Rate Increase in Consecutive Nucleophilic Aromatic Substitution Reactions of Trichlorotrinitrobenzene: The Synthesis of 1-(Alkylamino)-3,5-dichloro-2,4,6-trinitrobenzenes

Article abstract of DOI:10.1021/jo980374z

The title compounds are formed by the nucleophilic aromatic substitution reaction between symtrichlorotrinitrobenzene and amines. The yields and relative rates of formation depend critically on the degree of alkylation of the nucleophile. Contrary to the usual behavior, the introduction of a second and third donor is facilitated in the case of ammonia and monoalkylamines, while this is not the case for secondary amines. This behavior is rationalized on the basis of intramolecular hydrogen bonding and substantiated by an X-ray analysis of 3,5-dichloro-2,4,6-trinitroaniline.

Full text of DOI:10.1021/jo980374z

5164
J . Org. Chem. 1998, 63, 5164-5168
Ra te In cr ea se in Con secu tive Nu cleop h ilic Ar om a tic Su bstitu tion
Rea ction s of Tr ich lor otr in itr oben zen e: Th e Syn th esis of
1-(Alk yla m in o)-3,5-d ich lor o-2,4,6-tr in itr oben zen es†
J . J ens Wolff,* Andreas Zietsch, Thomas Oeser, and Ion Bolocan‡
Organisch-Chemisches Institut der Universita¨t Heidelberg, Im Neuenheimer Feld 270,
D-69120 Heidelberg, Germany
Received February 27, 1998
The title compounds are formed by the nucleophilic aromatic substitution reaction between sym-
trichlorotrinitrobenzene and amines. The yields and relative rates of formation depend critically
on the degree of alkylation of the nucleophile. Contrary to the usual behavior, the introduction of
a second and third donor is facilitated in the case of ammonia and monoalkylamines, while this is
not the case for secondary amines. This behavior is rationalized on the basis of intramolecular
hydrogen bonding and substantiated by an X-ray analysis of 3,5-dichloro-2,4,6-trinitroaniline.
In tr od u ction
In the course of our work on 3-fold push-pull-
substituted arenes (1) as a new class of nonlinear-
optically active compounds,1-4 the study of their geomet-
ric and electronic structures,5,6 and their use as inter-
mediates for the construction of electron-rich hexaami-
nobenzene derivatives for electron-transfer studies,7,8 we
needed an easy access to substituted 1-amino-3,5-dichloro-
2,4,6-trinitrobenzenes (2). For example, their reaction
with an R,ω-diamine provides an easy access tos
otherwise strainedsmetacyclophanes (3) in unusually
high yields without the need of high-dilution conditions.7
It even proved possible to employ a similar, but 3-fold,
cyclization as a key step to give 4. Again, no high-
dilution conditions were necessary. Both 3 and 4 serve
as intermediates in the construction of bis-hexaami-
nobenzene cyclophanes, which are used to study electron-
transfer reactions.8 Compounds of type 2 are available
from the reaction of trihalogenotrinitrobenzene and
amines.9 By inspection of the different behavior observed
when 5 reacts with amines of different degrees of alky-
lation, we have noted an unusual increase in the con-
secutive SNAr reactions. These observations allow us to
rationalize our success in the syntheses of 3 and 4.
Resu lts a n d Discu ssion
If multiple nucleophilic aromatic substitution reac-
tions10-12 via Meisenheimer13,14 complexes are possible
with an electron-deficient arene, the rate of reaction is
expected to decrease with the introduction of each donor
substituent. For example, reaction of ammonia with 1,3-
dinitro-2,4,6-trifluorobenzene15 or tetrafluoro-1,3-dini-
trobenzene16 gives monosubstitution products in high
yields, and the Meisenheimer complex with methoxide
is 10 times more stable for 2,4-dinitroanisole than for 1,3-
dimethoxy-2,4-dinitrobenzene.17 We found that trinitro-
trichlorobenzene (5) does react with amines to form the
† Dedicated to Prof. Dr. Hermann Irngartinger on the occasion of
his 60th birthday.
‡ Permanent address: University of Ploies¸ti, Chemistry Department,
Bd. Bucures¸ti, 39, RO-2000 Ploies¸ti, Romania.
(1) Wortmann, R.; Glania, C.; Kra¨mer, P.; Matschiner, R.; Wolff, J .
J .; Kraft, S.; Treptow, B.; Barbu, E.; La¨ngle, D. Chem. Eur. J . 1997, 3,
1765-1773.
(2) Voigt-Martin, I. G.; Li, G.; Yakimanski, A.; Schulz, G.; Wolff, J .
J . J . Am. Chem. Soc. 1996, 118, 12830-12381.
(3) Voigt-Martin, I. G.; Gao, L.; Yakimanski, A.; Gross, H.; Wolff, J .
J . J . Phys. Chem. A 1997, 101, 7265-7276.
(10) Bunnett, J . F.; Zahler, R. E. Chem. Rev. 1951, 49, 273-412.
(11) Miller, J . Aromatic Nucleophilic Substitution; Elsevier: Am-
sterdam, 1968; Vol. 8.
(12) Terrier, F. Nucleophilic aromatic displacement: the influence
of the nitro group; VCH: New York, 1991.
(4) Zyss, J .; Ledoux, I. Chem. Rev. 1994, 94, 77-105.
(5) Wolff, J . J .; Nelsen, S. F.; Powell, D. R. J . Org. Chem. 1991, 56,
5908-5911.
(6) Wolff, J . J .; Irngartinger, H.; Gredel, F.; Bolocan, I. Chem. Ber.
1993, 126, 2127-2131.
(13) Terrier, F. Chem. Rev. 1982, 82, 77-152.
(14) Artamkina, G. A.; Egorov, M. P.; Beletskaya, I. P. Chem. Rev.
1982, 82, 427-459.
(7) Wolff, J . J .; Nelsen, S. F.; Powell, D. R.; Nuber, B. Angew. Chem.
1992, 104, 899-901; Angew. Chem., Int. Ed. Engl. 1992, 31, 882-884.
(8) Wolff, J . J .; Zietsch, A.; Irngartinger, H.; Oeser, T. Angew. Chem.
1997, 108, 637-639; Angew. Chem., Int. Ed. Engl. 1997, 36, 621-623.
(9) Koppes, W. M.; Lawrence, G. W.; Sitzmann, M. E.; Adolph, H.
G. J . Chem. Soc., Perkin Trans. 1 1981, 1815-1820.
(15) Sitzmann, M. E. J . Org. Chem. 1978, 43, 1241-1243.
(16) Burdon, J .; Fischer, D.; Parsons, I. W.; Tatlow, J . C. J . Fluorine
Chem. 1981, 18, 507-514.
(17) Crampton, M. R.; Ghariani, M. A. E.; Khan, H. A. J . Chem.
Soc., Perkin Trans. 2 1972, 1178-1182.
S0022-3263(98)00374-0 CCC: $15.00 © 1998 American Chemical Society
Published on Web 06/27/1998

Synthesis of 1-(Alkylamino)-3,5-dichloro-2,4,6-trinitrobenzenes
J . Org. Chem., Vol. 63, No. 15, 1998 5165
monosubstitution products 2, with the exception of the
very bulky dineopentylamine. However, the yields are
at least partiallysrestore a planar conformation.22 Then,
increased π conjugation should facilitate subsequent
substitutions. This should be especially pronounced for
ammonia, which is both the smallest amine nucleophile
and can form two intramolecular hydrogen bonds.23
Ammonia should therefore give the lowest yields of either
mono- or disubstitution products, which is borne out by
experiment. 2a is thus much more expeditiously syn-
thesized from 2d by cleavage of the tert-butyl group with
trifluoro acetic acid (cf. ref 9).
very different and depend on the degree of alkylation at
nitrogen. The reaction of secondary amines (6i-n ) is
easily stopped at the monosubstitution stage and thus
conforms to the expected behavior. Yields in the 60-
80% range are achieved even if 2 equiv of base is
employed. However, primary amines (6b-g) give only
yields around 15-20% even with limiting amounts of
nucleophile, regardless of whether an ancillary base like
Hu¨nig’s base (N-ethyldiisopropylamine) or sodium bicar-
bonate is employed. Only in the reaction to give the tert-
butyl derivative 2d is the yield higher. With ammonia,
the yield even drops to 2.6%; the bulk of the product
consists of starting material and triaminotrinitrobenzene
(1a ).
Conversely, the nitro groups in symmetrical trifluo-
rotrinitrobenzene 8 should suffer less from steric strain
(no structural data are available). This may contribute
to the known9,19 higher overall reactivity for 8 vs 5, as
evidenced also by its successful reaction with bis-neo-
pentylamine to give the monosubstitution product. More
importantly, the higher reactivity of 8 should also be
accompanied by a higher selectivity. Indeed, 8 reacts
with 4 (!) equiv of ammonia under otherwise comparable
conditions as 5 to give mono-, bis-, and tris-substitution
products in 47, 11, and 21% yields, respectively.9
To lend further proof to this rationalization, we have
performed an X-ray analysis of 2a .24 The ring is almost
planar, and there is significant bond length alternation
in the ring. The C-C bonds emanating from the C-NH2
[average: 1.404(4) Å] are longer than the remaining four
C-C [average: 1.378(4) Å] bonds in accordance with the
general behavior of o-nitroanilines.25,26 Although the
molecule shows 3-fold disorder in all of the oxygen
atoms,27 it is clear that the twist with respect to the ring
of the nitro groups in positions ortho to the amino group
is reduced in comparison to the overall twist in 5. While
one of the three positions available to each of them is
still quite twisted (by roughly 80°), the two remaining
positions are twisted by about (50-60°. We assume that
the most likely conformation of 2a has one of the o-nitro
groups rotated to achieve better hydrogen bonding with
the amino group and the other o-group is then twisted
more to relieve steric strain. Since rotation can be either
clockwise or counterclockwise, and on the left or right
nitro group, four conformations are possible that are
superimposed as a result of the X-ray analysis. In
accordance with this hypothesis, hydrogen positions could
not be located in contrast to the usual behavior in
hydrogen bonding between nitro and amino groups in the
ortho positions. The twist of substituents in 2a had been
estimated on the basis of its UV-vis spectrum.28 On the
basis of the X-ray structural data available then, the
We attempted to improve on these yields by use of the
hitherto unkown 1,3-dichloro-5-fluorotrinitrobenzene (7)
as substrate. Substrates with fluoride as a leaving group
are in general more reactive in SNAr reactions than those
with chloride because the nucleophilic attack to give a
Meisenheimer complex is rate limiting and facilitated by
the more electron-withdrawing halogen.10-12 For ex-
ample, picryl fluoride reacts about 200 times faster with
aniline than picryl chloride,18 and trifluorotrinitroben-
zene (8) is extremely sensitive to hydrolysis19 in contrast
to 5. However, reactions of 7 were tried with little
success. Already in the test reaction with dioctylamine,
which gives high yields of monosubstitution products, a
mixture of the possible two monosubstitution and two
disubstitution products results. To judge from the rela-
tive amounts of reaction products, the acceleration ef-
fected by F over Cl is less than 3-fold in this substrate.
All of these unexpected observations are readily ex-
plained by the structure of the starting material 5 in the
solid state:20 the bulky chloro substituents cause the close
to perpendicular orientation of the nitro substituents
with respect to the benzene ring. Hence, there is little π
conjugation of the nitro substituents with the ring.
Introduction of dialkylamines does not change this situ-
ation because the steric strain is not relieved, possibly
even increased. However, substituents that can hydro-
gen bond to the oxygen of a nitro group21 will replace a
repulsive interaction with an attractive one and thuss
(22) A planarizing effect of intramolecular hydrogen bonds has been
noted in the comparison of the crystal structures of picramide and its
N-methyl-, and N-ethyl-, and N,N-dimethyl derivatives: Butcher, R.
J .; Gilardi, R.; Flippen-Anderson, J . L.; George, C. New J . Chem. 1992,
16, 679-692.
(23) Note, however, that the steric bulk of an NH2 substituent as
probed by A values is higher than that of a Cl substituent. A values
read (in kcal‚mol-1): Cl, 0.53-0.64; NH2, 1.23; NHMe, 1.29; NMe2,
1.53; see: Eliel, E. L.; Wilen, S. H.; Mander, L. N. Stereochemistry of
Organic Compounds; Wiley: New York, 1994; p 696f.
(24) See the Supporting Information. The authors have also depos-
ited atomic coordinates for 2a with the Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK.
(25) Holden, J . R.; Dickinson, C. J . Phys. Chem. 1977, 81, 1505-
1514.
(18) Parker, R. E.; Read, T. O. J . Chem. Soc. 1962, 3149-3153.
(19) Shaw, G. C., III; Seaton, D. L. J . Org. Chem. 1961, 26, 5227-
5228.
(20) Gerard, F.; Hardy, A.; Becuwe, A. Acta Crystallogr., Sect. C
1993, 49, 1215-1218. Computations at the HF 6-31G* level also find
that nitrobenzene with the nitro group in the planar conformation is
more susceptible to attack by nucleophiles than with the nitro group
in the perpendicular conformation: Politzer, P.; Lane, P.; J ayasuriya,
K.; Domelsmith, L. N. J . Am. Chem. Soc. 1987, 109, 1899-1901.
(21) NH‚‚‚ON hydrogen bonds have been described as weaker as
comparable OH‚‚‚ON interactions. However, they are structure-
determining even in intermolecular cases; see, for example: Panunto,
T. W.; Urba`nczyk-Lipkowska, Z.; J ohnson, R.; Etter, M. C. J . Am.
Chem. Soc. 1987, 109, 7786-7797. For semiempirical computations
of their strength, see, for example: Vinson, L. K.; Dannenberg, J . J .
J . Am. Chem. Soc. 1989, 111, 2777-2781.
(26) Sadova, N. I.; Vilkov, L. V. Russ. Chem. Rev. 1982, 51, 87-
105.
(27) Cf. the disorder of nitro groups in the dipotassium salt of
trinitrophloroglucinol: Wolff, J . J .; Nelsen, S. F.; Powell, D. R.; Desper,
J . M. Chem. Ber. 1991, 124, 1727-1731.
(28) Kamlet, M. J .; Minesinger, R. R.; Hoffsommer, J . C.; Dacons,
J . C.; Adolph, H. G. J . Chem. Soc. B 1968, 1147-1153.

5166 J . Org. Chem., Vol. 63, No. 15, 1998
Ta ble 1. Yield s a n d Ch em ica l Sh ifts of NH P r oton s for 2
Wolff et al.
2a
2b
2ca
2d
2e
2f
2g
2h
2ia
2j
2k
2l
2m
2n
% yield
δNH
2.6
19
5.73
14
4.97
43
3.94
13-28
18
5.81
15
6.64
d
5.94
46
77
63
58
45
36
b
7.77c
7.26c
a
b
d
Reference 23. In CDCl3, unless noted otherwise. c DMSO-d6. By reaction of 2e with ethyl chloroformate.
acetamide, mp 151-153 °C from water; N-methyltrimethyl-
acetamide, mp 92-94 °C; 4,4-dimethylglutarimide, colorless
needles, mp 146-146.5 °C, first from 50% EtOH, then water).
2d and 2i were obtained as described previously.29
authors assumed a twist angle of 65-70° with respect
to the plane through the benzene ring for the nitro group
in the 4-position. They discussed several possibilities for
the twist of the remaining substituents and arrived at a
“best guess” of twist angles of 40-45° for the nitro groups
in the 2,6 positions. Neither of these estimations seems
to be confirmed for 2a in the solid state, with the
exception of the p-nitro group.
4,4-Dim eth ylp ip er id in e (6l): bp 140-142 °C, 76-78 °C
1
(150 mbar); 60% yield; H NMR (CDCl3) δ 0.83 (s, 6 H), 1.20
(m, 4 H), 1.24 (br s, 1 H), 2.68 (m, 4 H); 13C NMR (CDCl3) δ
28.44, 28.87, 39.79, 42.72. Meth yln eop en tyla m in e (6n ): bp
1
88-90 °C (lit.36 bp 88-90 °C); 52% yield; H NMR (CDCl3) δ
0.69 (br s, 1 H), 0.79 (s, 9 H), 2.19 (s, 2 H), 2.31 (s, 3 H); 13C
NMR (CDCl3) δ 27.65, 31.18, 37.49, 65.06. Bis(2,2-d im eth -
ylp r op yl)a m in e (d in eop en tyla m in e) (6o): bp 46-47 °C/
The reduced steric bulk of the unsubstituted amino
group and its capability to form two hydrogen bonds
should not only provide for a kinetic acceleration in SN-
Ar reactions but should also lead to a thermodynamic
stabilization. Thus, in reversible SNAr reactions, the
electronically weaker donor ammonia should be capable
of replacing the more strongly donating mono- and
especially dialkylamines. Such cases have been noted
before by us29 and also (without explanation) in the
reaction of tris[(3,5-dichloro-2,4,6-trinitrophenyl)amino]-
1,3,5-triazine with ammonia to give sym-trinitrotriami-
nobenzene.30 A related exchange for monoalkylamines
occurs in 1-(dialkylamino)-2,4-dinitronaphthalenes.31
In turn, the attractive effect of hydrogen bonding
should be annihilated if the steric bulk at the amino
nitrogen is increased. Preparatively, this is reflected by
the higher selectivity observed with tert-butylamine. Also,
the chemical shift for the NH proton of 2 in CDCl3 follows
closely the size of the alkyl substituent; it is shifted
considerably to higher field for the t-Bu derivative 2d .
Intramolecular hydrogen bonding is therefore weakest
in 2d (see Table 1).
Taken together, these observations allow us to explain
the success in the crucial cyclization steps leading to 3
and 47,8 because in both cases monoalkylamines are
employed as the reacting species. Thus, a type of “zipper
effect” is noted: as soon as the first amino site has
reacted, the reaction of the second one will be facilitated.
Therefore, the intramolecular cyclization becomes more
favored with respect to the intermolecular oligomeriza-
tion.
1
22 Torr (lit. bp37 153-154 °C); 71.6% yield (molar scale); H
NMR (CDCl3) δ 0.89 (br s, 1 H), 0.90 (s, 18 H), 2.33 (s, 4 H);
13C NMR (CDCl3) δ 27.82, 32.01, 63.61.
1,3-Dich lor o-5-flu or oben zen e.34 Diazonium tetrafluo-
roborate (189 mmol) (fm. diazotation of 200 mmol of 3,5-
dichloroaniline in aqueous HCl and subsequent precipitation)
on thermal decomposition and distillation after workup as
described gave 152 mmol (81.6% yield) of fluoro derivative:
bp 54 °C/20 Torr; 1H NMR (CDCl3) δ 7.01 (dd, J ) 1.7, 8.3 Hz,
2 H), 7.17 (dd, J ) 1.1, 1.6 Hz, 1 H); 13C NMR (CDCl3) δ 114.96
(d, J ) 24.6 Hz), 124.90 (d, J ) 3.6 Hz), 135.73 (d, J ) 11.5
Hz), 162.50 (d, J ) 252.6 Hz).
1,3-Dich lor o-5-flu or o-2,4,6-t r in it r ob en zen e (7). The
above fluorobenzene (8.38 g, 50.8 mmol) was nitrated in KNO3
(40.4 g) and 30% oleum (266.5 g) in analogy to the synthesis
of 5.33 The crude product after hydrolysis (12.93 g, mp 62-85
°C) was crystallized from CCl4 to give needles, mp 101-103
°C (4.532 g). An analytical sample was recrstallized twice, mp
101-102 °C. Workup of the mother liquors by addition of
pentane yielded a further crop: mp 98-101 °C (3.033 g, total
yield 7.565 g, 25.22 mmol, 49.6%); 1H NMR (CDCl3) no signal;
13C NMR (CDCl3) δ 123.75 (d, J ) 1.4 Hz), 138.12 (br d, J )
14.3 Hz), ca. 145.4 (br, obscured by following signal), 147.26
(d, J ) 277.5 Hz). Anal. Calcd for C6Cl2FN3O6 (299.99): C,
24.02; N, 14.01; Cl, 23.64. Found: C, 24.16; N, 13.80; Cl, 23.55.
Reaction with 1 equiv of Hu¨nig’s base and 1 equiv of dioctyl-
amine (6j) in toluene at 0 °C gave (after chromatography;
silica, 5% tolene in petroleum ether) 49.9% of 2j and 18.8% of
1-chloro-3-fluoro-5-(dioctylamino)-2,4,6-trinitrobenzene, along
with the disubstitution product 9 (4.7%) and a small amount
of 1-fluoro-3,5-bis(dioctylamino-2,4,6-trinitrobenzene). The
yield of 2j was not improved when the reaction was conducted
in dichloromethane at -85 to -10 °C.
1,3,5-Tr iflu or o-2,4,6-tr in itr oben zen e (8): mp 81.5-85.5
°C (CCl4); 13C NMR (CDCl3) δ 127.57 (br m), 149.90 (dt, J )
282.5, 3.7 Hz).
3,5-Dich lor o-2,4,6-tr in itr oa n ilin e (2a ). Meth od a . Pre-
cooled toluene solutions of 5 (2.919 g, 9.224 mmol, in 90 mL
solvent) and ammonia (6a ; 90 mL of a 0.205 M solution, 18.5
mmol) were mixed at -70 °C with stirring and then slowly
warmed to room temperature. The crude product (2.274 g)
Exp er im en ta l Section
Melting points: hotstage microscope, uncorrected. NMR
1
spectra: 300.133 MHz for H, 75.469 MHz for 13C, unless noted
otherwise. CAUTION: polyn itr o com pou n d s m a y be ex-
plosive! We h a ve n ot en cou n ter ed a n y violen t d ecom po-
sition with th e com pou n d s r epor ted h er e bu t a d vise th e
u se of specia l ca r e. Chemicals were obtained from com-
mercial sources with the exception of the following: 1,3,5-
tr ich lor o-32,33 and 1,3,5-tr iflu or o-2,4,6-tr in itr oben zen e (from
nitration of 1,3,5-trifluorobenzene, ref 19), 1,3-d ich lor o-5-
flu or oben zen e,34,35 N-m eth yl-n eop en tyla m in e (6n ),36 d i-
n eop en tyla m in e (6o),37 and 4,4-d im eth ylp ip er id in e38 (6l),
which were synthesized according to known procedures (amines
by LiAlH4 reduction of the corresponding amides: trimethyl-
(33) Hill, M. E.; Taylor, F., J r. J . Org. Chem. 1960, 25, 1037-1038.
Note: 266.5 g of oleum is required, not 266.5 mL, as written. The
formation of 1,2,3,5-tetrachloro-4,6-dinitrobenzene is minimal under
these conditions (ca. 2%; unpublished observations). For the kinetics
of this nitration process, see: Moodie, R. B.; Payne, M. A.; Schofield,
K. J . Chem. Soc., Perkin Trans. 2 1985, 1457-1464.
(34) Pavlath, A.; Ola´h, G. Acta Chim. Acad. Sci. Hung. 1956, 10,
227-232.
(29) Wolff, J . J .; Gredel, F.; Hillenbrand, D.; Irngartinger, H. Liebigs
Ann. Chem. 1996, 1175-1182.
(35) Cannoni de Degiorgi, A.; Zappi, E. V. Bull. Chim. Soc. Fr. 1938,
[5] 5, 1441-1446.
(30) Coburn, M. D. J . Heterocycl. Chem. 1966, 3, 365-366.
(31) Sekiguchi, S.; Suzuki, T.; Hosokawa, M. J . Chem. Soc., Perkin
Trans. 2 1989, 1783-1788.
(36) Pine, S. H.; Catto, B. A.; Yamaguchi, F. G. J . Org. Chem. 1970,
35, 3663-3666.
(37) Mosher, H. S.; Blanz, E. J ., J r. J . Org. Chem. 1957, 22, 445-
(32) Engelbertz, P. (Inv.), Chemische Fabrik Griesheim, D.R.P.
767510, 1936; Chem. Abstr. 1955, 49, 14803d.
446.
(38) Hoch, D.; Karrer, P. Helv. Chim. Acta 1954, 37, 397-402.

Synthesis of 1-(Alkylamino)-3,5-dichloro-2,4,6-trinitrobenzenes
J . Org. Chem., Vol. 63, No. 15, 1998 5167
mainly consisted of poorly soluble trinitrotriaminobenzene and
starting material. Chromatography (silica gel, chloroform)
gave 2a as a yellow powder (70 mg, 0.24 mmol, 2.6%) with
characterization as below. Meth od b. A mixture of trifluo-
roactic acid (5 mL), 2d (346 mg, 0.980 mmol), and dry
dichloromethane (10 mL) was kept at room temperature for
14 h. The mixture was diluted with CH2Cl2, washed with
water, saturated aqueous bicarbonate, and saturated brine,
and dried (Na2SO4). The solvent was evaporated and the
residue (290 mg, 0.976 mmol, 99%) recrystallized from n-
heptane/toluene to give yellow prisms (215 mg): mp 208-209
) 4.4 Hz, 1 H); 13C NMR (CDCl3) δ 45.20, 54.76, 101.46, 123.84,
136.65, 137.28, 138.88. Anal. Calcd for
C10H10Cl2N4O8
(385.12): C, 31.19; H, 2.62; N, 14.55; Cl, 18.41. Found: C,
31.37; H, 2.67; N, 14.36; Cl, 18.28.
1,3-Dich lor o-5-[(3,3-d ieth oxyp r op yl)a m in o]-2,4,6-tr in i-
tr oben zen e (2 g) was obtained from 5 and 2 equiv of
3-aminopropanal diethyl acetal (6g) in toluene first at -10 °C
and then at rt. Chromatography (silica, petroleum ether/ethyl
acetate ) 5/1) gave a yellow powder: mp 108-110 °C; 1H NMR
(CDCl3) δ 1.22 (t, J ) 7.1 Hz, 6 H), 1.87 (m, 2 H), 3.22 (m, 2
H), 3.50 (dq, J ) 9.4, 7.0 Hz), 2 H), 3.68 (dq, J ) 9.4, 7.1 Hz,
1
°C; H NMR (DMSO-d6) δ 7.77 (br s); 13C NMR (DMSO-d6) δ
2 H), 4.59 (t, J ) 4.2 Hz, 1 H), 6.64 (br t, J ) 4.1 Hz, 1 H); 13
C
122.36, 134.94, 135.26, 136.94. Anal. Calcd for C6H2Cl2N4O6
(297.01): C, 24.26; H, 0.68; N, 18.86, Cl, 23.87. Found: C,
24.35; H, 0.89; N, 19.00; Cl, 23.85.
NMR (CDCl3) δ 15.04, 32.46, 39.40, 63.28, 102.29, 123.36,
136.04, 136.26, 137.38. Anal. Calcd for 13H16Cl2N4O8
C
(427.20): C, 36.55; H, 3.78; N, 13.12; Cl, 16.60. Found: C,
36.73; H, 3.80; N, 13.04; Cl, 16.54.
1,3-Dich lor o-5-[(2,2-d im eth ylp r op yl)a m in o]-2,4,6-tr in i-
tr oben zen e (2b) was obtained at room temperature from a
solution of 5 (7.12 g, 22.5 mmol) in toluene (60 mL) and a
solution of 2,2-dimethylpropylamine (6b; 1.92 g, 22.5 mmol)
in the same solvent (120 mL). Chromatography (silica, PE/
toluene ) 7/3) and recrystallization from isooctane gave bright
yellow needles (1.51 g, 4.11 mmol, 18.3%): mp 178-179 °C;
1H NMR (CDCl3) δ 0.93 (s, 9 H), 2.82 (d, J ) 5.0 Hz, 2 H),
5.73 (br t, J = 5 Hz, 1 H); 13C NMR (CDCl3) δ 26.82, 31.88,
1,3-Dich lor o-5-(dioctylam in o)-2,4,6-tr in itr oben zen e (2j).
Solutions of 5 (1.869 g, 5.906 mmol) and dioctylamine (6j; 2.852
g, 11.81 mmol) in CH2Cl2 (50 + 50 mL) were combined at -70
°C, and the bath was slowly warmed; the reaction began at
-40 °C. The mixture was kept at -10 °C for 2 h and then
worked up as before. Chromatography (silica, PE/toluene )
95/5) gave a yellow-orange oil (2.369 g, 4.543 mmol, 76.9%).
The disubstitution product (yellow-orange oil, 326 mg, 0.421
mmol, 7.1%) was also isolated and characterized (see below):
1H NMR (CDCl3) δ 0.88 (pseudo-t, J ) 6.7 Hz, 6 H), 1.26 (m,
20 H), 1.48 (pseudo-p, J ) 6.9 Hz, 4 H), 2.98 (m, 4 H); 13C
NMR (CDCl3) δ 14.00, 22.58, 26.65, 28.03, 29.11, 29.13, 31.70,
55.21, 124.35, 136.52, 137.02, 138.47. Anal. Calcd for C11H12
-
Cl2N4O6 (367.14): C, 35.99; H, 3.29; N, 15.26; Cl, 19.31.
Found: C, 35.92; H, 3.37; N, 15.09; Cl, 19.25.
1,3-Dich lor o-5-[(1,1-d im et h ylet h yl)a m in o]-2,4,6-t r in i-
tr oben zen e (2d ) was obtained at -10 °C from a solution of 5
(7.00 g, 22.1 mmol) in toluene (300 mL) and a solution of tert-
butylamine (6d ; 3.23 g, 44.2 mmol) in the same solvent (100
mL). Filtration and chromatography (silica, PE/toluene ) 7/3),
followed by recrystallization from isooctane, gave pale yellow
52.72, 122.24, 140.01, 142.98, 146.68. Anal. Calcd for C22H34
-
Cl2N4O6 (521.44): C, 50.68; H, 6.57; N, 10.74; Cl, 13.60.
Found: C, 50.82; H, 6.33; N, 10.65; Cl, 13.74.
1-Ch lor o-3,5-bis(dioctylam in o)-2,4,6-tr in itr oben zen e (9):
1H NMR (CDCl3) δ 0.87 (pseudo-t, J ) 6.7 Hz, 12 H), 1.26 (m,
40 H), 1.42 (pseudo-p, J ) 6.9 Hz, 8 H), 2.91 (m, 8 H); 13C
NMR (CDCl3) δ 14.03, 22.60, 26.78, 28.36,29.17, 29.22, 31.75,
1
sheets (3.38 g, 9.57 mmol, 43.3%): mp 126-127 °C; H NMR
(CDCl3) δ 1.18 (s, 9 H), 3.94 (s, 1 H); 13C NMR (CDCl3) δ 30.62,
50.58, 122.08, 135.95, 143.43, 145.86. Anal. Calcd for C10H9-
Cl2N4O6 (353.11): C, 34.01; H, 2.85; N, 15.87; Cl, 20.08.
Found: C, 34.12; H, 2.89; N, 15.76; Cl, 20.10.
53.35, 121.53, 139.97, 144.82, 148.94. Anal. Calcd for C38H68
-
ClN5O6 (726.45): C, 62.83; H, 9.44; N, 9.64. Found: C, 63.13;
H, 9.51; N, 9.65.
1,3-Dich lor o-5-[(2-h yd r oxye t h yl)a m in o]-2,4,6-t r in i-
tr oben zen e (2e) was obtained at room temperature from
1,3-Dich lor o-5-piper idin o-2,4,6-tr in itr oben zen e (2k) was
obtained at -10 °C from a solution of 5 (14.0 g, 44.2 mmol) in
toluene (110 mL) and a solution of piperidine (6k ; 10.0 g, 88.3
mmol) in the same solvent (110 mL). Filtration and then
crystallization from isooctane gave yellow flakes (10.15 g, 27.80
mmol, 62.9%): mp 194-195 °C; 1H NMR (270 MHz, CDCl3) δ
1.58 (br m, 6 H), 3.06 (br m, 4 H); 13C NMR (68 MHz, CDCl3)
δ 23.16, 25.80, 52.10, 122.19, 140.58, 142.89, 145.93. Anal.
Calcd for C11H10Cl2N4O6 (365.13): C, 36.18; H, 2.76; N, 15.34;
Cl, 19.42. Found: C, 36.36; H, 2.82; N, 15.24; Cl, 19.67.
1,3-Dich lor o-5-(4,4-d im e t h ylp ip e r id in o)-2,4,6-t r in i-
tr oben zen e (2l) was obtained at -10 °C from a solution
of 5 (14.0 g, 44.2 mmol) in toluene (110 mL) and a solution
of 4,4-dimethylpiperidine (6l; 10.0 g, 88.3 mmol) in the
same solvent (110 mL). Filtration and then chromatography
(silica gel, ethyl acetate/PE ) 1/8) gave yellow prisms (10.15
g, 25.8 mmol, 58.4%): mp 160-162 °C; 1H NMR (CDCl3)
δ 0.94 (s, 6 H), 1.38 (m, 4 H), 3.05 (m, 4 H); 13C NMR
(CDCl3) δ 27.61, 28.18, 38.42, 47.76, 122.22, 140.60, 142.97,
146.06. Anal. Calcd for C13H14Cl2N4O6 (393.19): C, 39.71;
H, 3.59; N, 14.25; Cl, 18.03. Found: C, 39.89; H, 3.59;
N, 13.99; Cl, 18.00.
1,3-Dich lor o-5-[(2,2-d im eth oxyeth yl)-N-m eth yla m in o]-
2,4,6-tr in itr oben zen e (2m ) was obtained in analogy to the
synthesis of 2f from 5 (7.00 g, 22.1 mmol), (N-methylamino)-
acetaldehyde dimethyl acetal (6m ; 2.91 g, 22.5 mmol) and
Hu¨nig’s base (3.17 g, 10.0 mmol): yellow prisms; mp 68-69
°C (9.92 mmol, 45%; based on recovered starting material,
82%); starting material was also recovered (3.17 g, 10.0 mmol);
1H NMR (CDCl3) δ 2.89 (s, 3 H), 3.01 (d, J ) 5.2 Hz, 2 H),
3.31 (s, 6 H), 4.34 (t, J ) 5.3 Hz, 1 H); 13C NMR (CDCl3) δ
42.17, 54.30, 56.26, 102.67, 122.27, 140.63, 143.63, 146.73.
Anal. Calcd for C11H12Cl2N4O8 (399.15): C, 33.10; H, 3.03; N,
14.04; Cl, 17.76. Found: C, 33.18; H, 3.15; N, 13.97; Cl, 17.79.
1,3-Dich lor o-5-[N-m eth yl(2,2-d im eth ylp r op yl)a m in o]-
2,4,6-tr in itr oben zen e (2n ) was obtained at room tempera-
ture from a solution of 5 (5.11 g, 16.1 mmol) in toluene (100
a
solution of 5 (18.4 g, 58.2 mmol) in dichloromethane
(100 mL) at room temperature and a solution of ethanol-
amine (6e; 4.50 g, 73.8 mmol) in the same solvent (50 mL).
Filtration after 30 min and chromatography (silica, CH2Cl2)
gave a light yellow powder (2.57 g, 7.54 mmol, 28% of starting
material consumed) and recovered 5 (10.02 g, 31.67 mmol):
1H NMR (DMSO-d6) δ 3.00 (p, J ) 5.5 Hz, 2 H), 3.47 (t, J )
5.7 Hz, 2 H), 4.64 (br s, 1 H), 7.26 (br t, J ) 5.3 Hz, 1 H); 13C
NMR (DMSO-d6) δ 46.14, 59.17, 122.81, 136.26, 136.54, 137.04.
Anal. Calcd for C8H6Cl2N4O7 (341.07): C, 28.17; H, 1.77; N,
16.43; Cl, 20.79. Found: C, 28.18; H, 1.79; N, 16.45; Cl, 20.72.
1,3-Dich lor o-5-[[2-[(eth oxyca r bon yl)oxy]eth yl]a m in o]-
2,4,6-tr in itr oben zen e (2h ). Reaction of 2e with 1.9 equiv
of ethyl chloroformate and 2.3 equiv of pyridine in dichlo-
romethane, chromatography (silica, CH2Cl2), followed by crys-
tallization from cyclohexane gave fine yellow needles of 2h :
1
mp 90-92 °C; 90% yield; H NMR (CDCl3) δ 1.29 (t, J ) 7.2
Hz, 3 H), 3.36 (br m, 2H), 4.20 (q, J ) 7.2 Hz, 2 H), 4.27 (br t,
J ) 4.8 Hz, 2 H), 5.92 (br t, J ) 4.6 Hz, 1 H); 13C NMR (CDCl3)
δ 14.11, 43.83, 65.06, 65.10, 123.76, 135.85, 137.11, 138.98,
155.58. Anal. Calcd for C11H10N4O9Cl2 (413.13): C, 31.98; H,
2.44; N, 13.56; Cl, 17.16. Found: C, 31.96; H, 2.46; N, 13.52;
Cl, 17.07.
1,3-Dich lor o-5-[(2,2-d im eth oxyeth yl)a m in o]-2,4,6-tr in i-
tr oben zen e (2f). A solution of aminoacetaldehyde dimethyl
acetal (6f; 1.79 g, 17.0 mmol) and Hu¨nig’s base (2.20 g, 17.0
mmol) in dry toluene (60 mL) was added dropwise within 90
min to a stirred solution of 5 (5.00 g, 15.8 mmol) in the same
solvent (140 mL) at -15 °C. The yellow mixture was left in
the bath without further cooling and stirred overnight. The
hydrochloride was filtered, the solvent evaporated, and the
yellow residue chromatographed (silica, cyclohexane/ethyl
acetate ) 5/1) to give light yellow prisms: mp 105-106 °C
1
(1.10 g, 2.86 mmol, 18%); H NMR (CDCl3) δ 3.15 (t, J ) 4.9
Hz, 2 H), 3.37 (s, 6 H), 4.40 (t, J ) 4.7 Hz, 1 H), 5.81 (br t, J

5168 J . Org. Chem., Vol. 63, No. 15, 1998
Wolff et al.
mL) and a solution of (2,2-dimethylpropyl)methylamine (6n ;
3.26 g, 32.3 mmol) in the same solvent (120 mL). Repeated
crystallizaton from isooctane gave yellow needles (2.22 g, 5.82
mmol, 36.2%), mp 114-116 °C. More material was contained
in the mother liquors: 1H NMR (CDCl3) δ 0.87 (s, 9 H), 2.71
(s, 2 H), 2.99 (s, 3 H); 13C NMR (CDCl3) δ 27.64, 34.83, 46.50,
66.86, 122.55, 142.29, 143.41 (br), 146.66 (br). Anal. Calcd
for C12H14Cl2N4O6 (381.17): C, 37.81; H, 3.70; N, 14.70; Cl,
18.60. Found: C, 37.88; H, 3.71; N, 14.63; Cl, 18.72.
probably because of the excessive broadening known for this
type of resonance (and also detected in other members of 2
here). Anal. Calcd for C16H22F2N4O6 (404.37): C, 47.52; H,
5.48; N, 13.86. Found: C, 47.67; H, 5.71; N, 14.03.
Ack n ow led gm en t. This work was supported by
Deutsche Forschungsgemeinschaft and Fonds der Che-
mischen Industrie.
1-Bis[(2,2-d im et h ylp r op yl)a m in o]-3,5-d iflu or o-2,4,6-
tr in itr oben zen e (10) was obtained from bis(neopentyl)amine
(6o; 1.553 g, 9.873 mmol) and trifluorotrinitrobenzene (1.318
g, 4.935 mmol) in dry THF; 9 days at room temperature. Rapid
filtration over neutral alumina and recrystallization from
isooctane gave dull-orange plates: mp 209-210.5 °C (920 mg,
Su p p or tin g In for m a tion Ava ila ble: X-ray structure
determination summary for 2a and lists of coordinates, aniso-
tropic displacement factors, bond lengths, bond angles, and
torsional angles (6 pages). This material is contained in
libraries on microfiche, immediately follows this article in the
microfilm version of the journal, and can be ordered from the
ACS; see any current masthead page for ordering information.
1
2.28 mmol, 46.1%); H NMR (CDCl3) δ 0.91 (s, 18 H), 3.03 (s,
4 H); 13C NMR (CDCl3) δ 27.24, 36.99, 66.66, 131.38 (br d, J
) 15.8 Hz), 141.19 (t, J ) 3.4 Hz), 150.93 (dd, J ) 4.9, 275.7
Hz). The expected triplet for C-NO2 could not be detected,
J O980374Z