Synthesis of hydrohalocyclobutenes through dechlorination of hydrohalocyclobutanes in amide solvents

Article abstract of DOI:10.1016/j.jfluchem.2020.109506

In this study, we synthesized hydrohalocyclobutenes through the dechlorination of hydrohalocyclobutanes in N,N-dimethylformamide and N,N-dimethylacetamide. The structure of the reaction site ?CClR¹?CClR²– (R¹ = H, F; R² = H, F, Cl) of the reactants was critical for the efficient reductive dechlorination from the 1- and 2- positions. The reaction proceeded efficiently at the –CFCl–CFCl–, –CFCl?CCl₂–, and ?CHCl?CHCl– groups. Conversely, the –CFCl?CHCl– group could hardly afford the dechlorinated product. Based on these results, we propose a rational reaction mechanism.

Full text of DOI:10.1016/j.jfluchem.2020.109506

Journal Pre-proof
Synthesis of hydrohalocyclobutenes through dechlorination of
hydrohalocyclobutanes in amide solvents
Wenni Zhang, Fengniu Lu, Chengping Zhang, Qin Guo, Hengdao
Quan
PII:
S0022-1139(20)30057-9
DOI:
https://doi.org/10.1016/j.jfluchem.2020.109506
FLUOR 109506
Reference:
To appear in:
Journal of Fluorine Chemistry
Received Date:
Revised Date:
Accepted Date:
26 December 2019
3 March 2020
3 March 2020
Please cite this article as: Zhang W, Lu F, Zhang C, Guo Q, Quan H, Synthesis of
hydrohalocyclobutenes through dechlorination of hydrohalocyclobutanes in amide solvents,
Journal of Fluorine Chemistry (2020), doi: https://doi.org/10.1016/j.jfluchem.2020.109506
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2019 Published by Elsevier.

Synthesis
of
hydrohalocyclobutenes
through
dechlorination
of
hydrohalocyclobutanes in amide solvents
a
a
a
a
b,
Wenni Zhang , Fengniu Lu , Chengping Zhang , Qin Guo , Hengdao Quan *
a
Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing, 100081,
China
b
National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba
3
05-8565, Ibaraki, Japan
*
Corresponding Author: E-mail: hengdao-quan@aist.go.jp; Tel: 81-298-614196; Fax: 81-298-
614401
Graphical Abstract – Pictogram
R2
Cl
R2
DMF or DMAC
Cl
R1
R1
Hydrohalocyclobutane
Hydrohalocyclobutene
(
R = H or F, R = H, F or Cl)
1
2
Graphical Abstract – Synopsis
In this study, we synthesized hydrohalocyclobutenes through the dechlorination of
hydrohalocyclobutanes in N,N-dimethylformamide and N,N-dimethylacetamide. The structure of the
1
2
1
2
reaction site –CClR –CClR – (R = H, F; R = H, F, Cl) of the reactants was critical for the efficient
reductive dechlorination from the 1- and 2- positions. The reaction proceeded efficiently at the –CFCl–
CFCl–, –CFCl–CCl –, and –CHCl–CHCl– groups. Conversely, the –CFCl–CHCl– group could hardly
2
afford the dechlorinated product. Based on these results, we propose a rational reaction mechanism.
Highlights

Amide solvent is rarely reported as a dechlorination reagent.
1



No metal catalyst was applied so that this approach was facile and mild.
Dechlorination proceeded efficiently at the –CFCl–CFCl–, –CFCl–CCl
groups located in the molecular structure of reactants.
2
–, and –CHCl–CHCl–


The –CFCl–CHCl– group located in the molecular structure of reactants could hardly afford the
dechlorinated product.
A series of hydrohalocyclobutenes were prepared with high selectivity.
Abstract: In this study, we synthesized hydrohalocyclobutenes through the dechlorination of
hydrohalocyclobutanes in N,N-dimethylformamide and N,N-dimethylacetamide. The structure of the
1
2
1
2
reaction site –CClR –CClR – (R = H, F; R = H, F, Cl) of the reactants was critical for the efficient
reductive dechlorination from the 1- and 2- positions. The reaction proceeded efficiently at the –CFCl–
CFCl–, –CFCl–CCl
2
–, and –CHCl–CHCl– groups. Conversely, the –CFCl–CHCl– group could hardly
afford the dechlorinated product. Based on these results, we propose a rational reaction mechanism.
Keywords:
Hydrohalocyclobutenes,
Dechlorination,
N,N-dimethylformamide,
N,N-
dimethylacetamide, Elimination, 1,2-Dichloro
1
. Introduction
Dehalogenation and dehydrohalogenation are useful chemical processes [1], such as remedying soil
and groundwater [2–4] and handling organic liquids [5]. Additionally, these methods are common in
fluorine chemistry, since they constitute the most general method for the synthesis of fluorinated olefins
2

and acetylenes [6]. Formerly, the dehydrohalogenations (HX elimination, where X = F, Cl, Br) was
challenging as they required extreme reaction conditions [7, 8]. HCl elimination from C CFClCHF
affords C CF=CF with a 17% selectivity in a strongly basic NaOH environment at 230~250 °C [7].
HCl or HBr elimination from (CF CHCOCl or (CF CHCOBr affords (CF C=CO with a 24% or 57%
6
H
5
2
6
H
5
2
3
)
2
3
)
2
)
3 2
selectivity, respectively, in triethylamine at −78 °C [8]. Currently, essential methods of dehalogenation
include the H-X (X = F, Cl) exchange reaction [9–13] and 1,2-dihalo-elimination [14, 15]. Liquid-phase
H-X exchange is a reaction occurring between halocycloolefins and sodium borohydride (hydrogen
supplier) at ultra-low temperature in a solvent mixture of lithium aluminum hydride and ether [9–11].
This method is not preferred as it requires extreme reaction conditions. Catalytic gas-phase H-Cl exchange
occurs between halocycloolefins and hydrogen gas in a quartz reactor [12] catalyzed by chromium-nickel
or in a fixed-bed reactor [13] in the presence of a palladium catalyst. However, this method suffers low
selectivity of target product halocycloolefins. 1,2-Dihalo-elimination is usually conducted at a sufficiently
high temperature [14] or in alcohols or ethers using zinc dust activated by a small amount of anhydrous
zinc chloride [15, 16]. CFCl
2
CF
2
Cl generates CFCl=CF with a 92% selectivity via 1,2-dichlorine-
2
elimination in alcohol using zinc [16]. The 1,2-dihalo-elimination reaction using a metal catalyst remains
a primary method of dehalogenation.
In this paper, we report a facile method for the synthesis of perfluorocyclobutenes and
hydrohalocyclobutenes through dechlorination of halocyclobutanes and hydrohalocyclobutanes in N,N-
dimethylformamide (DMF) and N,N-dimethyl acetamide (DMAC) under mild conditions. Amides have
rarely been reported as suitable solvents for dechlorination. To verify the applicability of this novel
synthetic strategy, we investigated the following halocyclobutanes and hydrohalocyclobutanes: trans-1,2-
dichloro-3,3,4,4-tetrafluorocyclobutane
[HCFC-c334dd
(trans)],
cis-
and
trans-1,2-
dichlorohexafluorocyclobutane [CFC-c316bb (cis + trans)], 1,1,2-trichloro-2,3,3-trifluorocyclobutane
(HCFC-c333abc), and cis- and trans-1,2-dichloro-2,3,3-trifluorocyclobutane [HCFC-c343bcf (cis +
3

trans)]. The conformations of all reactants are shown in Scheme 1. The results illustrated that
dechlorination proceeded effectively at the –CFCl–CFCl–, –CFCl–CCl –, and –CHCl–CHCl– groups of
the reactants. However, the elimination of the chlorines at the 1- and 2- positions could hardly occur at
2
1
2
the –CFCl–CHCl– group. Therefore, the conformation of the reaction site of –CClR –CClR – groups was
significant for the efficient elimination of these two chlorines, and a reaction mechanism was developed.
Our synthetic method will significantly promote the applications of hydrohalocyclobutenes because they
are widely used as basic raw materials to produce fluorine-containing fine chemicals and polymer
materials such as rocket propellant composites [17], etchants [18], cleaning agents [19], heat pumping
fluids [20], fire extinguishing agents [21], blowing agents [22], sprays [23], and refrigerants [24]. We
believe the ease of synthesis will stimuli more and more applications in view of the environmental
advantages of hydrohalocyclobutenes (zero ozone depletion potentials values and low global warming
potentials values [25-26]).
2
. Results and Discussion
2
.1 Dechlorination of hydrohalocyclobutanes
The details of the elimination reactions for all the hydrohalocyclobutanes, including reaction routes,
conversion rates, and selectivities for each corresponding product are summarized in Scheme 2. The
results shown were averages of duplicate runs. The conversion rates of HCFC-c334dd (trans) (Eq 1),
CFC-c316bb (cis + trans) (Eq 2), and HCFC-c333abc (Eq 3) were 99.9 %, 91.0 %, and 95.7 % in DMF,
and 98.3 %, 95.6 %, and 90.1 % in DMAC, respectively. Neither dehydrochlorination nor dechlorination
occurred for HCFC-c343bcf (cis + trans) in both DMF and DMAC as illustrated (Eq 4).
HCFC-c334dd (trans) exhibited a relatively similar elimination reactivity in DMF (99.9 %) and DMAC
(98.3 %) (Eq 1). Additionally, HCFC-c334dd (trans) was both dehydrochlorinated and dechlorinated in
4

DMF and DMAC (Eq 1). HCFO-c1324xz was obtained by dehydrochlorination of HCFC-c334dd (trans)
with a higher selectivity in DMF (97.1 %) than in DMAC (21.6 %). Furthermore, dechlorination of
HCFC-c334dd (trans) afforded HFO-c1334zz with a lower selectivity in DMF (2.9 %) than in DMAC
(78.4 %). HCFC-c334dd (trans) was mainly dehydrochlorinated while dechlorination occurred slightly in
DMF (Eq 1). Oppositely, dechlorination of HCFC-c334dd (trans) occurred more easily than
dehydrochlorination in DMAC.
HCFO-c1323xzc was obtained by dehydrochlorination of HCFC-c333abc with a slightly higher
selectivity in DMF (13.4 %) than in DMAC (12.2 %) (Eq 3). The higher selectivity of HCFO-c1324xz
(
Eq 1) than that of HCFO-c1323xzc (Eq 3) confirmed that the dehydrochlorination proceeded more easily
in (Eq 1) than in (Eq 3). This differentiation could be rationalized by the easier hydrogen elimination from
the –CF –CF –CHCl–CHCl– group than that from the –CF –CH –CCl –CFCl– group because fluorine
and chlorine in the former group induced stronger relative acidity of hydrogen than in the latter [27–30].
Additionally, the chlorine in –CHCl– can be eliminated more easily than that in –CCl – [31–33].
2
2
2
2
2
2
Furthermore, the selectivities of HCFO-c1324xz (Eq 1) and HCFO-c1323xzc (Eq 3) in DMF and DMAC
suggested that the dehydrochlorination proceeded more easily in DMF than in DMAC. DMF is more
alkaline than DMAC [34] because heating decomposes it into dimethylamine, which is strongly alkaline
[
35, 36]. Since the basicity of the amide solvent affects the ease of dehydrohalogenation of
hydrohalocyclobutanes, the obtained results in both solvents were justified [27].
Both the cis- and trans- isomers of CFC-c316bb were solely dechlorinated in DMF (91.6 % conversion)
and in DMAC (95.6 % conversion) (Eq 2) as CFC-c316bb did not contain hydrogen atoms. This
dechlorination afforded only PFO-c1316 (Eq 2). The dechlorination of HCFC-c333abc afforded HCFO-
c1333xyc with a little lower selectivity in DMF (86.6 %) than in DMAC (87.8 %) (Eq 3). The relation
between the selectivities of the dechlorinated products (Eq 1, Eq 2, and Eq 3) was: PFO-c1316 (Eq 2) >
5

HCFO-c1333xyc (Eq 3) > HCFO-c1334zz (Eq 1); this was due to the stability of the intermediate
CF -CF-CF-CF - -CF -CF-CCl-CH - -CF -CH-CH-CF -
-
2
2
2
2
2
2
unsaturated cyclic chloronium ion as:
Cl
>
Cl
>
Cl
[37–
3
1
9]. The conversion rates of CFC-c316bb (cis + trans) (Eq 2), and the selectivities of HCFO-c1334zz (Eq
) and HCFO-c1333xyc (Eq 3) in DMF and in DMAC suggested that the dechlorination proceeded better
in DMAC than in DMF in all cases; this can be attributed to the stronger acidity of DMAC due to the
hydrogenation at the α-position [34, 40].
The dehydrochlorinated product HCFO-c1323xzc, as well as the dechlorinated product HCFO-
c1333xyc, exhibited similar selectivity in DMF and DMAC (Eq 3). The weak relative acidity of hydrogen,
induced by fluorine and chlorine from –CF
the dehydrochlorination was disfavoured [28–31, 41]. Therefore, the basicity of the solvent was not a
deciding factor in the dehydrochlorination of –CF –CH –CCl –CFCl– (Eq 3).
2
–CH
2
–CCl
2
–CFCl–, prevented the hydrogen from leaving, so
2
2
2
HCFC-c343bcf (cis + trans) were not dehydrochlorinated (Eq 4). The extremely weak acidity of
hydrogen, induced by fluorine and chlorine from –CF –CFCl–CHCl–CH –, prevented the elimination
28–31, 41]. Moreover, the failure of dechlorination of HCFC-c343bcf (cis + trans) suggested that
dechlorination would hardly occur in the –CFCl–CHCl– moiety of –CF –CFCl–CHCl–CH –; this
CF -CF-CH-CH -
2
2
[
2
2
-
2
2
probably was because the intermediate unsaturated cyclic chloronium ion
Cl
was
unstable [37–39].
2
.2 Mechanism of dechlorination
1
2
1
The mechanism of dehydrohalogenation of hydrohalocyclobutanes containing a –CHY –CClY – (Y
2
=
H, Cl; Y = H, Cl) group in DMF or DMAC (Scheme 3) was rationalized by our proposed mechanism
6

of dehydrofluorination of hydrofluorocycloalkanes [27]. The side products originating from DMF and
3
+
3
DMAC were inferred as Y (HN )(CH
3
)
2
(Y = H, CH CO) based on their nature and were not definitely
3
characterized. The hydrogen chloride was eliminated from the hydrohalocyclobutanes via an E1cB
elimination.
DMAC (CH
dimethylamine (HN(CH
actual active species in the dehydrochlorination of hydrohalocyclobutane are dimethylamine and DMAC
3
CON(CH
3
)
2
) is thermally stable, but DMF (HCON(CH
3
)
2
) decomposes into
)
3 2
) and carbon monoxide (CO) easily under heating [35, 36]. Therefore, the
3
3
(
Scheme 3, Y = H and CH
3
CO in Y N(CH
3
)
2
) under the current reaction conditions (160 °C in DMF and
3
1
70 °C in DMAC). First, the lone pair electrons of nitrogen in Y N(CH
3
2
) attacked and removed the acidic
β-hydrogen of chlorine in hydrohalocyclobutane [29, 30, 34, 42] by forming a protonated intermediate,
3
+
namely, Y (HN )(CH
3
2
) [42]. The elimination of hydrogen led to the formation of a carbanion whose
electron pair was stabilized by the strong induction effect of chlorine and fluorine [32, 33, 35, 43–46].
–
This chlorine was then removed as a chloride anion (Cl ), generating hydrohalocyclobutene as the final
–
3
+
–
product. The Cl was stabilized by forming electrically neutral [Y (HN )(CH ) ]Cl with the protonated
3
2
3
+
intermediate (Y (HN )(CH
3
2
) ) [47, 48].
For the dehydrohalogenations of –CF
2
–CHCl–CHCl–CF
2
– (HCFC-c334dd (trans) (Eq 1)), –CF –
2
CFCl–CCl –CH – (HCFC-c333abc (Eq 3)), and –CF
2
2
2
2
–CFCl–CHCl–CH – (HCFC-c343bcf (cis + trans)
(
Eq 4)), the relative acidity of β-hydrogen induced by fluorine and chlorine was –CF
2
–CHCl–CHCl–
CF
2
– > –CF
2
–CFCl–CCl
2
–CH
2
– > –CF
2
–CFCl–CHCl–CH
2
– [28–30]. Therefore, the ease of hydrogen
+
+
leaving these groups followed an order of –CF
2
–C Cl–CHCl–CF
2
– > –CF
2
–CFCl–CCl
2
–C H– > –CF
2
–
+
+
CFCl–CHCl–C H– > –CF
2
–CFCl–C Cl–CH
2
–. Conversely, the strength of the C–Cl and C–F bonds
– > –CFCl– > –CF – [31–
–CHCl–CHCl–CF –, –CF
promotes the following order of the halogens leaving ability: –CHCl– > –CCl
2
2
3
3]. According to the above rules, the ease of dehydrohalogenation of –CF
2
2
2
–
7

CFCl–CCl
2
–CH
2
– and –CF
2
–CFCl–CHCl–CH
2
– was ordered as –CF
2
–CH=CCl–CF
2
– > –CF
2
–CFCl–
CCl=CH– > –CF
2
–CFCl–CH=CH– > –CF
2
–CF=CCl–CH
2
–, which agreed with the order of selectivity
for the dehydrohalogenated products as following: HCFO-c1324xz (97.1 % in DMF and 21.6 % in DMAC)
by the dehydrochlorination of HCFC-c334dd (trans) (Eq 1) > HCFO-c1323xzc (13.4 % in DMF and 12.2 %
in DMAC) by the dehydrochlorination of HCFC-c333abc (Eq 3) > –CF
in DMF or DMAC) and –CF –CF=CCl–CH – (not produced in DMF or DMAC) by the
dehydrochlorination of HCFC-c343bcf (cis + trans) (Eq 4).
2
–CFCl–CH=CH– (not produced
2
2
1
2
1
The mechanism of dechlorination of hydrohalocyclobutanes containing –CClR –CClR – (R = H, F;
2
R = H, F, Cl) group in DMF or DMAC is proposed in Scheme 4. The side products resulting from DMF
and DMAC were inferred as [(CH
3
)
2
NC(O)Cl]·HCl and [(CH
3
)
2
NC(O)CH Cl]·HCl with respect to their
2
nature and not definitely characterized.
1
2
Initially, the lone pair electrons of the chlorine in –CClR –CClR – attacked and removed the acidic
hydrogen of amides [34, 40] and left as HCl. In DMF, the reacted acidic hydrogen was adjacent to the
carbonyl of (CH
3
2
) NC(O)H [34, 40], while in DMAC, α-hydrogen (the hydrogen located on the carbon
adjacent to the carbonyl) of (CH
3
)
2
NC(O)CH
3
was acidic [34] and could react with chlorine. The
–
elimination of hydrogen led to the formation of an amide anion intermediate (CH
3
)
2
NC (O) [49–51] in
–
DMF and (CH
3
)
2
NC(O)C H
2
[52, 53] in DMAC, of which the nitrogen carrying the lone pair electrons
hydrogen-bonded with HCl [54, 55] forming hydrochloride amide anion intermediates [(CH
3
)
NC–
2
–
(
O)]·HCl [54] in DMF and [(CH
3
)
2
NC(O)C H
2
]·HCl [55] in DMAC. Regarding hydrohalocyclobutane
losing one chlorine atom, the electron cloud density around another chlorine atom was weakened because
of the strong electron-withdrawing ability of the –CF – group [37–39]. The weakening of the electron
cloud density caused the formation of the intermediate containing an unsaturated cyclic chloronium ion
2
+
+
–
C–Cl –C– [37–39]. In DMF, the Cl of the chloronium ion intermediate was removed by the negatively
8

–
charged carbonyl of the hydrochloride amide anion intermediate [(CH
3
)
2
NC (O)]·HCl, and then stabilized
NC (O)Cl ]·HCl, which finally became the chlorinated amide
NC(O)Cl]·HCl [49–51]. Conversely, in DMAC, the hydrochloride amide anion
–
+
by forming the electrically neutral [(CH
hydrochloride [(CH
intermediate [(CH
3 2
)
3 2
)
–
–
3
)
2
NC(O)C H
2
]·HCl rearranged into [(CH
3
)
2
NC(O )=CH ]·HCl because of the stronger
2
electron-withdrawing ability of the oxygen on the carbonyl [52, 53, 55]. Therefore, the electrophilic Cl+
–
of the chloronium ion intermediate attacked the unsaturated bond of [(CH
3
)
2
NC(O )=CH
2
]·HCl and
+
–
underwent an addition reaction forming [(CH
chlorinated amide hydrochloride [(CH NC(O)CH
chloronium on intermediate generated hydrohalocyclobutene as the final product.
3
)
2
NC (O )CH
2
Cl]·HCl [52, 53], which finally became the
+
3
)
2
2
Cl]·HCl [52, 53]. The leaving of Cl from the
The –CF
2
–CHCl–CHCl–CF
2
– [HCFC-c334dd (trans) (Eq 1)], –CF
2
–CFCl–CFCl–CF – [CFC-c316bb
2
(
[
cis + trans) (Eq 2)], –CF
2
–CFCl–CCl
2
–CH
2
– [HCFC-c333abc (Eq 3)], and –CF
2
–CFCl–CHCl–CH –
2
1
2
HCFC-c343bcf (cis + trans) (Eq 4)] groups follow the structure –CClR –CClR –. During the
+
dechlorination of these groups, the formed chloronium ion intermediate –C–Cl –C– was a cyclic triangle
structure after the leaving of the first chlorine. The stability of the cyclic triangle structure depended on
two factors. First, a uniform inductive effect of the atoms near the cyclic triangle stabilized the chloronium
ion intermediate [37–39]. Second, the structural symmetry of the chloronium ion intermediate was
conducive to its stability [37–39]. Based on the above factors, the stability of the intermediate unsaturated
-
CF -CF-CF-CF -
-CF -CF-CCl-CH -
-CF -CH-CH-CF -
2
2
2
2
2
2
cyclic chloronium ion was
CF -CF-CH-CH -
Cl
>
Cl
>
Cl
>
-
2
2
Cl
CFCl–CCl
CF –CF=CF–CF
, which resulted in the ease of dechlorination of –CF
–, –CF –CHCl–CHCl–CF –, and –CF –CFCl–CHCl–CH
– > –CF –CF=CCl–CH – > –CF –CH=CH–CF – > –CF
2
–CFCl–CFCl–CF
2
–, –CF –
2
2
–CH
2
2
2
2
2
– in the following order: –
–CF=CH–CH –. This order
2
2
2
2
2
2
2
2
agreed with the selectivity order for the dechlorinated products as following: PFO-c1316 (100 % in DMF
and 100 % in DMAC) by the dechlorination of CFC-c316bb (cis + trans) (Eq 2) > HCFO-c1333xyc (86.6 %
9

in DMF and 87.8 % in DMAC) by the dechlorination of HCFC-c333abc (Eq 3) > HFO-c1334zz (2.9 %
in DMF and 78.4 % in DMAC) by the dechlorination of HCFC-c334dd (trans) (Eq 1) > –CF –CF=CH–
CH – (not produced in DMF or DMAC) by the dechlorination of HCFC-c343bcf (cis + trans) (Eq 4).
2
2
The conformational effect influences the ratio of cis- and trans- products afforded by elimination [23].
Generation of comparable cis- and trans- products from the elimination of cyclic halides is frequently
reported despite the theoretically easier trans-elimination [11, 33, 56, 57]. The dechlorinated product
HFO-c1334zz was derived from the trans-elimination of two antiperiplanar chlorine atoms in HCFC-
c334dd (trans) (Eq 1), and the dehydrochlorinated product HCFO-c1324xz was derived from cis-
elimination of coperiplanar chlorine and hydrogen in HCFC-c334dd (trans) (Eq 1). However, all the
dechlorinated and dehydrochlorinated products from (Eq 2) and (Eq 3) originated from both cis- and
trans- elimination of chlorine and hydrogen or two chlorine atoms at coperiplanar and antiperiplanar
positions.
3
. Conclusions
The dechlorination of hydrohalocyclobutanes in DMF and DMAC was investigated using a series of
hydrohalocyclobutanes with different extents of fluorination or chlorination. The dechlorination of the –
CFCl–CFCl–, –CFCl–CCl –, and –CHCl–CHCl– groups proceeded well. The elimination of 1- and 2-
chlorines from the –CFCl–CHCl– group was much more difficult. We thus noted the importance of the
2
1
2
conformation of the reaction site in the –CClR –CClR – group of reactants for the smooth elimination of
1
- and 2- chlorines from hydrohalocyclobutanes. We proposed a rational mechanism based on the
experimental results. Our study demonstrates a facile approach for synthesizing hydrohalocyclobutenes
with high selectivity under relatively mild conditions and provides an in-depth understanding of the
reaction mechanism that can aid the production of various hydrohalocycloolefins in the future.
1
0

4
. Experimental
4
.1 Chemicals
The reagents trans-1,1,2,2-tetrafluoro-3,4-dichlorocyclobutane [HCFC-c334dd (trans), 99.0 + %], cis-
and trans-1,1,2,2,3,4-hexafluoro-3,4-dichlorocyclobutane [CFC-c316bb (cis + trans), 99.0 + %], 1,1,2-
trifluoro-2,3,3-trichlorocyclobutane (HCFC-c333abc, 99.0 + %), cis- and trans-1,1,2-trifluoro-2,3-
dichlorocyclobutane [HCFC-c343bcf (cis + trans), 99.0 + %], DMF and DMAC were purchased from
Wako Pure Chemical Industries, Ltd. Chloroform-d (CDCl
3
, 99.8 atom % D) was obtained from Aldrich
Chem. Co. (Japan). CFCl (CFC-11, 99.0 + %) was purchased from Synquest Labs, Lnc.
3
4
.2 Instrument
A 2000 mL stainless steel reactor was used for all experiments with a Magmix stirrer (MRK Co., Ltd.).
1
13
19
The H, C, and F NMR spectra of HCFO-c1324xz were cited from the literature [58], as well as
1
9
those of HFO-c1334zz [17]. The F NMR spectra of HCFC-c334dd (trans), CFC-c316bb (cis + trans),
PFO-c1316, HCFC-c333abc, HCFO-c1333xyc, and HCFC-c343bcf (cis + trans) were recorded on a
1
3
Bruker AVANCE 400 (400 MHZ) at 25 °C with CFCl
3
as internal reference in CDCl solvent. The C
3
1
and H NMR spectra of HCFC-c334dd (trans), CFC-c316bb (cis + trans), PFO-c1316, HCFC-c333abc,
HCFO-c1333xyc, and HCFC-c343bcf (cis + trans) were recorded on a Bruker AVANCE 400 (400 MHZ)
at 25 °C in CDCl . The patterns were compared with those of authentic samples.
3
The GC-MS equipment consisted of a Shimadzu GCMS-QP2010 and a Shimadzu GC-2014plus. The
capillary column was DB-VRX of 30 m length and 0.32 mm inner diameter (film: 0.10 mm) from Agilent
Technologies Inc. The operating conditions of the GC were as follows: the column temperature was
1
1

initially 40 °C; then, it was increased to 230 °C at a rate of 10 °C/min; and then it was held at 230 °C for
min. Both the injection port and the thermal conductivity detector were maintained at 200 °C, and the
8
carrier gas He was introduced at a rate of 10 mL/min.
We used a Shimadzu GC-2014S gas chromatograph with a DB-WAX column of 30 m length and 0.25
mm inner diameter (film: 0.25 μm) from Agilent Technologies Inc. The operating conditions of the GC
were as follows: 40 °C for 10 min; 10 °C/min to 240 °C; hold for 10 min. Both the injection port and the
thermal conductivity detector were maintained at 240 °C, and the carrier gas was a mixture of H
and air introduced at a rate of 3 mL/min.
2
, He,
4
.3 Experiment procedure
The dechlorination reactions of all reactants including HCFC-c334dd (trans), CFC-c316bb (cis + trans),
HCFC-c333abc, and HCFC-c343bcf (cis + trans) were identically designed and conducted according to
the following conditions. The molar ratio of DMF or DMAC and each reactant was 2/1. The specific
amounts of all reagents were 50.4 g of HCFC-c334dd (trans) and 37.3 g of DMF, 50.3 g of HCFC-c334dd
(trans) and 44.5 g of DMAC, 23.3 g of CFC-c316bb (cis + trans) and 14.6 g of DMF, 23.3 g of CFC-
c316bb (cis + trans) and 17.4 g of DMAC, 19.8 g of HCFC-c333abc and 13.9 g of DMF, 20.0 g of HCFC-
c333abc and 16.4 g of DMAC, 8.0 g of HCFC-c343bcf (cis + trans) and 6.6 g of DMF, and 6.2 g of
HCFC-c343bcf (cis + trans) and 6.2 g of DMAC, respectively. The mixtures of DMF or DMAC with
each reactant were placed into a 2000 mL stainless steel reactor equipped with an electric heater and an
agitating device. The reactor was heated to 160 °C in DMF and 170 °C in DMAC, and stirred for 6 h
under magnetic stirring. The products from the above system were detected by GC, GC-MS, and NMR.
The results from GC-MS and GC deviated less than 0.1% from those concluded from the analyses of
NMR spectra.
1
2

4
4
.4 Analytic results
.4.1 HCFC-c334dd (trans)
6
F F 7
F
5
F
8
1
4
3
2
Cl
H
9
1
2
H
Cl
1
0
11
+
+
+
+
+
MS data (m/z): 197 (M ), 177 (M –HF), 157 (M –H
2
F
2
), 148 (M –CH
2
Cl), 145 (M –CH
2
F
2
), 142
+
+
+
+
+
+
(
M –HFCl), 129 (M –CH
2
FCl), 113 (M –CH
Cl
2 2
), 101 (M –C
2
H
Cl
2 2
), 98 (M –C
2
H
2
F
2
Cl), 80 (M –
+
+
C
2
HF
3
Cl), 63 (M –C
2
H F
2 2
Cl
2
), 44 (M –C
2
H
2
F
3
Cl
2
).
19F NMR (377 MHz, CDCl
): δ –112.58 (dm, 2F, J = 210.37 Hz, F-5 and F-7), –128.32 (dm, 2F, J =
3
2
10.37 Hz, F-6 and F-8).
1H NMR (400MHz, CDCl
): δ 4.35 (dtm, 2H, J = 9.20, 7.20 Hz, H-9 and H-10).
): δ 114.00 (ddt, 2C, J = 304.92, 286.84, 26.11 Hz, C-1 and C-4), 58.30
3
13C NMR (101 MHz, CDCl
m, 2C, C-2 and C-3).
3
(
4
.4.2 CFC-c316bb (cis)
6
F F 7
F
5
F
8
1
4
2
3
F
F
9
1
2
Cl
Cl
1
0
11
1
3

+
+
+
+
+
+
MS data (m/z): 233 (M ), 214 (M –F), 183 (M –CF
2
), 179 (M –FCl), 162 (M –Cl
2
), 148 (M –
), 43 (M –C Cl ).
): δ –118.39 (d, 2F, J = 218.66 Hz, F-5 and F-8), –130.54 (d, 2F, J = 218.66
+
+
+
+
+
CF
2
Cl), 117 (M –C
2
F
3
Cl), 113 (M –CF
2
Cl
2
), 95 (M –C
2
F
6
), 63 (M –C
2
F
4
Cl
2
2
F
5
2
19F NMR (377 MHz, CDCl
3
Hz, F-6 and F-7), –137.67 (s, 2F, F-9 and F-12).
13C NMR (101 MHz, CDCl
3
): δ 111.36 (ddm, 2C, J = 301.51, 301.51 Hz, C-2 and C-3), 103.95 (dm,
2
C, J = 297.45 Hz, C-1 and C-4).
4
.4.3 CFC-c316bb (trans)
6
F F 7
F
5
F
8
1
4
2
3
F
F
9
1
2
Cl
Cl
1
0
11
+
+
+
+
+
+
MS data (m/z): 233 (M ), 214 (M –F), 183 (M –CF
2
), 179 (M –FCl), 162 (M –Cl
2
), 148 (M –
), 43 (M –C Cl ).
): δ –122.46 (d, 2F, J = 216.02 Hz, F-5 and F-8), –126.42 (d, 2F, J = 216.02
+
+
+
+
+
CF
2
Cl), 117 (M –C
2
F
3
Cl), 113 (M –CF
2
Cl
2
), 95 (M –C
2
F
6
), 63 (M –C
2
F
4
Cl
2
2
F
5
2
19F NMR (377 MHz, CDCl
3
Hz, F-6 and F-7), –128.17(s, 2F, F-9 and F-12).
13C NMR (101 MHz, CDCl
3
): δ 111.36 (ddm, 2C, J = 301.51, 301.51 Hz, C-2 and C-3), 105.14 (dm,
2
C, J = 299.41 Hz, C-1 and C-4).
4
.4.4 PFO-c1316
1
4

7
F F 8
F
6
F
9
1
4
3
2
F
5
F
10
+
+
+
+
+
+
MS data (m/z): 162 (M ), 143 (M –F), 131 (M –CF), 124 (M –F
2
), 112 (M –CF
2
), 100 (M –C
2
2
F ),
+
+
+
+
+
+
+
9
3 (M –CF
3
), 81 (M –C
2
F
3
), 74 (M –CF
4
), 62 (M –C
2
F
4
), 55 (M –CF
5
), 50 (M –C
3
F ), 43 (M –
4
C
2
F
5
).
19F NMR (377 MHz, CDCl
): δ –119.68 (t, 4F, J = 11.31 Hz, F-6, F-7, F-8, and F-9), –128.24 (quint,
3
2
2
F, J = 11.40 Hz, F-5 and F-10).
13C NMR (101 MHz, CDCl
3
): δ 133.70 (dquint, 2C, J = 338.86, 24.75 Hz, C-2 and C-3), 112.75 (tm,
C, J = 280.93 Hz, C-1 and C-4).
4
.4.5 HCFC-c333abc
7
F H 12
F
6
H
8
1
4
2
3
F
5
Cl
9
Cl
Cl
1
0
11
+
+
+
+
+
), 128 (M+
MS data (m/z): 213 (M ), 194 (M –F), 164 (M –CH
2
Cl), 147 (M –CFCl), 141 (M –H
2
Cl
2
+
+
+
+
+
–
CH
2
Cl
2
), 116 (M –C
2
H
2
Cl
2
), 97 (M –C
2
H
2
FCl
Cl
2
), 82 (M –C
2
HCl
3
), 78 (M –C
2
H
2
F
2
Cl
2
), 64 (M –
+
+
C
2
HFCl
3
), 63 (M –C
2
H
2
FCl
3
), 44 (M –C
2
H
2
F
2
3
).
19F NMR (377 MHz, CDCl
): δ –101.39 (dtd, 1F, J = 202.45, 10.18, 2.64 Hz, F-6), –110.94 (dq, 1F, J
3
=
202.45, 11.31 Hz, F-7), –114.14 (m, 1F, F-5).
1H NMR (400 MHz, CDCl
3
): δ 3.44 (m, 1H, H-8), 3.39 (m, 1H, H-12).
1
5

13C NMR (101 MHz, CDCl
J = 303.61, 29.34, 25.55 Hz, C-1), 78.30 (ddd, 1C, J = 25.60, 14.34, 11.46 Hz, C-3), 52.40 (ddd, 1C, J =
4.09, 22.47, 1.62 Hz, C-4).
): δ 114.00 (ddd, 1C, J = 290.48, 288.96, 24.14 Hz, C-2), 109.64 (ddd, 1C,
3
2
4
.4.6 HCFO-c1323xzc
F
7
H
8
1
2
4
3
6
5
F
F
Cl
Cl
9
1
0
+
+
+
+
+
+
MS data (m/z): 177 (M ), 164 (M –CH), 158 (M –F), 145 (M –CHF), 141 (M –HCl), 122 (M –
+
+
+
+
+
HFCl), 117 (M –C
2
HCl), 97 (M –C
2
HFCl), 93 (M –CHCl
2
), 79 (M –C
HF
2 2
Cl), 62 (M –C
2
HFCl
2
).
19F NMR (377 MHz, CDCl
): δ –105.75 (dm, 1F, J = 190.01 Hz, F-6), –111.58 (dm, 1F, J = 190.01 Hz,
3
F-7), –113.16 (dm, 1F, J = 72.38 Hz, F-5).
1H NMR (400 MHz, CDCl
13C NMR (101 MHz, CDCl
3
): δ 6.55 (m, 1H, H-8).
3
): δ 132.57 (td, 1C, J = 26.71, 10.23 Hz, C-3), 118.97 (d, 1C, J = 22.62 Hz,
C-2), 115.47 (s, 1C, C-4), 113.51 (d,1C, J = 42.82 Hz, C-1).
4
.4.7 HCFO-c1333xyc
7
F H 10
F
6
H
8
1
4
3
2
F
5
Cl
9
1
6

+
+
+
+
+
+
MS data (m/z): 142 (M ), 140 (M –H
2
), 128 (M –CH
2
), 123 (M –F), 121 (M –H
2
F), 94 (M –CHCl),
+
+
+
+
+
+
9
3 (M –CH
2
Cl), 87 (M –HFCl), 75 (M –CHFCl), 74 (M –CH
2
FCl), 68 (M –HF
2
Cl), 62 (M –
+
+
C
2
H
2
FCl), 57 (M –CF
2
Cl), 50 (M –C
3
H
2
FCl).
19F NMR (377 MHz, CDCl
): δ –114.28 (m, 2F, F-6 and F-7), –114.88 (m, 1F, F-5).
3
1H NMR (400 MHz, CDCl
13C NMR (101 MHz, CDCl
): δ 2.90 (d, 2H, J = 12.00 Hz, H-8 and H-10).
): δ 139.37 (dt, 1C, J = 346.73, 126.97 Hz, C-2), 116.24 (d, 1C, J = 22.73
3
3
Hz, C-1), 112.00 (t, 1C, J = 24.95 Hz, C-3), 41.02 (td, 1C, J = 23.38, 13.33 Hz, C-4).
4
.4.8 HCFC-c343bcf (cis)
6
F H 7
F
5
H
8
1
4
2
3
Cl
Cl
9
1
2
F
H
1
0
11
+
+
+
+
+
+
MS data (m/z): 179 (M ), 178 (M –H), 165 (M –CH
2
), 160 (M –F), 158 (M –H
2
F), 145 (M –CH
3
F),
+
+
+
+
+
+
1
30 (M –CH
2
Cl), 124 (M –HFCl), 118 (M –C
2
H
2
Cl), 112 (M –CHFCl), 107 (M –HCl
2
), 93 (M –
+
+
+
CH
3
Cl
2
), 81 (M –C
2
H
3
Cl
2
), 62 (M –C
2
H
3
FCl
2
), 50 (M –C
3
H
3
FCl ).
2
19F NMR (377 MHz, CDCl
): δ –99.38 (ddt, 1F, J = 199.43, 9.43, 3.77 Hz, F-5), –117.34 (dm, 1F, J =
3
1
3
99.43 Hz, F-6), –129.94 (d, 1F, J = 7.54 Hz, F-10).
1H NMR (400 MHz, CDCl
3
): δ 4.56 (dtdd, 1H, J = 14.20, 9.33, 4.60, 0.92 Hz, H-8), 3.10 (dm, 1H, J =
.60 Hz, H-7), 2.56 (ddtd, 1H, J = 19.20, 14.00, 9.60, 2.80 Hz, H-11).
13C NMR (101 MHz, CDCl
3
): δ 114.72 (ddd, 1C, J = 296.64, 286.34, 24.24 Hz, C-2), 109.66 (ddd, 1C,
J = 303.10, 27.17, 25.05 Hz, C-1), 52.79 (ddd, 1C, J = 20.10, 11.11, 6.77 Hz, C-3), 40.57 (dd, 1C, J =
2.93, 22.12 Hz, C-4).
2
1
7

4
.4.9 HCFC-c343bcf (trans)
6
F H 7
F
5
H
8
1
4
2
3
Cl
H
9
1
2
F
Cl
1
0
11
+
+
+
+
+
+
MS data (m/z): 179 (M ), 178 (M –H), 165 (M –CH
2
), 160 (M –F), 158 (M –H
2
F), 145 (M –CH
3
F),
+
+
+
+
+
+
1
30 (M –CH
2
Cl), 124 (M –HFCl), 118 (M –C
2
H
2
Cl), 112 (M –CHFCl), 107 (M –HCl
2
), 93 (M –
+
+
+
CH
3
Cl
2
), 81 (M –C
2
H
3
Cl
2
), 62 (M –C
2
H
3
FCl
2
), 50 (M –C
3
H
3
FCl ).
2
19F NMR (377 MHz, CDCl
): δ –104.05 (dm, 1F, J = 200.94 Hz, F-5), –108.45 (dtd, 1F, J = 200.94,
3
1
8
3.20, 9.43 Hz, F-6), –112.88 (m, 1F, F-10).
1H NMR (400 MHz, CDCl
3
): δ 4.44 (ttdd, 1H, J = 7.20, 6.87, 1.02, 0.93 Hz, H-9), 3.24 (tdm, 1H, J =
.00, 2.40 Hz, H-8), 2.80 (dttd, 1H, J = 14.70, 13.73, 13.20, 1.10 Hz, H-7).
13C NMR (101 MHz, CDCl
3
): δ 115.10 (ddd, 1C, J = 299.26, 280.98, 23.53 Hz, C-2), 105.33 (ddd, 1C,
J = 294.62, 29.69, 25.35 Hz, C-1), 51.81 (dd, 1C, J = 28.08, 16.87 Hz, C-3), 38.20 (td, 1C, J = 22.22, 8.89
Hz, C-4).
It is our pleasure to submit the manuscript entitled " Synthesis of hydrohalocyclobutenes through
dechlorination of hydrohalocyclobutanes in amide solvents " for consideration for Journal of Fluorine
Chemistry as an original paper. No conflict of interest exits in the submission of this manuscript, and
manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors
that the work described was original research that has not been published previously, and not under
consideration for publication elsewhere, in whole or in part.
Yours sincerely,
Acknowledgement
1
8

This research did not receive any specific grant from funding agencies in the public, commercial, or
not-for-profit sectors.
1
9

References
1] R.E. Doherty, A history of the production and use of carbon tetrachloride, tetrachloroethylene,
[
trichloroethylene and 1,1,1-trichloroethane in the United States, Environ. Forensics 1 (2000) 69–81.
2] D.R. Burris, C.A. Delcomyn, B.L. Deng, L.E. Buck, K. Hatfild, Kinetics of tetrachloroethylene-
reductive dehalogenation catalyzed by vitamin-B-12, Environ. Toxicol. Chem. 17 (1998) 1681–1688.
3] D.R. Burris, C.A. Delcomyn, M.H. Smith, A.L. Robert, Reductive dechlorination of
[
[
tetrachloroethylene and trichloroethylene catalyzed by vitamin B12 in homogeneous and heterogeneous
systems, Environ. Sci. Technol. 30 (1996) 3047–3052.
[
4] G. Glod, W. Angst, C. Holliger, R.P. Schwarzenbach, Corrinoid-mediated reduction of
tetrachloroethene, trichloroethene, and trichlororfluoroethene in homogeneous solutions: reactions
kinetics and reaction mechanisms, Environ. Sci. Technol. 31 (1997) 253–260.
[
5] J.B. Hoke, G.A. Gramiccloni, E.N. Balko, Catalytic hydrodechlorination of chlorophenols, Appl.
Catal. B 1 (1992) 285–296.
6] M. Hudlicky, Organic Fluorine Chemistry, Virginia Polytechnic Institute and State University,
Virginia, 1971, pp. 142–144.
7] M. Prober, The synthesis and polymerization of some fluorinated styrenes , J. Am. Chem. Soc. 75
1953) 968–973.
8] I.L. Knunyants, Y.A. Cheburkov, M.D. Bargamova, Perfluorodimethylketene and
[
1
[
(
[
perfluoromethacrylic acid communication 1. hexafluoroisobutyryl chlorides from fluorinated ethers, Bull.
Acad. Sci. Ussr. D. Chem. Sci. 12 (1963) 1265–1268; Chem. Abstr. 59 (1963) 17175b.
[
9] G. Fuller, J.C. Tatlow, Some isomeric hexafluorocyclobutanes and pentafluorocyclobutenes, J.
Chem. Soc. (1961) 3198–3203.
10] K. Kučnirová, O. Šimůnek, M. Rybáčková, J. Kvíčala, Structural assignment of
[
fluorocyclobutenes by 19F NMR spectroscopy – comparison of calculated 19F NMR shielding constants
with experimental 19F NMR shifts, Eur. J. Org. Chem. 27–28 (2018) 3867–3874.
2
0

[
11] W.J. Feast, D.R.A. Perry, R. Stephens, Fluorocyclopentanes-V: lithium aluminium hydride
reduction of octafluoro-, 1,2-dichlorohexafluoro-, and 1-chloroheptafluorocyclopentene and 1H,2-chloro-
octafluorocyclohexene, Tetrahedron 22 (1966) 433–439.
[
12] T. Sugimoto, T. Suzuki, J. Konagawa, Method for producing hydrogen-containing fluoroolefin
compound, Patent No. US8318991B2 (2012).
13] A.A. Stepanov, N.I. Delyagina, V.F. Cherstkov, Catalytic synthesis of polyfluoroolefins, Russ. J.
Org. Chem. 46 (2010) 1290–1295.
14] B. Gething, C.R. Patrick, M. Stacey, J.C. Tatlow, A New General Route to Aromatic
Fluorocarbons, Nature 183 (1959) 588–589.
15] A.L. Henne, W.G. Finnegan, Perfluoro-2-butyne and its hydrogenation products, J. Am. Chem.
Soc. 71 (1949) 298–300.
16] E.A. Belmore, W.M. Ewalt, B.H. Wojcik, Production of polyperfluorovinyl chloride, Ind. Eng.
Chem. 39 (1947) 338–342.
17] M.J. Nappa, J.A. Creazzo, A.C. Sievert, E.N. Swearingen, Aerosol propellants comprising
unsaturated fluorocarbons, Patent No. US2007/0098646A1 (2007).
[
[
[
[
[
[
[
18] T. Suzuki, T. Sugimoto, M. Nakamura, Plasma etching method, Patent No. EP2194569A1 (2009).
19] M.J. Nappa, M.A. Schweitzer, A.C. Sievert, E.N. Sweaingen, Solvent compositions comprising
unsaturated fluorinated hydrocarbons, Patent No. US7846355B2 (2010).
20] K.C. Maris, M.B. Sflulet, N. Mully, Compositions comprising ionic liquids and fluoroolefins and
use thereof in absorption cycle systems, Patent No. CN102089400A (2011).
21] M.J. Nappa, E.N. Sweaingen, A.C. Sievert, Fire extinguishing and fire suppression compositions
comprising unsaturated fluorocarbons, Patent No. US8287752B2 (2012).
22] J.A. Creazzo, M.J. Nappa, A.C. Sievert, E.N. Swearingen, Methods for making foams using
blowing agents comprising unsaturated fluorocarbons, Patent No. US8558040B2 (2013).
[
[
[
2
1

[
23] B. Mueller, U. Bergemann, R. Bayersdorfer, Propellant-containing hair styling composition,
Patent No. US2013/0280178A1 (2013).
24] T.J. Leck, T.F. Saturno, G.A. Bell, Refrigerant additive compositions containing
perfluoropolyethers, Patent No. US8758641B2 (2014).
25] T.J. Wallington, M.P. Sulbaek Andersen, O.J. Nielsen, Atmospheric chemistry of short-chain
[
[
haloolefis: photochemical ozone creation potentials (POCPs), global warming potentials (GWPs), and
ozone depletion potentials (ODPs), Chemosphere 129 (2015) 135–141.
[
26] W. Liu, D. Meinel, C. Wieland, Hartmut Spliethoff Investigation of hydrofloroolefis as potential
working flids in organic Rankine cycle for geothermal power generation, Energy 67 (2014) 106–116.
27] W.N. Zhang, C.P. Zhang, Q. Guo, F.N. Lu, H.D. Quan, Synthesis of hydrofluorocycloolefins
through dehydrofluorination of hydrofluorocycloalkanes in amide solvents, J. Fluor. Chem. 226 (2019)
09342.
[
1
[
[
28] D.V. Banthorpe, Elimination Reactions, Elsevier, Amsterdam, 1963.
29] W.H. Saunders, S.R. Fahrenholtz, E.A. Caress, J.P. Lowe, M. Schrieber, Mechanisms of
elimination reactions. VI. The effect of the leaving group on orientation in E2 reactions, J. Am. Chem.
Soc. 87 (1965) 3401–3406.
[
30] R.A. Bartsch, J.F. Bunnett, Kinetics of reactions of 2-hexyl halides and 2-hexyl p-
bromobenzenesulfonate with sodium methoxide in methanol. Evidence that orientation of olefin-forming
elimination is not determined by the steric requirements of halogen leaving groups, J. Am. Chem. Soc.
9
0 (1968) 408–417.
31] R.P. Smith, J.C. Tatlow, Fluorocyclohexanes. Part I. cis- and trans-1H : 2H-
decafluorocyclohexanes, J. Chem. Soc. (1957) 2505–2511.
32] C.H. DePuy, G.F. Morris, J.S. Smith, R.J. Smat, Electronic effects in elimination reactions. V.
bimolecular cis eliminations. 2-arylcyclopentyl tosylates, J. Am. Chem. Soc. 87 (1965) 2421–2428.
[
[
2
2

[
33] S.F. Campbell, F. Lancashire, R. Stephens, J.C. Tatlow, Fluorocyclohexanes—XII: novel
elimination reactions of 1H,2-chloro/-deca fluorocyclohexane and 1H,2-chloro/-1-chloronona
fluorocyclohexane, Tetrahedron 23 (1967) 4435–4439.
[
34] A. Bagno, G. Scorrano, Acid-base properties of organic solvents, J. Am. Chem. Soc. 110 (1988)
577–4582.
35] A. Sharma, V.P. Mehta, E.V. Eycken, A convenient microwave-assisted desulfitative
dimethylamination of the 2(1H)-pyrazinone scaffold using N,N-dimethylformamide, Tetrahedron 64
2008) 2605–2610.
36] S.T. Ding, N. Jiao, N,N-dimethylformamide: a multipurpose building block, Angew. Chem. Int.
Ed. 51 (2012) 1–13.
37] M.D. Struble, M.T. Scerba, M. Siegler, T. Lectka, Evidence for a symmetrical fluoronium ion in
solution, Science 340 (2013) 57–60.
38] C.R. Pitts, M.G. Holl, T. Lectka, Spectroscopic characterization of a [C-F-C] fluoronium ion in
solution, Angew. Chem. 130 (2018) 1942–1945.
39] S.Y. Cai, Y. Shen, P. Lu, Y.G. Wang, Condition-controlled selective synthesis of coumarins and
flavones from 3-(2-hydroxyphenyl) propiolates and iodine, Tetrahedron Lett. 52 (2011) 4164–4167.
40] V. Lucchini, G. Modena, G. Scorrano, R. A. Cox, K. Yates, Definition of the protonation equilibria
of weak organic bases, J. Am. Chem. Soc. 104 (1982) 1958–1959.
41] D.E.M. Evans, W.J. Feast, R. Stephens, J.C. Tatlow, Fluorocyclohexanes. Part VIII. Lithium
aluminium hydride reduction of decafluorocyclohexene, J. Chem. Soc. (1963) 4828–4834.
42] M. Hudlicky, Elimination of hydrogen fluoride from fluorinated succinic acids. (III) kinetics of
dehydrofluorination of erythro- and threo-α-bromo-α′-fluorosuccinic acids, J. Fluor. Chem. 25 (1984)
53–361.
43] M. Hudlicky, Dehydrohalogenations of cis- and trans-1-bromo-2-flurocyclohexanes, J. Fluor.
Chem. 32 (1986) 441–452.
4
[
(
[
[
+
[
[
[
[
[
3
[
2
3

[
44] M. Pánková, J. Závada, J. Sicher, The steric course of eliminations in simple open-chain’ onium
compounds: the contributions of syn- and anti-elimination mechanisms, Chem. Commun. (1968) 1142–
145.
45] J. Sicher, J. Závada, M. Pánková, The interpretation of trans- to cis-olefin ratios in bimolecular
elimination processes, Chem. Commun. (1968) 1147–1148.
46] E.L. Stogryn, S.J. Brois, The valence isomerization of 1,2-divinylaziridines. synthetic and kinetic
studies, J. Am. Chem. Soc. 89 (1967) 605–609.
47] C. Bolchi, M. Pallavicini, M. Binda, L. Fumagalli, E. Valoti, From carnitinamide to 5-
aminomethyl-2-oxazolidinones, Tetrahedron Asymmetry 23 (2012) 217–220.
48] T. Blitzkea, A. Porzela, M. Masaoudb, J. Schmidt, A chlorinated amide and piperidine alkaloids
from Aloe sabaea, Phytochemistry 55 (2000) 979–982.
49] G. Semler, G. Schaeffer, Process for the preparation of chloroformic acid aryl esters and cyclic
carbonates, Patent No. US4085129A (1978).
50] R.W. Guthrie, G.L. Kaplan, F.A. Mennona, J.W. Tilley, R.W. Kierstead, M. O’Donnell, H.
1
[
[
[
[
[
[
Crowley, B. Yaremko, A.F. Welton, Propenyl carboxamide derivatives as antagonists of platelet-
activating factor, J. Med. Chem. 33 (1990) 2856–2864.
[
51] A.D. Naik, K. Robeyns, C.F. Meunier, A.F. Leonard, A. Rotaru, B. Tinant, Y. Filinchuk, B.L. Su,
Y. Garcia, Selective and Reusable Iron(II)-Based Molecular Sensor for the Vapor-Phase Detection of
Alcohols, Inorg. Chem. 53 (2014) 1263–1265.
[
52] S. Silva, C.D. Maycock, Efficient α-chlorination of carbonyl containing compounds under basic
conditions using methyl chlorosulfate, Tetrahedron 59 (2018) 1233–1238.
[
53] W.J. Zhang, C.Z. Yin, X. Yang, H.L. Liu, X.L. Zheng, M.L. Yuan, R.X. Li, H.Y. Fu, H. Chen,
3
Cu(II)-Mediated keto C(sp )–H bond α-acyloxylation of N,N-dialkylamides with aromatic carboxylic acids,
Org. Biomol. Chem. 15 (2017) 7594–7599.
2
4

[
54] M.M. Saleh, C.A. Laughton, T.D. Bradshaw, C.J. Moody, Development of a series of bis-triazoles
as G-quadruplex ligands, RSC Adv. 7 (2017) 47297–47308.
55] Y. Okada, H. Taguchi, Y. Nishiyama, T. Yokoi, Simple approach towards the synthesis of 5-
methyl-2-hydroxypyrazine derivatives from dipeptidyl chloromethyl ketones, Tetrahedron 35 (1994)
231–1234.
56] M. Hanack, E.J. Carnahan, A. Krowczynski, W. Schoberth, L.R. Subramanian, K. Subramanian,
[
1
[
Preparation and solvolysis of 1-cyclobutenyl nonaflates. Generation of stabilized vinyl cation species, J.
Am. Chem. Soc. 101 (1979) 100–108.
[
57] A. Barrow, A.E. Pedler, J.C. Tatlow, Fluorocyclohexanes—XIII: 1H,2H,3H,4H-
octafluorocyclohexanes, Tetrahedron 25 (1969) 1213–1217.
58] G. Yang, C.P. Zhang, H.E. Yang, H.D. Quan, Synthesis of 1H-polychlorofluorocycloolefins, J.
Fluorine Chem. 216 (2018) 96–101.
[
2
5

Fa
Fb
Fb
Fa
Fb
Fc
Fb
Fc
Fb
Fc
Fc
Fb
Cla
Ha
Ha
Fa
Fa
Fa
Cla
Fa
Cla
Cla
Cla
Cla
HCFC-c334dd (trans)
HCFC-c316bb (cis)
HCFC-c316bb (trans)
Fa
Fb
Ha
Hb
Fa
Fb
Ha
Hb
Fa
Fb
Ha
Hb
Fc
Clc
Clb
Fc
Hc
Fc
Clb
Cla
Cla
Clb
Cla
Hc
HCFC-c333abc
HCFC-c343bcf (cis)
HCFC-c343bcf (trans)
Scheme 1. Conformations of all reactants
2
6

F4
H
F4
H
F4
H
DMF, 160℃, 6h
or DMAC, 170℃, 6h
H
Cl
Cl
Cl
H
(Eq 1)
HCFC-c334dd (trans)
Conversion (%)
HCFO-c1324xz
Selectivity (%)
97.1
HFO-c1334zz
Selectivity (%)
2.9
Solvent
DMF
DMAC
9
9
9.9
8.3
21.6
78.4
F6
F6
DMF, 160℃, 6h
or DMAC, 170℃, 6h
Cl
Cl
(Eq 2)
CFC-c316bb (cis/trans = 3/2)
PFO-c1316
Selectivity (%)
100
Conversion (%)
Solvent
DMF
9
9
1.0
5.6
DMAC
100
F3
F3
F3
Cl
H
H
H
H
DMF, 160℃, 6h
H
or DMAC, 170℃, 6h
Cl
Cl
Cl
Cl
Cl
(Eq 3)
HCFC-c333abc
HCFO-c1323xzc
Selectivity (%)
13.4
HCFO-c1333xyc
Selectivity (%)
86.6
Conversion (%)
Solvent
DMF
DMAC
9
9
5.7
0.1
12.2
87.8
F3
H
H
DMF, 160℃, 6h
or DMAC, 170℃, 6h
Cl
Cl
H
(Eq 4)
HCFC-c343bcf (cis/trans = 1/1)
Scheme 2. Novel methods for preparation of hydrohalocyclobutenes
2
7

-Cl-
-
H+
1
CY2
1
CY2
1
CY2
Y C
Y C
Y C
Cl
H
Cl
1
(
(
Y =H, Cl)
2
Y =H, Cl)
H+
H
Cl-
+
+
H
N
Y3
N
Y3
Y3
N
Cl
3
(
Y =H, CH CO)
3
Scheme 3. Mechanism of dehydrochlorination of hydrohalocyclobutanes
2
8

-
Cl
-Cl
CR2
1
CR2
R1
CR2
R1C
CR2
R1C
R C
C
Cl
Cl
Cl
Cl
Cl
1
(
(
R =H, F)
2
R =H, F, Cl)
H
C
H
H
H C
N
H
3
N
CH3
CH3
H C
3
C
O
C
O
(
CH ) NC(O)H
(CH ) NC(O)CH3
3
2
3 2
+Cl
+Cl
HCl
N
HCl
N
H
H
H C
3
C
CH3
CH3
H C
C
O
C
3
[
(CH ) NC(O)] HCl
O
[(CH ) NC(O)CH ] HCl
3 2 2
3
2
+Cl
Rearrangement
HCl
HCl
N
CH3
CH3
H
H C
N
Cl
3
H
C
C
O
H C
C
O
3
[(CH3)2NC(O)=CH2] HCl
[
(CH ) NC(O)Cl] HCl
3 2
+Cl
HCl
N
Cl
CH3
CH3
H
H
C
C
O [(CH ) NC(O)CH Cl] HCl
3
2
2
HCl
N
Cl
CH3
CH3
H
H
C
C
O
[(CH3)2NC(O)CH2Cl] HCl
Scheme 4. Mechanism of dechlorination of hydrohalocyclobutanes
2
9