Full text of DOI:10.1007/BF02659533

S Y N T H E S I S OF S U B S T I T U T E D C H L O R O A C E T Y L E N E S
F R O M M E T H Y L K E T O N E S
S. F . V a s i t e v s k i t , A . N. S i n y a k o v ,
UDC 542.91:547.314'131
M . S . S h v a r t s b e r g , and I. L. K o t l y a r e v s k i i
E a r l i e r it was shown that the reaction of 4-acetyl-3,5-dimethylpyrazole (Ia) with phosphorus pentachlc-
ride leads to the formation of the vicinal dichloride 4-a,~-dichloroviny[-3,5-dimethylpyrazoie (IVa) in addition
to 4-~-chlorovtnyl- and 4-,y,~-dichloroethyl-3,5-dimethylpyrazols aIIa) and (Ha) [1]. In reaction with sodium
amide in liquid ammonia compound (U/a) eliminates a molecule of hydrogen chloride and is converted into 4-
•
~-chloroethynyl-3,5-dimethylpyrazole
(Via). Byvarying the conditions it is possible to c a r r y out the reaction
of the ketone (Ia) with phosphorus pentachlorlde selectively in any of the above-mentioned directions.
During investigation of the effect of the specific characteristics of the structure of compound (Ia) on its
behavior inthis reaction we founcl that N-methyiated pyrazolyl ketones (Ib-d) can also be converted with yields
of 50-90~ either into the "normal" products from substitution of the carbonyl oxygen by chlorine (lib-d) and
(IIIb-d) or to the corresponding ~,~-dichloroethylenes (IVb.-d):
I HCCI~CHs (II)
NaNH,
RCOCHs Pch+
RCCITCHz(III )
(v)
(I)
--
.','aNH,
RCCI=CCI,
. - - BCCI=CHC!
(IV)
. BC_==CCI
(VI)
(VII)
\ /--CH,<"
H'T- I
\
/
\ /--CH,
N
N
N
H
[
~Hs
CHs
N
--CH, (dl
--CHsCl (e), C,Hs (0
N
I
I
CH,
CI~
The formation of the dichlorides (IV) is aided by increased temperature (60-80°C) and by an excess of
phosphorus pe~achloride [2.2-2.3 moles/mole (I)]. With a l a r g e r excess of phosphorus pentachiorlde further
chlorination of the compounds occurs. With 3 moles of phosphorus pentachlorlde at 80~C in benzene the ketches
(Ib, c) give pyrazolyitrichlorosthylenes
(VIIb, c) with yields of 75%. The reaction takes place in stages, and
the dichlorides (IVb-c) are converted quantitatively into compounds (VIIb, c) after 1 h under t h e s e conditions.
Chlorination at the ~ position of the side chain is probably the resu[t from phosphorylation of the intermediate
vinyl chlorides followed by degradation of the phosphorus-cont~ining products [2]:
--H~.I RCCI~CHPCI+ - P c , : RCCI=CHCI PCls +
I
RCCI=CH, P c , . RCCI~CHzPCI~_I
--PCJ,* RCClaCHICI
--, RCCI=,CCIPCI4 _---~" RCCI~CCI~
t
--HCl
"HCl
]
From comparison of the data in [2-4] it evidently follows that the vinyl compounds are phosphoryiated more
readily in benzene than in POCl.~. In accordance with this only the chlorides (Hb) and (IIIb) are formed from
4-acetyl-l,3-dlmethylpyrazole (Ib) in POCls, in spite of the 35% excess of PCls, whereas it is not possible to
avoid the formation of the vicimt dichloride ([Vb) completely in benzene even with an equimoiar amount of
l~Cl~.
Institute of Chemical Kinetics and Combustion, Siberian Branch of the Academy of Sciences of the USSR,
Novostbtrsk. Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimfcheslmya, No. 10, pp. 2288-2292,
Cctober, 1976. Origiml article submitted August 13, 1975.
I
~
mattrial it protccwd by copyrl~t r~tered in the name o f Pl~aon PubUsh~t Corporation, 227 West 17th Street, New York, N. It'. 10011. No
~
I
[of ti~ ImbUcat~n may be nri~____oed, storedin a retrieval system, or mmmtltted, in +myform or by ~ y meant, electronk, mechm~cul, photocopying,
]
2134

In addition, it ts c l e a r that the prese~ed scheme does not exhaust all the possible paths of "anomalous"
chlorination in the ketone -- Pcl5 system [5]. In contrast to the pyrazolyl ketones (Ib, c), 4-acetyl-l,3,5-tri-
methylpyrazole (Id) with 4-5 moles of phosphorus pentachtoride gives mainly 4-u ~-dichlorovinyl-5-chloro-
methyl-l,3-dimethyl-l,3-dimethylpyrazole (ive), and its precursor (according to GLC data) is the dichloride
(IVd).
It is not impossible that in the 4-chlorovinylderivatives of pyrazole chlorination at the /J position i8
facilitated on account of the electron-donating characteristics of the 4-pyrazolyl radical [6]. However, this
reaction is due not only to the structure of the ketone but is even due rather to the conditions of its r e a l i z a -
tion and has general significance. Thus, with a 30% excess of phosphorus pentacbloride in benzene at 60°C
acetophenone is converted into a mixture of ([If) and (nTf), containing as little as ~3% of the ~,~-dichtoride
(l"Vf). With a larger amount of phosphorus pentachloride at 60-80°C compound (IVf) and ,~,~ ,/J-trichtoro-
ethylbenzene become the main reaction products. The production of 3-(u,~-dichlorovinyl)-4,5,5-trtmethyl-
A3-buteno[ide from the corresponding ketone or s-substituted vinyl chloride has also been described [4].
All this clearly gives reason to state that ~-chlorovinyt or ~,/~-dichlorovinyl aromatic derivatives can in
general be synthesized selectively from methyl aryl ketones with phc6phorus pentachloride by controlling the
reaction conditions. It sh(xtld be noted that the vicinal dichlorides can, in addition, be obtained from r~-
chloromethyl ketones.
As known, the action of bases on ~-arylvinyl chlorides leads to monosubstltuted acetylenes. By using
sodium amide in ammonia as base, we synthesized compounds (Vb-d) with yields of 40-85%, calculated on
compound ([). The elimination of hydrogen halides from dichloroethylenes as a method for the synthesis of
halogencecety[enes has not been sufficiently developed on account of secondary reactions between the ha[o-
genoacetytene and bases. The exception is sodium (or lithium) chloroacetylide, which is formed almost quan-
titatively in the reaction of 1,2- or 1,1-dichtorosthylene with sodium amide (or lithium amide) in ammonia and
phenytlithium (or methyllithium) in ether [7, 8]. The absence of side reactions of exchange of the halogen in
the case of 4-/~-chloroethynyt-3,5-dimethylpyrazole
(Via) is probably explained by the fact that the sodium
salt, i n t h s form of which it is obtained, is insufficiently soluble with ammonia and is s i m i l a r in this respect
to the chloroacetylide.
It can be supposed that the rates of dehydrochlorination of other vicinal dichlorides (IV) by sodium amide
are also higher than the rates of the succeeding processes. In fact, by using the stoichiometric amount of the
base, we obtained the chloroacetytenes (VIc, d, f) from t h e s e compounds with yields of 80-90%. With an ex-
cess of sodium amide compounds (VI) underwent further transformations and could not be isolated. Compounds
(IVb, d, f) were successfully dehydrochlori=ated to (VIb, d, f) with a 25% alcohol solution of potassium hydr-
oxide.
The structures and individualities of the synthesized compounds were proved by elemental analysts,
PMR and IB spectra, GLC, and TLC. Inthe PMR spectra of the victnal dichlorides (IV) and the acetylenes
(V) there are signals for the vinyl (6.08-6.33 ppm) and ethynyl (2.99-3.10 ppm) protons, respectively. The
presence of a monosubstituted acetylene group in (V) and a disubstituted acetylene in (VI) is confirmed by ab-
sorption at 2112-2125 and 3315-3325 cm-1 and at 2217-2230 cm-1 in the IR spectra of t h e s e compounds. In
the PMR spectrum of the t~chloride (IVe), in addition to signals for the ethylene protons (6.33 ppm), the CH3
groups at the nitrogen (3.77 ppm), and the ring carbon (2.17 ppm), there is a signal for the CHz group (4.49
ppm) formed as a result of substitution of the H atom in one of the C-methyls by chlorine. Elimination of HCI
by the action of the stoichiometrtc amount of sodium amide on (ive) leads to the chloroacetylene (Vie). The
upfletd shift of the signal for the chloromethyl group with slight change inthe position of the signal for the C-
methyl group in its PMB spectrum on replacement of the nonpotar solvent by an aromatic solvent makes it
possible reliably to establish [9] that the second of them is at the 3 position of the hetero ring. Consequently,
the trichloride (Ire) Is 4-u ~-dichlorovinyt-5-chtoromethyl-l,3-dimethylpyrazole. The configuration and
tsomertc purity of compound (IV) was not determined.
E X P E R I M E N T A L
4-Ethynyl-lp3-dimethylpyrazole
(Vb). A mixture of 9 g of compound (Ib) [10] and 18.5 g of phosphorus
pentachioride in 30 ml of phosphorus oxychloride was heated at 90-100°C u-ill compound (Ib) had disappeared
from the reaction mixture (GLC co,~rol). On cooling, the mi~ure was diluted with 300 ml of ether and neu-
tralized with a 20~ aqueous solution of sodium hydroxide. The obtained ether solution of compounds (IZb) and
(IIIb) was dried with potassium carbonate, added to sodium amlde (from 3 g of sodium) in 200 mt of ammonia,
and stirred for 1 h. The ammonia was removed by the addition of moist ether. AHer chromatography on
2135

TABLE 1. Di- and TrichlorovtnylDerivatives of Pyrazole
CI foumt
(~mPom-~e.h-.o. I Empiric a1.
calcu-
Com-~ ~
PMR spectram
(CC14, 6, ppm)
bp.'C
(p, mm Hg) t_e~_ ether) formula
lated,
or uD
6,31 (CHCI~); 3,74
N,3C4H(s5);-H)2,25 (3-CHs);
t08--it0 (3) 3t,5--32,5
C+HaCI2NI
(XVb) 5t,81
37.08
34.33
,~-97 (t)
28--29
1,5400
6,26 (CHGI---------C(); 3.71
C~HsCI2Nz
C~HmCIzN~
CsH.CIsN2
(IVc) 5i.Ol
(IVd) 5~.71
(NCHa); 2,32 (5-CI-~);
7.3t (3-H)
6.08 (CHCI=C<); 3.62
(NCHs); 2.12 and 2.21
(3-and 5-CHs)
94--96 (t)
i,5640"
6,33 (CSCi=~); 3.77
I ii8--t20 (t)
0re) 60*
~+NCH~); 4,49 (CH~CI);
, i7 (3-CH.)
3.7I(NCHs); 2.i7 (3-CH,);
7.3I (5-H)
47.13
i25--t26 (5)
i, 5576
47--48
C+H+CIsNs
CTH~CIzNz
(Vllb~ 74,3!
47.t7
47.26
3.7I (NCHs); 2.24 (5-CHs);
(Vllcl 77,7 i26--i28 (4)
7.30 (3-H)
*The crude product.
aluminum oxide (of V activity) in a 1:1 mixture of ether and petroleum ether we obtained 6.8 g (87%) of com-
pound (Vb); mp 34.5-35.5°C (from petroleum ether). Found %: N 23.27. CTHsN2. Calculated %: N 23.31.
PMR spectrum (carbontetrachlortde, 5, ppm): 2.99 (HC=C); 3.76 (NCHs); 2.24 (3-CH3); 7.12 (5-H). IR
spectrum (carbontetrachloride, ¢, cm-1): 2125, (C~ C), 3325 (HC- C).
4-Ethynyl-l,5-dimethylpyrazole (Vc). The reaction of 10 g of ([c) [10] with 18.2 g of phosphorus penta-
chloride in 80 ml of benzene was realized at 40-600C for 5 h. The reaction mass was treated as described
above. A 9.2-g yield of the mixture of chlorides was isolated by distillation; bp 110-130°C (6 mm Hg). Ac-
cording to PMR and GLC data, it contained 6.6 g (58.2%i of (Hc) [PMR spectrum, 5, ppm: 5.23 and 5.27
(CH2=CC1); 3.68 (NCH3); 2.27 (5-CH3); 7.44 (3-H)] and 2.6 g (18.7%) of (Ivc). The obtained mixture of com-
pounds (Hc) and (IVc) was dehydrochlorfnated with sodium amide (from 10 g of sodium) in 1 liter of ammonia.
Compound (Vc) was separated from the accompanying compounds by chromatography on aluminum oxide (V
activity) in a 2:1 mixture of ether and petroleum ether. The yield was 3.5 g [69% on (IIc)]; mp 63-63.5°C
(from petroleum ether). Found %: N 23.21. CtHsNz. Calculated %: N 23.31. PMR spectrum (chloroform,
5, ppm): 3.10 (HC=C); 3.74 (NCH3); 2.32 (5-CH~); 7.48 (3-H). IR spectrum (carbontetrachloride, v, cm-l):
2123 (C ~ C); 3323 (HC• - C).
4-Ethynyt-l,3,5-trtmetbylpyrazole (Vd) was obtained similarly [11].
4-u ~-Dichlorovinyl-l,3-dtmethylpyrazole (IVb). A mixture of 30 g of compound (lb) and 95.5 g of phos-
phorus pentachlortde in 240 ml of benzene was stirred at 40°C until the vigorous reaction had ceased and then
at 60°C for 6.5 h. Alter the usual treatment 21.5 g (51.8%) of compound (IVb) was isolated by distillation
(Table 1).
The dichlorides (Wc,d) and trichlorides (We) and (VIib, c) were prepared by a s i m i l a r method (Table 1).
In the preparation of compounds (VIib, e) and (We) 3.2 and 4.6 moles, respectively, of phosphorus p e ~ c h l o r i d e
were used for 1 mole of compound (I). The reaction was carried out at 80°C.
~-Dichlorovinylbenzene ~¢f). a. To a stirred solution of 100 g of w-chlorcacetophenone in 500 ml of
benzene at 20"C we added 162 g of phosphorus pent~tchloride in two portions. The temperature was gradually
raised to 60"C, and the reaction mass was kept at this temperature for 4 h. On cooling, it was poured into a
mixture of chloroform, saturated sodium bicarbonate solution, and ice. The organic layer was dried with
potassiumcarbonate and submitted to fractional distillation+ The fractions (43.5 g) boiling at 85-88°C (1 mm
Hg), ~D20 1.5855, cormtsted of the practically pure compound (Wf). PlVIR spectrum (5, ppm): 6.26 (CHCI=
C ( ) , 6.9-7.3 m (CiHs). The predistillate (7.8 g, bp 80-85"C/1 mm Hg, t ~20 1.5730) co~L~ined in additionto
(Wf) compounds (El) and 0Trf), which were identified by GLC by comparison with the mixture of chlorides ob-
tained by the action of phosphorus pentachloride on the acstophenone (If) (1.3 mole/mole) at 60+C. The f r a c -
tionm (38.5 g) boiling at 88-95°C (1 rnm Hg) (nD~° 1.5680-1.5760) represented a mixture of mainly three com-
pounds, i . e . , (VIf), ~,~ ~-4richloroethylt>enzene, and possibly a ,~ j+-trichlorovinyibenzene.
2 1 3 6

T A B L E 2. Substituted Chloroacetylenes (VI)
C1 found/
calculated,
"b
rap, "C (from
petroleum
ether)
IPMR spectrum
(CC14, 5, ppm)
Yield,
Empirical
formula
Coii1-
pound
"Ca~,
era-!
23,07
32--33
n~ t.sst3t
83--84
3,70 (NCH,);
2,20 (3-CH,);
7,28 (5-H)
3,59 (NCH,);
2,t7 (5-GHs);
7,25(3-H)
2230
22i7
2230
85,8(b)
C~HTC'INs
CTH~C1Ns
(Vlb)
(VIC)
(vld)
22,94
22,9t
22,94
89,4 (a)
2t .02
2i,03
C,H.CINs
89,7 (a)
3,54 (NCHs); 7
2,i0 and 2,t
88,2 (b)
(3- and 5-CH,)
6,8-7,3M(C4HI} 2230
bp
68--70° C,HiCt
n~ i,5775 [i2]
(vzo 79,0 (a)
(i2 ram)
58,5 (b)
*The method of preparation is given in parentheses.
?Purified by chromatography on aluminum oxide (V activity) in a 2:1
mixture of ether and petroleum ether.
b. F r o m 7.2 g of (If) and 30.2 g of phosphorus pentachloride in 200 ml of benzene at 80°C (10 h) we ob-
tained 8.3 g of a product consisting predominantly of (IVf) and ~ ,a,~-trichloroethylbenzene.
4-~-ChloroethynyL-1,3,5-trimethylpyrazole
(VId). a.
A 6.1-g sample of compound (IVd) in 150 ml of
ether was added to sodium a m i d e (from 1 g of sodium) in 300 ml of a m m o n i a and stirred for 0.5 h. The com-
pound (VId), isolated in the usual way, was sublimed at 70-80°C (1 m m Hg). The yield was 4.5 g (89.7%). Its
constants are given in Table 2.
b. A n 8.4-g sample of compound (IVd) in 10 m[ of benzene was gradually added to a solution of 3.6 g of
potassium hydroxide in 12 ml of ethanol, stirred at 80°C for 4 h, and poured into a mixture of ether and ice.
The organic layer was removed, the aqueous layer was extracted with chloroform, and the combined solution
of the product was dried with potassium carbonate.
ARer sublimation 6.1 g (88.2%) of compound (VId) was
obtained. The chloroacetylenes (VIb, c, f) were synthesized the same way (Table 2).
4-~-Chlorosthynyl-5-chloromethyl-l,3-dimethylpyrazole
(Vie). C o m p o u n d (Vie) was obtained from 9.5
g of the unpurified compound (IVe) and sodium amide (from 1.1 g of sodium) as described for (VId). Yield was
2.5 g (37.3%); m p 81-82~C (from petroleum ether). Found %: C 47.12; H 3.84; Cl 34.79. CsHeCI2N2. Cal-
culated %: C 47.31; H 3.97; Cl 34.92.
P M R spectrum (carbontetrachloride, 5, ppm): 3.88 (NCH3); 4.63
(CH2CI; in chloroform 4.63, benzene 4.00); 2.21 (3-CH3; in chloroform 2.30, benzene 2.18). IIR spectrum
(carbon tetrachlorlde, #, cm-i): 2230 (C-= C).
C O N C L U S I O N S
1. Depending on the conditions, the reaction of methyl aryl ketones with phosphorus pentachloride leads
to products from substitution of the carbonyl oxygen by chlorine, a,~-dichlorovinylarenes, or compounds with
higher degrees of chlorination.
2. By eliminating a molecule of hydrogen chloride under the influence of an equimolar amount of sodium
amlde in ammonia, substituted ~, ~-dichlorcethylenes give high yields of the respective 1-chloroacetylenes.
3. The synthesis of a series of ethynyl- and j-chloroethynylpyrazoles from methylpyrazolyl ketones
was realized.
L I T E R A T U R E C I T E D
1.
M . S . Shvartsberg, S. F. Vasilevskfi, R. Z. Sagdeev, and I. L. Kotlyarevskii, Izv. Akad. Nauk SSSR,
Ser. I~im., 927 (1969).
2.
3.
4.
A . V . Fokfn, A. F. Kolomiets, and V. S. Shchennikov, Zh. Cbshch. Khim., 42, 802 (1972).
K . N . Anisimov, Izv. Akad. Nauk SSSR, Cr~d. Khim. Nauk, 803 (1954).
A . A . Avetlsyan, A. N. Dzhandzhapanyan,
Soedin., 310 (1974).
L. E. Astsatryan, and M . T. Dangyan, Khim. Geterotsikl.
5.
6.
M . S . N e w m a n and L. L. Wood, J. A m . C h e m . Soc., 81, 4300 (1959).
C. WiJnberger and C. L. Habraken, J. Heterocyctic Chem., 6, 545 (1969).
2137

7.
8.
H.G. Viehe, Chem. B e r . ,
H.G. Viehe, Chem. B e t . , 92, 1950 (1959).
~
1270 (1959).
9.
J . L . Elguero and R. Jacquier, J . Chim.-Phys. Phys.-Chim. Biol., 63, 1242 (1966).
10.
S . P . Mal'tseva, V. M. Kosareva, and B. I. Stepanov, Izv. Vyssh. Uchebn. Zaved. Khtm. Khim.
Tekhnot.,
~
475 (1974).
11.
12.
M . S . Shvartsberg, S. F. Vasitevsidi, V. G. Kostrovskii, and I. L. Kottyaxevskii, Khim. Geterotsikl.
Soedin., 1055 (1969).
V.D. YasnopoPsldi, Physicochemical Constants of Compounds with an Acetylenic Bond [in Russian],
Izd. Akad. Nauk AzSSR, Baku (1966), p. 81.
R E A C T I O N S O F
S O M E
H A L O A C E T Y L E N E S
W I T H S O D I U M A M I D E
M . S. S h v a r t s b e r g , S . F . V a s i l e v s k i t ,
and A . N. S i n y a k o v
U D C 542.91:647.314'121:546.33'171
Substituted chloroacetylenes are formed with high yields in the reaction of l-aryl(heteroaryl)-l,2-di-
chloroethylenes with an equimolar amount of N a N H 2 in a m m o n i a [1]. With an excess of the base the chloro-
acetylenes as a rule undergo further transformations. In this connection w e investigated the reaction of
N a N H z with certain chLoroacetytenes, which were obtained earlier from vicinal dichloroethytenes.
In reaction with sodium a m i d e in a m m o n i a phenylchloroacetylene (1) exchanges the halogen atom by the
metal to the extent of >-60~, and this can be interpreted as nucleophilic substitution of the phenylacetylene
residue at the "positivlzed" halogen by an a m i n o group [2]. At the same time, phenylacetonitrile (III) is
formed with a yield of 16% as a result of the competing nucteophilic substitution of the chlorine at the sp-
carbon atom:
~'-~ C~I6C~--C- H,O , CoH~C~_CH
CoHsC~---CCI--
(II)
[,x]L -(1) ""~i:'""[
C~I[~Cf'~--C/CCi
C~Hs~---CNH21 -- CoHsCH~N
•
\N.,
~
J
(m)
In 4-chloroethynyl-l,3,6-trimethylpyrazoLe (IVa), in contrast to (I), the halogen is substituted almost
exclusively by an amino group, and exchange of chlorine for sodium only takes place to a s m a l l degree. The
reaction product, obtained with a yield of 80~, is an isomer of the expected pyrazolyiacetonitrile and has the
composition CsHttN3. In its PMB spectrum (Fig. 1), together with the signals for the CH3 group at the nitro-
gen (3.79 ppm) and one CH3 group at the ring carbon (2.26 ppm), there are signals at 3.22, 3.90, and 1.45 ppm,
corresponding to one, two, and two protons in intensity. They must clearly be assigned to the acetylene pro-
ton, the CHz group formed during substitution of a hydrogen atom in one of the C-methyls of the initiaL com-
?ound (IVa), and the amino group which has substituted this hydrogen. The presence of the amino group and
the ethynyt group in the obtained compound is also confirmed by the IB spectrum. The chemical shift of the
protons of the C-methyl group changes much tess than the shift of the protons of the methylene group in the
transition from a nonpolar to an aromatic solvent (Fig. 1). Since the shift induced by benzene on account of
the solvent (SCDC[s -- 6CsH6) is a quantity in the order of 0.5 ppm for 5-CH3 in substituted pyrazoles and 0.1
ppm for 3-CHs [3, 5], the aminomethyt group in the obtained compound is at position 5 of the hetero ring, and
Institute of Chemical Kinetics and Combustion, Siberian Branch of the Academy of Sciences of the USSR,
Novosiblrsk.
Translated from Izvestiya Akademii Nauk SSSR, Serlya Khimicheskaya, No. 10, pp. 2292-2296,
October, 1976. Original article submitted August 13, 1976.
This material la lWOteel~l by ¢opyi~'tt registered in the nnm¢ of Plenum PubHg~g Corpot.ffon, 227 West 17th Street, New York, N. E 1001I. No part
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2138