Chlorination of aniline and methyl carbanilate by N-chlorosuccinimide and synthesis of 1,3,5-trichlorobenzene

Article abstract of DOI:10.1080/00397910802499542

Aniline undergoes regioselective trichlorination by N-chlorosuccinimide (NCS) in acetonitrile in good yield. The product 2,4,6-trichoroaniline was converted into 1,3,5-trichlorobenzene by reduction of its diazonium salt. Reaction of the methyl carbamate of aniline with NCS gave only the 2,4-dichlorophenyl carbamate. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802499542

This article was downloaded by: [Pennsylvania State University]
On: 10 June 2012, At: 22:52
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic
Organic Chemistry
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
Chlorination of Aniline
and Methyl Carbanilate
by N-Chlorosuccinimide
and Synthesis of 1,3,5-
Trichlorobenzene
Matthew C. Davis a
a Chemistry and Materials Division, Michelson
Laboratory, Naval Air Warfare Center, China Lake,
California, USA
Available online: 25 Feb 2009
To cite this article: Matthew C. Davis (2009): Chlorination of Aniline and Methyl
Carbanilate by N-Chlorosuccinimide and Synthesis of 1,3,5-Trichlorobenzene,
Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 39:6, 1100-1108
To link to this article: http://dx.doi.org/10.1080/00397910802499542
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-
and-conditions
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,

sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden.
The publisher does not give any warranty express or implied or make any
representation that the contents will be complete or accurate or up to
date. The accuracy of any instructions, formulae, and drug doses should be
independently verified with primary sources. The publisher shall not be liable
for any loss, actions, claims, proceedings, demand, or costs or damages
whatsoever or howsoever caused arising directly or indirectly in connection
with or arising out of the use of this material.

Synthetic Communications1, 39: 1100–1108, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802499542
Chlorination of Aniline and Methyl Carbanilate
by N-Chlorosuccinimide and Synthesis
of 1,3,5-Trichlorobenzene
Matthew C. Davis
Chemistry and Materials Division, Michelson Laboratory, Naval Air
Warfare Center, China Lake, California, USA
Abstract: Aniline undergoes regioselective trichlorination by N-chlorosuccini-
mide (NCS) in acetonitrile in good yield. The product 2,4,6-trichoroaniline was
converted into 1,3,5-trichlorobenzene by reduction of its diazonium salt. Reaction
of the methyl carbamate of aniline with NCS gave only the 2,4-dichlorophenyl
carbamate.
Keywords: Aniline, N-chlorosuccinimide, chlorination, diazonium
The synthesis of 2,4,6-trichloroaniline (1) has almost[1] invariably been
accomplished by chlorination of aniline with chlorine[2–9] or sulfuryl
chloride.[7,10,11] Although the latter reactions typically provide 1 in high
yield, these reagents require special handling because of their highly
corrosive nature. In addition, chlorine and, especially, sulfur dioxide
emissions must be strictly controlled.[12]
More convenient reagents for aromatic chlorinations are N-chloro
reagents such as N-chlorosuccinimide (NCS). The chlorination of aniline
and substituted anilines with N-chloro reagents, including NCS, has been
studied.[13–15] The main concern was determining the ortho=para
regioselectivity of monochlorination. However, it was hinted that further
chlorination was possible as small amounts of 2,4-dichloroaniline
Received August 5, 2008.
Address correspondence to Matthew C. Davis, Chemistry and Materials
Division, Michelson Laboratory, Naval Air warefare Center, China Lake, CA
93555. E-mail: matthew.davis@navy.mil
1100

Chlorination of Aniline
1101
impurity had also formed.[15,16] Further literature study found that
4-bromoaniline and 3,5-difluoro-4-iodoaniline had been shown to undergo
dichlorination at the 2,6-position in chloroform with NCS or N-chloro-2,4-
dichloroacetanilide.[17,18] Thus, it appeared aniline might undergo
trichlorination with N-chloro reagents under the appropriate conditions.
Initial conditions for the trichlorination of aniline were based on the
recent work of Manka and Kaszynski.[18] Treating aniline with 3 equiva-
lents of NCS in chloroform in the presence of 1 equivalent of trifluoroa-
cetic acid gave 1 by thin-layer chromatographic (TLC) analysis. The
other major component of the mixture was 2,4-dichloroaniline. This
partial success was hampered by the fact that the reaction was dark
purple, presumably from oxidation; no isolation of the products was
attempted.
Nickson and Roche-Dolson studied the reaction of NCS upon deac-
tivated anilines.[19] They found that acetonitrile was the solvent of choice
for monochlorination of, for example, 2- or 4-nitroaniline. It seemed rea-
sonable to assume that both 4-chloroaniline and 2,4-dichloroaniline
might also behave as deactivated anilines. Reacting these two compounds
with NCS (1 and 2 equivalents, respectively) in refluxing acetonitrile both
gave 1. Subsequently, aniline was treated in the same way with 3 equiva-
lents NCS and, remarkably, 1 was isolated in 88% yield (Scheme 1).
Pouring the reaction mixture into water caused precipitation of crude 1
as a purple solid, while the by-product succinimide was washed away.
Crude 1 was readily purified by treatment with charcoal followed by
filtration through silica gel.
During preparations of larger batches of 1 by this procedure, it was
discovered that addition of the third equivalent of NCS is accompanied
by a strong exotherm. The solution adopted was to check the reaction
by proton nuclear magnetic resonance and TLC after the second equiva-
lent of NCS had been added. Typically, after 1 h of reflux, the formation
of 2,4-dichloroaniline was complete, the heating was shut off, and the last
equivalent of NCS was added portionwise to control the exotherm.
Scheme 1. Reagents and conditions: a) N-chlorosuccinimide, MeCN, reflux.

1102
M. C. Davis
Scheme 2. Reagents and conditions: a) MeOH, reflux; b) N-chlorosuccinimide,
MeCN, reflux.
A cheap and more efficient substitute for NCS is trichloroisocyanuric
acid (TCICA).[20] Juenge et al. obtained a low yield of 2- and 4-chloro-
anilines from reaction of TCICA with aniline in carbon tetrachloride.[21]
Preliminary experiments showed that 1 is formed by reaction of aniline
with TCICA in acetonitrile. The reaction was conducted at 0 ꢀC but was
accompanied by a much greater degree of colored by-product formation
than with NCS.
It was believed that the free amine of aniline and=or its reaction pro-
ducts undergoes oxidation to colored by-products. The methyl carbamate
of aniline (2) was synthesized from phenyl isocyanate and methanol.
Refluxing 2 with NCS in acetonitrile was essentially a colorless reaction
(Scheme 2). But even with 5 equivalents of NCS, chlorination only went
as far as methyl 2,4-dichlorophenylcarbamate (3). Apparently, carbamate
is more reactive than amide, as Zanka and Kubota[22] only isolated
4-chlorophenylacetamide when acetanilide was reacted with 3 to 5
equivalents NCS in 2-propanol.
In the study by Manka and Kaszynski,[18] they sought to prepare
2,6-dichloro-3,5-difluoro-4-iodoaniline by chlorination of 3,5-difluoro-
4-iodoaniline (4). Chlorination of the latter with 2 equivalents of
NCS in refluxing acetonitrile gave the unreported mono-chlorinated
product (5) (Scheme 3). Further study of conditions (longer reaction
time, more NCS) that might provide the dichlorinated product was not
pursued.
The deamination of 1 to prepare 1,3,5-trichlorobenzene (6) was
investigated.[23–27] The recent conditions of Mehilal et al.[9] were used
with slight modification (Scheme 4). After diazotization of 1 in aqueous
sulfuric acid, hexanes were added, making a two-phase reaction mixture.
This solved the problem of foaming, because nitrogen is generated during
the addition of the reducing solution, as well as dissolving 1, as it preci-
pitated from the acid phase. In addition, it was found that aqueous

Chlorination of Aniline
1103
Scheme 3. Reagents and conditions: a) N-iodosuccinimide, MeCN; b) N-chloro-
succinimide, MeCN, reflux.
sodium hypophosphite was a suitable replacement for aqueous hypo-
phorus acid in the reduction step. The yield of the deamination was 97%.
In conclusion, 2,4,6-trichloroaniline (1) can be synthesized readily from
aniline and N-chlorosuccinimide. This reaction, coupled with the facile
diazotization=deamination sequence, makes a convenient laboratory
preparation of 1,3,5-trichlorobenzene (6).
EXPERIMENTAL
The melting points were collected on an electrothermal capillary melting-
point apparatus and are not corrected. All NMR data were collected on a
Bruker Avance II 300-MHz spectrometer (1H at 300 MHz, 13C at
75 MHz, 19F at 282 MHz). NMR data (free induction decays) were
processed using NUTS software from Acorn NMR (Livermore, CA).
1
All H, 13C, and 19F spectra are referenced to solvent, tetramethylsilane
or fluorotrichloromethane. Aniline 99.5% ACS reagent, N-chlorosuccini-
mide (NCS) 98%, N-iodosuccinimide (NCI), acetonitrile (MeCN) 99.5%
ACS reagent, phenyl isocyanate 98%, and sodium hypophosphite hydrate
were purchased from Sigma-Aldrich (Milwaukee). Silica gel (32–63 mm,
˚
60 A) was purchased from Scientific Adsorbents Inc. (Atlanta). All other
reagents were obtained commercially and used as received. Elemental
analyses were made by Atlantic Microlab, Inc. (Norcross, GA).
Scheme 4. Reagents and conditions: a) 1. 70% H2SO4, NaNO2, 0 ꢀC; b) 2.
hexanes, NaH2PO2, H2O, 0 ꢀC to rt.

1104
M. C. Davis
2,4,6-Trichloroaniline (1)
A 5-L, two-necked, round-bottomed flask equipped with magnetic stirbar
was charged with 50 g freshly distilled aniline (0.54 mol) in 1 L MeCN.
One neck was equipped with a reflux condenser and N2 purge, and the
second neck was glass stoppered. The solution was brought to reflux.
N-Chlorosuccimide (86 g, 1 equiv) was added through the glass-stoppered
neck in one portion. The color of the reaction became purple-brown.
After 1 h, a second addition of 86 g NCS (1 equiv) was made in one por-
tion After 1 h, NMR of the reaction mixture showed only traces of NCS
remained in addition to formation of primarily 2,4-dichloroaniline. The
final addition of 86 g NCS (1 equiv) was made in eight ꢁ10-g portions,
as the reaction occurs with a vigorous exotherm. After the addition,
TLC showed the reaction was complete. The mixture was cooled to rt
and poured into 3 L vigorously stirred H2O. After stirring 1 h, the light
purple solid was collected on a coarse-porosity glass frit, washed with
1 L H2O, and air-dried on the frit for 2 h. The crude was dissolved in
1 L Et2O and washed with 500 mL H2O and 500 mL brine. The organic
layer was dried with anhydrous MgSO4 and filtered. The filtrate was
treated with 11 g Darco G-60 for 1 h. The mixture was filtered through
diatomaceous earth, and the solvent was rotary evaporated. The
red-brown solid was dissolved in 1 L hexanes. The solution was filtered
through 300 g SiO2 on a medium-porosity glass frit that removed most
of the color. The filtrates were rotary evaporated, leaving 111.6 g of the
title compound as a pale yellow solid that was >97% by 1H NMR
(88%). Recrystallization from EtOH gave the title compound in analyti-
cally pure form as soft, colorless needles. Mp 68–70 ꢀC [lit.[4] 77.5 ꢀC].
dH (CDCl3): 7.13 (s, 2H), 4.36 (bs, NH2); dC (CDCl3): 139.24, 127.81,
122.06, 119.92. Elemental analysis calculated for C6H4Cl3N: C, 36.68;
H, 2.05; N, 7.13. Found: C, 36.87; H, 1.93; N, 7.07.
Methyl Phenylcarbamate (2)
A 100-mL, round-bottomed flask equipped with magnetic stirbar was
charged with 50 mL anhydrous MeOH. With vigorous stirring, 5 g phe-
nyl isocyanate (0.04 mol) was added in one portion. The mixture was
refluxed for 30 min, and the solvent was rotary evaporated. The remain-
ing colorless liquid spontaneously crystallized. The colorless crystals
were slurried with 20 mL hexanes and filtered (6.1 g, 97%). Mp
37–39 ꢀC [lit.[28] 47 ꢀC]. dH (CDCl3): 7.45–7.36 (m, 2H), 7.36–7.26 (t,
J ¼ 7.4 Hz, 2H), 7.07 (t, J ¼ 7.4 Hz, 1H), 6.82 (bs, NH), 3.78 (s, 3H);
dC (CDCl3): 154.33, 138.08, 129.21, 123.64, 118.99, 52.48. Elemental

Chlorination of Aniline
1105
analysis calculated for C8H9NO2: C, 63.56; H, 6.00; N, 9.27. Found: C,
63.46; H, 6.01; N, 9.28.
Methyl 2,4-Dichlorophenylcarbamate (3)
A 100-mL, round-bottomed flask equipped with magnetic stirbar was
charged with 1.51g 2 (0.01 mol), 6.65g NCS (0.05 mol, 5 equiv), and
20mL MeCN. The mixture was refluxed for 12h. After cooling, the mixture
was poured into 250 mL 5% Na2SO3, and a solid precipitated. The solid was
filtered on a coarse-porosity glass frit and washed well with water. After air
drying, the crude was recrystallized from hexanes to give the title compound
as colorless needles (1.8g, 82%). Mp 58–62 ꢀC. dH (CDCl3): 8.12 (d,
J ¼ 8.9 Hz, 1H), 7.35 (d, J ¼ 2.2 Hz, 1H), 7.24 (dd, J ¼ 8.9 and 2.4 Hz,
1H), 7.09 (bs, NH), 3.80 (s, 3H); dC (CDCl3): 153.67, 133.72, 128.92,
128.39, 128.12, 122.70, 120.81, 52.88. Elemental analysis calculated for
C8H7Cl2NO2: C, 43.66; H, 3.21; N, 6.37. Found: C, 43.84; H, 3.09; N, 6.32.
3,5-Difluoro-4-iodoaniline (4)
A 100-mL, round-bottomed flask equipped with magnetic stirbar was
charged with 2.43g 3,5-difluoroaniline (18.8 mmol) in 30mL MeCN. The
mixture was cooled in an ice bath, and 4.24g NIS (18.8 mmol, 1 equiv) were
added all at once. The cooling bath was removed, and the mixture was stir-
red at rt for 30min. After this time, TLC showed the reaction was complete.
The mixture was poured into a mixture of 200 mg Na2SO3 dissolved in
200 mL H2O. The mixture was extracted twice with 50-mL portions of
Et2O. The organic phases were collected and washed with 50mL H2O fol-
lowed by 50mL brine. After drying with anhydrous MgSO4, the solvent
was evaporated, leaving 4.3 g of a tan solid (89%). The title compound
was obtained as colorless needles by recrystallization from heptane. Mp
104–106 ꢀC (lit.[29] 112–114 ꢀC). dH (CDCl3): 6.26 (d, J ¼ 8.1 Hz, 1H), 3.95
1
3
(bs, NH2); dC (CDCl3): 163.36 (dd, JCF ¼ 243 Hz and JCF ¼ 8.7 Hz),
3
2
4
149.46 (t, JCF ¼ 13.0 Hz), 98.51 (dd, JCF ¼ 28.1 and JCF ¼ 2.4 Hz),
2
55.18 (t, JCF ¼ 30.3 Hz). Elemental analysis calculated for C6H4F2IN: C,
28.26; H, 1.58; N, 5.49. Found: C, 28.10; H, 1.42; N, 5.44.
2-Chloro-3,5-difluoro-4-iodoaniline (5)
A 100-mL, round-bottomed flask equipped with magnetic stirbar was
charged with 2.43 g 4 (16.9 mmol), 4.5 g NCS (33.7 mmol, 2 equiv), and

1106
M. C. Davis
50 mL MeCN. The mixture was refluxed for 18 h, then poured into a mix-
ture of 1 g Na2SO3 dissolved in 200 mL H2O. The mixture was extracted
twice with 50-mL portions of Et2O. The organic phases were collected
and washed with 50 mL H2O followed by 50 mL brine. After drying with
anhydrous MgSO4, the solvent was evaporated, leaving 4.46 g of a tan
solid. The title compound was obtained as clear tan needles by recrystal-
lization from heptane (2.36 g, 48%). Mp 67–70 ꢀC. dH (CDCl3): 6.39 (dd,
3JHF ¼ 9.2 Hz and 5JHF ¼ 1.9 Hz, 1H), 4.37 (bs, NH2); dC (CDCl3): 161.21
(dd, 1JCF ¼ 243.7 Hz and 3JCF ¼ 8.1 Hz), 158.59 (dd, 1JCF ¼ 243.7 Hz and
3
3
3JCF ¼ 8.8 Hz), 145.50 (dd, JCF ¼ 13.0 Hz and JCF ¼ 4.4 Hz), 102.46
2
4
3
(dd, JCF ¼ 23.0 Hz and JCF ¼ 4.0 Hz), 97.97 (dd, JCF ¼ 29.0 Hz and
4JCF ¼ 2.7 Hz), 55.35 (dd, JCF ¼ 32.7 Hz and JCF ¼ 30.4 Hz); dF
2
2
5
4
(CDCl3): ꢂ92.92 (t, JFH and JFF ¼ 2.0 Hz, 5-F), ꢂ96.07 (dd,
3JFH ¼ 9.3 Hz and JFF ¼ 3.1 Hz, 3-F). Elemental analysis calculated
4
for C6H3ClF2IN: C, 24.90; H, 1.04; N, 4.84. Found: C, 25.10; H, 1.09;
N, 4.88.
1,3,5-Trichlorobenzene (6)
A 500-mL, round-bottomed flask equipped with magnetic stirbar was
charged with 55 mL 70% H2SO4 and stirred, then 11 g 1 (0.056 mol)
were added portionwise. After all the solid was added, the mixture
was allowed to stir until all the solids dissolved, forming an orange
solution. The mixture was then placed in an ice bath to stir, and a
solution of 7.7 g NaNO2 (0.112 mol, 2 equiv) in 11 mL H2O was added
dropwise over 30 min. After the addition, the mixture was stirred for
15 min. Cold hexanes were added to prevent foaming and to dissolve
the product. An aqueous solution of sodium hypophosphite was added
dropwise. The evolution of N2 occurred shortly afterward. The color
gradually changed from orange to colorless. After stirring for
30 min, the ice bath was removed, and the mixture was stirred at rt
for several hours. The phases were split, and the aqueous layer was
further extracted with hexanes. The combined extracts were washed
with H2O, saturated NaHCO3, and then brine. After drying over
MgSO4 and filtration, the filtrate was filtered through SiO2 to remove
the color. The colorless filtrates were rotary evaporated, leaving the
crude product as a white solid. The entire mixture was poured onto
250 mL H2O, and the solids were collected on a coarse-porosity glass
frit and washed with copious H2O. After air drying on the frit, the
crude solid weighed 8.5 g (84%). Mp 57–60 ꢀC [lit.[9] 62 ꢀC] dH (CDCl3):
7.28; dC (CDCl3): 135.79, 127.45. Elemental analysis calculated for
C6H3Cl3: C, 39.72; H, 1.67. Found: C, 39.97; H, 1.68.

Chlorination of Aniline
1107
ACKNOWLEDGMENTS
The financial support of Timothy I. Mahoney (NAWCWD Pilot Plant)
is gratefully acknowledged. Thanks to Juanita K. Morton (NAWCWD)
for assistance in purchasing the hypophosporous acid. Thanks to Ann
M. Moorehead, Cynthia M. Kitchens, and the staff of the NAWC
Technical Library (China Lake) for obtaining Ref. 9.
REFERENCES
1. Muathen, H. A. Oxidative halogenation of aromatic compounds with metal
halides and sodium bismuthate. Helv. Chim. Acta. 2003, 86, 164–168.
2. Hofmann, A. W. Metamorphosen des indigo’s: Erzeugung organischer basen,
welche chlor und brom enthalten. Ann. 1845, 53, 1–57.
3. Meyer, V.; Sudborough, J. J. Weiteres uber die esterbildung aromatischer
¨
sa¨uren. Ber. 1894, 27, 3146–3153.
4. Sudborough, J. J. Chlorination of aniline. J. Chem. Soc. 1894, 65, 1028–1031.
5. Chattaway, F. D.; Irving, H. 2:4:6-Trichloroaniline. J. Chem. Soc. 1933,
142–143.
6. Orloff, H. D.; Napolitano, J. P. Preparation of 2,4,6-trichloroaniline. U.S.
Patent 2,675,409, Apr. 13, 1954.
7. Werner, F.; Roxo, B.; Mannes, K.; Trescher, V. Process for the preparation
of 2,4,6-trichloroaniline. U.S. Patent 4,447,647, May 8, 1984.
8. Kim, C.-U.; Jin, H.-J.; Lee, S.-B.; Lee, J.-M. A study on the synthesis of 2,4,6-
trichloroaniline by chlorination of aniline. Hwahak Konghak 1990, 28, 230–236.
9. Mehilal; Salunke, R. B.; Agrawal, J. P. A newly developed synthesis of 1,3,5-
trichlorobenzene (syn. TCB) from aniline. Indian J. Chem., Sect. B. 2002, 41,
604–607.
10. Wengho¨ffer, L. Ueber das verhalten von sulfurylchlorid und aethylschwefel-
sa¨urechlorid gegen anilin und anilide. J. Prakt. Chem. 1877, 16, 448–466.
¨
11. Eller, W.; Klemm, L. Uber die einwirkung von sulfurylchlorid auf aroma-
tische amine. Ber. 1922, 55, 217–224.
12. U.S. Clean Air Act. Public Law 101–549, 1990.
13. Chao, T. H.; Cipriani, L. P. The chlorination of N,N-dimethylaniline. J. Org.
Chem. 1961, 26, 1079–1081.
14. Searle, N. E.; Cupery, H. E. Synthesis of carbon-14 labeled 3-(p-chlorophe-
nyl)-1,1-dimethylurea. J. Org. Chem. 1954, 19, 1622–1627.
15. Neale, R. S.; Schepers, R. G.; Walsh, M. R. The chlorinations of reactive
anilines. J. Org. Chem. 1964, 29, 3390–3393.
16. Lindsay Smith, J. R.; McKeer, L. C.; Taylor, J. M. Highly selective aromatic
chlorinations, part 2: The chlorination of substituted phenols, anisoles,
anilines, and related compounds with N-chloroamines in acidic solution.
J. Chem. Soc. Perkin Trans. 2, 1988, 2, 385–391.
17. Reed, W. W.; Orton, K. J. P. The wandering of bromines in the chlorination
of bromoanilines. J. Chem. Soc. 1907, 91, 1543–1554.

1108
M. C. Davis
18. Manka, J. T.; Kaszynski, P. Synthesis and thiolation of 1,3-difluoro-2,4,6-
trihaloanilines and benzenes. J. Flourine Chem. 2003, 124, 39–43.
19. Nickson, T. E.; Roche-Dolson, C. A. A convenient procedure for the
chlorination of deactivated anilines. Synthesis 1985, 669–670.
20. Tilstam, U.; Weinmann, H. Trichloroisocyanuric acid: A safe and efficient
oxidant. Org. Process Res. Dev. 2002, 6, 384–393.
21. Juenge, E. C.; Beal, D. A.; Duncan, W. P. Chlorination of aromatic systems
with trichloroisocyanuric acid under polar and free-radical conditions. J. Org.
Chem. 1970, 35, 719–722.
22. Zanka, A.; Kubota, A. Practical and efficient chlorination of deactivated
anilines and anilides with NCS in 2-propanol. Synlett 1999, 1984–1986.
23. Jackson, C. L.; Lamar, W. R. On certain derivatives of trichlorodinitroben-
zol. Am. Chem. J. 1896, 18, 664–685.
24. Doyle, M. P.; Dellaria, J. F. Jr.: Siegfried, B.; Bishop, S. W. Reductive
deamination of arylamines by alkyl nitrites in N,N-dimethylformamide: A
direct conversion of arylamines to aromatic hydrocarbons. J. Org. Chem.
1977, 42, 3494–3498.
25. Lahoti, R. J.; Parameswaran, V.; Wagle, D. R. Reduction of aryldiazonium
salts to arenes. Indian J. Chem., Sect. B 1981, 20, 767–769.
26. Wassmundt, F. W.; Kiesman, W. F. Efficient catalysis of hydrodediazonia-
tions in dimethylformamide. J. Org. Chem. 1995, 60, 1713–1719.
27. Mitsuhashi, H.; Kawakami, T.; Suzuki, H. A mild one-pot deamination of
aromatic amines bearing electron-withdrawing groups: Calcium hypopho-
sphite as a dediazonation reagent in nonaqueous media. Tetrahedron Lett.
2000, 41, 5567–5569.
28. Hentschel, W. Ueberfuhrung von carbanilsa¨urea¨ther in amidobenzoe¨sa¨ure.
¨
Ber. 1885, 18, 977–981.
29. Tomcufcik, A. S.; Seeger, D. R. The synthesis of the 30-fluoro and 30,50-
difluoro derivatives of 4-amino-4-deoxy-N10-methylpteroylglutamic acid
(methotrexate). J. Org. Chem. 1961, 26, 3351–3356.