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New Methods of Preparative Organic Chemistry. Transfer of Diazo Groups

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The machine program for the determination of
fundamental rings is written in the problem-oriented
F O R T R A N language. It has already been tested o n
the IBM@ 7010,7090, and 360 Model 40 machines (the
last with a 64 K core memory). A series of different
structural-formula graphs with u p to 1 2 condensation
points were fed into the machine in the short topological form described by Morganr*l, and the fundamental
rings present in each were determined by computer.
The results were expressed in the form of a list: a
heading line that can accommodate u p t o 24 two-digit
numbers gives the various ring sizes. Under these, in a
fourteen line matrix, the individual ring members are
given in the order of their occurrence in the ring
(cf. Scheme 6).
["I
It may happen that in a highly complicated molecule
so many condensation points and fundamental rings
exist that the available space in the memory of the
computer does not suffice for all steps of the complete
ring-recognition process. Then the machine prints a
message showing which of the condensation points it
was unable to consider. After that the result can
easily be completed by intellect~iallycompleting the
algorithm. These limitations can be overcome, if
necessary, by using a computer with a larger memory
o r by writing the program in a machine-oriented
language instead of F O R T R A N .
The authors would like to thank W . Schwier and
M . Wildgrube fiv substantial niuthen!atical contributionA.
Received: June 20th, 1966
[A 588 1El
German version: Angew. Chem. 79, 802 (1967)
Translated by Express Translation Service, London
Cf. Section 3, 1121.
New M e t h o d s of P r e p a r a t i v e O r g a n i c Chemistry[**'
Transfer of Diazo Groupsf'[
BY M. REGITZ [*I
BASED ON WORK CARRIED OUT WITH D. STADLER, H. SCHWALL, A. LIEDHEGENER,
H. J. GEELHAAR, F. MENZ, J. HOCKER, J. R W E R , AND W. ANSCHUTZ
When an arenesulfonyl azide, particularly p-toluenesulfonyl azide, reacts, in the prewnce
of a base, with a compound containing an active methylene group, the two hydrogen
atoms of the active methylene group are replaced by a diazo group to form a diazo
compound and an arenesulfonamide. The method may be used for the synthesis of t h e
diazo derivatives of' cyclopentadienes, cyclohexadienes, I ,3-dicarbonyl, 1,3-disulfony/,
and I ,3-ketosulfonyl compounds, ketones, carbonic acid esters, and b-iminoketones.
Secondary reactions can lead to azo compounds and heterocycles such as I,2,3-triazoles,
1,2,3-thiadiazoles, and pyrazolin-4-ones. Azidinium salts react in the same way, but in
this case an acidic reaction medium is necessary, a fact that is sometimes advantageour.
I. Introduction
Two main routes have been used so far for the synthesis of aliphatic diazo compounds. In one case,
compounds in which the future diazo C atom already
[*I Doz. Dr. M. Regitz
Institut fur Organische Chemie der Universitat
66 Saarbrucken 15 (Germany)
["*I The articles in this series have been published in five volumes
by Verlag Chemie, Weinheim/Bergstrasse. An English edition has
also been published. The present article. together with procedures
will appear in Volume VI of the series.
[ l ] XIlIth report on reactions ol' compound; containing active
methylene groups with azides. From the Habilitation Thesis
of M . Regitz, Universitat des Saarlandes, Saarbrucken, 1965;
supplemented by more recent work.
Angew. Chem. infernut. Edit. 1 Vul. 6 (1967)
/ Nu. 9
carries a substituent containing nitrogen are converted
into diazo compounds by condensations, e.g. by
diazotization of amines in accordance with eq. (a) o r
by the Forster reaction (b). T h e starting materials for
the second route are substances in which the future
diazo C atom carries a functional group with two
adjacent N atoms. Some important examples are the
deacylation (c) of the N-acyl-N-nitrosoalkylamines,
the cleavage (d) and (e) of P-(N-alkyl-N-nitrosoamino)ketones and arenesulfonyl hydrazones by alkali, and
the dehydrogenation (f) of hydrazones [21.
.
.-
[2] For individual methods, see B. Eisrert in: Neuere Methoden
der praparativen organischen Chemie. 3rd Edit., Verlag Chemie
GmbH., WeinheimiBergstr. 1949, Vol. I, p. 359; R . Huisgen,
Angew. Chem. 67, 439 (1955); F. Weygand and H. J. Bestmann,
Angew. Chem. 72, 535 (1960).
733
the proton activity of (2), since the carbanion ( 5 ) is
the actual reacting species. The acidic p-toluenesulfonamide ( 3 ) is generally separated from ( 4 ) as a salt (6).
>C-CH,-CI
?-NO
f5H
II
0
OR@
-on@,
- :c=cn-co-
-ROH,
X=N,
(d)
[p-CH,- C,H,-SO,-NH]@
/ \
on@
>C=N -NH- SO,- A r
- H 2 0 , -ArS02G+
>C=N,
(e)
>c=N-NH,
w
>C=N,
(f)
-H2
In contrast to these methods, the transfer of the diazo
groups in accordance with reaction (g) involves the
transfer of an existing Nz group from a donor to an
acceptor in exchange for two H atoms, with formation
of a new diazo compound.
Mo
The preparation of a diazo compound from an azide
(phenyl azide) was first carried out by 0. Dirnroth [41 in
1910. The reaction with the malonic ester amide (7)
led via the triazole (8) to the diazomalonic ester
amide (9).
n
The lirst compounds that come to mind as donors might be
the aliphatic diazo compounds. However, these can be ruled
out on two grounds. Firstly, they react in accordance with
eq. (g) only in special cases 11 ~ 3 1 ;secondly they would have to
be prepared by one of'the conventional methods (reactions (a)
to (f)), so that any advantage of the present method is lost.
Curtius and Klavehn 151 later prepared methyl diazomalonate amide (11) from dimethyl malonate and
p-toluenesulfonyl azide, the triazolone (10) being assumed to occur as an intermediate.
11. Transfer of Diazo Groups from Sulfonyl Azides
Sulfonyl azides, which can be readily obtained from
sulfonyl chlorides by halogen-azide exchange, do not
suffer from the above disadvantage. The surprising
discovery that azides transfer Nz groups is plausible
since they are isoelectronic with diazo compounds, so
that e.g. sulfonyl azides may be regarded as sulfonyl
diazoamides. Azides and diazo compounds also exhibit pronounced similarities in reactivity, as is seen
e.g. in the Curtius degradation of carboxylic acid
azides as a counterpart of the Wolff rearrangement,
the formation of imenes and carbenes, or even the
1,3-dipolar cycloadditions of both classes of compounds.
The Nz group of p-toluenesulfonyl azide ( I ) , which is
the azide component used in almost every case, is
exchanged in a one-step reaction for two H atoms of an
active methylene compound (2), with formation of
p-toluenesulfonamide (3) and the diazo compound
( 4 ) . The transfer of the diazo group is carried out in
the presence of a base whose strength corresponds to
[3] D. G . Furnum and P. Yutes, Proc. chem. Soc. (London) 1960,
224.
734
More recently, Doering and De Puy 161 synthesized
diazocyclopentadiene (14) (see Section A.l), evidently
with n o knowledge of the above-mentioned work. This
synthesis provided the incentive for our own investigations in this field, which, along with other investigations, are reported below.
A. Synthesis of Diazo Compounds
1. D i a z o c y c I o p e n t a d i,enes
Cyclopentadienyl-lithium (12), which can be obtained
from cyclopentadiene and phenyl-lithium, reacts with
p-toluenesulfonyl azide in ether to form diazocyclopentadiene (14) 161. The "azo coupling product" (13)
and the triazene (15) are regarded as hypothetical
intermediates, the decomposition of which yields
~
[ 4 ] 0 . Dirnroth, Liebigs Ann. Chem. 373, 356 (1910).
[ 5 ] Th. Curtius and W. Klavehn, J. prakt. Chem. 121 112, 76(1926).
[6] W . V.E. Doering and C . H. De Puy, J. Amer. chem. Soc. 75,
5955 (1953).
Angew. Chem. internat. Edit.
Yol. 6 (1967)/ No. 9
@
.... LiO
+
0
0
: N = N - E - T o s ( p ) -+
Li@
N = N - N - Tos(p )
1 (131
(12)
@$EN:
...
(14)
a
*
- -p-TosNHLi
1
(a):
\
x = co
N
(b): X = S O z
I
N
lithium p-toluenesulfonamide and diazocyclopentadiene (14).
The use of the rather expensive phenyl-lithium as the
base can be avoided by carrying out the reaction in the
presence of diethylamine without a solvent "1, or even
better, in acetonitrile (yield of (14) 84 %)[a]. The
analogous synthesis of l-diazo-2,3,4-triphenylcyclopentadiene (16) (yield 97 %) and l-diazo-2,3,4,5tetraphenylcyclopentadiene( I 7) (yield 95 %) in acetonitrile/piperidine is superior to the transfer of diazo
groups with phenyl-lithium [9,101 and with diethylamine [ I l l . 2,5-Diphenylcyclopentadiene(18) gives the
two isomeric diphenyldiazocyclopentadienes (20) and
(21) [81. The formation of these products is readily
explained as involving the mesomeric carbanion (19),
formed from (18) and piperidine, which contains two
nucleophilic centers.
H
an additional CO or SO2 group in the meso position
(vinylogy principle).
Diazoanthrone (23a) is obtained in this way in 94 %
yield from anthrone (22a) and p-toluenesulfonyl azide
in ethanol/piperidine [121. A compound to which the
same structure was assigned, and which was formed
from (22a) and methylsulfonyl azide in pyridinel
piperidinecl31, was found to be a mixture of 66 % of
anthraquinone azine (24a) and 27 % of 9-diazoanthrone (23a) [*21. This conversion of a methylene
component into an azine is generally possible only if
the initially formed diazo compound is unstable to
bases, and if the reaction conditions for the diazo
group transfer coincide with those required for the
decomposition of the diazo compound.
Base-catalysed decompositions of diazo compounds
into azines and nitrogen are known. Compound (23)
also decomposes to give (24) when treated with
pyridine/piperidine. Consequently, it is very doubtful
that Pe[z[131 isolated a compound (23), since this is
not stable under the reaction conditions used. The two
mechanistically possible paths A (first order) and B
(second order) were not studied kinetically.
R-C-R'
m,
R
.-N=C,
R'
!
.@.
R-C-R'
rlrp
2nd order
2. D i a z o c y c l o h e x a d i e n e s
The only dibenzocyclohexa-1,4-diene derivatives (22)
that have been used so far for diazo group transfers are
those in which the CH2 group is further activated by
___
[7] Th. Weil and M . Cuis, J. org. Chemistry 28, 2472 (1963).
[8} M. Regitz and A . Liedhegener, Tetrahedron 23, 2701 (1967).
[9] P. L. Parison and B. J . Williams, J. chern. SOC.(London) 1961,
4153.
[lo] F. Klages and K . Bott, Chern. Ber. 97, 735 (1964).
[Ill D . Lloydand F.J. Wusson,J. chern. SOC.(London) 1966,408.
Angew. Chem. internat. Edit.
Vol. 6 (1967) No. 9
Since the proton-activating action of the arenesulfonyl
group is weaker than that of the carbonyl group[14],
the transfer of a diazo group onto thioxanthene S,Sdioxide (226) requires the use of potassium ethoxide as
the base, but it then gives a 98 % yield of (236) [121.
However, if the addition of azide is carried out over a
relatively long period (ca. 30 min), the 9-diazothioxanthene S,S-dioxide (23b) that is formed undergoes
C2HsO 0 - catalysed decomposition into nitrogen and
10,lO'-azinobis(thioxanthene S,S-dioxide) (24b). The
reaction of (22b) with p-toluenesulfonyl azide in
ether/tetrahydrofuran gives only 45 % of (23b) [lo].
[I21 M . Regifz, Chem. Ber. 97, 2742 (1964).
[13] W. Pelz, US.-Pat. 2950273 (August 23, 1960), Agfa AG.
[14] S. Hiinig and 0.Boes, Liebigs Ann. Chem. 579, 28 (1953).
135
3. 2 - D i a z o - l , 3 - d i o x o C o m p o u n d s
2-Diazo-l,3-dioxo compounds (26) are usually synthesized by diazotization of suitable amines. Since
these amines are generally prepared from the F-dicarbonyl compounds (2.51, the synthesis is considerably
shortened by the transfer of diazo groups onto (25).
The possibility of keto-enol tautomerism in the P-diketones
is of no importance to the transfer reaction, since the keto
form and the enol form react with bases to give the same
mesomeric anion, which reacts with the sulfonyl azide. Owing
even weak bases
to the high CH or OH (enol) acidity of (D),
such as piperidine or triethylamine can cause anion formation. Whenever possible the use of such weak bases is
preferred to the use of alkali metal hydroxides or alkoxides
since side reactions can often be avoided and higher yields
can be obtained. Cyclic P-dicarbonyl compounds fixed in the
trans configuration occasionally also give azo compounds
(27) or tautomers as secondary products of the diazo synthesis, which will be discussed more fully in Section 1I.B.
((29) + (31)). Since (29) couples Hith (30) to give the
dipotassium salt (ZS), the formation of (32) vin 2-diazoindan1,3-dione (30) may be ruled out.
Diazo group transfers onto P-diketones of the benzoylacetone or dibenzoylmethane type are best carried out
in methylene chloride/piperidine. In contrast to the
usual high yields (see Table l), p-nitrodibenzoyldiazomethane (33) is formed in a yield of only 29 %. This
is mainly due to deacylation of (33) in both of the
a) 2- D i a z o - 1 , 3- d i k e t o n e s
Investigations on the structure of hydrindantin 1153
led to the synthesis of 2-diazoindan-l,3-dione (30) by
diazo group transfer. The reaction was found to
proceed satisfactorily, not only in ethanol/potassium
ethoxide 116,171 but also in ethanol/triethylarnine1151,
which gives (30) in 85 % yield; in aqueous-ethanolic
potassium hydroxide solution, on the other hand, the
reaction leads to 2-diazo-1',3,3'-trioxo-l,2'-bisindanylidene (32) [16J.
The transfer of diazo groups onto (31) is preceded by autocondensation of the indan-1,3-dione in the presence of KOH
2
possible directions to give p-nitrobenzoyldiazomethane
(34) and benzoyldiazomethane (35) 1181. This cleavage
is prevented by reaction of p-nitrodi benzoylmethane
with p-toluenesulfonyl azide in ethanol in the presence
Table 1. 2-Diazo-1.3-diketones synthesized.
I
Solvent, base
Ethanolltriethylamine
EtherMiethylamine
73
78
108
91
67
86
81
82
70
76
149-150
276-279
226
107
Benzoyl-2-pyridylcarbon yldiazomethane
Ethanolltriethylamine
Ethanol-waterlpotassium hydroxide
Dimethylformamide/triethylamine
Ethanollpiperidine
Etherltriethylamine
Methylene chloridelpiperidine
Methylene chloridelpiperidine
Acetylbenzoyldiazomethane
Ethanolltriethylamine
71
2-Diazo-4,5-benzoindan-l,3-dione
5-Diazobarbituric acid
3-Diazo-1.2.3 4-tetrahydroquinoIine-2.4-dione
Di benzoyldiazomethane
,
[151 M . Regitz, H . Schwall, G. Heck, B. Eistert, and G. Bock,
Liebigs Ann. Chem. 690, 125 (1965).
I161 M. Regirz and G . Heck, Chem. Ber. 97, 1482 (1964).
[17] A . Schonberg and K. Junghans, Chem. Ber. 98, 820 (1965),
use methanol/sodium methoxide.
736
I
87
63-64
I
2257
2193
2146
2141
2193
2155
2119
21 37
2174
2137
2119
2273
2212
2114
1181 M . Regitz and A . Liedhegener, Chem. Ber. 99, 3128 (1966).
[191 M. Regitz and D . Stadler, Liebigs Ann. Chem. 687,214 (1965).
[201 M . Rosenberger, P . Yates, J. B. Hendrickson, and W. Wov,
Tetrahedron Letters 1964, 2285.
[21] M . Regitz, Liebigs Ann. Chem. 676, 101 (1964).
Angew. Chem. internat. Edit. / Voi. 6 (1967) 1 No. 9
of catalytic quantities of triethylamine (yield of (33) :
80 %)
The versatility of the reaction for the synthesis of 2-diazo-l,3-diketones can be judged from
Table 1.
b) D i a z o m a l o n i c E s t e r a n d
a-Diazo-@-oxocarboxylicEsters
Diethyl diazomalonate (39) can be obtained by diazo
transfer in ether/diethylamine (yield 75 %) [2*1 or in
acetonitrile/triethylamine (yield 95
[1SJ, the resulting
product being almost pure. It can be purified by lowtemperature recrystallization (distillation is sometimes dangerous) from ether, a process that is very
useful for the purification of liquid diazo compounds
(18,421. The rate of the triethylamine-catalysed transfer
reaction decreases with decreasing polarity of the
solvent, i.e. in the order acetonitrile > methylene
chloride > ether.
x)
CH3- CO- CN, - CO-NH- TOS( p ) (44)
diazo-N-(p-toluenesu1fonyl)acetoacetamide (44), together with a considerable quantity of ethyl cc-diazoacetoacetate (42), which is contaminated with ethyl
diazoacetate (43) [18,211. (43) is evidently formed by
deacylation of (42).
A mechanistic argument similar to that outlined for
diethyl malonate also applies to the formation of (42)
and (44), particularly since (42) does not react with
sodium p-toluenesulfonamide to give the diazo derivative (44). Further evidence of the cyclic intermediate in the displacement reaction (triazoline
formation in accordance with (36) + (38); CO-CH3
instead of C02CzHs) is provided by the fact that the
reaction of t-butyl acetoacetate yields only traces of
(44), clearly because of steric hindrance to triazoline
formation.
f 37)
I
Diethyl diazomalonate (39) is formed only in traces
(3 %) from diethyl sodiomalonate (36) and p-toluenesulfonyl azide; the main product (97 % yield) is the
sodium salt of ethyl N-@-toluenesulfony1)diazomalonamide (40), which is formed by displacement of an
ethoxy group, and which gives (41) on acidification [18,211.
On the other hand, the synthesis of a-diazo-$-0x0carboxylic esters (45) under the conditions given for
the malonic ester, i.e. with acetonitrile/triethylamine,
proceeds without side reactions. Some examples are
listed in Table 2 [18.241.
Table 2. Esters (45) of a-Diazo-8-oxocarboxylic
acids CH3-CO-CNz-COzR.
The reaction cannot proceed via diethyl diazomalonate (39),
which does not react with sodium p-toluenesulfonamide to
give (4f) under the condition; used. A cyclic intermediate,
the triazoline (38) must be involved, (40) being formed by
ring cleavage between the azo and sulfonamide nitrogens
with elimination of ethanolrzzl. The formation of traces of
diethyl diazomalonate (39) can be explained in a similar
manner, but with elimination of sodium p-toluenesulfonamide; however, (39) could also be formed by a mechanism
involving the triazene (37) c18.231.
Ethyl acetoacetate reacts with p-toluenesulfonyl azide
in ethanol/sodium ethoxide to give only 31 % of a-
R
Ethyl
I-Propyl
n-Butyl
t-Butyl
Phenyl
Angew. Chem. infernal. Edit.
f Vol. 6 (1967) I No. 9
84
90
92
92
92
2217, 2141
2222,2137
2212, 2132
2212, 2132
21 32
The transfer of diazo groups onto a cyclic malonic
ester, i.e. 2,2-dimethyl-l,3-dioxane-4,6-dione
("Meldrum's acid") (46)in ethanolitriethvlamine leads. not
only to the expected diazo derivative (47) (53
but
also to its azo-coupling product with (46), this product
I
[22] Concerning the base-catalysed ring cleavage of triazolines,
see R. Huisgen, G . Szeimies, and L. Mobius, Chem. Ber. 99, 475
(1966).
[231 M . Regirz, Angew. Chem. 78, 684 (1966); Angew. Chem.
internat. Edit. 5, 681 (1966).
(Film) (cm-1)
)
I
xi,
[24] J . Hocker, Diploma Thesis, Universitat Saarbriicken, 1966.
131
5. a - D i a z o + -oxo Su If o n y 1 C o m p o u n d s
being in the tautomeric hydrazone form (48) (20 %) [191.
This secondary reaction, which greatly reduces the
yield of (47) is mainly due to the nucleophilic nature
of the carbanion of (46).
4. D i a z o m e t h y l e n e D i s u l f o n e s
The methylene disulfones (49) are sufficiently acidic
for conversion into diazo derivatives (50) with p toluenesulfonyl azide, even in aqueous-ethanolic
Until recently, the a-diazo-p-oxo sulfones were an
unknown class of compounds, and it is only by the
use of diazo group transfers that they have become
available. Attempts to synthesize the sulfonyl analogue
(55) of 2-diazoindan-l,3-dione (30) by the Forster
reaction (eq. b) were unsuccessful, since the P-0x0
sulfone gave (54) on oximation ( ( 5 1 ) + (54)). Compound (51) was therefore treated with p-toluenesulfonyl azide in ethanolic potassium hydroxide solution.
As in the case of “Meldrum’s acid” (see Section
II.A.3.b), the initially formed diazo compound (55)
immediately couples with the starting material ( 5 1 ) to
form the dipotassium salt of 3,3’-dihydroxy-2,2’-azothionaphthene 1,l ,l‘,l‘-tetroxide (52) (281, which is
converted into the hydrazone (53) on acidification.
The experiments would probably have stopped at this
point, had their continuation not been made possible
by a completely unexpected reaction. When attempts
aCozH
SOz-CH=NOH
(54)
potassium hydroxide solution; however, the less acidic
diamide (49f) must be converted into its lithium
compound by treatment with methyl-lithium in ether
before it will react in the usual manner to give diazomethionic bis(ethylani1ide) (50f)[lo]. A number of
data are given in Table 3.
(56)
(55)
were made to recrystallize the hydrazone (53) (which
is sparingly soluble in the usual solvents) from ethylene
glycol or dimethylformamide, “decoupling” 1291 took
place to give the p-0x0 sulfone (51) and the desired
a-diazo derivative (55). The reaction probably proceeds via an anionic intermediate (%), the polar
solvent acting as a proton-transfer agent. This assumption is supported by the fact that the reaction does not
take place in tetralin, even at 200 “C1281.
On the other hand, open-chain P-0x0 sulfones such
as p-toluenesulfonylacetone (57a) or p-toluenesulfonylacetophenone (576) react smoothly with p-toluenesulfonyl azide in ethanol/water/triethylamine to give
the diazo derivatives (58a) and (586) 1271. Ethyl p -
Table 3. Diazomethylene sulfones synthesized.
~ - T o sN,
(KBr) (cm-1)
99
121-122
135-136
164
88-90
97
’
pale yellow
yellowish green
yellowish green
almost colorless
almost colorless
yellowish green
70
75
85
84
46
50
2130
2117
2109
2145
2135
2118
Attempts to synthesize the a-diazo sulfones R-SOz-CNz-R’,
which have only recently become obtainable by another
route [251,we e unsuccessful in the case of (2,4-dinitrobenzyl)p-toluene sulfone [26,271.
738
P-H~C-C~H~-SO~-CH~-CO-R--+
(5 7)
(a): R = CH3 (70 %)
(b): R = CjHs (60 %)
~-H~C-C~H~-SOZ-CN~-CO-R
(58)
[251 J . Stratirig and A. M. van Leusen, Recueil Trav. chim. PaysBas 81, 966 (1962).
[26] M. Regitr, unpublished, Saarbriicken 1964.
[27] A. M. van Leusen, P. M . Smid, and J. Strafing, Tetrahedron
Letters 1965, 337.
[28] M Regitz, Chem. Ber. 98, 36 (1965).
[29] B. Eistert and K . Schank, Chem. Ber. 96, 2304 (1963).
Angew. Chem. internat. Edit. 1 Vol. 6 (1967) / No. 9
toluenesulfonylacetate (59a) and ethyl (1,l-dimethylethanesulfony1)acetate undergo diazo transfer only in
the presence of sodium ethoxide in ethanol/ether, but
the reaction then leads to the displacement of the
alkoxy group to give the sodium salts (60a) and (60b)
of N-(p-toluenesulfonyl)-a-diazo-a-sulfonylcarboxylic
amides [271 (for the analogous reaction of the esters of
$-ox0 acids, see Section IT.A.3.b).
R-SO~-CHZ--CO-OC~H~
p-Tos Nj
3
~
CzHsONa
Both side reactions can be avoided by the use of a
short reaction time at 0 to 5 “C. The initially formed
unstable adduct of p-toluenesulfonyl azide and the
anion of (61), which probably has the structure (69)
(R = Ar = phenyl), decomposes on addition of a
second equivalent of base to give the desired “azibenzil” (63) (70 %) and potassium p-toluenesulfonamide 1221. Decomposition by acids, on the other hand,
leads to elimination of N2 and formation of N-(ptoluenesu1fonyl)diphenylacetamide (62) in 80 % yield.
Similar behavior is observed with benzyl a-naphthyl
C6H5- C - C - CH,
Hz 11
0
(65)
6. a - D i a z o c a r b o n v l C o m D o u n d s
a) From Arylmethyl Ketones
Carbonyl compounds of the type R-CH2-CO-R
react with sulfonyl azides in the desired manner only
when their CH2 group is additionally activated by an
aromatic residue [141. Desoxybenzoin (61) reacts with
p-toluenesulfonyl azide in ethanol/potassium ethoxide
C&,-C-C-C6H,
H2
(61)
I
1
p - ~ o s c,n,on
~ ~
4
C6H5-C-C-C6H5
II II
0
C6H5,
C6H(
6
CH-<
+
NH-Tos(p)
C6H5-C-C-C6H5
II II
NZ 0
N O
I
N O
-+
I1
II
C6H5-C-C-C6H5
(62)
(63)
(64)
at 5 to 10 “C to give 23 % of benzoylphenyldiazomethane (“azibenzil”) (63), together with its decomposition product benzil monoazine (64) (24 %)
and N-(p-toluenesulfony1)diphenylacetamide (62)
and P-naphthyl ketones, which give phenyl-a(or (3)naphthoyldiazomethane and N-(p-toluenesulfony1)-a(or P)-naphthylphenylacetamide [30,311. The “diazosynthesis” proceeds normally with phenylacetone (65)
to give (66), whereas acid hydrolysis of the reaction
mixture yields N-(p-toluenesulfony1)-a-phenylpropionamide (67) and a-Cp-toluenesulfony1)amino-a-phenylacetone (68).
One mechanistic interpretation of these results is as
follows. Two isomeric structures (69) and (71) are
conceivable for the TosN3 adducts with the mesomeric
anion (70). Structure (71) can be ruled out simply
because it does not explain the formation of the rearrangement product. The 1,2,3-triazoline salt (69),
on the other hand, can undergo ring cleavage with
formation of a-diazo ketones (74) via the hypothetical
diazonium betaine (73) (with elimination of potassium
7
R-C-C-Ar
80
Fp: 51
R-F-F-Ar
N. <N
(,)To&
KO
*P-Tos%,
1
B
R - C = C -A r
I
:O: K@
B
p-TosN,
A
(70)
R-C-C-Ar
II I
O F
N
I
KO @:N-Tos(p)
(71)
I
(25 %). Compound (62) is formally a Wolff rearrangement product of (63) with p-toluenesulfonamide;
however, it was only partly obtained from (63) [30,311.
~~
[30] M . Regirz, Tetrahedron Letters 1964, 1403.
[31] M . Regitz, Chem. Ber. 98, 1210 (1965).
Angew. Chem. internat. Edii.
Vol. 6 (1967) 1 No. 9
p-toluenesulfonamide), or alternatively N2-elimination
to form the carbonium ion (76) may be followed by
anionotropic rearrangement to give the N-(p-toluenesulfony1)carboxylic amide (77). The formation of the
amino ketone (68) could result from a “short circuit
739
mechanism" leading via (72) to the isomer (75),
R = C H 3 , Ar = C6H5[311.
the intermediate occurrence of a 1,2,3-triazoline
(82) 1341, which isomerizes with ring cleavage to give
the diazonium betaine (85).
A number of substituted "azibenzils" were synthesized under
the above conditions, except that in the case of 4-nitrophenylbenzoyldiazomethane (yield 80 :4), triethylamine was used
instead of potassium ethoxide[3*1.
This principle can be used for the synthesis of Kdiazocycloalkanones (87) (diazocyclohexanone and
diazocamphor) ; the decomposition of the triazoline
adduct (86) has been formulated somewhat differently 1201.
b) F r o m E s t e r s of A r y l a c e t i c A c i d s
The diazo transfer onto ethyl p-nitrophenylacetate
(78) confirms the observations made on (3-0x0 esters
and malonic esters (see Section II.A.3.b). In ethanol/
potassium ethoxide, displacement of the ethoxy residue
gives N-@-toluenesulfony1)-diazo-(p-nitropheny1)acetamide (80) (yield 61 %), while reaction in pyridinel
piperidine leads to the diazo ester (79) (yield 7 2 %);
methyl diazo-(2,4-dinitrophenyl)acetate is synthesized
in a similar manner (yield 88 "/,) 1311.
The same principle has also been used for the synthesis
of u-diazobutyraldehyde from u-ethyl-p-dimethylaminoacrolein 1351.
d) F r o m 1 , 3 - D i k e t o n e s or (3-0x0 A l d e h y d e s
The transfer of diazo groups onto o-nitrobenzoylacetone (88) can be directed in such a way as to yield
acetyl-o-nitrobenzoyldiazomethane (89) (methylene
chloride/piperidine) or with additional deacetylation
to give o-nitrobenzoyldiazomethane (90) (ethanol/
water/piperidine) 1181.
The product obtained from (78) and methylsulfonyl
azide in methanol/potassium hydroxide, which was
thought to be (79) [131, is in fact N-(methylsulfony1)diazo-(pnitropheny1)acetamide ((80) with CH3S02
instead of p-Tos) 1311.
c) F r o m a - E n - P - a m i n o K e t o n e s
u-En-p-amino ketones of the type (81), which can be
obtained from benzoyl-acetaldehydes and N-methylaniline, form u-diazo ketones (83) and formamidines
(84) when heated with sulfonyl azides in chloroform1331. The formation of these products points to
This principle may be used for the synthesis of u-diazo
carbonyl compounds from methylene components
whose proton activities are too low for N2-transfer
from sulfonyl azides. However, the reaction proceeds
satisfactorily and uniformly only when the reactivities
of the two acyl groups are very different (for nonspecific cleavage, see Section II.A.3.a). Thus the
cleavage of arylcarbonylacetyldiazomethanes (cf. Section II.A.3.a) with aqueous potassium hydroxide leads
mainly, but not exclusively, to arylcarbonyldiazomethanes 123,361. The deacetylation of u-diazoacetoacetic esters (45) (for synthesis see Section II.A.3.b)
under solvolytic conditions that leave the ester group
intact (see Table 4) leads to very high yields of diazo-
P
7-C6H5
f-Ct3H5
(83)
N
--R
~-
R-&N2
+
9
/C=N-S02-Ar
IN\
H3C C6H5 (841
+
Pc -C&5
II
CH3-CO-CNz-COzR
H>&,N:o :NO
N
I
H3C/& H S
6 5
(45)
~
~
-
~
(85)
[32J W. Jugelt, Z . Chem. 5,455 (1965).
[33] R . Fusco, G. Bianchetti, D. Pocar, and R. Ugo, Chem. Ber.
96, 802 (1963).
740
+ Nz=CH-COzR
(91)
~
[34] The orientation of the addition to azides is similar to that
of the addition to enol ethers. See R. Huisgen, L. Mobius, and
G . Szeirnies, Chem. Ber. 98,1138 (1965); R. Huisgen and G . Szeirnies, Chem. Ber. 98, 1153 (1965).
[35] J. Kucera and Z . Arnold, Tetrahedron Letters 1966, 1109.
[36] M. Regitr and Liedhegener, unpublished, Saarbriicken 1966.
Angew. Chem. internat. Edit.
VoI. 6 (1967)
/ No. 9
Table 4. Diazoacetates NrCH-COrR (911 prepared by
deacetylation of 2-diazoacetoacetates.
I Reaction conditions
K
I Yield (%)
Acetonitrilelwaterlpotassium hydroxide;
2h
Methanol/sodium methoxide; 1 min
Methanolisodium methoxide; 1 min
Acetonitrile/water/poiassium hydroxide;
4h
Methanol/sodium methoxide; 30 min
Ethyl
Propyl
i-PropyI
t-Butyl
after introduction of a formyl group by Claisen
condensation 140-421. The scope of this principle can
be seen from Table 5 .
While the diazo transfer with deformylation has so
far been used only for the synthesis of diazomethylcarbonyl compounds (94), the analogous reaction of
the sodium salt of a-alkyl-a-acylacetaldehydes (95)
can be used for the synthesis of compounds of the type
(97) 1411.
61
55
55
68
69
8'
R-C-C=N,
8'
/H
R-C-C=C
Na@
(95)
acetic esters (91), and can compete with the usual
diazotization of amines[24J. In the case of t-butyl diazoacetate 1373 it is actually superior to the conventional
syntheses 138,391.
$-Ox0 aldehydes are more suitable for use in the adiazo ketone synthesis. The formyl group has a
stronger proton-activating effect in the diazo transfer
reaction [14J,and can also be more readily removed by
solvolysis than acetyl or arylcarbonyl groups. Thus the
sodium salts (93) react with p-toluenesulfonyl azide in
The cycloadduct (96) is assumed to occur as an intermediate, since the decomposition of this adduct would
explain the formation of the sodium salt of N-(ptoluenesulfony1)formamide together with (97). Some
examples of this type of reaction are given in
Table 6.
Table 6. 2-Diazo ketones R-CO-CN2-R
rransler with deformylation.
Yield
R
R-C-CH,
(92)
HCOOR/Na
8
B H
B.p.
( "Clmm)
(97) obtained by diazo
1
I R Diazo band
(film) (cm-1)
I R
R-C-C-CL
It
0 " N @ O (93)
Methyl
Ethyl
n-Propyl
n-Butyl
Methyl
Methyl
Ethyl
n-Propyl
60
75
65
68
Ethoxy
Phenyl
Methyl
Methyl
?I
21-82/22
102/12
58jC.4
68/41
77
[*I
56-59/25
2128, 2075
2128
2075
2075
['I
,
2083
2075, 2169
[*I The liquid diazo compounds were recrystallized fromether at -70 "C.
ethanol to give a-diazo carbonyl compounds (94).
Methylcarbonyl compounds (92) that d o not undergo
diazo transfer directly (see Section II.A.6.a) can be
smoothly converted into their diazo derivatives (94)
Table 5. Diazomethyl carbonyl compounds R-CO-CH-N2
obtained by diazo transfer with deformylation.
(94)
~
R
(94)
Yield (%)
M.p. ("C) or
b.p.
( "C/mm)
IR Diazo band
(KBr, Film)
(cm-1)
69
52
83
73
75
58
53
69
34
84
45/12
72-73/19
69/15
48-49
90-91
114-115
6810.1
64-66
71-73
68
2114
2198,2105
2227, 2110
7105
2179,2105
2165,2110
2114
2110
2112
21 10
a-Formylcycloalkanones (98), which have the same
structural characteristics as (95) (i.e. free a-alkyl-aacylacetaldehydes), evidently react by the same
mechanism to give a-diazocycloalkanones (99) ; triethylamine/methylene chloride has been found suitable
as the reaction medium [42,43J. The reaction is closely
related to the reaction of enamines discussed in
Section II.A.6.c.
~
Ethoxy
i-Propyl
t-Butyl
Phenyl
4-Methoxyphenyl
4-Nitrophenyl
2-Fury1
2-Thienyl
3-Pyridyl
Ferrocenyl
1371 M . Regitz, J. Hocker, and A . Liedhegener, Org. Syntheses,
in press.
[ 3 8 ] H . Reimlinger and L. Skattebol, Chem. Ber. 93,2162 (1960).
[39] E. Miiller and H . Huber-Emden, Liebigs Ann. Chem. 660, 54
(1962).
Angew. Chem. internat. Edit.
Vol. 6 (1967) 1 No. 9
( a ) : n = 3 (98%)
(d): n = 6 (87%)
(b): n =
(e): n
ff):n
4 (80%)
(c): n = 5 (89%)
=
9 (94%)
(40%)
= 10
[40]F. Menz, Diploma Thesis, Universitat Saarbriicken, 1966.
[41] F. Menz, Dissertation, Universitlt Saarbriicken.
1421 M. Regifz, F. Menz, and J . Riiter, Tetrahedron Letters 1966,
739.
I431 J . Riiter, Diploma Thesis, Universitat Saarbrucken, 1966.
74 1
Condensation of the a-formylcycloalkanones with
diethylamine to form enamines, which precedes the
addition of azide to form the triazoline (86), is impossible in this case on grounds of constitution.
Further evidence of the occurrence of a triazoline in the
reaction (98) + (99) is provided by the fact that about 50 %
of cyclododecanone-cc-carboxylicp-toluenesulfonamide (98')
is also foImed in the synthesis of 2-diazo-cyclododecan-I-one
(99f). One scheme that appears plausible is a competitive
to (106e) 1451. The triazole formation becomes understandable if the ring closure in the diazo imine is
considered from the point of view of the 1,3-dipolar
cycloaddition of the C=N2 dipole across the azomethine bond, since substituents having a -E effect
undoubtedly increase the nucleophilic strength of the
imino N atom.
[a): X
&
0
4
-+ (99f) + H-C\
NH-Tos(p)
=
H; (b): X = C1; (c): X = I ;
( d ) : X = CH,; ( e ) : X = OCH,
/C;N
N'? - Tos ( p )
HO H
decomposition of the adduct by two routes, one leading to
the formation of the diazo ketone (99f), while the other leads
to elimination of Nz to form a carbonium ion, which then
forms the P-keto amide by hydride shift. The same reaction
branching has been observed, though to a smaller extent, in
the synthesis of 2-diazocyclohexanone (99b) (431.
7. a - D i a z o I m i n e s a n d a - D i a z o I m o n i u m S a l t s
a-Diazo imines are generally regarded as nonexistent
since L. Wolfl[441 obtained, not a-diazo-fi-imino ketones, but their cyclic isomers, 1,2,3-triazoles, from
acyclic a-diazo-P-diketones and ammonia or primary
amines.
True a-diazo imines, i.e. 3-(arenesulfony1hydrazono)2-diazoindan-1 -ones ( I O I ) , which show no tendency
toward cyclization to give (102), have been obtained
by diazo group transfer onto 3-(arenesulfonylhydrazono)indan-1-ones (100) 1161.
N -NH -SO, - A r
N-NH-S02-Ar
f100)
(101)
1
0
The diazo imines (104a) and (104b) and the triazoles
(106c) to (106e) add on mineral acids such as HCl,
HBr, HC104 (the addition of HX is accompanied
by ring cleavage in the case of (106c)-(106e)) to give
salts of the 3-arylimino-2-diazoindan-1-ones (I05a)
to (105e). On deprotonation with aqueous potassium
hydroxide, the diazo compounds ( 1 0 4 ~ )and (104e)
can also be isolated, whereas (104d) immediately
cyclizes to form the triazole (106d).
B. Synthesis of Azo Compounds or Their Tautomers
Though the combination of two molecules having
active methylene groups by reaction with p-toluenesulfonyl azide is a one-step preparation, it is actually
a two-step reaction (both steps requiring a basic
medium) involving transfer of a diazo group followed
by azo coupling (eq. h).
+c+f
0
N-N
(102) AH-SOZ-Ar
Under the same conditions (ethanol/potassium ethoxide), the 3-aminoindenones (103a) and (103b)
also react to give stable diazo compounds (104a) and
(1046), whereas (103c) to (103e) are converted
directly into 1-aryl-4-oxoindeno[2,3-d]triazoles(106c)
1441 L.Wolfl, Liebigs Ann. Chern. 325,129 (1902); 394,23 (1912).
742
The azo synthesis from the methylene components naturally
requires only a half equivalent of sulfonyl azide. For the
second step, i.e. the actual azo coupling, the diazo component
must be strongly electrophilic; this condition is generally
satisfied when the Nz group is flanked by strongly electronattracting substituents.
[451 M . Regitz, Tetrahedron Letters 1965,3287; Angew. Chem.
77, 735 (1965); Angew. Chem. internat. Edit. 4, 710 (1965).
Angew. Chem. internat. Edit.
1 Vol. 6 (1967) 1 No. 9
Sodium F-naphthoxide (107) reacts with a half equivalent of p-toluenesulfonyl azide in ether to give 2,2'dihydroxy-1,l'-azonaphthalene (109) together with a
small amount of (108) [461.
.&=fox
0
0
( a ) : X = H2 (70%)
(111)
( 6 ) : X = (CHJ,
(70%)
( c ) : X = (CH,), ( 7 4 7'0)
X4
J + Hx-0
0
a
OH
0
+
a) (1071
b)H@
I
H..
I
N..
7
OH
(109)
Even when an excess of p-toluenesulfonyl azide is
used, the diazo compound (108) is formed in a yield
of only 9 %, together with (109). A number of other
examples are known, such as the synthesis of 3,3'-dimethyl-l,l'-diphenyl-4,4'-azopyrazol-5 - o n e (110)
using phenyl azide/piperidine 1131.
(IISb), (11%)
C. Synthesis of Heterocycles
1. 1 , 2 , 3 - T r i a z o l e s
(3-Dicarbonyl compounds fixed in the trans configuration, which satisfy the conditions given in Section
II.A.3.b for the diazo synthesis, can be readily converted into c/.,a'-azo compounds 119,471. Thus the 2,2'azocyclohexane-l,3-diones ( I I l a ) to ( I l l c ) were
obtained when the (3-diketones were heated with ptoluenesulfonyl azide in ethanollpiperidine, i.r. under
conditions that appear remarkable for azo coupling.
The azo compounds (111) and (113) exist as dienol chelates
( I I Z ) , at least in methylene chloride and chloroformf*9,481.
They exhibit a high absorption in the visible region (for
( l l l b ) : Amax = 425 my, E = 18650, CH~CIZ),
and their NMR
spectra in CDC13 contain n o signal corresponding to the
proton between the two carbonyl groups. Instead, they show
singlets at very low fields for the OH protons chelated in
accordance with (112) (for ( I l l b ) : 6 = 12.44 ppm) the ratio
of the areas of the signals corresponding to that of the other
protons present in the molecule.
3,3'-Azo - (2,4 - dioxo - 1,8,8 - trimethylbicyclo[3.2.1]octane) (113) is formed under the same conditions.
Azo compounds containing heterocycles, such as 4,4'dihydroxy-6,6'-dimethyl-3,3'-azo-2-pyrone(I14) or the
hydrazones (I15b) and ( I r k ) , are obtained by the
same principle. Compounds (115b) and ( I l k ) are
derived from unenolized P-dicarbonyl compounds [491;
it is therefore understandable that the high-energy unconjugated azo form ( I l l ) is by-passed. (Further
examples may be found in Sections I1 A.5 and I1 D.)
[46] J. M . Tedder and B. Webster, J. chern. SOC. (London) 1960,
4417, and further examples given there.
[47] M . Regitr and D . Stadler, Angew. Chem. 76, 920 (1964);
Angew. Chern. internat. Edit. 3, 748 (1964).
[48] D . Stadler, Dissertation, Universitat Saarbrucken, 1966.
[49] B. Eisrert and F. Geiss. Tetrahedron 7, 1 (1959).
Angew. Chem. internat. Edit. 1 VoI. 6 (1967)
No. 9
Diazo transfers onto p-imino ketones generally lead
directly to 1,2,3-triazoles (eq. (i)).
Apart from the exceptions in the indan system (Section JI.A.7), the anils of trans-fixed /3-diketones such
as cyclohexane-l,3-dione, 5,5-dimethyl-cyclohexane1,3-dione, and 5,5-pentamethylenecyclohexane-l,3dione follow scheme (i)r5Ol. Only some triazoles are
contaminated with small quantities of the diazo isomer, as can be seen from the presence of weak diazo
bands in the IR spectrum of the crude products. The
anils of open-chain (3-dicarbonyl compounds can also
be cyclized to 1,2,3-triazoles by diazo group transfer
in ethanol/potassium ethoxide. Thus benzoyl (or
(a): R
= C,H,;
(6): R
=
CH3
X = H, CH,, C1, I , OCH,, NO,
acetyl) acetaldehyde anils (116a) and (116b) give high
yields (60-90 %) of l-aryl-4-benzoyl-(or acetyl-)l,2,3triazoles ( I I 7 a ) and (II7b) 1401.
Dehydrogenation of a-pyridinealdehyde hydrazone
(118) yields, not c/.-pyridyldiazomethane (119), but
[SO] M . Regitr, Angew. Chem. 77, 428 (1965); Angew. Chern.
internat. Edit. 4, 431 (1965).
743
Table 7. 3-Acyl-11,2,3ltriazolo[3,4-alpyridines
and -quinolines
prepared.
Yield
R
the cyclic isomer 1,2,3-triazolo[3,4-a]pyridine (120)
( %)
M.p. ( " C )
157-- 158
Methyl
50
t-Butyl
90
2-Fury1
94
215
Phenyl
88
111-112
Methyl
84
147-148
2-Fury1
77
183
3-Pyridyl
75
160
Propyl
88
137-138
2-Thienyl
85
21 3
3-Pyridyl
65
213
Phenyl
85
167- 168
151,521.
A similar ring closure was observed in diazo group
transfers onto alkyl and aryl(2-pyridy1)methyl ketones
(121) in ethanol/potassium ethoxide [50,531. The diazo
stage (122) could not be isolated, but high yields of
J.
3-acyl-[1,2,3]triazolo[3,4-a]pyridines (123), their 7methyl derivatives (124), and 3-acyl-[l,2,3]triazolo[3,4-a]quinolines (125) were obtained. Some examples
are given in Table 7.
The ring cleavage of indeno[l,2-d][1,2,3]triazoleswith
mineral acids to give salts of the isomeric diazo
imines was mentioned in Section II.A.7. This ring
cleavage also takes place on treatment of the l-acyl[1,2,3]triazolo[3,4-a]pyridines (123) with perchloric
acid in dioxane, and leads via the hypothetical compound (126) to the yellow-orange perchlorates (127)
of the diazo stage (122), which could not be isolated
during the diazo transfer onto (121)[531. This is
95-96
UV-Absorption
(methanol)
Lmax(mp) (EX 10-3)
247 (3.8) shoulder;
254 (4.4); 287 (11.2);
305 (13.65)
248 (3.75) shoulder;
256 (4.35); 288
(10.95); 307 (13.3)
222 (15.0); 282 (9.15);
292 (10.0); 332 (25.1)
217 (17.7); 256 (8.85);
29'2 (10.65) shoulder;
319 (19.25)
219 (16.6); 245 (2.2);
252 (2.5); 309 (17.15)
226 (13.1); 281 (10.05);
291 (9.95); 339 (26.0)
227 (15.35); 269 (5.4):
278 (5.35); 291 (6.4);
329 (21.6)
229 (15.1); 253 (17.0);
262 (11.25) shoulder;
281 (7.35) shoulder;
291(11.95); 302 (15.25);
323 (16.3); 336(13.85)
301 (10.0) shoulder;
314(14.85); 337 (32.1);
353 (29.95)
239 (23.95); 296 (9.3)
shoulder; 309 (14.35)
shoulder; 332 (26.15);
344 (22.85)
249(22.1); 295 (11.7)
shoulder; 307 (15.75);
330 (23.45);
340 (19.9) shoulder
understable in that the salts (127) are cyclized by loss
of HC104, even in ethanol, with regeneration of the
triazoles (123), and the diazo compounds (122) expected initially cannot be isolated.
2. 1,2,3 - T h i a d i a z o l e s
Diazo group transfer and intramolecular cycloaddition
can be used in accordance with equation (j) for the
synthesis of 1,2,3-thiadiazoles. As has been known
for some time, this ring closure also takes place when
2-diazo-l,3-dioxo compounds are treated with hydrogen sulfide/ammonium hydrogen sulfide [541.
\
- HCLO,
fi-Thioxo carbonyl compounds (130) have recently
been described [55,561. A variant of this process, i.e. the
reaction of the sodium salts of p-0x0 aldehydes (128)
(instead of the sodium salts of 1,3-diketones) with isothiocyanates in acetonitrile leads via the sodium salt
(129) to high yields of formylacylthioacetamides(l31).
1541 H . Wieland and S . Bloch, Ber. dtsch. chem. Ges. 39, 1488
H. Hirzel, Ber. dtsch.chem.
Ges. 49, 1978 (1916).
(551 G. Barnikow, H . Kunzek, and D. Rich&. ,Liebigs Ann. Chem.
695, 49 (1966).
[56] G. Barnikow, Z. Chem. 6, 109 (1966); J. prakt. Chem. 141
32, 259 (1966).
(1906); H. Staudinger, .
I
Becker,
.
and
[51] J. H . Boyer, R . Borgers, and L.T. Wolford, J. Amer. chem.
SOC. 79, 678 (1957).
[52] J. D. Bower and G. R. Ramage, J. chem. SOC.(London) 1957,
4506.
1531 M . Regitz and A . Liedhegener, Chem. Ber. 99, 2918 (1966).
144
Angew. Chem. internat. Edit. / Vol. 6 (1967) No. 9
Table 8. 4-Acyl-5-alkyl(or aryl)amino-1,2,3-thiadiazolessynthesized.
R
Variant
A
B
R
C
M.P. ( "C)
( %)
YH-R'
B
q=S
(128) Na@
R-c-C-c-NH- R'
II
0
H I1
2s
93
90
C6Hs
CsH5
PH <7/
PHX
,,,A
77
89
82
80
189-190
128
117--118
109-1 1 1
88-90
Na@ (129)
1".
90-92
H
R-c-&-c
I1 I HII
0 CQ
108- I09
-NH-R~
132-1 34
172- 174
These can be used directly or after deformylation to
give (133) by diazo-group transfer 1571.
Diazo transfer from p-toluenesulfonyl azide onto
acylthioacetamides (130) takes place in ethanol
(variant A) or in methylene chloride/triethyIamine
(variant B) and gives high yields of 4-acyl-S-aryl(or
alkyl)amino-l,2,3-thiadiazoles (133) 1571 (for examples
see Table 8). In a few cases the same thiadiazoles were
obtained by 1,3-dipolar cycloaddition of diazo
carbonyl compounds to isothiocyanates, though only
R - c - c - c -NH- R'
::Ij(3
o?
c -c
-NH-R'
II
c
, R-F-II
OON S
(132)
4.
UV-Absorption
(CHzC1z)
(mu)(EX
248 (13.6); 348 (17.4)
242 (10.8); 282 (8.5)
shoulder ;
319 (12.8) shoulder);
361 (20.3)
327 (17.5)
332 (14.7)
249 (9.4); 297 (11.8);
318 (12.9)
282 (8.8) shoulder;
317 (17.1)
282 (9.0) shoulder;
320 (1 5.3)
282 (7.1);
330 (19.4)
272 (5.6); 354 (26.8)
However, the formyl group is split o f fas diethylformamide ((131) (130)) before the transfer reaction takes
place [573.
--f
The transfer of diazo groups onto N-(4-nitrophenyl)benzoylthiaocetamide (134) in ethanol gave 55 % of thiadiazole (136)
together with 21 % of isomeric 1-(4-nitrophenyl)-4-benzoyl5-mercapto-l,2,3-triazole (137), which isomerizes at its
melting point, probably via the diazo isome- (135), to the
thiadiazole (136). It is concluded from the experiments
carried out so far that (135) can cyclize by two routes, the
very high yield of (137) in the present case being due to a
particularly high N H activity (NO2 group in the p position).
However, it has also been shown that (136) isomerizes via
(135) to the triazole (137) under the conditions of the diazo
transfer (ethanol/triethylarnine), though only to a very small
extentC571. Thus the thiadiazole and the isomeric triazole are
evidently interconvertible by a Dimroth rearrangement [591
via a diazo isomer.
3. 3,5-Diacylpyrazolin-4-ones a n d
2,4-Bisdiazo-l,3,5-triketones
in moderate yields [581. The diazo isomer (132) could
not be isolated, since the cycloaddition (132) + (133)
is evidently faster than the transfer reaction (130) +
(132).
The formylated acylthioacetaniides (131) also give
thiadiazoles (133) on diazo transfer in acetonitrile/
diethylamine(variant C !)(see also Section A.6.c and d).
[S7] M . Regitz and A . Liedhegener, Liebigs Ann. Chem., in press.
The keto-en01 equilibrium of benzoylthioacetanilide (1301,
R=R'=CsHs, is also discussed.
I581 D.Martin and W .Mucke, Liebigs Ann.Chem.682,90 (1965).
Angew. Chem. internat. Edii. Vol. 6 (1967) J No. 9
Diazo-transfer reactions of 1,3,5-tricarbonyl compounds (138) in ethanol/potassium ethoxide yield
neither monodiazo compounds (139) nor 2,4-bisdiazo1,3,5-triketones (140), but give cyclic isomers of(139) ;
these are the 3,5-diacylpyrazolin-4-ones(141) [601, a
class of compounds that had previously been unknown.
Their formation can be interpreted as follows. The
initially formed (139) cyclizes by intramolecular azo
IS91 0. Dimroth, Liebigs Ann. Chem. 364, 183 (1909); ibid. 373,
336 (1910). For other examples of the Dimroth rearrangement
of 1,2,3-thiadiazoles, see J. Goerdeler and G. Gnad, Chem. Ber.
99, 1618 (1966).
[60] H . J. Geelhaar, Diploma Thesis, Universitat Saarbriicken,
7966.
745
solutions in acetonitrile/triethylamine are added dropwise to p-toluenesulfonyl azide. (For examples see
Table 10.)
However, the simultaneous pyrazolin-4-one ring
closure cannot be entirely prevented. A surprising
reaction is the thermal decomposition of 2,4-bisdiazo1,3,5-trioxo-1,5-diphenylpentane (148) in toluene,
which yields 65 % of dibenzoylacetylene (149) as the
principal product [611.
coupling (see also Sections II.A.5 and B) to give the
pyrazolin-4-one (141) (tautomeric relationships uncertain) before a second diazo group is introduced
((139)
(140)). (For examples see Table 9.)
9
H5C6-C - C’“C
8
C,H5-CH,/Cu0
- C - C,H5
II
II
Nz
Nz
8
1lOoc
- 2 N2; -CO
+ H ~ C G - C - C -~CC- C6H5
II
0
d
--f
Table 9. 3,5-Diacylpyrazolin-4-ones
synthesized.
1 Yield (%) 1 M.p. (“C)
IR’
Benzoyl
4-Methoxybenzoyl
Acetyl
2-Pyridylcarbonyl
3-Pyridylcarbonyl
4-Pyridylcarbonyl
4-Chlorobenzoyl
Benzoyl
Benzoyl
Benzoyl
Benzoyl
Benzoyl
Benz oy1
4-Chlorobenzoyl
88
79
61
71
63
91
81
D. Reactions of Methylene Groups
Activated by Cyanide
263
236
265
228
27 I
267
293
Diethyl acetonedicarboxylate (142) reacts in accordance with the same scheme, but with simultaneous
replacement of an ethoxy group by a p-toluenesulfonamide residue to give (143) (see also [1*1). In the case
On the other hand, the behavior of 4-nitrobenzyl
cyanide (152) is very complex. The primary product is
evidently always cyano-4-nitrophenyldiazomethane
(153), which is very unstable to bases. Thus when triethylamine or bulky secondary amines such as diiso-
of 1-benzenesulfonylacetylacetone (144), the monodiazo compound (145) can be isolated and then converted into the pyrazolin-4-one (147) by ring closure.
I-
2 p-TosN,
C,H,OH/C,H,OK
CH,CI,/N(C,H,),
(146)
(147)
Double transfer to form the bisdiazo compound (146)
also takes place in this case 1601. Double transfer is
also possible with the 1,3,5-triketones (138) if their
Table 10. 2.4-Bisdiazo 1.3.5-triketones (140) prepared.
lI401
R
Yield
4-Chlorophenyl
4-Methoxyphenyl
4-Methoxyphenyf
4-Chloropbenyl
Methyl
I-
746
M.P. (“C)
( %)
i R
Phenyl
The diazo transfer reactions of u-cyanoacetophenone
and ethyl cyanoacetate in ethanol/potassium ethoxide
are immediately followed by azo coupling to give the
azo enol ((150) and the hydrazone (151) respectively
[13,19,481 (see Section 1I.B).
IR Diazo band
(KBr) (cni-1)
~
Phenyl
57-61
4-Chlorophenyl
4-Methoxyphenyl
Pbenyl
Phenyl
Phenyl
52
21
14
28
31
107- 109
(decomp.)
131 (decomp.)
I 1 1 (decomp.)
107 (decomp.)
115 (decomp.)
84 (decomp.)
2146, 2114
2160,2137
2146,2110
2155,?119
2151,2114
2151
propylamine are used, the main product is the “carbene
dimer”, i.e. a,u’-dicyano-4,4‘-dinitrostilbene (154).
Potassium ethoxide in ethanol or potassium hydroxide
in methanol give partial retention of nitrogen and
formation of u,uf-dicyano-4,4‘-dinitrobenzaldehyde
azine (155). Ammonia, primary amines (methyl-,
ethyl-, i-propyl-, or ethanolamine), and sterically unhindered secondary amines (dimethylamine, piperidine, or morpholine) are incorporated directly into the
reaction product; a cyanide group is displaced with
formation of a-amino-u’-cyano-4,4’-dinitrobenzaldehyde azines (156) [481.
__.__
[61] H.J. Ceelhaar, Dissertation, Universitat Saarbriicken, 1967.
Angew. Chem. internat. Edit. 1 Vol. 6 (1967)
1 No. 9
Malonodinitrile exhibits a reaction that had not been
previously observed in reactions with p-toluenesulfonyl azide. I n aqueous sodium hydroxide ‘621 o r ethanol/
potassium ethoxide 1481, a very stable 1 :1 p-toluenesulfonyl azide adduct is formed. Formulae under discussion at present are the triazene structure (157) [621
and the triazole formulae f 158) 1481 and f 159) [63J.
T h e dissociation constants of the adduct agree with
the formula (159) [631; the cyclic structure is confirmed
by the p-toluenesulfonylations (161)
(162) a n d
(159)
(162). Compound (162) also has the expected
high acidity (pK,- 3.3 in acetone/water (1 :1) at 40°C),
and loses the ring p-toluenesulfonyl group on alkaline
hydrolysis 1631.
--f
--f
f 163)
Formula (158) may be ruled out since it is incompatible
with the dissociation constants of the adduct (water/
acetone (9:1), 20°C, pK1 = 3.2, pK2 = 7.81641).
Moreover, N-acylated nitrogen heterocycles are very
readily hydrolysed [65,661, whereas the above adduct
is stable. However, (158) may be an intermediate
in the formation of (159), since azide additions to
malonodinitrile in accordance with (158) have
been known for some time 167,681. Compound f 158)
should then readily be converted into (159) by
Dimroth rearrangement (see Section IT.C.2), particularly since the strongly electron-attracting p-toluenesulfonyl group favors ring cleavage t o form the diazo
(164)
(159) reacts with phenylmagnesium bromide t o give
(163), which yields the diazonium betaine (164) o n
removal of the p-toluenesulfonyl group and diazotization [481. Cleavage of f 159) with naphthalenesodium in
tetrahydrofuran yielded the corresponding aminotriazole (165), which was diazotized directly with
nitrous acid and coupled with P-naphthol t o form the
azo compound (166) 1631.
m
(159)
H2N-C=C-CN
---t
’ ’
HRN+N
a) H N 0 2
b) Il-Naphthol
C
‘ =C - CN
I
I
HNXN+N
(165)
*
iC-C-CN
p-TOS-N
$2
#
Jc-C-CN
HN
A,
-+
(159)
(160)
isomer (160). The subsequent ring closure (160)
+
When the reaction of malonodinitrile is carried out in
the presence of a weaker base such as triethylamine,
diazomalonodinitrile (167) is clearly formed first but
then adds o n the base to form the betaine (168)1641.
(159) of the electron-deficient terminal diazo nitrogen
atom now takes place with the more strongly nucleophilic amidine nitrogen atom, i.e. with the nitrogen
that is not p-toluenesulfonylated.
(161)
NC-CHz-CN
p-TosN,
NC-C-CN
II
Nz
+ N(c,H,),
?!
NC-C-CN
I
(162)
111. Diazo Group Transfer with Azidinium Salts
[62] J.P.Fleury, D.van Assche, and A.Bader, Tetrahedron Letters
1965,1399.
[63] W .Anschiitz, Diploma Thesis,Universitat Saarbriicken,l966.
[64] D.vart Assche, Dissertation, Strasbourg University, 1966.
[ 6 5 ] H . A. Staab, Chem. Ber. 89,1927 (1956); Angew. Chem. 74,
407 (1962); Angew. Chem. internat. Edit. I , 351 (1962).
[66] H . A. Staab and K . Wendel, Liebigs Ann. Chem. 694, 91
(1966); Chem. Ber. 93, 2902 (1960).
[67] J . R . E . Hoover and A . R . D ~ vJ., Amer. chem. SOC. 78, 5832
(1956).
1681 A. Dornow and J . Helberg, Chem. Ber. 93, 2001 (1960).
A n g e w . Chem. internat. E d i t . 1 Vol. 6 (1967)
1 No. 9
The preparative scope is considerably widened by
diazo transfers with azidinium salts. These are salts
(mainly tetrafluoroborates) of mesomeric cations having the general formula (169), and may be derived e.g.
from benzothiazole, benzimidazole, pyridine, or
quinoline 1691. In view of the relatively short-wave
[69] H. EaNi and F. Kersting, Liebigs Ann. Chem. 647, 1 (1961 ).
747
asymmetric stretching bands of the N2 groups (2175
cm-l), the azidinium salts may be regarded as Ndiazonium salts (or diazonium amidines) 1701; this
NO
I
C~H,
c)
BF,O
limit is probably reached when the proton activity of
a methylene compound is so low that anion formation
no longer occurs.
II
=N- N-N :
CI ~ H , BF?
HzC-C,
I
I
CH3
I
C2Hs
X--.
+ H zc: Z-..' )
(172)
I
(173)
C&-X(P)
CH3H' O,c,N.
H O
N
[I
&$'LNF--C-C
H3
N\ I
I
N-Cao.."
I
BFP
I
CH,
I
-
- 1171J
Nz=C-C\
,N-CSH~-X(P)
C=N
+ 1178
thiazolium fluoroborate (170) is as follows:
0
a>C=N-N=N:
+ (170)
,N-C6H4-X(p)
C=N
(169)
explains their ability to act as Nz-transfer agents. The
overall transfer reaction for 3-ethyl-2-azidobenzo-
(170)
::
0
0
J
-(
(174)
c,H,-x(~)
CH,
(175)
(b): X = C 1 (85%)
(a): X = H (97%)
(c): X = COOH (80%)
( d ) : X = COzC2H5 (8570) (e): X = NO2 (7770) (f):X = S 0 3 N a (58%)
Thus the azidinium salt (170) gives a resonancestabilized amidinium salt (171) 1711, which is probably
partly responsible for the smoothness of the reaction.
The reaction takes place in aqueous-alcoholic solution
or suspension at 0 to 80°C and at p H values of 0 to 8.
Since the reaction proceeds only in the neutral and
acid ranges, in which sulfonyl azides are unreactive,
it is particularly suitable for diazo compounds that
undergo coupling. Thus it has given good results in
the synthesis of 2-diazo-2,3-dihydrothionaphthen-3one 1,l-dioxide (55) (68 %) "21, a-cyano-a-diazoacetophenone (88 %) 1711, and 4-diazo-3-methyl-1 -phenylpyrazol-5-one (96 %) 1711, whereas the transfer from
p-toluenesulfonyl azide in basic media yields only
coupling products (see Sections II.A.5, B, and D).
Finally, the method has also proved suitable for the
synthesis of a-diazo-a-nitro carbonyl compounds 1731.
In addition to diazonitromethyl phenyl ketone (yield
23 %), methyldiazonitroacetate (yield 18 %) was synthesized for the first time. Some preparative examples
are shown in Table 11.
2 - Azido - 3 - ethylbenzothiazolium tetrafluoroborate
( I 70) reacts directly with 1-aryl-3-methylpyrazo1-5ones (172) (molar ratio 1:2) to give azopyrazolones
(175) [741 (see also Section II.B), for which the chelated
hydrazono-enol form (174) is deduced spectroscopically. The reaction proceeds in dimethyl-formamide/
water (1 :1) and at pH = 8. The diazopyrazolone (173)
occurs as an intermediate, and then couples with (172)
to give the dye. (The multi-stage mechanism is confirmed by kinetic measurements.) In the more strongly
acidic region (pH = 3 to 4), on the other hand, the
transfer reaction stops at the diazo stage (173).
IV. Ring Cleavage of Adducts of Azides to
Carbon-Carbon Multiple Bonds
Methyl acrylate adds on azides at room temperature
to form the colorless 1,2,3-triazolines (176), which are
converted by basic catalysis (triethylamine) into the
previously unknown esters ( I 77) of p-arylamino-a-diazocarboxylic acids [751. Esters of fumaric and crotonic
acids and some a$-unsaturated ketones react similarly,
Table 1 I . Results of diazo transfers with 3-ethyl-2-azidobenzothiazolium tetrafluoroborate.
Diazo compound
5-Diazobarbituric acid
2-Diazoindan-l,3-dione
2-Diazo-5,5-dimethylcyclohexane-l,3-dione
2,4-Bisdiazocyclohexane1,3-dione
I ,3,5-Trisdiazocyclohexane-2,4,6-trione
4-Diazo-3-phen yl-isoxazolone
I -Diazo-2-oxo- 1 ,Z-dihydronaphthalene
278
149
108
83
220
74
94
84
84
77
31
95
77
21
The requirement of an acidic to neutral reaction
medium appears to form the limit of the preparative
scope of the Nz transfer with azidinium salts. This
[70] H . Balli, Liebigs Ann. Chem. 647, 11 (1961).
[71] H . Balli and V .Muller, Angew.Chem.76, 573 (1964); Angew.
Chem. internat. Edit. 3, 644 (1964).
1721 H . Balli, Marburg, personal communication (June 9, 1964).
[73] H . Balli and R. Low, Tetrahedron Letters 1966, 5821.
748
except that the ring cleavage takes place even under
the conditions for cycloaddition, i.e. without the
addition of a base.
A cyclic stage (178) could also be involved in the
formation of ethyl a-diazo-N-arenesulfonylacetimid1741 H. Balli and R . Gipp, Liebigs Ann. Chem. 699, 1 3 3 (1966).
[751 R . Huisgen, G. Szeimies, and L. Mobius, Chem. Ber. 99,
475 (1966).
Angew. Chem. internat. Edit.
Vol. 6 (1967) / No. 9
because the diazo groups in (177) and (179) are
derived from azides.
L
J
The author and his co-workers are gratefirl to Professor
Dr. B. Eistert for his interest in and support of this
work. Thanks are also due to the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie
for their generous financial support.
f I 78)
ates ( I 79) from ethoxyacetylene and benzenesulfonyl
azidesI76J. Neither of these reactions involves a CHacidic starting material, but they are mentioned here
[A 589 1EI
Received: September 29th, 1966; revised: June 9th. 1967
German version: Angew. Chem. 79, 786 (1967)
Translated by Express Translation Service, London
[761 P. Griinnngrr, P . V . Finzi, and C . Scotti, Chem. Ber. 98, 623
(1965).
Higher Coordination Numbers of the Typical Elements‘’*I
BY R.F. HUDSONI*I
The bonding in electron-deficient molecules, e.g. the boron hydrides and certain metal
alkyls, and in molecules which appear to violate the rare gas rule, e.g. hydrogen bonded
complexes, interhalogen compounds and compounds of the typical elements with high
coordination numbers such as PC15 and s F 6 can be described by a simple molecular
orbital treatment involving delocalized ri-bonds. The contribution of d-orbitals to the
bonding in the interhalogen compounds and rare gas fluorides is very small. The sterenchemistry and physical properties of the P X j system are explained readily by the delocalization treatment and it is likely that here also the importance of spd hybridization
has been overemphasized in the past.
1. The Basis of the Octet Rule
The electronic structure of an atom is determined by
two main principles.
a) According to the Pauli principle, no two electrons
may have the same set of quantum numbers, and
hence only a limited set of orbitals is available.
b) In the ground state, the electrons occupy the
lowest levels, and Hund’s rule states that electrons
(which have the same spin) will occupy separate
degenerate levels until such levels are filled.
Spectroscopic examination leads to values of orbital
energies, which enables two fairly distinct kinds of
atom to be recognised:
1
I
core
I
I
1
Silicon
Phosphorus
Sulfur
2sZ
;2;
--f
ii. Transition elements
For example:
I
Scandium
Manganese
i. Typical elements
I
Here the difference in energy between 3s, 3p, and 3d,
4s levels is very high [ I ] (ca. 8-10 eV) so that the characteristic compounds of these elements use 3s and 3p
orbitals only[***] in most of their compounds. Thus
the typical valency of sulfur is 2, of phosphorus 3, and
of silicon 4 (through 3s
3p promotion). I t is the
size of the 3s + 3d energy difference, such that the 3d
orbitals are close to the continuum, which is responsible for the octet rule.
g
2p6
valency
electrons
excited
levels
39
39
3s2
3do
3dO
3d0
3p2
3p3
3p4
4sn
4sO
4so
valency
electrons
core
Is’
252
IS*
2s*
2ph
2ph
3s2
39
3p6
3pn
3dl
3dS
49
4s’
4pO
4pO
Here the 4s and 3d levels have similar energies and the
3d levels are partially occupied, leading to spd hybridisation of the orbitals. The use of 3d orbitals and their
importance in determining the stereochemistry and
[*I Dr. R. F. Hudson
- ~.
...
[I] E. Moore, Atomic Energy Levels, Vol. 1 , Circular 467 Nat.
University Chemical Laboratory, University of Kent
Canterbury, Kent (England)
[**I Based on a lecture given at the Review Symposium on
“Modern Views of Valency and Bonding” at Southampton on
April 21st and 22nd, 1966.
Bur. Standards, 1949.
[***I Excited levels contribute to all bonding orbitals, but this
is a secondary effect and will be neglected at this point. The influence of these orbitals will be considered i n somecases a t a later
stage.
.
Angew. Chem. internal. Edit. 1 Vul. 6 (1967)
Nu. 9
~~
749
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