Interesting similarities have been shown between the reactions of sym-trinitrobenzene with cycloalkanones, and with phloroglucinol. Previously unsuspected common intermediates have been shown to intervene. The structurally similar products in each case are tricyclic nitropropene nitronates. Protonation of these yields the corresponding nitronic acids in certain instances

Shindo, H.

Strauss, M. J.

Taylor, S. P. B.

English

NASA Technical Reports Server

''
,: ,
'Condensation Cyclization Reactions of Electron Deficient Aromatics.
IV. Tricyclic Nitropropene Nitronates from the Reaction of
Phloroglucinol and Cycloalkanones with sym-Trinitrobenzene.
Michael J. Strauss and Stephan P. B. Taylor
• •Department of Chemistry
University of Vermont
Burlington, VT 05401
and
H. Shindo
JEOL Inc.
Cranford, NJ 07016
Interesting similarities have been shown between the
reactions of syn-trinitrobenzene with cycloalkanones,
and with phloroglucinol. Previously unsuspected common
intermediates have been shown to intervene. The struc-
turally similar products in each case are tricyclic
nitropropene nitronates. Protonation of these yields
the corresponding nitronic acids in certain instances.
Fl
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V<V..
https://ntrs.nasa.gov/search.jsp?R=19730011432 2020-03-23T02:52:30+00:00Z
The reaction of simple acyclic ke tones with electron deficient aro-
oatics in the presence of secondary amines, has been shown to yield an
12interesting new type of bicyclic anion, 1. ' Acidification of such species
^^
1) M. J., Strauss and H. Schran, J. Org. Chem., 36, 856 (1971).
2) M. J. Strauss, T. C. Jensen, H. Schran, and R. 0' Conner, J. Org. Chem..
35, 383 (1970).
(X » NO,) many times gives a polymeric material, making it difficult to
characterize the previously unreported nitropropene nitronic acids which
night be expected to result. Because acidification of an alkaline mixture
of phloroglucinol and sym-trinitrobenzene (TNB) was reported to yield a
, Et2NH2 Hi
neutral compound, ^2, which closely resembles the type of compound which
34
'might be expected from the acidification of ^ (X and because
3) T. Severin, Chem. Ber't . £0, 2898 (1957).
4) T. Severin and M. Bohn, Chem. Ber. , 1.00., 211 (1967).
phloroglucinol can formally be considered a cyclic triketone which could
- ' ' ' \ \ ' • • .
12
condense with TNB in a manner analogous to simple ketones, ' it was of •
Interest to study the reaction of monocycllc ketones with TNB. The symmetry
of the anticipated products, 3 or 4. was expected to simplify pmr structural
&^ r^
analysis (previously made difficult by possible configurational isomerism
at C-4 and C-5 of 1), and we supposed that the rigid tricyclic structure of
^^
3^ if formed, might be favorable for intramolecular cycllzation to a struc-
ture analogous to 2. In addition, it was of interest to reinvestigate the
^^ ^
reaction of phloroglucinol and TNB to see whether the anionic precursor to
2 could be isolated.
NO-,
3a (n » 2)
3b. (n = 3)
3c (n - 4)
We report here some interesting and previously unsuspected similarities
between the phloroglucinol and simple cyclic ketone reactions, as well as a
structural and chemical characterization of the tricyclic nitropropene
nltronates 3b, 3c, and 9, as well as the protonated forms (nitronic acids)
of 3£ and^ . These latter nitronic acids are the first examples of protonated
1 2
nitropropene nitronates in the bicyclic series ' to be characterized, and
\\
their properties relative to the nitronic acids, -6, formed from protonation
^^ ^
of 2,4,6-trinitrocyclohexadienate sigma complexes, 5, are of considerable
^^ 0^  . •
Interest. . • ' , . - •
5) C. Moberg and 0. Wennerstrom, Acta. Chemica Scand., 25, 2355 (1971).
— -^ "^"^  ^^
H
Addition of excess diethylamine to a solution of THE in an excess of
cyclohexanone, results in an exothermic reaction which yields an intensely
colored solution. The visible spectrum of this mixture exhibits the double
naxltna characteristic of anionic sigma complexes, ^ . -The double maxima
6) M. J. Strauss, Chem. Rev., 70, 667 (1970).
rapidly disappears as a single new maxim vim develops at 500 run, character-
istic of the nitropropene nitronate function of^l_(X » S02). Isosbestic
points are observed at 470 and 570 run. On standing for 24 hr at ambient
temperature, crystals of product precipitate from solution. Recrystal-
llzation (see Experimental) yields bright red crystals, op 225°C, which
analyze correctly for a 1:1:1 adduct of amine,TNB, and cyclohexanone. The
100 MHz pmr spectrum and ir spectrum of this product when compared with pinr
1 2 6
and ir spectra of bicyclic anions formed from acyclic ketones and TNB, ' '
provide substantial evidence for structure 3b. An alternate structure in
which the C-6 keto bridge is cis to the C-3 CHN02 bridge is ruled out by
the J. _ (J, ,) coupling constant of 2.5 cps. The H-l - H-5 (H-2 - H-4)i,j *,«»
dihedral angle in 3b results in the observed value of .2.5 cps whereas that
in a structure like ^ would be about 8 cps. This result is not unexpected,
since ^  (n • 3) should be less thenaodynamically stable.
The configuration of C-3 in 3b cannot be unambiguously established.
We have provided some evidence that H-3 in ^ (X » NO., R =• H) is directed
7 127towards the keto bridge. In a series of anions like j^, ' ' the chemical
.7) M. J. Strauss and H. Schran, Tetrahedron Lett., 2349 (1971).
shift of H-3 is always between 5.0 and 5.95, whereas in 3b it is 6.26. The
f
direction of this shift is not directly explicable.
The structure of ,3b, coupled with the previously proposed mechanism of
secondary amine-acyclic ketone condensations with TNB, and the spectral
changes occurring in the TNB-diethylamine-cyclohexanone reaction mixture
(see Experimental), allow us to propose a reasonable mechanistic route to
the tricyclic product through the enamine sigma complex Jftj. This latter
type of complex likely forms from in situ generated enamine and TNB. Our
recently reported kinetic study of a related sequence involving tertiary
amines supports the intermediacy of tricyclic structures like 8.
^^
\
(CH2)
7a (n - 2)
7b (n - 3)
*^
7c (n = 4)
N(CH2CH3)2
jBa (n • 2)
8b (n «= 3)
8c (n - 4)
3c
The reaction of cycloheptanone with TNB and dlethylamine yielded the
tricyclic anion 3^ c. The reaction proceeded less rapidly than with cyclo-
hexanone, and purification of the product by column chromatography was
necessary. The pmr spectrum was essentially identical to that for JJb,
except for the added upfield methylene absorptions. The stereochemistry
of the bridge cannot unambiguously be established as the H-l and H-5 (H-2
and H-4) protons are not well resolved, and the J. _ (J_ ,) coupling constant
JL,j *t't
could not be determined.
\\
When an analogous reaction was attempted with cyclopentanone, the corres-
ponding tricyclic anion 3a could not be isolated. Although a small absorp-
\^^ *
tion at 500 nm (characteristic of the nitropropene nitronate function ln£)
was apparent in the visible spectrum of the reaction mixture, its rate of
development was several orders of magnitude less than that which developed
during formation of 3b. TLC of the cyclopentanone reaction mixture provided
evidence for several products. These exhibited double maxima in their
visible spectra, and are probably anionic sigma complexes formed by attack
of in situ generated enamine, cyclopentanoate anion, and diethylamine on
TNB. It seems apparent that cyclization of jja is unfavorable relative to
cyclization of 7b, and that the reaction terminates at the sigma complex
stage. Drieding models clearly show the distance between C-3 (C-5) and C-6
in 7a is almost 50% greater than in^Tb, when both intermediates are in the
most favorable conformation for intramolecular cyclization. This results
primarily from the rigidity of the cyclopentene ring in JTa.
It is interesting to note that Severin has reported the tetracyclic
structure^, which closely resembles^3, as resulting from acidification of
4
an alkaline solution of phloroglucinol and TNB. Since tautomeric ketpnic
structures can be written for phloroglucinol, the possibility for a mechan-
istic route to the anionic precursor of 2^ proceeding through anionic sigma
complex intermediates seems likely. We have reacted equivalent amounts of
phloroglucinol and TNB in DMSO solution with excess diethylamine. The same
visible spectral behavior of the reaction mixture is observed as in the
reactions leading to 3^ and JJc, except that the changes occur at a much more
rapid rate. After several minutes, the spectrum of the reaction mixture
consists of a single maximum at 500 nm, characteristic of the nitropropene
V
- _ • - . . ; . . . . . . • : - 8
f ' . • ' •
nitronate function. A red powder can be obtained upon workup of the reaction
mixture (Experimental). This material contains a minimum of five compounds
(TLC). Attempts at isolating pure products by chromatographic methods were
unsuccessful. A similar diversity of products has been shown to arise from
8the reaction of diethylamine, acetone, and TNB. The reaction was then
8) R. Foster and C. A. Fyfe, Tetrahedron, 22. 1831 (1966).
carried out with triethylamine, since we supposed the acidity of phloro-
glucinol would be sufficient so that a carbanionic mechanism for nitronate
formation could occur. It is known that for nonacidic ketones, i.e., acetone,
diethylketone, and cyclohexanone, secondary amines must be employed to effect
condensation-cyclization reactions with electron deficient aromatics through
9 10
enamine and immonium intermediates. ' For more acidic ketones, i.e., acetyl-
9) M. J. Strauss and H. Schran, J. Amer. Chem. Soc., J91, 3974 (1969).
10) M. J. Strauss and H. Schran, J. Org. Chem.. JJ£, 856 (1971).
acetone or dibenzyIketone, tertiary amines will effect such reactions through
carbanionic rather than enamine intermediates. The reaction of phloroglucinol,
triethylamine, and TNB gave good yields of a single product which analyzed
correctly for a 1:2:1 adduct.of phloroglucinol, amine, and TNB. The pmr
spectrum of this adduct is in accord with structure 9. The J. , coupling
*»*• 1,3
constant is less than 3 cps. Structure JQ, should be much less stable due
to repulsion of the two charge delocalized functions. Structure J^ .could
V;
N02
quite possibly be a precursor to the tetracyclic structure^ , isolated by
Severin upon treating a mixture of TNB, potassium hydroxide, and phloroglucinol
4
with 60% sulfuric acid. Formation of the tetra-anion 11 as an unstable
OH"
9 >
11
H1
N02
intermediate preceding protonation is quite reasonable, since the structurally
similar and isolable tetra-anion 12 has previously been characterized.
^^ ^^ *
11) K. Kohasi, Y. Ohkura, and T. Momose, Chem. Pharm. Bull. Japan, 19, 213
(1971).
\
10
NC
, 4
All our attempts to isolate ^ 2. by basificatlon followed by acidification of
9 were unsuccessful. A variety of different procedures were attempted (see
Experimental).
. Although we have previously had some difficulty in Isolating the nitronic
acids of the bicyclic nitropropene anions ^ , we thought it essential to do
so in the case of the structurally symmetric 3b. in order to compare the pmr
spectral properties of the anion with those of the acid and^ g.. After many
failures we found that by very carefully acidifying a methanol solution of
3b with concentrated HC1 at 15°, crystals of the nitronic acid 14^were formed
after 24 hours. These analyzed correctly for the expected acid and were
N02H
14
Et2NH
MeOH, HC1
readily converted back to the crystalline salt 3b_ by treatment with diethyl-
amlne. The pmr spectrum of 14 and 3b are quite similar, except for a few
significant changes. Since the olefinic proton is a sharp singlet in^ l4,
protonation must have occurred on nitronate oxygen. There are no absorptions
for the triethylammonium cation. The strong carbonyl band at 1710 cm in
the infrared spectrum of 14^ appears at the same frequency as that in^3b, clearly
showing that cyclization to a structure analogous to^has not occurred.
By a similar acidification of J^ with methanolic HC1 solution (anhydrous)
yellow crystals of an acidic compound were obtained. The pmr, ir, and
elemental analysis of this material provide evidence for structure^13. The
olefinic proton Ha in 13 remains a sharp singlet, and is unshifted from its
HoO
. 0
NO-
corresponding position in^ . This is not unexpected since removal of charge
12from nitronate oxygen only slightly affects electron density at this site.
12) M. J. Strauss and S. P. B. Taylor, J. Org. Chem., JJ6, 3059 (1971).
•\\
• - • • • ' . / . . ' . - • - . • • . ' 1 2
The ammonium absorptions of J^ are absent from the spectrum of 13, and the
triplet from the craJ02 proton on the one carbon bridge in the latter is
unshifted from that in 9. In aqueous solution 13 readily dissociates to
anionic species containing the nitropropene nitronate function with absorp-
tion maxima at 500 nm. "
The mechanistic details of these protic equilibria are presently the
subject of extensive investigation, and the scope of the phloroglucinol
reaction is being extended to a variety of other electron deficient aromatics.
Experimental Section
f^ fS**^ *****************'** i>^ «^ *M
All melting points are uncorrected. Ir and uv spectra were recorded
with Perkin-Elmer Model 21 and Model 402 spectrophotometers, respectively.
Pmr spectra were recorded with JEOL MH-100 and PS-100 spectrometers, and
chemical shifts are reported with respect to internal tetramethylsilane.
Elemental analyses were performed by G. I. Robertson Laboratory, Florham
Park, New Jersey.
«. • • •" •
Rcfetion qf_^gy_clohgxggqrie^_gigitliylaming, and,TNB.— Sym-TNB (2.0g, .094
mol) was dissolved in a minimum amount of cyclohexanone at 40°. Diethylamine
(2 ml) was then added, and the resulting exothermic reaction was cooled in
a water bath at 15° (caution should be exercised with large scale preparations)
After standing for 24 hrs, crystalline product is sometimes deposited from
the reaction solution. If no crystals are deposited the reaction mixture
can be washed with anhydrous diethyl ether until a red powder is obtained.
Recrystallization from a 1:2 methanol-ether mixture yields red crystals of
3b, mp 225-226°. These analyzed correctly for a 1:1:1 adduct.
•\\
13
Anal. Calcd for C^ H^ N^ : C, 50.11; H, 6.30; N, 14.61. Found: .
C, 50.27; H, 6.42; N, 14.80.
A methanolic solution of 3b shows intense absorption at 510 nm,
characteristic of the nitropropene nitronate function.
Since 3b is the first tricyclic nitropropene nitronate isolated, and
since its symmetry allows a detailed interpretation of the pmr spectrum, a
complete analysis of the latter is included here (DMSO-dg).
, Et2HH2
3b
Proton
Ha
HO
Hc -
Hd
He, Hf
Hg, Hh
cation
Chemical Shifts (6) and Splittings
1H (t, J - 2.5 cps) 6.30; irrad HC (s)
IB (s) 8.21 . • • •
2H (m) 4.30; irrad H<j or Hc (d, J'S'2.5 cps)
2H (m) 2.58; irrad Hc (sharp m)
4H (m) 2.2
1H (m) 1.8; 1H (m) 1.35
6H (t) '1.1; 4H (q) 3.0; 2H (br) 6.6
14
The ir spectrum of 3b (KBr) shows absorptions at 2860, 1730, 1550, 1460,
^^ V-
1378, 1265, 880, 778, and 753 cm"1.
Protonatjlgq _of ^3b.— A saturated solution of 3b in methanol at 25° was
- flushed with dry nitrogen and cooled to 10°. Concentrated HC1 was then added
until the orange color of 3b disappeared. Cooling the resulting yellow solu-
^^* . •" - .
tion for 24 hrs at 10°C resulted in the formation of yellow needles of the
••-••
nitronic acid 14, mp 165°. -
Anal. Calcd for C12H13N30?: C, 46.35; H, 4.22; H, 13.50. Found:
C, 46.10; H, 4.27; N, 13.42.
Addition of diethylamine to 14 yields a red powder, which when recrystal-
lized from methanol-ether solution gave red crystals of 3b, mp 226°, with
spectral properties identical to those of the originally prepared anion. In
all hydrolylic solventsi JLA dissociates to yield solutions having an intense
absorption at 510 nm. --
The pmr spectrum of 14 (acetone-^ ) is quite similar to J3b, except for
the absence of the cationic absorptions in the latter; 6 7.86 (CH=CNO_H, s),
6 6.42 (CHN02, t), 6 4.55 (NO^ H, s, exchange rapid with H20 present in small
quantities), 6.4.40 (2H, bridgehead a to N02, m), 6 2.71 (2H, bridgehead a
to carbonyl, m), 6 2.41 (411, methylene, m), and 6 1.70 (2t[, methylene, m).
The ir (KBr) of 14 shows absorptions at 1725, 1647, 1610, 1558, 1525, 1315,
1070, 905, and 778 cm"1.
,^  Diethvlamine , and TNB_. — Sym-TNB (l.Og,
.047 mol) was dissolved in a minimum amount of cycloheptanone at 40 .
Diethylamine (2 ml) was then added. After standing at room temperature for
three weeks the total reaction mixture was chromatographed on a neutral
\
silica gel column (3/4" x 15") with THF containing 0.12 diethylamine.
Various eluent fractions were evaporated down and the resulting oils were
chromatographed by TLC (silica gel) . Those fractions containing a single
component (major product) were combined, and the resulting material was
recrystallized from a 1:3 me thanol: ether solution to give bright red crystals
of 3c, mp 215°. This product had an intense visible absorption at 510 nm in
methanol solution, and analyzed correctly for the expected 1:1:1 adduct.
The carbon analysis was not within the standard limit of ±.3% as the material
was difficult to dry.
Anal. Calcd for C._H-,N.O_: C, 51.25; H, 6.58; N, 14.06. Found:
— — — . . I/ £O 4 /
C, 50.69; H, 6.81; N, 13.81. The nmr spectrum (DMSO-dg) of 3c^  was quite
similar to that of 3b, except for additional upfield methylene absorptions;
6.8.18 (<)0NC=CH-C=N00 , s) , 5 5.8 (CHNO-, t) , 6 4.02 (2H, bridgehead o to N0_,i ~~ / — / ~ z
m), 6 2.72 (2E, bridgehead a to carbonyl, m) , 6 2.0-1.5 (8H, methylenes, br) ,
+ +
« 1.15 (6H, CH,CH0NH0, t), and 5 2.9 (4H, CH,CH0NH0, q).
~~ ^j / z ~~ j ~~* /
The ir spectrum of 3c (KBr) shows absorptions at 1718, 1630, 1560, 1425,
^^ M*
1377, 1260, 887, 726, and 745 cm"1.
Reactionof Cyclopentanone, Diethylamine, andTNB. — Attempts to
prepare the bicyclic adduct 3a by methods similar to those described for 3b
•j
and 3c were unsuccessful. TLC of the reaction mixture after 2 hrs or after
*** ... ;
2 weeks showed more than 4 major products.
Reacti^nofPjil.cToglucino I_, Diethylamine i ,
 L_an4 TNB . — Although the
visible spectrum of a mixture of phloroglucinol, TNB, and diethylamine does
show evidence for initial formation of a sigma complex, followed by cycliza-
tion to the bicyclic nitropropene nitronate, no crystalline product could be
\Y
• ' ' ' • : . • • • - • - •
 v
 " ' 1 6
obtained from this reaction. The in situ generated enamine of diethylamine
and phloroglucinol must be of considerably different reactivity from those
of simple cyclic ketones since a variety of products are observed to form
(TLC).
. - f
React iono.fPlilorogjaicingl, Triethylamine, and TNB.— Sym-TNB (l.Og,
.047 mol) and phloroglucinol*2H20 (l.Og, .061 mol) were dissolved in a
mixture of 4 ml of THF and 1 ml of DMF. To this mixture 3 ml of triethyl-
andne were slowly added and the mixture was cooled to 10-15°. After 1 hr,
the reaction mixture was washed with four 50 ml portions of anhydrous ether.
The resulting oil was recrystallized from a 1:3 methanol:ether solution to
yield orange crystals , mp 123-124°, which analyze correctly for^ i?.
Anal. Calcd for C24H39N5Og: C, 53.20; H, 7.25; H, 12.98. Found:
C,^ 53.11;,H,,7.62;,N, 12.91. The*pmr^spectrumv"of^ (DHSO-dg) shows absorp-
tions at & 8.1 (02NC-CH-C-N02, s), & 5.9 (2H, (CH3CH2)3NH, br), 6 5.6 (CHN02>
t), « 5.0 (0"-C=CH-C=0, s), 6 4.17 (2H, bridgehead a to N02, m), 5 3.08 (12H,
(CH3CH2)3NH, q), 6 2.93 (2§, bridgehead a to carbonyl, d), and 6 1.15 (18H,
(CH3CH2)3NH, t). The ir spectrum of 9 (KBr) shows absorptions at 1720, 1550,
1520, 1235, and 1225 cm.* . The electronic spectrum shows two intense peaks
of equal intensity at 510 and 272 nm (MeOH). The latter absorption undoubtedly
arises from the hydroxy enolate anion function in^ , as it is not observed in
3b or
of9_. — A saturated solution of 9 in methanol at 25° was
cooled to 10°. A saturated solution of methanolic HC1 was then added until
the orange color of JJ, disappeared and a yellow solution resulted. Cooling
this solution at 0°C for 2 days resulted in the formation of yellow crystals
of the nitronic acid 13, mp 93-94°.
' - - '•• - '


Condensation cyclization reactions of electron deficient aromatics.  4:  Tricyclic nitropropene nitronates from the reaction of phloroglucinol and cycloalkanones with sym-trinitrobenzene

Condensation cyclization reactions of electron deficient aromatics. 4: Tricyclic nitropropene nitronates from the reaction of phloroglucinol and cycloalkanones with sym-trinitrobenzene

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