A new synthesis of N,N′-Bis(dimethylaminomethylene)hydrazine

Article abstract of DOI:10.1055/s-0028-1083192

N,N′-Bis(dimethylaminomethylene)hydrazine was synthesized in a one-step procedure from N,N′-diformylhydrazine and tert-butoxy- bis(dimethylamino)methane (Bredereck-Simchen reagent) or N,N-dimethylformamide dimethylacetal. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1083192

3380
SHORT PAPER
A New Synthesis of N,N¢-Bis(dimethylaminomethylene)hydrazine
A
N
ew Synthesis of
N
,
N
i
¢
-Bis(d
l
imethy
l
lamino
i
methylene)hy
K
drazine antlehner,*a,b Jochen Mezger,b Edmont V. Stoyanov,b Sylvia Leonhardtb
a
b
Received 14 May 2008; revised 11 July 2008
Dedicated to Professor H. Groß on the occasion of his 80th birthday
In connection with our ongoing search for new formylat-
ing reagents for aromatic compounds,4 we were interested
in compound 4. Orthoformic acid derivatives very often
show a comparable mode of reaction and reactivity
against NH-acidic compounds such as N,N-dimethylchlo-
romethyleniminium chloride or the DMF/POCl3-adduct.
Thus, treatment of diformylhydrazine 2 with t-butoxy-
bis(dimethylamino)methane (Bredereck–Simchen re-
agent; 5) in a molar ratio of 1:2 provided 4 directly with
89% yield (Scheme 2).
Abstract: N,N¢-Bis(dimethylaminomethylene)hydrazine was syn-
thesized in a one-step procedure from N,N¢-diformylhydrazine and
tert-butoxy-bis(dimethylamino)methane (Bredereck–Simchen re-
agent) or N,N-dimethylformamide dimethylacetal.
Key words: condensation reaction, Bredereck–Simchen reagent,
building block, iminium salts
In a recently published paper, a simplified general synthe-
sis of 1,2,4-triazoles was described starting from N,N-
dimethylformamide azine dihydrochloride (3).1 The bis-
iminium salt 3 is accessible from the reaction of hydrazine
hydrate with excess N,N-dimethylchloromethyleniminium
chloride (N,N-dimethylformamidchloride; 1) prepared in
situ from N,N-dimethylformamide and thionylchloride1,2
or oxalylchloride1 in N,N-dimethylformamide. The bis-
iminium salt 3 can also be obtained from N,N¢-diformyl-
hydrazine 2 and the pure amide chloride 1, prepared by
the action of phosgene, thionylchloride or oxalylchloride
on N,N-dimethylformamide (Scheme 1).3
With the more easily accessible N,N-dimethylformamide
dimethylacetal (6), the hydrazine derivative 2 can also be
transformed into the azine 4, however with distinctly low-
er yield (68%). From the NMR spectra, it can be conclud-
ed that product 4 consists of only one isomer.
The azine 4 reacted with excess methyliodide to give the
iodide 7a (Scheme 3).2 We envisaged salts of this type as
conceivable reagents which could be used for electro-
philic aromatic substitution reactions. In order to examine
this possibility, we prepared the (strongly hygroscopic)
salt 7b from 4 and dimethylsulfate. For characterisation of
7b by elemental analysis, it was converted into the tet-
raphenylborate 7c by reaction with sodium tetraphenyl-
borate in acetonitrile.
In the reaction of N,N¢-diacetylhydrazine with thionyl-
chloride in N,N-dimethylformamide, the bis-iminium salt
3 is also formed with somewhat lower yield.2 N,N¢-
Bis(dimethylaminomethylene)hydrazine (4) can be liber-
ated by treating 3 with sodium ethoxide in ethanol3 or by
the addition of potassium carbonate to an aqueous solu-
tion of 3 and a subsequent time consuming (2 days) ex-
traction of 4 with ether.2 Compound 4 can be used as the
starting material in the synthesis of 1,3,4-thiadiazole3 and
1,2,4-triazoles,1,2 however it was shown that 1,2,4-triaz-
oles can be prepared, without isolation of 4, directly from
the bis-iminium salt 3 and primary amines.1
Unfortunately, the salt 7b, even in combination with
equimolar amounts of aluminium chloride or trifluo-
romethanesulfonic acid, did not react with either o-xylene
or with toluene. In the attempted reaction of 4 with tolu-
ene, in the presence of two equivalents of trifluo-
romethanesulfonic acid, we could not detect any
aldehyde.
H2NNH2⋅H2O
Cl
2 H C+
+
CH
+
H
H
Cl–
2 Cl–
N
N
NMe2
Me2N CH
OHC NH NH CHO
3
NMe2
base
– 2 HCl
1
2
CH
N N CH
NMe2
Me2N
4
Scheme 1
SYNTHESIS 2008, No. 21, pp 3380–3382
x
x.
x
x
.
2
0
0
8
Advanced online publication: 16.10.2008
DOI: 10.1055/s-0028-1083192; Art ID: T07908SS
© Georg Thieme Verlag Stuttgart · New York

SHORT PAPER
A New Synthesis of N,N¢-Bis(dimethylaminomethylene)hydrazine
3381
After cooling to r.t., the column was replaced by a distilling appara-
tus with air cooler and the product was obtained by vacuum distil-
lation of the residue under reduced pressure (bp 112–115 °C/14
Torr). The distillate solidified to yellowish crystals (mp 73–74 °C),
which were recrystallized from PE.
Yield: 63 g (89%); mp 78–79 °C (Lit.1 79–81 °C, Lit.2 75–76 °C).
IR (ATR): 2884, 1621, 1363 cm–1.
NMe2
OCMe3
NMe2
+ 2 H
C
5
– 2 Me3COH, – 2 HNMe2
89%
2
OMe
C
OMe
4
1H NMR (500 MHz, CDCl3): d = 2.83 [s, 6 H, N(CH3)2], 7.80 (s,
1 H, CH=).
+ 2 H
NMe2
6
13C NMR (125 MHz, CDCl3): d = 38.2 [N(CH3)2], 156.0 (CH=).
– 4 MeOH
68%
Anal. Calcd for C6H14N4: C, 50.67; H, 9.92; N, 39.40. Found: C,
50.28; H, 9.81; N, 39.36.
Scheme 2
N,N¢-Bis(dimethylaminomethylene)hydrazine (4) from N,N¢-
Diformylhydrazine (2) and N,N-Dimethylformamide Dimeth-
ylacetal (6)
Me
N
X–
MeX
4
CH
N CH
NMe2
Me2N
+ NaBPh4
+
N,N¢-Diformylhydrazine (2; 44 g, 0.50 mol) and N,N-dimethyl-
formamide dimethylacetal (6; 178 g, 1.50 mol) were mixed under
exclusion of moisture. The mixture was heated with stirring, where-
by methyl formate and MeOH were distilled off by means of a 70
cm Vigreux column with a column head top. In the course of the dis-
tillation the bath temperature was raised to a maximum value of
140 °C. After cooling, the volatile compounds (bp <80 °C/15 Torr)
were removed in vacuo. The residue was distilled without a column
through an air-cooled distillation apparatus. The colorless distillate
solidified on cooling to give pale-yellow crystals (mp 73 °C), which
were recrystallised from PE.
– NaMeSO4
7a: X = I
7c
7b: X = MeSO4
7c: X = BPh4
Scheme 3
Two new simple methods for the preparation of N,N¢-
bis(dimethylaminomethylene)hydrazine 4 have been de-
veloped starting from N,N¢-diformylhydrazine and
orthoamide derivatives 5 or 6. From 4 and dimethylsulfate
the iminium salt 7b has been obtained. Adducts from 7b
and AlCl3 of CF3SO3H did not react with alkylaromatic
compounds in the sense of an electrophilic aromatic sub-
stitution.
Yield: 48.5 g (68%); mp 78–79 °C.
1-Methyl-1,2-bis(dimethylaminomethylene)hydrazinium
Methylsulfate (7b)
To N,N¢-bis(dimethylaminomethylene)hydrazine (4; 7.1 g, 50.0
mmol) in anhyd MeCN (50 mL), was added dropwise, dimethylsul-
fate (6.62 g, 53.0 mmol) with stirring, under exclusion of moisture
within 10 min. The mixture was allowed to stand for 12 h and then
heated under reflux for 3 h. The MeCN was removed in vacuo by
means of a rotary evaporator. To the residue was added anhydrous
toluene (10 mL). The separated salt was filtered with exclusion of
moisture and dried under oil-pump vacuum.
t-Butoxy-bis(dimethylamino)methane (Bredereck–Simchen re-
agent, purchased from Acros) and N,N-dimethylformamide dimeth-
ylacetal (Acros, Aldrich, Fluka) are commercial chemicals, which
can be also prepared according published procedures.5,6 Petroleum
ether (PE), where used, had a boiling range of 40–80 °C.
IR spectra have been measured on a Perkin-Elmer IR Spectrum One
(ATR mode). NMR spectra have been recorded on Bruker Avance
500 (1H: 500 MHz, 13C: 125 MHz) and Bruker DPX 250 (1H: 125
MHz) spectrometers. TMS was used as internal standard; d values
are reported in ppm. Elemental analyses have been obtained from a
Carlo Erba Elemental Analyzer 1106.
Yield: 13.12 g (98%).
1H NMR (250 MHz, CD3CN): d = 2.84–3.01 [m, 6 H, N(CH3)2],
3.15 (s, 3 H, N+CH3), 3.38 [s, 6 H, N(CH3)2], 3.53 (s, 3 H,
CH3OSO3), 7.57 (s, 1 H, N=CHN), 7.81 (s, 1 H, N+=CHN).
1-Methyl-1,2-bis(dimethylaminomethylene)hydrazinium
Tetraphenylborate (7c)
N,N¢-Bis(dimethylaminomethylene)hydrazine N,N-Dimethyl-
formamide Azine (4) from N,N¢-Diformylhydrazine (2) and
t-Butoxy-bis(dimethylamino)methane (Bredereck–Simchen
Reagent)
The methylsulfate 7b (1.94 g, 7.0 mmol) was dissolved in anhyd
MeCN (25 mL). To the boiling solution was added a solution of so-
dium tetraphenylborate (2.40 g, 7.0 mmol) in anhyd MeCN (10 mL)
with stirring. The boiling mixture was filtered and the filtrate evap-
orated. The residue was extracted several times with boiling THF
and the hot extracts are filtered. From the combined extracts, color-
less crystals separated, which were washed with Et2O.
A two-necked flask was fitted with a dropping funnel and a 30 cm
Vigreux column. The receiver tube was protected with a KOH dry-
ing tube against moisture. In this apparatus the Bredereck–Simchen
reagent (183 g, 1.05 mol) was rapidly added with magnetic stirring
to N,N¢-diformylhydrazine (44.0 g, 0.50 mol) by means of the drop-
ping funnel. The mixture was slowly heated with stirring. At about
80 °C, the mixture began to boil spontaneously and t-BuOH dis-
tilled off. The bath temperature was raised slowly to about 105 °C
with complete removal of t-BuOH by distillation (amount of distil-
late ~61 g). Dimethylamine was evolved during the distillation. The
volatile parts (bp <50–60 °C/15 Torr) were removed from the reac-
tion mixture by evaporation in vacuo (bath temperature 120 °C).
Yield: 2.10 g (63%); mp 164 °C.
IR (ATR): 3048, 2992, 1697 (C=N+), 1624 (C=N) cm–1.
Anal. Calcd for C31H37BN4: C, 78.15; H, 7.83; N, 11.76. Found: C,
77.97; H, 7.80; N, 11.87.
The salt was nearly insoluble in all common deuterated solvents,
thus NMR data are not available.
Synthesis 2008, No. 21, 3380–3382 © Thieme Stuttgart · New York

3382
W. Kantlehner et al.
SHORT PAPER
(2) Bartlett, R. K.; Humphrey, I. R. J. Chem. Soc. C 1967, 1664.
(3) Föhlisch, B.; Braun, R.; Schultze, K. W. Angew. Chem., Int.
Ed. Engl. 1967, 6, 361; Angew. Chem. 1967, 79, 318.
(4) (a) Kantlehner, W.; Leonhardt, S.; Ziegler, G.; Scherr, O.;
Kreß, R.; Goeppert, A.; Sommer, J. Z. Naturforsch., B:
Chem. Sci. 2007, 62, 995. (b) For a review, see: Kantlehner,
W. Eur. J. Org. Chem. 2003, 2530.
(5) Bredereck, H.; Simchen, G.; Kantlehner, W.; Horn, P.;
Wahl, R.; Hoffmann, H.; Grieshaber, P. Chem. Ber. 1968,
101, 41.
Acknowledgment
The present work was supported by the Bundesministerium für Bil-
dung und Forschung, Bonn, in the frame of an alliance research pro-
ject as the subproject ‘Electrophilic Substitution Reactions on
Aromatic Compounds with Novel Reagents in Conventional Sol-
vents and Novel Ionic Liquids’ (FKZ 03 CO 3421). We are indebted
to BASF AG, Ludwigshafen and Bayer AG, Leverkusen for the gift
of chemicals.
(6) Kantlehner, W.; Speh, P. Chem. Ber. 1972, 105, 1340.
References
(1) Naik, A. D.; Marchand-Brynaert, J.; Garnia, Y. Synthesis
2008, 149.
Synthesis 2008, No. 21, 3380–3382 © Thieme Stuttgart · New York