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New Reagents for Synthesis of Heterocyclics from Carbodiimides and Phosgeniminium Salts.

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[2] a ) R . A p p r l . F . Knoll, H . Vrltmann, Angew. Chem. 88, 340 (1976): Angew.
Chem. Int. Ed. Engl. 15,315 (1976); b) R. A p p r l , H. Veltrnutin, Tetrahedron
Lett., in press.
[3] H . J. Busirntinn, Angew. Chem. 77, 609 (1965); Angew. Chem. I n t . Ed.
Engl. 4. 583 (1965); Chem. Ber. 95, 58 11962).
[4] H . Schmidburr. H . Stiihler, W t'ornberger, Chem. Ber. JUS, 1084 (1972).
New Reagents for Synthesis of Heterocyclics from
Carbodiimides and Phosgeniminium Salts[']
meric with ( 3 ) are in fact trichlorides of 1,1,3,5-tetrasubstituted
biurets (7), which they yield upon hydrolysis. Aminolysis
or ammonolysis of ( 5 ) afford the corresponding biguanides
(8) (Table 1).
The synthetic potential of (1,3-dichloro-2,4-dicyclohexyl-2,4diaza-3-buteny1idene)dimethylammoniumchloride (5 N ) in
heterocyclization reactions is demonstrated by the synthesis
of triazolinimine ( 1 2), triazinimine (13), and benzotriazepine
( 1 4 ) (see Table 1).
By Asher Elgaui and Heinz Gunter Vieher]
(Dichloromethy1ene)dimethylammonium salts ("phosgeniminium salts") ( I ) are stable electrophilic reagents of the
Mannich-Bohme and Vilsmeier-Haack-Arnold type"]. These
salts add readily to electron rich multiple bonds: with cyanamide ( 2 ), for example, they yield the versatile azatrimethinecyanine (3jC3l.
R-N
12)
(1)
(3)
k
NMe,
Y Y
R-N
k NMe,
Y Y
It is now found that carbodiimides ( 4 ) form the adducts
( 5 ) with (1). The same products arise also from ( 1 ) and
N,N'-disubstituted ureas (6). Biselectrophiles (5) being isoR-N=C=N-R
(41
16j
R-NH-C-NH-R
Procedures :
Y
( 5 a): A mixture of dicyclohexylcarbodiimide ( 4 a ) and
o
R-N=C-N-C=NMe,
&1 A1
"'"J
s
C1'
I . NH3
2. HCI04
NaHCO,
R-NH-C-N-C-NMe,
8 6
faj,
K
= Cyclohexyl;
(7)
(I) (molar ratio 1 : 1) in chloroform is stirred at room tempera-
(5)
B
R-NH-C-NI1
NH
-NMe, (81
8 H SHC10,
( b ) . R = CH,
tureuntil ( I ) hasdissolved. The solvent is partially evaporated
and ether is added to precipitate ( 5 a) as a white hygroscopic
solid.
( 5 b ) : 1,3-Dimethylurea ( 6 b ) and ( 1 ) (molar ratio 1 :2)
are refluxed in chloroform for about 1 h until all ( I ) has
dissolved; work-up is the same as for ( 5 a ) .
( 1 4 ) : A refluxing mixture of ( 5 a ) (3.68g) and o-phenylenediamine ( 1 1 ) (10.8g) in methylene chloride (40ml) is stirred
Table 1. Properties of the new compounds.
K
Cpd.
Yield
M.p.
IK [cm-']
C"/.l
rC1
(in CHCI,)
95
94
95
95
Oil
154
2940, 2860, 1720, 1630, 1bLU
2960, 2700, 1720, 1655
3000, 2940, 2880, 1640, 1500
80
190
3440, 3360, 2930,2850, 1595, 1565. 1500, 1100
30
92
72
[*I
1.0-2.5 (20H, m), 3.5 (ZH, m). 3.8 (6H, s)
3.2-3.4 (m)
1.0-2.0 (20H, m), 2.95 (6H, s), 3.5-3.8 (2H. m),
5.0 ( I H, d, J = 7.5 Hz) [b]
1.0-2.1 (20H, m), 3.05 (6H, s), 3.3-3.5 (2H.m),
5.3---5.7 ( 4 H , br.) [b]
2930, 2860, 1630, 1580
1.0-2.0(20H,m),2.70(6H,s),2.8(2H,m),7.3(5H,
m)
154
2925, 2850, 1635, 1590, 1535
80
140
2930, 2850, 1635, 1585, 1538, 1492
70
I42
3440,3030.2930
1.2--1.9(18H,m),2.6(2H,m),3.07(6H,s),3.5(1H,
m), 4.2 ( I H. m), 7.4 (3 H, m). 8.3 (2 H, m)
1.3-2.0 (20H, m), 3.44 (6H, s). 4 . 1 4 . 2 ( 2 H , m),
7.5 ( 3 H , m), 8.42 ( 2 H , m). 10.2 ( I H, d, J = 7 H z ) [b]
1.0-1.9 (18 H, m),2.3 (2H, m), 3.13 (6H. s). 3.5 and
374(2H,m),4.20(1H,m),6.9-7.1(4H,m)
[a] In CDCl3, TMS =O.
[b] N H protons, exchangeable with F3C-C02D.
[c] Protonation at the exocyclic imino nitrogen since CH-NH
-~
'H-NMR (8 values) [a]
~
Dr. A. Elgavi
Bar llan University
Ramat-Gan (Israel)
Prof. Dr. H. G. Viehe
Laboratoire de Chimie Organique
Universitk de Louvain
Place Louis Pasteur, 1
B-1348 Louvain-la-Neuve (Belgium)
Angrw. Chern. I n t . Ed. Etigl. 16 (1977) N o . 3
coupling can be observed
overnight. The solution is then concentrated and dry ether
is added to precipitate the hydrochloride of ( 1 4 ) (4.6g, 87 %).
The free base ( 1 4 ) is obtained by treatment with concentrated
KOH at O T , and recrystallization from ethanol/water.Compounds ( 1 2 ) and (13) were prepared analogously.
Received: January 20. 1977 [Z 653a IE]
German version: Angew. Chem. 89, 188 (1977)
181
CAS Registry numbers:
( I ), 33842-02-3; ( 4 a ) , 538-75-0; ( 4 b ) , 4852-30-6; ( 5 a ) , 61 740-88-3; ( 5 b ) ,
61740-89-4; (66),96-31-1; ( 7 ~ ) 61740-90-7;
,
( 8 ~ )61740-92-9;
,
(9), 100-63-0;
(lo), 618-39-3: (11),95-54-5, (12), 61740-93-0; (13), 61740-94-1 : (13).HCI,
61 740-95-2; ( I 4 ) , 61 740-96-3; ( 1 4 ) . HCI, 61 740-97-4
14)
i
~-
- CH&I
[l] Iminium Chemistry, Part 16.-Part 15: B. Carllaux, P . George, F . T a m uch, 2. Janousek, H . G . Viehe, Chimia 30, 387 (1976).
[2] For reviews see H.Blihme, H . G . Viehe: lminium Salts in Organic Chemistry. Wiley, New York 1976.
131 Z. Janousek, H . G . Viehe, Angew. Chem. 85, 90 (1973); Angew. Chem.
Int. Ed. Engl. 12, 74 (1973).
r
H5C6,
Reactions of Acyl Chlorides/Triethylamine or Ketenes
with Phosgeniminium Salts[']
By Heinz Giinter Viehe, Brigitte Le CleJ and Asher E/gaui[*]
a-Chloro-P-(chlorocarbony1)enamines(3) are known to
arise from the addition of phosgene to ynamines['] or from
the condensation of phosgene with monosubstituted acetamides in the presence of base^[^,^!
We have now found that (3) can be obtained in good
yields from the reaction of monosubstituted acetyl chlorides
and (dichloromethylene)dimethylammoniumsalts ("phosgeniminium salts") (2)15] (Table 1).
//0
R-CHZ-C,
+
C1
H3C\@ ,c1
N=C\
H3C/
C1
Cl0
R
Yield
[%I
C6Hs 70
(3a)
75
( 3 b ) CI
( 3 ~ ) CH3
70
CzHs 60
(3d)
["C/torr]
IR [cm-'1
(in CHC13)
dec.
7&75/0.1
70-74/0.1
75-80/0.3
1700, 1555
1685, 1550
1715, 1555
1710, 1550
B.p.
'H-NMR
(6 value) [a]
3.18 (6H,s), 7.32 (5H, s)
'3.17(~)
2.20(3H,s),3.10(6H,~)
1.14 (3H, t), 2.60 (2H,
qh 3.08 (6H, t)
[a] In CDC13,TMS=O.
Thus phenylacetyl chloride ( 1 a ) condenses with (2) in
the presence of triethylamine to yield (3 a). No reaction occurs
in the absence of a base, which indicates that either phenylketene, the corresponding acylammonium salt, or the acyl chloride enolateL6]is the reactive intermediate.
If the starting material is diphenylacetyl chloride ( 4 ) , the
new dichloro p-lactam ( 5 ) is obtained instead of the adduct
(3). This heterocycle arises alternatively and equally well
from diphenylketene (6) and (2).
[*] Prof. Dr. H. G. Viehe, Dr. B. Le Clef
Universitt de Louvain, Lahoratoire de Chimie Organique
Place L. Pasteur, 1
B-1348 Louvain-la-Neuve (Belgium)
Dr. A. Elgavi
Bar Ilan University
Ramat-Gan (Israel)
182
+
(2) -
1
c4O
H5C6>r
1
(71
The intermediate (7) can be detected by NMR spectroscopy.
When diphenylketene (6) and (2) are heated to 4 5 T , broad
peaks appear at 13= 4.25 and 7.45 ppm which correspond most
probably to the N-dimethyl and phenyl signals. These absorptions disappear on the formation of ( 5 ) .
Compounds ( 3 ) , being reactive derivatives of malonamic
acid, are well established reagents, particularly for the synthesis
of heterocycle^[^^ 'I. ( 5 ) as the first representative of the reactive
class of 4,4-dichloroazetidin-2-one merits further synthetic
interest [*I.
Experimental
Table 1. d u h s t i t u t e d P-chloro-b-(dimethy1amino)acryloylchlorides (3).
Cpd.
,C=C=o
1
H&6
(3 a ) : Triethylamine (2.02 g, 0.02 mol) is added dropwise
at room temperature to a stirred suspension of (2) (1.65g,
0.02 mol) in a dry chloroform solution containing phenylacetyl
chloride (1.54g, 0.02mol). Stirring is continued until (2) is
completely dissolved. The solvent is then evaporated and the
product is extracted with refluxing ether. After filtration and
evaporation of the solvent ( 3 a ) is recrystallized from ether/
petroleum ether.
( 5 ) : Compounds (2) (1.62g, 0.01 mol) and (6) (1.94g,
0.02mol) are added to dry chloroform (30ml). The stirred
solution is refluxed until (2) has completely disappeared.
The solvent is evaporated and ( 5 ) is recrystallized from cyclohexane [colorless needles, m.p. 152-153 "C, yield 72 %; IR
(CHC13) 1775cm-' (C=O); NMR (CDC13/TMS=O): 6=3.0
(3H, s), 7.1-7.75ppm (lOH, m)]. The N-ethyl analog of ( 5 )
was obtained analogously [m.p. 138-1 39 "C, yield 73 %; IR
(CHC13): 1775cm-'; NMR (CDCI,/TMS=O): 6 = 1.4ppm
(3H, t), 3.45 (2H, q), 7.1-7.7 (IOH, m)].
Received: January 20, 1977 [ Z 653b IE]
German version: Angew. Chem. 89, 189 (1977)
CAS Registry numbers:
( I a ) , 103-80-0; ( I b ) , 79-04-9; ( I c ) , 79-03-8; ( I d ) , 141-75-3: (2), 33842-02-3:
( 3 a ) , 57243-90-0; (3b), 57243-88-6: ( 3 c L 57243-87-5; ( 3 d ) , 19698-31-8:
( 4 ) , 1871-76-7; ( 5 ) , 61741-05-7; ( 5 ) N-Et analog, 61741-06-8: ( 6 ) , 525-06-4
[l] Phosgeniminium Chemistry, Part 23.-Part 22: B. Stefander. H . G . Viehe.
Angew. Chem. 89,182 (1977);Angew. Chem. Int. Ed. Engl. 1'6,189 (1977).
[2] R. Buyle, H . G. Viehe, Tetrahedron 24, 3987 (1968).
[3] R. Btryle, H. G . Viehe, Tetrahedron 24,4217 (1968); L. Ghosez, J . Marrhond-Brynaerf in H . Bohrne, H . G . Viehe: Iminium Salts in Organic
Chemistry. Wiley-Interscience, New York 1976.
[4] G. Winters, N . Dimola, E. Oppici, G. Nafhansohn, Farmaco Ed. Sci.
30, 620 (1975).
[5] Z . Janousek, H . G. Viehe in H . Biihme, H. G . Viehe: lminium Salts
in Organic Chemistry. Wiley-Interscience, New York 1976.
[6] R. Giger, R. Affain, M . Rey, A. S. Dreidiny, Helv. Chim. Acta 53, 120
(1970); W 7: Brady, G . A . Scherubel, J. Org. Chem. 39, 3790 (1974).
[7] R . Buyfe, H. G . Viehe, Tetrahedron 25, 3447, 3453 (1969).
181 J . P. Decfercy, G. Germain, M . Van Meemwhe, to be published.
Angew. Chem. fnr. Ed. Engl. 16 (1977) N o .
3
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