43). According to Exper. 32, with 11 (1.5 g, 6.5 mmol) and (2-
thienyl)boronic acid (1 g, 7.8 mmol). Purification by CC (SiO (34 g), 2.5 Â 17cm; hexanes/AcOEt 9 :1 ! 6 :1)
2
gave 0.89 g (59%) of 43. Yellow oil. TLC (hexanes/AcOEt 9 : 1): Rf 0.67. UV (MeOH): 204 (4.34), 249 (3.90),
334 (4.08). 1H-NMR (CDCl3): 7.95 (dd, 1 arom. H); 7.52 (m, 2 arom. H); 7.40 (m, 2 arom. H); 7.11 (m, 1 arom.
H); 2.97( q, MeCH2); 1.31 (t, MeCH2). Anal. calc. for C12H11NO2S (233.3): C 61.78, H 4.75, N 6.00; found:
C 61.55, H 4.60, N 6.90.
39. 3-(3-Ethyl-4-nitrophenyl)thiophene (44). According to Exper. 32, with 11 (1.38 g, 6 mmol) and (3-
thienyl)boronic acid (1 g, 7.8 mmol). Purification by CC (SiO (33 g), 2.5 Â 17cm; hexanes/AcOEt 9 :1 ! 6 :1)
2
gave 1.35 g (96%) of 44. Yellow oil. TLC (hexanes/AcOEt 9 :1): Rf 0.65. UV (MeOH): 205 (4.46), 311 (4.02).
1H-NMR (CDCl3): 7.96 (d, 1 arom. H); 7.85 7.49 (m, 3 arom. H); 7.45 7.38 (m, 2 arom. H); 2.98 (q, MeCH2);
1.31 (t, MeCH2). Anal. calc. for C12H11NO2S (233.3): C 61.78, H 4.75, N 6.00; found: C 61.81, H 4.76, N 6.82.
40. 4-Ethenyl-2-ethyl-1-nitrobenzene (45). Tributyl(ethenyl)stannane (1.9 g, 5 mmol), bis(dibenzylidene-
acetone)palladium(0) (0.2 g, 0.34 mmol), and Ph3P (0.35 g, 1.33 mmol) were added under Ar to a soln. of 11
(1.36 g, 5.9 mmol) in abs. toluene (30 ml). The mixture was heated under reflux for 22 h. After cooling, the

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mixture was evaporated, the residue dissolved in AcOEt (50 ml) and washed with 10% ammonia in H2O (3Â).
After re-extraction of the aq. phase (2 Â 30 ml AcOEt), the combined org. phase was dried and evaporated.
Purification by CC (SiO2 (33 g), 2.5 Â 16 cm; hexanes ! hexanes/AcOEt 8 :1) gave 0.88 g (83%) of 45. Yellow
oil. TLC (hexanes/AcOEt 9 :1): Rf 0.82. UV (MeOH): 205 (4.40), 227(3.96), 289 (3.95). 1H-NMR (CDCl3):
7.87 (d, 1 arom. H); 7.33 (m, 2 arom. H); 6.71 (2d, CH2ˆCH); 5.86 (d,1 H, CH2ˆCH); 5.43 (d, 1 H, CH2ˆCH);
2.92 (q, MeCH2); 1.28 (t, MeCH2). Anal. calc. for C10H11NO2 (177.2): C 67.78, H 6.26, N 7.90; found: C 67.34,
H 6.14, N 8.30.
41. Methyl 4-Ethyl-3-nitrobenzoate (47). A soln. of 4-ethyl-3-nitrobenzoic acid (46) [70] (5 g, 26 mmol) in
dry MeOH (30 ml) and conc. H2SO4 soln. (1 ml) was heated to reflux for 3 h. After cooling down to r.t. CH2Cl2
(50 ml) was added to the mixture, which was then extracted with sat. NaHCO3 soln. (50 ml). The aq. phase was
re-extracted with CH2Cl2 (2 Â 50 ml) and the combined org. phase dried (Na2SO4) and evaporated: 4.89 g (91%)
of 47. Light yellow oil. TLC (hexanes/AcOEt 9 :1): Rf 0.59. UV (MeOH): 203 (4.05), 225 (4.35), 250 (sh, 3.78),
283 (sh, 3.17), 316 (sh, 2.70). 1H-NMR (CDCl3): 8.48 (d, HÀC(2)); 8.15 (dd, HÀC(6)); 7.44 (d, HÀC(5)); 3.93
(s, COOMe); 2.93 (q, MeCH2); 1.28 (t, MeCH2).
42. tert-Butyl 4-Ethyl-3-nitrobenzoate (48). A soln. of 46 [70] (5.9 g, 30 mmol), dicyclohexylcarbodiimide
(6.8 g, 33 mmol), tBuOH (2.4 g, 33 mmol), and 4-pyrrolidinopyridine (445 mg, 3 mmol) in dry CH2Cl2 (100 ml)
was stirred for 3 h at r.t. and then filtered over diatomaceous earth. The filtrate was washed with H2O, 5%
AcOH, and H2O (100 ml each), dried (Na2SO4), and evaporated. Purification by CC (SiO2 (100 g), 5 Â 16 cm;
hexanes (300 ml), then hexanes/AcOEt 15 :1 (800 ml) and 9 :1 (300 ml)) gave 5.57g (74%) of 48. Light yellow
oil. TLC (hexanes/AcOEt 9 :1): Rf 0.55. UV (MeOH): 202 (4.12), 224 (4.39), 248 (sh, 3.83), 282 (sh, 3.24), 316
(sh, 2.89). 1H-NMR (CDCl3): 8.38 (d, HÀC(2)); 8.07( dd, HÀC(6)); 7.39 (d, HÀC(5)); 2.90 (q, MeCH2); 1.56 (s,
tBu); 1.21 (t, MeCH2).
43. S-Phenyl 4-Ethyl-3-nitrobenzenecarbothioate (49). According to Exper. 42, with 46 [70] (1.96 g,
10 mmol), dicyclohexylcarbodiimide (2.27g, 11 mmol), thiophenol (2.2 g, 20 mmol), N,N-dimethylpyridin-4-
amine (245 mg, 2 mmol), and CH2Cl2 (100 ml). CC (SiO2 (43 g), 2.5 Â 21 cm; hexanes ! hexanes/AcOEt 10 :1)
gave 2.57g (89%) 49. Light yellow solid. M.p. 79 808. TLC (hexane/AcOEt 9 :1): Rf 0.45. UV (MeOH): 240
1
(4.14). H-NMR ((D6)DMSO): 8.37( d, HÀC(2)); 8.19 (dd, HÀC(6)); 7.73 (d, HÀC(5)); 7.52 (s, 5 arom. H);
2.88 (q, MeCH2); 1.22 (t, MeCH2).
44. 4-Ethyl-3-nitro-N,N-diphenyl-benzenecarboxamide (50). A mixture of 46 [70] (1.95 g, 10 mmol) and
thionyl chloride (10 ml) was refluxed for 4 h. After cooling, the reagent was evaporated and the remaining 4-
ethyl-3-nitrobenzoyl chloride (2.2 g, 9.9 mmol, 99%) dissolved in dioxane (10 ml). To this soln. was added under
cooling diphenylamine (6.8 g, 40 mmol) in dioxane (10 ml). After stirring for 30 min at r.t. and 2 h at reflux, the
mixture was poured on ice, acidified with conc. HCl soln. and extracted with CH2Cl2. The combined org. phase
was dried (Na2SO4) and evaporated and the crude product purified by CC (SiO2 (150 g), 4.5 Â 23 cm; hexane/
AcOEt 4 :1 ! 1:1): 2.72 g (97%) of 50. Light yellow solid. M.p. 139 1408. TLC (hexane/AcOEt 3 :1): Rf 0.37.
UV (MeOH): 234 (4.19), 268 (sh, 3.98), 345 (sh, 2.86). 1H-NMR ((D6)DMSO): 7.95 (d, HÀC(2)); 7.64 (dd,
HÀC(6)); 7.41 (d, HÀC(5)); 7.38 7.19 (m, Ph2N); 2.81 (q, MeCH2); 1.11 (t, MeCH2).
45. 4-Ethyl-N,N-diisopropyl-3-nitrobenzenecarboxamide (51). According to Exper. 44, with 46 [70] (1.95 g,
10 mmol), thionyl chloride (10 ml) (4 h), 4-ethyl-3-nitrobenzoyl chloride (2.12 g, 9.8 mmol, 98%) in dioxane
(10 ml), and diisopropylamine (4.5 g, 6.3 ml, 45 mmol) in dioxane (10 ml) (20 min): 2.72 g (97%) of 51. Light
yellow solid. M.p. 55 608. TLC (hexane/AcOEt 1 :1): Rf 0.74. UV (MeOH): 229 (3.96), 286 (sh, 3.22).
1H-NMR ((D6)DMSO): 7.80 (s, 1 arom. H); 7.56 (s, 2 arom. H); 3.58 (m, 2 Me2CH); 2.81 (q, MeCH2); 1.23 (br., 2
Me2CH, MeCH2).
46. 4-Ethyl-N-methyl-3-nitro-N-phenylbenzenecarboxamide (52). According to Exper. 45 with 46 [70]
(1.97g, 10 mmol), thionyl chloride (10 ml), N-methylphenylamine (4.5 g, 4.5 ml, 42 mmol), and dioxane (2 Â
10 ml). Purification by CC (SiO2 (93 g), 3.5 Â 21 cm; hexane/AcOEt 5 :1 ! 1:1) gave 2.48 g (87%) of 52. Light
yellow solid. M.p. 83 848. TLC (hexane/AcOEt 1:1): Rf 0.74; UV (MeOH): 231 (4.06), 241 (sh, 4.04), 295 (sh,
3.38), 328 (sh, 2.89). 1H-NMR ((D6)DMSO): 7.79 (d, HÀC(2)); 7.44 (dd, HÀC(6)); 7.35 7.17 (m, HÀC(5),
PhN); 3.37( s, MeN); 2.71 (q, MeCH2); 1.09 (t, MeCH2). Anal. calc. for C16H16N2O3 (284.32): C 67.59, H 5.67,
N 9.85; found: C 67.61, H 5.88, N 9.74.
47. 3-Ethyl-4-nitrobenzonitrile (54). Finely powdered 9 (9.4 g, 57mmol) was added to conc. HCl soln.
(30 ml) and H2O (150 ml) at 608, the resulting soln. rapidly cooled to 08, and the resulting suspension diazotized
at 0 58 with NaNO2 (4.3 g, 62 mmol) in H2O (20 ml). After stirring for 10 min at 08, the mixture was added to a
cooled (08) soln. of CuCN (10.8 g, 0.1 mol) and NaCN (14.6 g, 0.3 mol) in H2O (80 ml). The mixture was stirred
at 08 for 1 h and then warmed to 508 for 45 min. After cooling, the filtered mixture was extracted with AcOEt.
The org. phase was washed with 1m NaOH (90 ml) and H2O (90 ml), dried (Na2SO4), and evaporated.

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Helvetica Chimica Acta Vol. 87(2004)
Purification by CC (SiO2 (120 g), 6 Â 14 cm; hexanes ! hexanes/AcOEt 15 :1) gave 3.41 g (34%) of 54. Orange
solid. M.p. 65 668. TLC (hexanes/AcOEt 9 :1): Rf 0.39. UV (MeOH): 202 (4.22), 216 (sh, 3.97), 225 (sh, 3.92),
249 (3.88), 282 (sh, 3.40), 322 (sh, 2.97). 1H-NMR (CDCl3): 7.90 (d, HÀC(5)); 7.68 (d, HÀC(2)); 7.63 (dd,
HÀC(6)); 2.90 (q, MeCH2); 1.30 (t, MeCH2). Anal. calc. for C9H8N2O2 (176.2): C 61.38, H 4.58, N 15.90; found:
C 61.25, H 4.51, N 15.86.
48. 3-Ethyl-4-nitrobenzoic Acid (55). A soln. of KOH (640 mg) in H2O (5.7ml) was added to a suspension
of 54 (2 g, 11.4 mmol) in EtOH (20 ml). After 2.5 h reflux, the mixture was cooled to r.t. and evaporated. The
residue was suspended in H2O (20 ml) and acidified with conc. HCl soln. The precipitate was collected, dried at
808, and purified by CC (silanized SiO2 (40 g), 3 Â 17cm; hexanes/AcOEt, 9 :1 ! 1:1): 1 g (44%) of 55. Yellow
solid. M.p. 186 1888. TLC (AcOEt): Rf 0.24. UV (MeOH): 202 (4.21), 219 (sh, 3.91), 252 (3.85), 291 (sh, 3.44),
1
333 (sh, 2.96). H-NMR ((D6)DMSO): 13.59 (br., COOH); 8.03 (s, 1 arom. H); 7.95 (m, 2 arom. H); 2.32 (q,
MeCH2); 1.18 (t, MeCH2).
49. tert-Butyl 3-Ethyl-4-nitrobenzoate (56). According to Exper. 42, with 55 (480 mg, 2.5 mmol),
dicyclohexylcarbodiimide (560 mg, 2.7mmol), tBuOH (370 mg, 5 mmol), 4-pyrrolidinopyridine (100 mg,
0.67mmol), and CH 2Cl2 (15 ml). Purification by CC (SiO2 (20 g), 2 Â 13 cm; hexanes ! hexanes/AcOEt 15 :1)
gave 450 mg (72%) of 56. Light yellow oil. TLC (AcOEt): Rf 0.31. UV (MeOH): 202 (4.29), 220 (sh, 3.96), 250
(3.90), 289 (sh, 3.41), 330 (sh, 2.97). 1H-NMR (CDCl3): 7.96 (d, HÀC(2)); 7.89 (dd, HÀC(6)); 7.82 (d, HÀC(5));
2.90 (q, MeCH2); 1.59 (s, tBu); 1.29 (t, MeCH2). Anal. calc. for C9H8NO4 (195.2): C 62.14, H 6.82, N 5.57; found:
C 62.22, H 7.01, N 6.15.
50. 2-(3-Nitro[1,1'-biphenyl]-4-yl)propan-1-ol (57). According to Exper. 18.1, with 35 (1.5 g, 6.6 mmol),
t
paraformaldehyde (0.22 g, 7.3 mmol), DMSO (10 ml), tBuOK (160 mg, 1.3 mmol), and BuOH (2 ml): 1.29 g
(76%) of 57. Yellow oil. TLC (hexanes/AcOEt 7:3): Rf 0.45. UV (MeOH): 205 (4.55), 248 (4.42), 304 (sh,
3.20). 1H-NMR (CDCl3): 7.95 (d, HÀC(2)); 7.77 (dd, HÀC(6)); 7.59 7.39 (m, 6 arom. H); 3.82 (m,
CH(Me)CH2); 3.54 (m, CH(Me)CH2); 1.73 (br., OH); 1.35 (d, CH(Me)CH2). Anal. calc. for C15H15NO3
(257.3): C 70.02, H 5.88, N 5.44; found: C 70.56, H 6.13, N 5.40.
51. 2-(4-Nitro[1,1'-biphenyl]-3-yl)propan-1-ol (58). According to Exper. 18.1, with 36 (1.19 g, 5.2 mmol),
t
t
paraformaldehyde (173 mg, 5.8 mmol), DMSO (10 ml), BuOK (0.16 g, 1.3 mmol), and BuOH (2 ml): 0.91 g
(68%) of 58. Yellow oil. TLC (hexanes/AcOEt 7:3): Rf 0.47. UV (MeOH): 204 (4.53), 231 (sh, 4.03), 281
(3.94), 336 (3.70). 1H-NMR (CDCl3): 7.85 (d, 1 arom. H); 7.65 (d, 1 arom. H); 7.59 7.38 (m, 6 arom. H); 3.83
(m, CH(Me)CH2); 3.62 (sext., CH(Me)CH2); 1.73 (br., OH); 1.37 (d, CH(Me)CH2). Anal. calc. for C15H15NO3
(257.3): C 70.02, H 5.88, N 5.44; found: C 69.67, H 5.73, N 5.30.
52. 2-(4'-Methoxy-4-nitro[1,1'-biphenyl]-3-yl)propan-1-ol (59). According to Exper. 18.1, with 37 (1.03 g,
4 mmol), paraformaldehyde (135 mg, 4.4 mmol), DMSO (10 ml), tBuOK (0.12 g, 1 mmol), and tBuOH (2 ml)
to give 0.65 g (57%) of 59. Yellow solid. M.p. 103 1058. TLC (hexanes/AcOEt 7:3): Rf 0.45. UV (MeOH): 204
(4.56), 232 (4.13), 305 (4.01). 1H-NMR (CDCl3): 7.84 (d, 1 arom. H); 7.53 (m, 4 arom. H); 6.99 (dd, 2 arom. H);
3.83 (m, MeO, CH(Me)CH2); 3.66 (m, CH(Me)CH2); 1.60 (br., OH); 1.36 (d, CH(Me)CH2). Anal. calc. for
C16H17NO4 (287.3): C 66.89, H 5.96, N 4.88; found: C 66.78, H 5.83, N 4.77.
53. 2-(3',4'-Dimethoxy-4-nitro[1,1'-biphenyl]-3-yl)propan-1-ol (60). tBuOK (122 mg, 1 mmol) was added to
a mixture of 38 (1.44 g, 5 mmol) and paraformaldehyde (180 mg, 6 mmol) in DMSO (5 ml). After stirring for
1.5 h at r.t., the mixture was neutralized, diluted with sat. NaCl soln. (15 ml), and extracted with AcOEt. The
org. phase was dried (Na2SO4), filtered, and evaporated. The crude product was purified by CC (SiO2 (38 g),
3 Â 14 cm; hexane/AcOEt): 1.47g (93%) of 60. Yellow solid. M.p. 108 1098. TLC (hexanes/AcOEt 1:1): Rf
0.34. UV (MeOH): 244 (4.07), 316 (3.94), 352 (sh, 3.85). 1H-NMR ((D6)DMSO): 7.84 (d, HÀC(5)); 7.76 (dd,
HÀC(2)); 7.68 (d, HÀC(6)); 7.29 (dd, HÀC(6')); 7.27 (s, HÀC(2')); 7.06 (d, HÀC(5')); 4.78 (t, OH); 3.86 (s,
MeO); 3.80 (s, MeO); 3.60 (m, CH(Me)CH2); 3.32 (m, CH(Me)CH2); 1.29 (d, CH(Me)CH2). Anal. calc. for
C17H19NO5 (317.34): C 64.34, H 6.03, N 4.41; found: C 64.19, H 5.87, N 4.35.
54. 2-(4-Nitro-4'-phenoxy[1,1'-biphenyl]-3-yl)propan-1-ol (61). According to Exper. 53, with 39 (1.27g,
4 mmol), paraformaldehyde (145 mg, 4.8 mmol) in DMSO (5 ml), and tBuOK (100 mg, 0.8 mmol): 1.24 g
1
(89%) of 61. Yellow oil. TLC (hexanes/AcOEt 3 :1): Rf 0.33. UV (MeOH): 236 (4.11), 292 (4.05). H-NMR
((D6)DMSO): 7.86 (d, 1 arom. H); 7.77 (m, 3 arom. H); 7.67 (dd, 1 arom. H); 7.42 (m, 2 arom. H); 7.18 (d, 1 arom.
H); 7.09 (m, 4 arom. H); 4.80 (t, OH); 3.59 (m, CH(Me)CH2); 3.30 (m, CH(Me)CH2); 1.28 (d, CH(Me)CH2).
55. 2-[2-Nitro-5-(thianthren-1-yl)phenyl]propan-1-ol (62). According to Exper. 53, with 40 (1.16 g,
t
3.2 mmol), paraformaldehyde (120 mg, 3.8 mmol) in DMSO (10 ml), and BuOK (80 mg, 0.6 mmol): 720 mg
(57%) of 62. Light yellow solid. M.p. 147 148 8. TLC (hexanes/AcOEt 1:1): Rf 0.67. UV (MeOH): 255 (4.36),
277 (sh, 4.00), 334 (sh, 3.41). 1H-NMR ((D6)DMSO): 7.91 (d, 1 arom. H); 7.66 (dd, 1 arom. H); 7.60 (m, 2 arom.

Helvetica Chimica Acta Vol. 87(2004)
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H); 7.49 7.28 (m, 7arom. H); 4.83 ( t, OH); 3.57( m, CH(Me)CH2); 3.30 (m, CH(Me)CH2); 1.28 (d,
CH(Me)CH2). Anal. calc. for C21H17NO3S2 (395.50): C 63.78, H 4.33, N 3.54; found: C 63.51, H 4.26, N 3.45.
56. 2-[5-(Naphthalen-1-yl)-2-nitrophenyl]propan-1-ol (63). According to Exper. 18.1, with 41 (0.99 g,
3.6 mmol), paraformaldehyde (0.13 g, 4.3 mmol), DMSO (10 ml), tBuOK (0.12 g, 1 mmol), and tBuOH (2 ml):
0.104 g (69%) of 63. Yellow oil. TLC (hexanes/AcOEt 7:3): Rf 0.63. UV (MeOH): 218 (4.77), 286 (3.91).
1H-NMR (CDCl3): 7.91 (m, 3 arom. H); 7.78 (dd, 1 arom. H); 7.60 7.39 (m, 6 arom. H); 3.80 (m, CH(Me)CH2);
3.66 (sext., CH(Me)CH2); 1.62 (br., OH); 1.35 (d, CH(Me)CH2). Anal. calc. for C19H17NO3 ¥ 0.5 AcOEt (351.4):
C 71.77, H 6.02, N 3.99; found: C 71.85, H 5.87, N 3.61.
57. 2-[5-(Naphthalen-2-yl)-2-nitrophenyl]propan-1-ol (64). According to Exper. 18.1, with 42 (740 mg,
2.7mmol), paraformaldehyde (100 mg, 3.2 mmol), DMSO (10 ml), tBuOK (85 mg, 0.7mmol), and tBuOH
(2 ml): 0.572 g (69%) of 64. Yellow oil. TLC (hexanes/AcOEt 7:3): Rf 0.63. UV (MeOH): 212 (4.61), 235
1
(4.57), 274 (sh, 4.14), 303 (sh, 4.09), 340 (sh, 3.85). H-NMR (CDCl3): 8.04 (s, 1 arom. H); 7.91 (m, 3 arom. H);
7.78 (d, 1 arom. H); 7.68 (m, 2 arom. H); 7.52 (m, 2 arom. H); 3.88 (m, CH(Me)CH2); 3.67( sext., CH(Me)CH2);
1.78 (br., OH); 1.41 (d, CH(Me)CH2). Anal. calc. for C19H17NO3 (307.4): C 74.25, H 5.58, N 4.56; found:
C 74.22, H 5.47, N 4.35.
58. 2-[2-Nitro-5-(2-thienyl)phenyl]propan-1-ol (65). According to Exper. 18.1, with 43 (0.8 g, 3.4 mmol),
t
paraformaldehyde (125 mg, 4.1 mmol), DMSO (5 ml), BuOK (85 mg, 0.7mmol), and tBuOH (1 ml): 0.747 g
(82%) of 65. Yellow oil. TLC (hexanes/AcOEt 7:3): Rf 0.51. UV (MeOH): 203 (4.32), 253 (3.91), 310 (4.02),
334 (sh, 3.98). 1H-NMR (CDCl3): 7.82 (d, 1 arom. H); 7.65 (d, 1 arom. H); 7.54 (dd, 1 arom. H); 7.40 (m, 2 arom.
H); 7.12 (m, 1 arom. H); 3.83 (m, CH(Me)CH2); 3.64 (sext., CH(Me)CH2); 1.61 (br., OH); 1.36 (d,
CH(Me)CH2). Anal. calc. for C13H13NO3S ¥ 0.25 H2O (267.8): C 58.30, H 5.08, N 5.23; found: C 58.58, H 4.97,
N 5.13.
59. 2-[2-Nitro-5-(3-thienyl)phenyl]propan-1-ol (66). According to Exper. 58, with 44 (0.8 g, 3.4 mmol):
0.747 g (82%) of 66. Yellow oil. TLC (hexanes/AcOEt 7:3): Rf 0.42. UV (MeOH): 205 (4.47), 242 (sh, 3.93),
297(3.95). 1H-NMR (CDCl3): 7.82 (d, 1 arom. H); 7.65 (d, 1 arom. H), 7.53 (m, 2 arom. H); 7.40 (m, 2 arom. H);
3.82 (m, CH(Me)CH2); 3.68 (sext., CH(Me)CH2); 1.68 (br., OH); 1.35 (d, CH(Me)CH2). Anal. calc. for
C13H13NO3S ¥ 0.25 H2O (267.8): C 58.30, H 5.08, N 5.23; found: C 58.58, H 4.97, N 5.13.
60. 2-(5-Ethenyl-2-nitrophenyl)propan-1-ol (67). According to Exper. 18.2, with 45 (0.7g, 4 mmol),
t
t
paraformaldehyde (120 mg, 4 mmol), DMF (10 ml), BuOK (0.1 g, 0.8 mmol), and BuOH (2 ml): 0.136 g
(17%) of 67. Yellow oil. TLC (hexanes/AcOEt 7:3): Rf 0.41. UV (MeOH): 206 (4.44), 231 (4.04), 282 (3.89),
332 (sh, 3.47). 1H-NMR (CDCl3): 7.75 (d, HÀC(3)); 7.42 (s, HÀC(6)): 7.37 (dd, HÀC(4)); 6.72 (2d, CH2ˆCH);
5.85 (d, 1 H, CH2ˆCH); 5.44 (d, 1 H, CH2ˆCH); 3.78 (m, CH(Me)CH2); 3.57( sext., CH(Me)CH2); 1.65 (br.,
OH); 1.32 (d, CH(Me)CH2). Anal. calc. for C11H13NO3 (207.2): C 63.76, H 6.32, N 6.76; found: C 63.76, H 6.04,
N 6.74.
61. Methyl 4-(2-Hydroxy-1-methylethyl)-3-nitrobenzoate (68). According to Exper. 18.1, with 47 (630 mg,
3 mmol), paraformaldehyde (135 mg, 4.5 mmol), DMSO (7ml), tBuOK (40 mg, 0.33 mmol), and tBuOH
(1 ml): 280 mg (39%) of 68. Yellow oil. TLC (hexanes/AcOEt 7: 3): Rf 0.24. UV (MeOH): 202 (4.16), 226
(4.22), 278 (sh, 3.22), 322 (sh, 2.86). 1H-NMR (CDCl3): 8.36 (d, HÀC(2)); 8.18 (dd, HÀC(6)); 7.58 (d,
HÀC(5)); 3.93 (s, COOMe); 3.78 (m, CH(Me)CH2); 3.54 (sext., CH(Me)CH2); 1.69 (t, OH); 1.32 (d,
CH(Me)CH2). Anal. calc. for C11H13NO5 (239.2): 55.23, H 5.48, N 5.85; found: C 55.22, H 5.48, N 5.72.
62. tert-Butyl 4-(2-Hydroxy-1-methylethyl)-3-nitrobenzoate (69). According to Exper. 18.1, with 48 (5.52 g,
t
t
22 mmol), paraformaldehyde (990 mg, 33 mmol), DMSO (10 ml), BuOK (320 mg, 2.6 mmol), and BuOH
(3 ml): 5.5 g (89%) of 69. Yellow oil. TLC (hexanes/AcOEt 7:3): Rf 0.44. UV (MeOH): 202 (4.14), 226 (4.33),
276 (sh, 3.21), 315 (sh, 2.85). 1H-NMR (CDCl3): 8.27( d, HÀC(2)); 7.58 (dd, HÀC(6)); 7.53 (d, HÀC(5)); 3.76
(m, CH(Me)CH2); 3.50 (sext., CH(Me)CH2); 1.81 (t, OH); 1.57(s, tBu); 1.31 (d, CH(Me)CH2). Anal. calc. for
C14H19NO5 (281.3): C 59.78, H 6.81, N 4.98; found: C 59.53, H 6.75, N 4.77.
63. S-Phenyl 4-(2-Hydroxy-1-methylethyl)-3-nitrobenzenecarbothioate (70). According to Exper. 53, with
t
49 (860 mg, 3 mmol), paraformaldehyde (120 mg, 3.9 mmol), DMSO (10 ml), and BuOK (75 mg, 0.6 mmol):
300 mg (35%) of 70. Yellow oil. TLC (hexanes/AcOEt 2 : 1): Rf 0.51. UV (MeOH): 236 (4.13), 323 (sh, 2.68).
1H-NMR ((D6)DMSO): 8.25 (dd, HÀC(2)); 8.14 (d, HÀC(6)); 7.78 (d, HÀC(5)); 7.52 (m, 2 arom. H PhS); 7.35
(m, 3 arom. H); 4.82 (t, OH); 3.51 (m, CH(Me)CH2); 3.29 (m, CH(Me)CH2); 1.22 (d, CH(Me)CH2).
64. 4-(2-Hydroxy-1-methylethyl)-3-nitro-N,N-diphenylbenzenecarboxamide (71). According to Exper. 53,
with 50 (1.73 g, 5 mmol), paraformaldehyde (180 mg, 6 mmol), DMSO (10 ml), and tBuOK (125 mg, 1 mmol):
530 mg (28%) of 71. Yellow solid. TLC (CH2Cl2/MeOH 24 :1): Rf 0.56. 1H-NMR ((D6)DMSO): 7.81 (d,
HÀC(2)); 7.63 (dd, HÀC(6)); 7.48 (d, HÀC(5)); 7.38 7.20 (m, Ph2N); 4.75 (t, OH); 3.41 (m, CH(Me)CH2);
3.14 (sext., CH(Me)CH2); 1.13 (d, CH(Me)CH2).

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Helvetica Chimica Acta Vol. 87(2004)
65. 4-(2-Hydroxy-1-methylethyl)-N,N-diisopropyl-3-nitrobenzenecarboxamide (72). According to Ex-
t
per.53, with 51 (1.39 g, 5 mmol), paraformaldehyde (180 mg, 6 mmol), DMSO (10 ml), and BuOK (125 mg,
1 mmol): 1.49 g (97%) of 72. Yellow solid. M.p. 104 1068. TLC (hexane/AcOEt 1:1): Rf 0.24. UV (MeOH):
230 (3.96), 288 (sh, 3.15), 326 (sh, 2.80). 1H-NMR ((D6)DMSO): 7.69 (d, HÀC(2)); 7.63 (d, HÀC(6)); 7.54 (dd,
HÀC(5)); 4.80 (t, OH); 3.60 (br., CH(Me)CH2); 3.52 (t, 2 Me2CH); 3.22 (sext., CH(Me)CH2); 1.37 1.13 (br.,
CH(Me)CH2, 2 Me2CH). Anal. calc. for C16H24N2O4 (308.38): C 62.32, H 7.84, N 9.08; found: C 62.36, H 7.66,
N 8.94.
66. 4-(2-Hydroxy-1-methylethyl)-N-methyl-3-nitro-N-phenylbenzenecarboxamide (73). According to Ex-
t
per. 53, with 52 (2.26 g, 5 mmol), paraformaldehyde (180 mg, 6 mmol), DMSO (10 ml), and BuOK (125 mg,
1 mmol): 1.43 g (91%) of 73. Brown oil. TLC (hexane/AcOEt 1 :1): Rf 0.26. UV (MeOH): 231 (4.08), 242 (sh
4.04), 314 (sh 3.13). 1H-NMR ((D6)DMSO): 7.64 (s, HÀC(2)); 7.44 (s, HÀC(5), HÀC(6)); 7.33 7.17 (m, PhN);
4.73 (t, OH); 3.41 (m, CH(Me)CH2); 3.37( s, MeN); 3.12 (sext., CH(Me)CH2); 1.12 (d, CH(Me)CH2). Anal.
calc. for C17H18N2O4 (314.35): C 64.96, H 5.77, N 8.91; found: C 64.97, H 5.39, N 8.63.
67. 4-(2-Hydroxy-1-methylethyl)-3-nitrobenzonitrile (74). According to Exper. 18.1, with 53 [71] (325 mg,
2 mmol), paraformaldehyde (72 mg, 2.4 mmol), DMSO (5 ml), tBuOK (60 mg, 0.5 mmol), and tBuOH
(0.5 ml): 190 mg (46%) of 74. Light yellow solid. M.p. 78 798. TLC (hexanes/AcOEt 7:3): Rf 0.32. UV
(MeOH): 203 (4.20), 224 (4.35), 278 (sh, 3.10). 1H-NMR (CDCl3): 8.03 (d, HÀC(2)); 7.78 (dd, HÀC(6)); 7.51
(d, HÀC(5)); 3.87 3.61 ( m, CH(Me)CH2); 3.57( sext., CH(Me)CH2); 1.69 (br., OH); 1.32 (d, CH(Me)CH2).
Anal. calc. for C10H10N2O3 (206.2): C 58.25, H 4.89, N 13.59; found: C 58.18, H 4.95, N 13.22.
68. 3-(2-Hydroxy-1-methylethyl)-4-nitrobenzonitrile (75). According to Exper. 18.1, with 54 (530 mg,
3 mmol), paraformaldehyde (110 mg, 3.6 mmol), DMSO (5 ml), tBuOK (90 mg, 0.75 mmol), and tBuOH
(0.75 ml): 140 mg (26%) of 54 and 80 mg (13%) of 75. Light yellow solid. M.p. 111 1128. TLC (hexanes/AcOEt
7:3): Rf 0.51. UV (MeOH): 203 (4.28), 219 (sh, 4.00), 241 (sh, 3.82), 289 (sh, 3.37), 316 (sh, 2.99). 1H-NMR
(CDCl3): 7.83 (d, HÀC(6)); 7.79 (d, HÀC(2)); 7.64 (d, HÀC(6)); 3.84, 3.73 (2m, CH(Me)CH2); 3.48 (sext.,
CH(Me)CH2); 1.58 (br., OH), 1.33 (d, CH(Me)CH2). Anal. calc. for C10H10N2O3 (206.2): C 58.25, H 4.89,
N 13.59; found: C 58.18, H 4.77, N 13.56.
69. tert-Butyl 3-(2-Hydroxy-1-methylethyl)-4-nitrobenzoate (76). According to Exper. 18.1, with 56
(930 mg, 3.7mmol), paraformaldehyde (170 mg, 5.7mmol), DMSO (5 ml), tBuOK (115 mg, 0.9 mmol), and
tBuOH (1 ml): 260 mg (25%) of 76. Yellow oil. TLC (hexanes/AcOEt 7:3): Rf 0.52. UV (MeOH): 202 (4.35),
220 (sh, 4.05), 244 (sh, 3.90), 282 (sh, 3.51), 326 (sh, 2.06). 1H-NMR (CDCl3): 8.09 (d, HÀC(2)); 7.91 (dd,
t
HÀC(6)); 7.71 (d, HÀC(5)); 3.78 (m, CH(Me)CH2); 3.48 (sext., CH(Me)CH2); OH not visible; 1.59 (s, Bu);
1.32 (d, CH(Me)CH2). Anal. calc. for C14H19NO5 (281.3): C 59.78, H 6.81, N 4.98; found: C 59.77, H 6.76, N 4.90.
70. 3-(2-Nitrophenyl)butan-2-one (79). Under Ar and with stirring, Na metal (0.35 g, 0.014 mol) was
i
dissolved in PrOH (15 ml) by heating to 808. The soln. was cooled to r.t., (2-nitrophenyl)acetone (ˆ1-(2-
nitrophenyl)propan-2-one; 77) [6][54] (2.5 g, 0.015 mol) was added, the violet soln. stirred for 10 min, and then
MeI (4.0 g, 0.029 mol) was added dropwise ( ! brown). After stirring for 30 min, the mixture was evaporated,
the residue dissolved in AcOEt (200 ml) and washed several times with H2O, and the org. layer dried (Na2SO4)
and evaporated. Purification by CC (AcOEt/hexanes 1 :4) gave 1.5 g (52%) of 79. Syrup. TLC (AcOEt/hexanes
1:4): Rf 0.43. UV (MeOH): 206 (4.13), 257(3.73), 333 (sh, 2.99). 1H-NMR (CDCl3): 7.92 (d, HÀC(3)); 7.58 (t,
HÀC(5)); 7.47 7.36 (m, 2 arom. H); 4.36 (q, MeCH); 2.20 (s, MeCO); 1.47( d, MeCH). Anal. calc. for
C10H11NO3 (193.2): C 62.17, H 5.74, N 7.25; found: C 62.42, H 5.59, N 7.62.
71. 3-(2-Nitrophenyl)pentan-2-one (80). According to Exper. 70, with EtI (4.8 g, 0.032 mol): 1.42 g (43%) of
80. Syrup. TLC (AcOEt/hexanes 1:4): Rf 0.59. UV (MeOH): 207(4.13), 256 (3.67), 332 (sh, 2.83). 1H-NMR
(CDCl3): 7.85 (d, HÀC(3)); 7.57 (t, HÀC(5)); 7.46 7.36 (m, 2 arom. H); 4.18 (t, MeCH2CH); 2.18 (s, MeCO);
2.15 2.04 (m, 1 H, CH2); 1.79 1.68 (m, 1 H, CH2); 0.84 (t, MeCH2CH). Anal. calc. for C11H13NO3 (207.2):
C 63.76, H 6.32, N 6.76; found: C 63.98, H 6.23, N 6.74.
72. 3-(2-Nitrophenyl)hex-5-en-2-one (81). According to Exper. 71, with allyl bromide (5.0 g, 0.035 mol):
2.6 g (85%) of 81. Syrup. TLC (AcOEt/hexanes 1:4): Rf 0.48. UV (MeOH): 209 (4.10), 256 (3.62), 295 (sh,
3.14), 330 (sh, 2.80). 1H-NMR (CDCl3): 8.09 (d, HÀC(3)); 7.62 (t, HÀC(5)); 7.46 7.36 (m, 2 arom. H); 5.61 (m,
CH2ˆCH); 4.96 (m, CH2ˆCH); 4.39 (t, ArCH); 2.86 2.77 (m, 1 H, CH2); 2.48 (m, 1 H, CH2); 2.18 (s, MeCO).
Anal. calc. for C12H13NO3 (219.2): C 65.74, H 5.98, N 6.39; found: C 65.68, H 6.05, N 6.22.
73. 2-(2-Nitrophenyl)-1-phenylpropan-1-one (82). To a soln. of 2-(2-nitrophenyl)-1-phenylethanone (78)
i
[55] (2.5 g, 0.01 mol) in PrOH (5 ml) was added under Ar and with stirring a soln. of Na (0.3 g, 0.013 mol) in
iPrOH (5 ml). After stirring for 10 min, MeI (4.0 g, 0.029 mol) was added dropwise. The mixture was stirred for
30 min and then evaporated, the residue dissolved in AcOEt (200 ml), the soln. washed several times with H2O,
dried (Na2SO4), and evaporated, and the residue was purified by CC (AcOEt/hexanes 1:4): 2.56 g (97%) of 82.

Helvetica Chimica Acta Vol. 87(2004)
643
Orange syrup. TLC (AcOEt/hexanes 1:4): Rf 0.69. UV (MeOH): 206 (4.35), 245 (4.19), 276 (sh, 3.65), 332 (sh,
2.86). 1H-NMR (CDCl3): 7.92 (d, HÀC(3)); 7.66-7.29 (m, 8 arom. H); 5.37( q, CH); 1.58 (d, Me). Anal. calc. for
C15H13NO3 (255.3): C 70.58, H 5.13, N 5.49; found: C 70.65, H 5.16, N 5.51.
74. 2-(2-Nitrophenyl)-1-phenylbutan-1-one (83). According to Exper. 73, with EtI (4.5 g, 0.03 mol): 1.73 g
(64%) of 83. Orange syrup. TLC (AcOEt/hexanes 1:4): Rf 0.69. UV (MeOH): 205 (4.36), 245 (4.15), 273 (sh,
3.66), 333 (sh, 2.92). 1H-NMR (CDCl3): 8.00 7.34 (m, 9 arom. H); 5.25 (t, CH); 2.24 (m, 1 H, CH2); 1.89 (m,
1 H, CH2); 0.05 (t, Me). Anal. calc. for C16H17NO3 (271.3): C 71.36, H 5.61, N 5.20; found: C 71.32, H 5.56,
N 5.13.
75. 2-(2-Nitrophenyl)-1-phenylpent-4-en-1-one (84). According to Exper. 73, with allyl bromide (4.0 g,
0.028 mol): 2.42 g (83%) of 84. Orange syrup. TLC (AcOEt/hexanes 1:4): Rf 0.54. UV (MeOH): 206 (4.36),
246 (4.18), 277 (sh, 3.66), 331 (sh, 2.98). 1H-NMR (CDCl3): 7.96 7.31 (m, 9 arom. H); 5.67( m, CH2ˆCH); 5.46
(t, ArCH); 5.01 (m, CH2ˆCH); 2.89 (m, 1 H, CH2); 2.55 (m, 1 H, CH2). Anal. calc. for C17H15NO3 (281.3):
C 72.58, H 4.98, N 5.37; found: C 72.59, H 5.40, N 4.73.
76. 1-(2-Nitrophenyl)propan-2-ol (85). A soln. of 77 (1.79 g, 0.01 mol) in MeOH (12 ml) was treated with
NaBH4 (0.57g, 0.015 mol) under stirring for 30 min. After addition of ice (50 g), a yellow precipitate separated.
Purification by recrystallization from EtOH gave 1.18 g (65%) of 85. Yellow crystals: M.p. 45 468. TLC
1
(CHCl3/MeOH 9 :1): Rf 0.66. UV (MeOH): 206 (4.06), 258 (3.64), 332 (sh, 2.77). H-NMR (CDCl3): 7.91 (d,
HÀC(3)); 7.58 (t, HÀC(5)); 7.43 7.23 (m, 2 arom. H); 4.11 (dd, MeCH); 3.15 (m, 1 H, CH2); 2.96 (m, 1 H,
CH2); 1.62 (br., OH); 1.30 (d, MeCH). Anal. calc. for C9H11NO3 (181.2): C 59.66, H 6.12, N 7.73; found: C 59.71,
H 5.99, N 7.62.
77. 2-(2-Nitrophenyl)-1-phenylethanol (86). According to Exper. 76, with 78 (2.41 g, 0.01 mol): 2.3 g (94%)
of 86. Yellowish crystals. M.p. 70 728. TLC (CHCl3/MeOH 9 :1): Rf 0.63. UV (MeOH): 208 (4.26), 257(3.65),
333 (sh, 2.77). 1H-NMR (CDCl3): 7.94 (d, HÀC(3)); 7.50 (t, HÀC(5)); 7.43 7.31 (m, 7arom. H); 5.03 ( dd, CH);
3.40 (m, 1 H, CH2); 3.22 (m, 1 H, CH2); 1.98 (br., OH). Anal. calc. for C14H13NO3 (243.3): C 69.12, H 5.39,
N 5.76; found: C 69.09, H 5.28, N 5.74.
78. 3-(2-Nitrophenyl)butan-2-ol (87). According to Exper. 76, with 79 (1.93 g, 0.01 mol). After addition of
ice, the resulting oil was extracted with AcOEt. The org. phase was dried (Na2SO4) and evaporated, and the
residue was purified by CC (CHCl3/MeOH 9 :1): 1.74 g (89%) of 87. Orange syrup. TLC (CHCl3/MeOH 9 :1): Rf
0.64. UV (MeOH): 206 (4.09), 255 (3.60), 332 (sh, 2.93). 1H-NMR (CDCl3): 7.72 (m, H o to NO2); 7.58 7.33 (m,
3 H, arom. H); 4.01 3.86 (m, CHOH); 3.28 (q, ArCH); 1.31 (d, MeCHOH); 1.26 (d, MeCHAr). Anal. calc. for
C10H13NO3 (195.2): C 61.53, H 6.71, N 7.17; found: C 61.65, H 6.35, N 7.69.
79. 3-(2-Nitrophenyl)pentan-2-ol (88). According to Exper. 78, with 80 (2.07g, 0.01 mol): 1.78 g (85%) of
88. Orange syrup. TLC (AcOEt/hexanes 1:4): Rf 0.64. UV (MeOH): 206 (4.15), 258 (3.60), 332 (sh, 2.82).
1H-NMR (CDCl3): 7.65 (d, H o to NO2); 7.55 7.30 (m, 3 arom. H); 3.96 (m, CHOH); 3.18 3.01 (q, ArCH);
1.85 1.64 (m, EtCH2); 1.19 (d, MeCHOH); 0.74 (d, MeCH2). Anal. calc. for C10H13NO3 (209.2): C 63.14, H 7.23,
N 6.68; found: C 63.44, H 7.07, N 6.86.
80. 3-(2-Nitrophenyl)hex-5-en-2-ol (89). According to Exper. 78, with 81 (2.19 g, 0.01 mol): 1.94 g (88%) of
89. Orange syrup. TLC (AcOEt/hexanes 1:4): Rf 0.20. UV (MeOH): 206 (4.08), 255 (3.53), 333 (sh, 2.78).
1H-NMR (CDCl3): 7.68 7.29 (m, 4 arom. H); 5.65 5.51 (m, CH2ˆCH); 4.93 (m, 2 CH2ˆCH); 4.03 (m,
CHOH); 3.27( m, ArCH); 2.60 2.44 (m, CH2); 1.15 (d, MeCHOH). Anal. calc. for C12H15NO3 (221.2): C 65.14,
H 6.83, N 6.33; found: C 65.40, H 6.71, N 6.23.
81. 2-(2-Nitrophenyl)-1-phenylpropan-1-ol (90). According to Exper. 78, with 82 (2.55 g, 0.01 mol): 2.05 g
(80%) of 90. Orange syrup. TLC (CHCl3/MeOH 9 :1): Rf 0.66. UV (MeOH): 207(4.31), 248 (3.59), 333 (sh,
2.94). 1H-NMR (CDCl3): 7.73 (m, H o to NO2); 7.68 7.30 (m, 8 arom. H ); 4.68 (m, CHOH); 3.75 (m, MeCH);
1.15 (d, MeCH). Anal. calc. for C15H15NO3 (257.3): C 70.02, H 5.88, N 5.44; found: C 70.00, H 5.97, N 5.25.
82. 2-(2-Nitrophenyl)-1-phenylbutan-1-ol (91). According to Exper. 78, with 83 (2.69 g, 0.01 mol): 2.33 g
(86%) of 91. Orange syrup. TLC (AcOEt/hexanes 1:4): Rf 0.32. UV (MeOH): 206 (4.32), 251 (3.62), 281 (sh,
3.41), 333 (sh, 3.05). 1H-NMR (CDCl3): 7.68 7.28 (m, 9 arom. H ); 4.85 (m, CHOH); 3.60 3.40 (m, ArCH);
1.60 1.19 (m, OH, CH2); 0.65 (t, MeCH2). Anal. calc. for C16H17NO3 (271.3): C 70.83, H 6.32, N 5.16; found:
C 70.68, H 6.31, N 4.96.
83. 2-(2-Nitrophenyl)-1-phenylpent-4-en-1-ol (92). According to Exper. 78, with 84 (2.81 g, 0.01 mol): 2.52 g
(89%) of 92. Orange syrup. TLC (AcOEt/hexanes 1:4): Rf 0.29. UV (MeOH): 207(4.35), 251 (3.71), 288 (sh,
3.44), 333 (sh, 2.96). 1H-NMR (CDCl3): 7.68 7.25 (m, 9 arom. H ); 5.54 (m, CH2ˆCH); 4.91 4.77 (m, CHOH,
CH2ˆCH); 3.79 (m, ArCH); 2.41 (m, CH2). Anal. calc. for C16H17NO3 (283.3): C 72.07, H 6.05, N 4.94; found:
C 72.22, H 5.75, N 4.93.

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Helvetica Chimica Acta Vol. 87(2004)
84. Cyclopentanol 95: (1RS,2RS)-2-(2,4-Dinitrophenyl)cyclopentanol (97) and (1RS,2SR)-2-(2,4-Dinitro-
phenyl)cyclopentanol (98). NaBH4 (1.33 g, 35 mmol) was added slowly to a suspension of 2-(2,4-dinitrophe-
nyl)cyclopentanone (93) [56] (2 g, 8 mmol) in MeOH (50 ml), so that the temp. was kept below 258. After
stirring for 3 h at r.t., the mixture was acidified with conc. HCl soln. (pH 2) and evaporated. The residue (20 ml)
was dissolved in H2O (50 ml) and extracted with CH2Cl2 (2 Â 40 ml). The combined org. layer was dried
(Na2SO4) and evaporated, and the crude product purified by CC (SiO2 (62 g), 4 Â 16 cm; hexanes/AcOEt,
6 :1 ! 2 :1): 370 mg (18%) of 97 and 800 mg (39%) of 98 as yellow oils.
Data of 97: TLC (hexanes/AcOEt 7:3): Rf 0.46. UV (MeOH): 206 (4.12), 253 (4.05), 323 (sh, 2.95).
1H-NMR ((D6)DMSO): 8.63 (d, HÀC(3')); 8.41 (dd, HÀC(5')); 7.89 (d, HÀC(6')); 4.67(br., OH); 4.19 ( s,
HÀC(1)); 3.25 (m, HÀC(2)); 2.05 (m, 1 HÀC(3)); 1.94 (m, 1 HÀC(5)); 1.91 (m, 1 HÀC(4)); 1.89 (m, 1
HÀC(3)); 1.65 (m, 1 HÀC(5)); 1.64 (m, 1 HÀC(4)). 13C-NMR ((D6)DMSO): 150.27, 145.55, 142.31 (C(2'),
C(4'), C(1')); 132.81 (C(6')); 125.51 (C(5')); 118.56 (C(3')); 73.30 (C(1)); 45.92 (C(2)); 35.14 (C(5)); 29.12
(C(3)); 21.97(C(4)).
Data of 98: TLC (hexanes/AcOEt 7:3): Rf 0.31. UV (MeOH): 207(4.11), 262 (4.02), 322 (sh, 3.03).
1H-NMR ((D6)DMSO): 8.62 (d, HÀC(3')); 8.42 (dd, HÀC(5')); 7.91 (d, HÀC(6')); 4.92 (d, OH), 4.12 (m,
HÀC(1)); 3.26 (m, HÀC(2)); 2.14 (m, 1 HÀC(3)); 1.98 (m, 1 HÀC(5)); 1.77 (m, CH2(4)); 1.64 (m, 1 HÀC(3));
1.55 (m, 1 HÀC(5)). 13C-NMR ((D6)DMSO): 150.51, 145.53, 145.08 (C(2'), C(4'), C(1')); 130.21 (C(6')); 126.71
(C(5')); 118.89 (C(3')); 78.56 (C(1)); 48.51 (C(2)); 34.14 (C(5)); 31.90 (C(3)); 21.53 (C(4)). Anal. calc. for
C11H12N2O5 (257.2): C 52.38, H 4.80, N 11.11; found: C 52.39, H 4.87, N 11.13.
85. 2-(2,4-Dinitrophenyl)cyclohexanol (96). According to Exper. 84, with 2-(2,4-dinitrophenyl)cyclohex-
anone (94) [56] (2 g, 7.6 mmol), NaBH (1.25 g, 33 mmol), and MeOH (50 ml). Purification by CC (SiO2 (54 g),
4
3.5 Â 14 cm; hexanes/AcOEt, 8 :1 ! 3 :1) gave 1.13 g (56%) of 96. Yellow oil. TLC (hexanes/AcOEt 7:3): Rf
0.45. UV (MeOH): 203 (4.13), 248 (4.04), 314 (sh, 3.05). 1H-NMR ((D6)DMSO): 8.59 (d, HÀC(3')); 8.43 (dd,
HÀC(5')); 7.95 (d, HÀC(6')); 4.66 (d, OH); 3.58 (m, CH (chx)); 2.58 (m, CH (chx)); 1.98 1.13 (m, 8 CH (chx)).
Anal. calc. for C12H14N2O5 ¥ 0.24 C4H8O2 (AcOEt) (288.3): C 54.16, H 5.59, N 9.72; found: C 53.94, H 5.88,
N 9.62.
86. (1,2,3,4-Tetrahydro-8-nitro-naphthalen-1-yl)methanol (99) [57]. According to Exper. 18.1, with a 1.5 :1
mixture of 1,2,3,4-tetrahydro-5-nitro- and 1,2,3,4-tetrahydro-6-nitronaphthalene [72], paraformaldehyde
t
t
(450 mg, 15 mmol), DMSO (10 ml), BuOK (370 mg, 3 mmol), and BuOH (3 ml): 960 mg (31%) of 99. Red
oil. TLC (hexanes/AcOEt 7:3): Rf 0.52. UV (MeOH): 207(4.15), 263 (3.56), 294 (sh, 3.30), 332 (sh, 2.94).
1H-NMR ((D6)DMSO): 7.57 (d, HÀC(7)); 7.38 (d, HÀC(5)); 7.30 (d, HÀC(6)); 4.85 (br., CH2OH); 3.50 (m,
HÀC(1)); 3.35, 3.29 (2m, CH2OH); 2.84 (m, HÀC(4)); 2.76 (m, HÀC(4)); 2.03 (m, HÀC(2)); 1.77 (m,
HÀC(3)): 1.64 (m, HÀC(2), HÀC(3)). 13C-NMR ((D6)DMSO): 151.06 (C(8)); 140.08 (C(4a)); 133.40 (C(5));
130.78 (C(8a)); 126.50 (C(6)); 121.60 (C(7)); 68.85 (CH2OH); 34.83 (C(1)); 28.95 (C(4)); 22.85 (C(2)); 17.08
(C(3)).
87. 2-Methyl-1-nitronaphthalene (100) [73]. A soln. of 2-methylnaphthalene (14.2 g, 0.1 mol) in AcOH
(50 ml) was cooled to 108. Then, under stirring, fuming HNO3 (8 ml) was added dropwise. After 2 h, the soln.
was diluted with H2O (150 ml) and then extracted with CH2Cl2 (150 ml). The org. phase was washed with
NaHCO3 soln. (foaming), dried (Na2SO4), and evaporated. The residue was recrystallized from MeOH (20 ml):
13.0 g (68%) of 100. Yellow needles. M.p. 79 808 ([73]: 80 818). TLC (Et2O): Rf 0.63. UV (MeOH): 220
(4.76), 265 (4.02), 317 (sh, 3.53), 344 (sh, 3.31). 1H-NMR (CDCl3): 7.86 (m, HÀC(4), HÀC(5)); 7.70 (d,
HÀC(8)); 7.61-7.50 (m, HÀC(6), HÀC(7)); 7.37 (d, HÀC(3)); 2.47( s, Me).
88. 2-Ethyl-1-nitronaphthalene (101) [74]. According to Exper. 87, with 2-ethylnaphthalene (5 g) and
fuming HNO3 (3 ml). CC (SiO2; AcOEt/hexanes 1:8) gave 5.66 g (88%) of 101. Yellow syrup. TLC (AcOEt/
hexanes 1 :4): Rf 0.51. UV (MeOH): 221 (4.74), 265 (4.04), 316 (sh, 3.50), 345 (sh, 3.28). 1H-NMR (CDCl3): 7.79
(m, HÀC(4), HÀC(5)); 7.70 (d, HÀC(8)); 7.48 (m, HÀC(6), HÀC(7)); 7.38 (d, HÀC(3)); 2.75 (q, MeCH2);
1.30 (t, MeCH2).
89. 2-(1-Nitronaphthalen-2-yl)ethanol (102). A soln. of 100 (5.5 g, 30.4 mmol) and paraformadehyde
(8.87g, 30.4 mmol) in DMSO (150 ml) was treated with tBuOK (1.3 g) in tBuOH (15 ml) for 15 min at r.t. and
then for 2 h at 808. After cooling, the mixture was neutralized with HCl, diluted with H2O (200 ml), and
extracted with AcOEt (3 Â 150 ml). The org. phase was dried (Na2SO4) and evaporated, and the resulting syrup
was purified by CC (SiO2; AcOEt/hexanes 1 :4). The residue of the main fraction was recrystallized from
EtOH: 5.4 g (85%) of 102. Yellow crystals. M.p. 117 118 8. TLC (AcOEt/hexanes 1:4): Rf 0.11. UV (MeOH):
221 (4.81), 266 (4.04), 287(sh, 3.84), 314 (sh, 3.48), 3.44 (sh, 3.31). 1H-NMR (CDCl3): 7.88 (m, HÀC(4),
HÀC(5)); 7.61 (d, HÀC(8)); 7.56 (m, HÀC(5), HÀC(7)); 7.46 (d, HÀC(3)); 3.79 (t, CH2OH); 3.03 (t, CH2);
1.64 (t, OH). Anal. calc. for C12H11NO3 (217.2): C 66.35, H 5.10, N 6.45; found: C 66.43, H 5.20, N 6.47.

Helvetica Chimica Acta Vol. 87(2004)
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90. 2-(1-Nitronaphthalen-2-yl)propan-1-ol (103). According to Exper. 89, with 101 (2.0 g, 10 mmol),
paraformaldehyde (4,0 g, 0.13 mol), tBuOK (0.45 g, 0.33 mmol), and DMSO (15 ml) at 808 for 48 h. 1.4 g (61%)
of 103. Brownish syrup. TLC (Et2O): Rf 0.42. UV (MeOH): 223 (4.79), 266 (4.00), 284 (sh, 3.80), 315 (sh, 3.45),
359 (sh, 3.21). 1H-NMR (CDCl3): 7.96 (d, HÀC(5)); 7.88 (d, HÀC(8)); 7.70 7.54 (m, 3 arom. H); 3.85
(t, CH2OH); 3.18 (m, MeCH); 1.64 (s, OH); 1.39 (d, MeCH).
91. 1-Methyl-8-nitronaphthalene (104). According to [74]. M.p. 63 658. 1H-NMR (CDCl3): 7.98 (d,
HÀC(5)); 7.77 (d, HÀC(4)); 7.62 (d, HÀC(7)); 7.46 (m, HÀC(2), HÀC(3), HÀC(6)); 2.53 (s, Me).
92. 2-(8-Nitronaphthalen-1-yl)ethanol (105). Protecting gas was used until to the addition of BF3 ¥ Et2O. To
a suspension of NaBH4 (363 mg, 9.6 mmol) in diglyme (5 ml) was added under cooling (8-nitronaphthalen-1-
yl)acetic acid (106) [58] (734 mg, 3.2 mmol). After stirring for 10 min in the ice-bath, BF3 ¥ Et2O (2.4 ml,
19 mmol) in diglyme (5 ml) was dropped slowly to the mixture. After stirring for 90 min at r.t., the mixture was
cooled to 08 again, BF3 ¥ Et2O (1.2 ml, 9.6 mmol) in diglyme (5 ml) was added, and the mixture was stirred for 1 h
at r.t. The mixture was poured on ice and extracted with AcOEt (3 Â 50 ml), the combined org. phase washed
with ice water (5Â) to remove the diglyme, dried (Na2SO4), and evaporated, and the crude product purified by
CC (SiO2 (22g), 2.5 Â 15 cm; toluene/AcOEt 9 :1): 552 mg (79%) of 105. Yellow solid. M.p. 53 548. TLC
(hexanes/AcOEt 1:1): Rf 0.62. UV (MeOH): 209 (sh, 4.50), 220 (4.72), 246 (sh, 3.69), 343 (sh, 3.17). 1H-NMR
(CDCl3): 8.01 (dd, 1 arom. H); 7.83 (dd, 1 arom. H); 7.65 7.43 (m, 4 arom. H); 3.86 (t, CH2CH2OH); 3.07( t,
CH2CH2OH); 1.51 (s, CH2CH2OH). Anal. calc. for C12H11NO3 (217.2): C 66.35, H 5.10, N 6.45; found: C 66.33,
H 5.14, N 6.42.
93. 1-(8-Nitronaphthalen-1-yl)ethanol (108). NaBH4 (450 mg, 13 mmol) was added slowly to a suspension
of 1-(8-nitronaphthalen-1-yl)ethanone (107) [59] (500 mg, 2.3 mmol) in MeOH (40 ml). After stirring
overnight at r.t., NaBH4 (450 mg, 13 mmol) was added. After stirring for 3 days at r.t., the mixture was acidified
with 2n HCl and evaporated. The residue (20 ml) was dissolved in H2O (25 ml) and extracted with Et2O (2 Â
25 ml), the combined org. phase dried (Na2SO4) and evaporated, and the crude product purified by CC (SiO2
(22 g), 2 Â 14 cm; hexanes ! hexanes/AcOEt 3 :7): 245 mg (49%) of 108. Brown solid. M.p. 70 738. TLC
(hexanes/AcOEt 4 :1): Rf 0.37. UV (MeOH): 209 (sh, 4.50), 221 (4.71), 238 (sh, 3.81), 282 (sh, 3.54), 335 (sh,
3.26). 1H-NMR (CDCl3): 8.03 (dd, 1 arom. H); 7.97 (dd, 1 arom. H); 7.86 (dd, 1 arom. H); 7.77 (dd, 1 arom. H);
7.63 (t, 1 arom. H); 7.46 (t, 1 arom. H); 5.21 (q, CH); 2.05 (br., OH); 1.55 (d, Me). Anal. calc. for C12H11NO3
(217.2): C 66.35, H 5.10, N 6.45; found: C 66.85, H 5.23, N 6.18.
94. (8-Nitronaphthalene-1-yl)methanol (110) [60] and (5-Nitronaphthalen-1-yl)methanol. Under Ar and
under cooling, 8-nitronaphthalene-1-carboxylic acid (109)/5-nitronaphthalene-1-carboxylic acid 5 :1 [75] (7.1 g,
33 mmol) was added to a suspension of NaBH4 (1.9 g, 50 mmol) in diglyme (55 ml). BF3 ¥ Et2O (10 ml, 80 mmol)
in diglyme (15 ml) was dropped slowly during 3 h to the mixture. After stirring for 2 h at r.t., the mixture was
poured on ice and extracted with AcOEt (3 Â 100 ml). The combined org. phase was washed with ice water (5 Â
70 ml) to remove the diglyme and sat. NaHCO3 soln. (2 Â 50 ml), dried (Na2SO4), and evaporated, and the
crude product was purified by CC (SiO2 (60 g), 4 Â 14 cm; toluene/AcOEt 9 :1): 3.57g (53%) of 110 and 920 mg
(14%) of (5-nitronaphthalen-1-yl)methanol as yellow solids.
Data of 110: M.p. 63 658 ([60]: 72 738). TLC (CH2Cl2/MeOH 10 :1): Rf 0.73. UV (MeOH): 218 (4.63),
240 (sh, 3.87), 288 (3.47). 1H-NMR ((D6)DMSO): 8.28 (d, 1 arom. H); 8.04 (t, 2 arom. H); 7.82 (d, 1 arom. H);
7.64 (q, 2 arom. H); 5.29 (t, CH2OH); 4.75 (d, CH2OH).
Data of (5-Nitronaphthalen-1-yl)methanol: M.p. 119 1208. TLC (CH2Cl2/MeOH 10 :1): Rf 0.63. UV
(MeOH): 209 (sh, 4.51), 216 (4.59), 244 (sh 3.85), 332 (3.50). 1H-NMR ((D6)DMSO): 8.48 (d, 1 arom. H); 8.24
(d, 1 arom. H); 8.18 (dd, 1 arom. H); 7.73 (m, 3 arom. H); 5.50 (t, CH2OH); 5.01 (d, CH2OH). Anal. calc. for
C11H9NO3 (203.2): C 65.02, H 4.46, N 6.89; found: C 64.85, H 4.40, N 6.77.
95. (1-Nitronaphthalen-2-yl)methanol (113). A soln. of 2-methyl-1-nitronaphthalene (100; 5.53 g, 0.03 mol)
in CCl4 (40 ml) was treated with N-bromosuccinimide (5.25 g, 0.03 mol) by heating to 808 and then with
dibenzoyl peroxide (10 mg). The reaction was complete after 5 h reflux. The mixture was cooled to filter off the
precipitate of succinimide. The filtrate was evaporated, yielding crude 2-(bromomethyl)-1-nitronaphthalene
(111), which was used without further purification in the next step. A mixture of 111 and AcOK (6.3 g) in AcOH
(100 ml) refluxed for 2 h. After stirring at r.t. overnight followed by evaporation, the crude syrupy acetate 112
was dissolved in EtOH (50 ml), 1n NaOH (200 ml) was added, and the mixture was stirred overnight at r.t. Then
the soln. was extracted with CH2Cl2 (3 Â 50 ml), the org. phase dried (Na2SO4) and evaporated, and the residue
purified by CC (SiO2; AcOEt/hexanes 1:4): 0.83 g (14%) of 113, which crystallized on treatment with EtOH.
Yellowish crystals. M.p. 170 1718.
96. (3-Nitronaphthalen-2-yl)methanol (114). According to [61].

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97. (3-Nitro-2-thienyl)methanol (115) [62]. To cold Ac2O (50 ml) was added dropwise fuming HNO3
(25 ml). This soln. was then added slowly (40 min) to (2-thienyl)methyl acetate in Ac2O (120 ml, À108). The
mixture was stirred for 3.5 h at À208 to 08, then 1 h at r.t., and afterwards poured onto ice. After extraction with
Et2O (2 Â 200 ml), the org. phase was washed with H2O (2 Â 250 ml), treated with NaHCO3, again washed with
H2O, dried (CaCl2), and evaporated to give
a mixture of (3-nitro-2-thienyl)methyl and (5-nitro-2-
thienyl)methyl acetate (53.1 g, 70%). The mixture was refluxed in 10% H2SO4 soln. (950 ml) for 75 min,
treated hot with charcoal, filtered, and after cooling extracted with Et2O (4 Â 200 ml). The org. phase was
washed with sat. NaHCO3 soln., dried (CaCl2), and evaporated and the dark syrup (38 g) purified by CC (SiO2;
toluene ! toluene/AcOEt 10 :1): 26.7g (65%) of (5-nitro-2-thienyl)methanol and 3.7g (9%) of 115. 115: M.p.
65 668 ([62]: 71 728), after recrystallization from Et2O/hexanes 1:1. TLC (toluene/AcOEt 3 :1): Rf 0.50. UV
(MeOH): 212 (4.18), 222 (sh, 4.05), 267(3.98), 299 (sh, 3.64). 1H-NMR (CDCl3): 7.58 (d, HÀC(4)); 7.18 (d,
HÀC(5)); 5.16 (s, CH2OH); 2.81 (br., CH2OH).
98. 2-(3-Nitro-2-thienyl)propan-1-ol (118) [63]. According to Exper. 18.1, with 2-ethyl-3-nitrothiophene
(116) [63] (2 g, 13 mmol), paraformaldehyde (382 mg, 13 mmol), DMSO (15 ml), tBuOK (150 mg, 1.3 mmol),
t
and BuOH (4 ml): 1.94 g (80%) of 118. Yellow oil. TLC (hexanes/AcOEt 7:3): Rf 0.32. UV (MeOH): 216
(4.06), 272 (3.83), 295 (sh, 3.61). 1H-NMR (CDCl3): 7.55 (d, 1 arom. H); 7.13 (d, 1 arom. H); 4.21 (sext.,
CH(Me)CH2); 3.79 (d, CH(Me)CH2); 1.78 (br., OH); 1.39 (d, CH(Me)CH2).
99. 2-(3-Nitro-2-thienyl)ethanol (120) and 2-(3-Nitro-2-thienyl)-propane-1,3-diol. According to Exper. 18.1
with 2-methyl-3-nitrothiophene (119) [64] (4 g, 28 mmol), paraformaldehyde (840 mg, 28 mmol), DMSO
(30 ml), tBuOK (160 mg, 1.4 mmol), and tBuOH (4 ml) for 15 min at 708: 1.08 g (27%) of 119, 1.72 g (35%) of
120, and 1.48 g (26%) of the propanediol.
Data of 120: Red-yellow oil. TLC (hexanes/AcOEt 1:1): Rf 0.86. UV (MeOH): 216 (4.09), 272 (3.87), 301
(sh, 3.56). 1H-NMR (CDCl3): 7.57 (d, 1 arom. H); 7.10 (d, 1 arom. H); 3.96 (t, CH2CH2O); 3.46 (t, CH2CH2O);
1.78 (br., OH). Anal. calc. for C6H7NO3S (173.2): C 41.61, H 4.07, N 8.09; found: C 41.61, H 4.27, N 8.10.
2-(3-Nitro-2-thienyl)propane-1,3-diol: Colorless solid. M.p. 66 688. TLC (hexanes/AcOEt 1:1): Rf 0.32.
UV (MeOH): 217(4.07), 274 (3.83), 298 (sh, 3.60). 1H-NMR (CDCl3): 7.60 (d, 1 arom. H); 7.18 (d, 1 arom. H);
4.34 (m, CH(CH2OH)2); 4.11 (m, CH(CH2OH)2); 3.99 (m, CH(CH2OH)2); 2.20 (br., 2 OH). Anal. calc. for
C7H9NO4S (203.2): C 41.37, H 4.46, N 6.86; found: C 41.42, H 4.58, N 6.80.
100. 2-(2-Nitrobenzo[b]thien-3-yl)ethanol (121). According to Exper. 18.1, with 3-methyl-2-nitrobenzo[b]-
t
thiophene (122) [65] (1 g, 5 mmol), paraformaldehyde (155 mg, 5 mmol), DMSO (20 ml), BuOK (58 mg,
t
0.5 mmol), and BuOH (3 ml) for 1 h at 808: 655 mg (58%) of 121. Yellow-brown solid. M.p. 106 1078. TLC
(hexanes/AcOEt 4 :1): Rf 0.13. UV (MeOH): 212 (4.14), 237(sh, 4.02), 330 (4.13). 1H-NMR (CDCl3): 7.98 (dd,
1 arom. H); 7.80 (dd, 1 arom. H); 7.61 7.46 (m, 2 arom. H); 4.01 (t, CH2CH2O); 3.62 (t, CH2CH2O); 1.66 (br.,
OH). Anal. calc. for C10H9NO3S (223.3): C 53.80, H 4.06, N 6.27; found: C 54.04, H 4.09, N 6.37.
101. 5'-Protected Thymidine Derivatives: General Procedure. To a cold soln. (08) of diphosgene (6 mmol) in
dry THF (8 ml) was added the appropriate alcohol (5 mmol) and Et3N (5 mmol) in dry THF (8 ml). After
stirring for 1 h at 08, the mixture was filtered and the filtrate evaporated to give the corresponding alkyl
carbonochloridate in approximately quantitative yield.
Thymidine (1 mmol) was co-evaporated with dry pyridine (3 Â 3 ml) and then dissolved in dry pyridine
(3 ml). The soln. was cooled to À408, then a soln. of the alkyl carbonochloridate (1.35 mmol) in dry CH2Cl2
(3 ml) was added dropwise, and after stirring for 5 h at À50 to À208, the mixture was diluted with H2O (10 ml)
and extracted with CH2Cl2 (3 Â 10 ml). The org. phase was dried (Na2SO4) and evaporated, and the residue co-
evaporated with toluene (3 Â 10 ml) and purified by CC (SiO2 (20 g), 2 Â 14 cm; CH2Cl2, then CH2Cl2/MeOH
100 :1, 100 :2, 100 :3, 100 :3.5 and 100 :4 (100 ml each)). The products eluted in the order thymidine 3',5'-
dicarbonate, 3'-carbonate, and 5'-carbonate. The fractions were evaporated and the resulting solid foams dried
at 358 in vacuo.
102. Thymidine 5'-[2-(2-Nitrophenyl)propyl Carbonate] (123), 3'-[2-(2-Nitrophenyl)propyl Carbonate]
(179), and 3',5'-Bis[2-(2-nitrophenyl)propyl Carbonate] (180). According to Exper. 101, with thymidine (0.242 g,
1 mmol): 0.359 g (80%) of 123, 9 mg (2%) of 179, and 92 mg (14%) of 180 as yellow solid foams.
Data of 123: TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.31. UV (MeOH): 206 (4.37), 263 (4.05), 332 (sh,
2.75). 1H-NMR (CDCl3): 8.66, 8.64 (2s, 1 H, NH, diastereoisomers); 7.77 (m, 1 arom. H); 7.59 (m, 1 arom. H);
7.43 (m, 2 arom. H); 7.33, 7.30 (2s, 1 H, HÀC(6)); 6.31 (m, HÀC(1')); 4.49 4.09 (m, HÀC(3'), HÀC(4'),
CH2(5')), CH(Me)CH2,); 3.80 (m, CH(Me)CH2); 2.61 (2d, OHÀC(3')); 2.39 (m, 1 HÀC(2')); 2.18 (m, 1
HÀC(2')); 1.75 (2s, MeÀC(5)); 1.38 (2d, CH(Me)CH2). Anal. calc. for C20H23N3O9 (449.4): C 53.45, H 5.16,
N 9.35; found: C 53.14, H 5.21, N 9.16.

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Data of 179: TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.38. UV (MeOH): 206 (4.26), 262 (4.03), 329 (sh,
2.75). 1H-NMR (CDCl3): 8.18 (br., NH); 7.81 (m, 1 arom. H); 7.61 (m, 1 arom. H), 7.44 (m, 2 arom. H,
HÀC(6)); 6.15 (m, HÀC(1')); 5.25 (m, HÀC(3')); 4.33 (m, CH(Me)CH2,); 4.14 (m, HÀC(4')); 3.90 (m,
CH2(5')); 3.78 (m, CH(Me)CH2); 2.44 (m, CH2(2'), OHÀC(5')); 1.93 (s, MeÀC(5)); 1.38 (m, CH(Me)CH2).
Anal. calc. for C20H23N3O9 (449.4): C 53.45, H 5.16, N 9.35; found: C 53.43, H 5.24, N9.01.
Data of 180: TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.68. UV (MeOH): 205 (4.50), 259 (4.22), 333 (sh,
3.29); 1H-NMR (CDCl3): 8.32 (s, NH); 7.80 (m, 2 arom. H); 7.61 (m, 2 arom. H); 7.45 (m, 4 arom. H); 7.30 (m,
HÀC(6)); 6.36 (m, HÀC(1')); 5.13 (m, HÀC(3')), 4.48 4.17( m, HÀC(4'), 2 CH(Me)CH2, CH2(5')); 3.80 (m, 2
CH(Me)CH2); 2.49 (m, 1 HÀC(2')); 2.22 (m, 1 HÀC(2')), 1.87, 1.77 (2s, MeÀC(5)); 1.40 (d, 2 CH(Me)CH2).
Anal. calc. for C30H32N4O13 (656.6): C 54.88, H 4.91, N 8.53; found: C 54.91, H 5.01, N 8.28.
103. Thymidine 5'-[2-(4-Chloro-2-nitrophenyl)propyl carbonate] (124). According to Exper. 101, with 23:
0.344 g (71%) of 124. Colorless foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.41. UV (MeOH): 206 (sh,
4.37), 212 (4.43), 263 (4.05), 332 (sh, 2.75). 1H-NMR (CDCl3): 8.75 (br., NH); 7.77 (d, arom. HÀC(3'')); 7.54
(dd, HÀC(5'')); 7.39 (d, HÀC(6'')); 7.27 (dd, HÀC(6)); 6.29 (m, HÀC(1')); 4.46 4.07( m, CH(Me)CH2,
HÀC(3'), HÀC(4'), CH2(5')); 3.74 (m, CH(Me)CH2); 2.49 (m, OHÀC(3')); 2.37( m, 1 HÀC(2')), 2.18 (m, 1
HÀC(2')); 1.82 (d, MeÀC(5)); 1.34 (dd, CH(Me)CH2). Anal. calc. for C20H22ClN3O9 (483.9): C 49.65, H 4.58,
N 8.68; found: C 49.54, H 4.67, N 8.61.
104. Thymidine 5'-[2-(4-Bromo-2-nitrophenyl)propyl Carbonate] (125), 3'-[2-(4-Bromo-2-nitrophenyl)-
propyl Carbonate] (181), and 3',5'-Bis[2-(4-bromo-2-nitrophenyl)propyl Carbonate] (182). According to
Exper. 101 with 24: 0.396 g (75%) of 125, 11 mg (2%) of 181, and 98 mg (12%) of 182 as colorless foams.
Data of 125: TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.51. UV (MeOH): 204 (sh, 4.39), 212 (4.42), 263
(4.07), 333 (sh, 2.75). 1H-NMR (CDCl3): 8.67(br., NH); .789 ( d, HÀ(3'')); 7.68 (dd, HÀC(5'')); 7.30 (m,
HÀC(6''), HÀC(6)); 6.30 (m, HÀC(1')); 4.43 4.07( m, CH(Me)CH2, HÀC(3'), HÀC(4'), CH2(5'); 3.73 (sext.,
CH(Me)CH2); 2.59 (br., OHÀC(3')); 2.37( m, 1 HÀC(2')); 2.15 (m, 1 HÀC(2')); 1.82 (2s, MeÀC(5)); 1.34 (dd,
CH(Me)CH2). Anal. calc. for C20H22BrN3O9 (528.3): C 45.47, H 4.20, N 7.95; found: C 45.45, H 4.23, N 7.89.
Data of 181: TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.59. UV (MeOH): 203 (4.41), 212 (4.42), 261 (4.09),
334 (sh, 2.90); 1H-NMR (CDCl3): 8.40 (br., NH); 7.93 (d, HÀ(3'')); 7.71 (dd, HÀC(5'')); 7.39 (d, HÀC(6'')); 7.34
(s, HÀC(6)); 6.12 (m, HÀC(1')); 5.22 (d, HÀC(3')); 4.35, 4.20 (2m, CH(Me)CH2); 4.12 (m, HÀC(4')); 3.90 (m,
CH2(5')); 3.78 (sext., CH(Me)CH2); 2.54 2.34 (m, OHÀC(5'), CH2(2')); 1.90 (s, MeÀC(5)); 1.35 (d,
CH(Me)CH2). Anal. calc. for C20H22BrN3O9 (528.3): C 45.47, H 4.20, N 7.95; found: C 45.38, H 4.37, N 7.47.
Data of 182: TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.83. UV (MeOH): 202 (4.52), 214 (4.56), 256
(4.16), 334 (sh, 3.06). 1H-NMR (CDCl3): 8.62 (br., NH), 7.90 (2d, 2 HÀC(3'')); 7.80 (m, 2 HÀC(5'')); 7.30 (m, 2
H(6''), HÀC(6)); 6.32 (m, HÀC(1')); 5.10 (t, HÀC(3')); 4.43 4.14 (m, 2 CH(Me)CH2, HÀC(4'), CH2(5')); 3.73
(sext., 2 CH(Me)CH2); 2.41 (m, 1 HÀC(2')); 2.23 (m, 1 HÀC(2')); 1.83 (2s, MeÀC(5)); 1.34 (d, 2 CH(Me)CH2).
Anal. calc. for C30H30Br2N4O13 (814.4): C 44.24, H 3.71, N 6.88; found: C 44.37, H 3.88, N 7.21.
105. Thymidine 5'-[2-(4-Iodo-2-nitrophenyl)propyl Carbonate] (126). According to Exper. 101 with 25:
0.414 g (72%) of 126. Colorless solid foam. TLC (toluene/AcOEt/ MeOH 5 :4 :1): Rf 0.54. UV (MeOH): 203
(4.43), 228 (4.30), 261 (4.09), 332 (sh, 2.87). 1H-NMR (CDCl3): 8.45 (br., NH); 8.05 (d, HÀC(3'')); 7.87 (dd,
HÀC(5'')); 7.26 (dd, HÀC(6)); 7.18 (d, HÀC(6'')); 6.29 (m, HÀC(1')); 4.45 4.06 (m, CH(Me)CH2, HÀC(3'),
HÀC(4'), CH2(5')); 3.71 (sext., CH(Me)CH2); 2.37( m, OHÀC(3'), 1 HÀC(2')), 2.16 (m, 1 HÀC(2')); 1.82 (dd,
MeÀC(5)); 1.33 (dd, CH(Me)CH2). Anal. calc. for C20H22IN3O9 (575.3): C 41.76, H 3.85, N 7.30; found: C 41.49,
H 3.98, N 7.40.
106. Thymidine 5'-[2-(5-Chloro-2-nitrophenyl)propyl Carbonate] (127), 3'-[2-(5-Chloro-2-nitrophenyl)-
propyl Carbonate] (183), and 3',5'-Bis[2-(5-chloro-2-nitrophenyl)propyl Carbonate] (184). According to
Exper. 101, with 26: 0.334 g (69%) of 127, 19 mg (4%) of 183, and 43 mg (6%) of 184. Colorless solid foams.
Data of 127: TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.40. UV (MeOH): 207(4.32), 263 (4.15), 335 (sh,
2.92). 1H-NMR (CDCl3): 8.75 (br., NH); 7.74 (d, 1 arom. H); 7.41 (d, 1 arom. H); 7.34 (dd, 1 arom. H); 7.29 (s,
HÀC(6)); 6.31 (m, HÀC(1')); 4.47 4.08 ( m, CH(Me)CH2 , HÀC(3'), HÀC(4'), CH2(5')); 3.82 (m,
CH(Me)CH2); 2.66 (d, OHÀC(3')); 2.37( m, 1 HÀC(2')); 2.17( m, 1 HÀC(2')); 1.80 (2s, MeÀC(5)); 1.34 (d,
CH(Me)CH2). Anal. calc. for C20H22ClN3O9 (483.9): C 49.65, H 4.58, N 8.68; found: C 49.31, H 4.57, N 8.54.
Data of 183: TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.55. UV (MeOH): 207 (4.37), 263 (4.17), 331 (sh,
2.96). 1H-NMR (CDCl3): 8.31 (br., NH); 7.78 (dd, 1 arom. H); 7.40 (m, 2 arom. H, HÀC(6)); 6.12 (m, HÀC(1'));
5.23 (m, HÀC(3')); 4.38 (m, HÀC(4')); 4.24 4.11 (m, CH(Me)CH2); 3.84 (m, CH2(5'), CH(Me)CH2); 2.59
2.36 (m, OHÀC(5'), CH2(2')); 1.90 (s, MeÀC(5)); 1.36 (d, CH(Me)CH2). Anal. calc. for C20H22ClN3O9 (483.9):
C 49.65, H 4.58, N 8.68; found: C 49.58, H 4.70, N 8.02.

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Helvetica Chimica Acta Vol. 87(2004)
Data of 184: TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.79. UV (MeOH): 207(4.64), 262 (4.32), 327(sh,
3.34). 1H-NMR (CDCl3): 8.03 (br., NH); 7.76 (m, 2 arom. H); 7.37 (m, 4 arom. H); 7.26 (m, HÀC(6)); 6.32 (m,
HÀC(1')); 5.11 (m, HÀC(3')); 4.46 4.12 (m, 2 CH(Me)CH2, HÀC(4'), CH2(5')); 3.82 (m, 2 CH(Me)CH2);
2.46 (m, 1 HÀC(2')), 2.22 (m, 1 HÀC(2')); 1.80 (2s, MeÀC(5)); 1.36 (d, 2 CH(Me)CH2). Anal. calc. for
C30H30Cl2N4O13 (725.5): C 49.67, H 4.17, N 7.72; found: C 49.55, H 4.32, N 7.42.
107. Thymidine 5'-[2-(5-Bromo-2-nitrophenyl)propyl Carbonate] (128), 3'-[2-(5-Bromo-2-nitrophenyl)-
propyl Carbonate] (185), and 3',5'-Bis[2-(5-bromo-2-nitrophenyl)propyl Carbonate] (186). According to
Exper. 101 with 27: 0.39 g (74%) of 128, 16 mg (2%) of 185, and 98 mg (12%) of 186. Colorless foams.
Data of 128: TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.42. UV (MeOH): 205 (4.41), 265 (4.18), 337(sh,
2.95). 1H-NMR (CDCl3): 8.71 (br., NH); 7.65 (d, 1 arom. H); 7.57 (d, 1 arom. H); 7.51 (dd, 1 arom. H); 7.29 (s,
HÀC(6)); 6.31 (m, HÀC(1')); 4.28 4.11 (m, CH(Me)CH2 , HÀC(3'), HÀC(4'), CH2(5')); 3.80 (m,
CH(Me)CH2); 2.64 (br., OHÀC(3')); 2.37( m, 1 HÀC(2')); 2.05 (m, 1 HÀC(2')); 1.80 (2s, MeÀC(5)); 1.35
(d, CH(Me)CH2). Anal. calc. for C20H22BrN3O9 (528.3): C 45.47, H 4.20, N 7.95; found: C 45.09, H 4.14, N 7.54.
Data of 185: TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.54. UV (MeOH): 202 (4.36), 264 (4.18), 333 (sh,
3.02). 1H-NMR (CDCl3): 7.98 (br., NH); 7.69 (dd, 1 arom. H); 7.58 (d, 1 arom. H); 7.52 (dd, 1 arom. H); 7.38 (dd,
HÀC(6)); 6.12 (m, HÀC(1')); 5.23 (m, HÀC(3')); 4.38 (m, HÀC(4')); 4.24 4.10 (m, CH(Me)CH2); 3.91 3.74
(m, CH2(5'), CH(Me)CH2); 2.56 2.34 (m, CH2(2')); OHÀC(5') not visible; 1.91 (s, MeÀC(5)); 1.36 (d,
CH(Me)CH2). Anal. calc. for C20H22BrN3O9 (528.3): C 45.47, H 4.20, N 7.95; found: C 45.15, H 4.21, N 7.57.
Data of 186: TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.78. UV (MeOH): 202 (4.61), 216 (sh, 4.42), 263
(4.34), 333 (sh, 3.33). 1H-NMR (CDCl3): 8.12 (br., NH); 7.67 (m, 2 arom. H); 7.53 (m, 4 arom. H); 7.26 (m,
HÀC(6)); 6.33 (m, HÀC(1')); 5.11 (m, HÀC(3')); 4.46 4.11 (m, 2 CH(Me)CH2, HÀC(4'), CH2(5')); 3.79 (m, 2
CH(Me)CH2); 2.46 (m, 1 HÀC(2')); 2.22 (m, 1 HÀC(2')); 1.80 (2s, MeÀC(5)); 1.35 (d, 2 CH(Me)CH2); Anal.
calc. for C30H30Br2N4O13 (814.4): C 44.24, H 3.71, N 6.88; found: C 44.28, H 3.72, N 6.80.
108. Thymidine 5'-[2-(5-Iodo-2-nitrophenyl)propyl Carbonate] (129), 3'-[2-(5-Iodo-2-nitrophenyl)propyl
Carbonate] (187), and 3',5'-Bis[2-(5-iodo-2-nitrophenyl)propyl Carbonate] (188). According to Exper. 101, with
28: 0.42 g (73%) of 129, 17mg (3%) of 187, and 0.1 g (11%) of 188. Colorless foams.
Data of 129: TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.46. UV (MeOH): 204 (4.41), 267(4.16), 335 (sh,
3.19). 1H-NMR (CDCl3): 8.51 (br., NH); 7.74 (m, 2 arom. H); 7.47 (d, 1 arom. H); 7.29 (2s, HÀC(6)); 6.31 (m,
HÀC(1')); 4.46 4.10 (m, CH(Me)CH2, HÀC(3'), CH2(5'), HÀC(4')); 3.75 (m, CH(Me)CH2); 2.49 (br.,
OHÀC(3')); 2.37( m, 1 HÀC(2')); 2.18 (m, 1 HÀC(2')); 1.80 (2s, MeÀC(5)); 1.35 (d, CH(Me)CH2). Anal. calc.
for C20H22IN3O9 (575.3): C 41.76, H 3.85, N 7.30; found: C 41.46, H 3.88, N 7.18.
Data of 187: TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.53. UV (MeOH): 202 (4.49), 267(4.17), 333 (sh,
3.19). 1H-NMR (CDCl3): 7.78 (br., NH); 7.73 m( , 2 arom. H); 7.51 (dd, 1 arom. H); 7.39 (dd, HÀC(6)); 6.12 (m,
HÀC(1')); 5.23 (m, HÀC(3')); 4.36 (m, CH(Me)CH2); 4.20 (m, 1 H, CH(Me)CH2); 4.13 (m, HÀC(4')); 3.87
(m, CH2(5')); 3.74 (sext., CH(Me)CH2); 2.69 (br., OHÀC(5')); 2.56 2.39 (m, CH2(2')); 1.91 (s, MeÀC(5)); 1.35
(d, CH(Me)CH2). Anal. calc. for C20H22IN3O9 (575.3): C 41.76, H 3.85, N 7.30; found: C 42.22, H 3.85, N 7.20.
Data of 188: TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.84. UV (MeOH): 202 (4.69), 267(4.30), 333 (sh,
3.45). 1H-NMR (CDCl3): 8.26 (br., NH); 7.74 (m, 4 arom. H); 7.49 (m, 2 arom. H); 7.27 (m, HÀC(6)); 6.34 (m,
HÀC(1')); 5.12 (m, HÀC(3')); 4.45 4.10 (m, 2 CH(Me)CH2, HÀC(4'), CH2(5')); 3.75 (m, 2 CH(Me)CH2);
2.45 (m, 1 HÀC(2')); 2.24 (m, 1 HÀC(2')); 1.80 (2s, MeÀC(5)); 1.35 (d, 2 CH(Me)CH2). Anal. calc. for
C30H30I2N4O13 (908.4): C 39.67, H 3.33, N 6.17; found: C 39.61, H 3.39, N 5.99.
109. Thymidine 5'-[2-(2-Bromo-6-nitrophenyl)propyl Carbonate] (130). According to Exper. 101, with 30:
0.248 g (47%) of 130. Colorless foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.27. UV (MeOH): 203 (4.38),
1
208 (sh, 4.35), 263 (4.03), 342 (sh, 2.90). H-NMR (CDCl3): 8.28 (br., NH); 7.76 (dd, 1 arom. H); 7.47 (dd, 1
arom. H); 7.32 (s, HÀC(6)); 7.22 (m, HÀC(4)); 6.30 (t, HÀC(1')); 4.56 4.28 (m, CH(Me)CH2, HÀC(3'),
CH2(5')); 4.09 (m, HÀC(4')); 3.75 (m, CH(Me)CH2); 2.35 (m, 1 HÀC(2')); 2.25 (br., OHÀC(3')); 2.14 (m, 1
HÀC(2')); 1.80 (2s, MeÀC(5)); 1.35 (d, CH(Me)CH2). Anal. calc. for C20H22BrN3O9 (528.3): C 45.47, H 4.20,
N 7.95; found: C 45.21, H 4.21, N 7.48.
110. Thymidine 5'-[2-(2-Iodo-6-nitrophenyl)propyl Carbonate] (131) According to Exper. 101 with 31:
0.362 g (55%) of 131. Colorless foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.41. UV (MeOH): 203 (4.47),
227(sh, 4.17), 263 (4.06), 336 (sh, 2.80). 1H-NMR (CDCl3): 8.09 (dd, br. s, 1 arom. H, NH); 7.49 (dd, 1 arom. H);
7.32 (m, HÀC(6)); 7.06 (m, HÀC(4)); 6.30 (t, HÀC(1')); 4.54 4.28 (m, CH(Me)CH2, HÀC(3'), CH2(5')); 4.10
(m, HÀC(4')); 3.72 (m, CH(Me)CH2); 2.34 (m, 1 HÀC(2')); 2.15 (m, 1 HÀC(2')); 2.06 (br., OHÀC(3')); 1.80
(2s, MeÀC(5)); 1.39 (m, CH(Me)CH2). Anal. calc. for C20H22IN3O9 ¥ 0.5 H2O (584.3): C 41.11, H 3.97, N 7.19;
found: C 41.45, H 3.94, N 6.73.

Helvetica Chimica Acta Vol. 87(2004)
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111. Thymidine 5'-[2-(2,4-Dinitrophenyl)propyl Carbonate] (132), 3'-[2-(2,4-Dinitrophenyl)propyl Carbo-
nate] (189), and 3',5'-Bis[2-(2,4-dinitrophenyl)propyl Carbonate] (190). According to Exper. 101, with 32:
0.366 g (74%) of 132, 15 mg (3%) of 189, and 52 mg (7%) of 190. Colorless foams.
Data of 132: TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.43. UV (MeOH): 204 (4.39), 259 (4.29), 334 (sh,
2.81). 1H-NMR (CDCl3): 8.61 (m, NH, HÀC(3'')); 8.41 (dd, HÀC(5'')); 7.69 (d, HÀC(6'')); 7.25 (2s, HÀC(6));
6.26 (m, HÀC(1')); 4.49 4.05 (m, CH(Me)CH2, HÀC(3'), HÀC(4'), CH2(5')); 3.86 (sext., CH(Me)CH2); 2.53
(m, OHÀC(3')); 2.38 (m, 1 HÀC(2')); 2.16 (m, 1 HÀC(2')); 1.84 (2s, MeÀC(5)); 1.41 (m, CH(Me)CH2). Anal.
calc. for C20H22N4O11 (494.4): C 48.59, H 4.49, N 11.33; found: C 48.12, H 4.49, N 11.28.
Data of 189: TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.48. UV (MeOH): 206 (4.34), 259 (4.28), 327(sh,
2.73). 1H-NMR (CDCl3): 8.69 (br., NH); 8.65 (s, HÀC(3'')); 8.44 (d, HÀC(5'')); 7.72 (t, HÀC(6'')); 7.41 (2s,
HÀC(6)); 6.13 (t, HÀC(1')); 5.22 (m, HÀC(3')); 4.42 (m, 1 H, CH(Me)CH2); 4.26 (t, 1 H, CH(Me)CH2); 4.12
(m, HÀC(4')); 3.86 (m, CH2(5'), CH(Me)CH2); 2.63 (m, OHÀC(5')); 2.52 2.32 (m, CH2(2')); 1.89 (s,
MeÀC5)); 1.41 (d, CH(Me)CH2). Anal. calc. for C20H22N4O11 (494.4): C 48.59, H 4.49, N 11.33; found: C 48.35,
H 4.67, N 10.88.
Data of 190: TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.73. UV (MeOH): 204 (4.61), 254 (4.48), 324 (sh,
3.15). 1H-NMR (CDCl3): 8.62 (m, 2 HÀC(3'')); 8.54 (br., NH); 8.43 (m, 2 HÀC(5'')); 7.71 (m, 2 HÀC(6'')); 7.15
(s, HÀC(6)); 6.26 (m, HÀC(1')); 5.06 (m, HÀC(3')); 4.50 4.16 (m, 2 CH(Me)CH2, HÀC(4'), CH2(5')); 3.89
(m, 2 CH(Me)CH2); 2.42 (m, 1 HÀC(2')); 2.22 (m, 1 HÀC(2')); 1.84 (2s, MeÀC(5)); 1.42 (d, 2 CH(Me)CH2).
Anal. calc. for C30H30N6O17 (746.6): C 48.26, H 4.05, N 11.26; found: C 48.58, H 4.21, N 11.04.
112. Thymidine 5'-[2-(2,6-Dinitrophenyl)propyl Carbonate] (133), 3'-[2-(2,6-Dinitrophenyl)propyl Carbo-
nate] (191), and 3',5'-Bis[2-(2,6-dinitrophenyl)propyl Carbonate] (192). According to Exper. 101, with 33:
0.386 g (78%) of 133, 20 mg (4%) of 191, and 30 mg (4%) of 192. Colorless foams.
Data of 133: TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.44. UV (MeOH): 205 (4.40), 261 (4.03), 333 (sh,
2.81). 1H-NMR ((D6)DMSO): 11.31 (br., NH); 8.13 (d, HÀ(3''), HÀC(5'')); 7.77 (t, HÀC(4'')); 7.39 (2s,
HÀC(6)); 6.16 (m, HÀC(1')); 5.42 (d, OHÀC(3')); 4.42 4.18 (m, CH(Me)CH2, HÀC(3'), CH2(5')); 3.89 (m,
HÀC(4')); 3.47( m, CH(Me)CH2); 2.09 (m, CH2(2')); 1.71 (2s, MeÀC(5)); 1.28 (d, CH(Me)CH2). Anal. calc.
for C20H22N4O11 ¥ 1.5 H2O (521.4): C 46.07, H 4.83, N 10.74; found: C 46.14, H 4.46, N 10.74.
Data of 191: TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.49. UV (MeOH): 207(4.29), 261 (4.04), 324 (sh,
2.74). 1H-NMR (CDCl3): 8.23 (br., NH); 7.79 (d, HÀC(3''), HÀC(5'')); 7.58 (t, HÀC(4'')); 7.40 (2s, HÀC(6));
6.13 (t, HÀC(1')); 5.24 (m, HÀC(3')); 4.45 (m, CH(Me)CH2); 4.14 (m, HÀC(4')); 3.91 (m, CH2(5')); 3.62 (sext.,
CH(Me)CH2); 2.51 2.33 (m, OHÀC(5'), CH2(2')); 1.90 (s, MeÀC(5)); 1.39 (d, CH(Me)CH2). Anal. calc. for
C20H22N4O11 (494.4): C 48.59, H 4.49, N 11.33; found: C 48.55, H 4.66, N 10.93.
Data of 192: TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.72. UV (MeOH): 207 (4.56), 231 (sh, 4.27), 254
(sh, 4.17), 325 (sh, 3.05). 1H-NMR (CDCl3): 8.52 (br., NH); 7.78 (t, 2 HÀC(3''), 2 HÀC(5'')); 7.57 (m, 2
HÀC(4'')); 7.29 (2s, HÀC(6)); 6.32 (m, HÀC(1')); 5.13 (m, HÀC(3')); 4.64 4.21 (m, 2 CH(Me)CH2, HÀC(4'),
CH2(5')); 3.75 3.57 (m, 2 CH(Me)CH2); 2.46 (m, 1 HÀC(2')); 2.25 (m, 1 HÀC(2')); 1.80 (2s, MeÀC(5)); 1.35
(d, 2 CH(Me)CH2). Anal. calc. for C30H30N6O17 (746.6): C 48.26, H 4.05, N 11.26; found: C 48.35, H 4.15,
N 11.10.
113. Thymidine 5'-[2-(2,5-Dinitrophenyl)propyl Carbonate] (134). According to Exper. 101, with 34: 0.342 g
(68%) of 134. Colorless foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.34. UV (MeOH): 205 (4.47), 258
(4.26), 334 (sh, 3.02). 1H-NMR (CDCl3): 9.11 (br., NH); 8.33 (d, HÀC(6'')); 7.23 (m, HÀC(4'')); 7.87 (dd,
HÀC(3'')); 7.27 (s, HÀC(6)); 6.28 (m, HÀC(1')); 4.51 4.17( m, CH(Me)CH2, HÀC(3'), CH2(5')); 4.10 (m,
HÀC(4')); 3.74 (m, CH(Me)CH2); 3.03 (m, OHÀC(3')); 2.38 (m, 1 HÀC(2')); 2.17( m, 1 HÀC(2')); 1.79 (d,
MeÀC(5)); 1.43 (d, CH(Me)CH2). Anal. calc. for C20H22N4O11 ¥ 0.5 H2O (503.4): C 47.71, H 4.60, N 11.13;
found: C 48.08, H 4.67, N 11.01.
114. Thymidine 5'-[2-(3-Nitro[1,1'-biphenyl]-4-yl)propyl Carbonate] (135) and 3'-[2-(3-[1,1'-biphenyl]-4-
yl)propyl Carbonate (193). According to Exper. 101, with 57: 0.236 g (45%) of 135 and 32 mg (6%) of 193. Light
yellow foams.
Data of 135: TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.43. UV (MeOH): 205 (4.63), 250 (4.48), 313 (sh,
3.22). 1H-NMR (CDCl3): 8.43 (br., NH); 7.96 (d, arom. HÀC(2'')); 7.78 (dd, arom. HÀC(6'')); 7.59 7.36 (m, 6
arom. H); 7.29 (m, HÀC(6)); 6.29 (m, HÀC(1')); 4.48 4.18 (m, CH(Me)CH2, HÀC(3'), CH2(5')); 4.09 (m,
HÀC(4')); 3.79 (m, CH(Me)CH2); 2.34 (m, 1 HÀC(2')); 2.12 (m, 1 HÀC(2')); 1.94 (br., OHÀC(3')); 1.87, 1.77
(2s, MeÀC(5)); 1.38 (m, CH(Me)CH2). Anal. calc. for C26H27N3O9 (525.5): C 59.42, H 5.18, N 8.00; found:
C 59.11, H 5.22, N 7.87.
1
Data of 193: TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.51. H-NMR (CDCl3): 7.99 (d, arom. HÀC(2''));
7.96 (br., NH); 7.80 (d, arom. HÀC(6'')); 7.59 7.37 (m, 6 arom. H, HÀC(6)); 6.12 (t, HÀC(1')); 5.23 (m,