Identification of alkylarene chloromethylation products using gas-chromatographic retention indices

Article abstract of DOI:10.1134/S1070363207040196

Gas-chromatographic retention indices on standard nonpolar polydimethylsiloxane stationary phases allow identification of products formed by known organic reactions even without using mass-spectrometric data. The efficiency of this approach was demonstrated by the example of identification of previously uncharacterized chloromethyl derivatives of alkylarenes, including structural isomers of compounds containing several chloromethyl groups, directly in reaction mixtures. Chromatographic analysis of such reaction mixtures allows identification of positional isomers of the starting alkylarenes even when they are present simultaneously. The retention indices were determined for the first time for more than 50 alkyl-(chloromethyl)arenes, by-products of chloromethylation, and chloromethyl derivatives of the simplest alkyl phenyl ketones. Nauka/Interperiodica 2007.

Full text of DOI:10.1134/S1070363207040196

ISSN 1070-3632, Russian Journal of General Chemistry, 2007, Vol. 77, No. 4, pp. 611 619.
Pleiades Publishing, Ltd., 2007.
Original Russian Text I.G. Zenkevich, A.A. Makarov, 2007, published in Zhurnal Obshchei Khimii, 2007, Vol. 77, No. 4, pp. 653 662.
Identification of Alkylarene Chloromethylation Products
Using Gas-Chromatographic Retention Indices
I. G. Zenkevich and A. A. Makarov
Research Institute of Chemistry, St. Petersburg State University,
Universitetskii pr. 26, St. Petersburg, 198504 Russia
e-mail: izenkevich@mail15.com
Received November 23, 2006
Abstract Gas-chromatographic retention indices on standard nonpolar polydimethylsiloxane stationary
phases allow identification of products formed by known organic reactions even without using mass-spec-
trometric data. The efficiency of this approach was demonstrated by the example of identification of pre-
viously uncharacterized chloromethyl derivatives of alkylarenes, including structural isomers of compounds
containing several chloromethyl groups, directly in reaction mixtures. Chromatographic analysis of such
reaction mixtures allows identification of positional isomers of the starting alkylarenes even when they are
present simultaneously. The retention indices were determined for the first time for more than 50 alkyl-
(chloromethyl)arenes, by-products of chloromethylation, and chloromethyl derivatives of the simplest alkyl
phenyl ketones.
DOI: 10.1134/S1070363207040196
The most widely used approach to identification of
previously uncharacterized organic compounds in-
volves their isolation followed by determination of
various physicochemical constants (boiling and melt-
ing points, refractive indices, etc.) or of more informa-
tive spectral characteristics (primarily NMR and mass
spectra). However, as applied to reaction mixtures
containing a large number of components with similar
properties (including isomers), the use of this ap-
proach is restricted by the possibilities of isolation
and purification of the components. Therefore, for
many relatively simple organic compounds the physi-
cochemical constants and spectral characteristics are
still unknown. Examples of such compounds are prod-
ucts of radical chlorination of alkylarenes RAr, (chlo-
roalkyl)arenes, which can be obtained only as insepar-
able mixtures. Therefore, the physicochemical con-
stants and even the mass spectra of the majority of
An alternative approach to identification of organic
compounds is based on the use of modern methods of
chromatography spectroscopy and does not require
isolation of components from complex mixtures.
However, at present it is mostly applied to identifica-
tion of compounds previously characterized by mass
spectra and/or chromatographic retention indices. The
natural limitation of this approach is the lack of the
required reference data in the existing databases. This
particularly concerns the retention indices, because the
majority of these parameters are still scattered over
original papers and have not been systematized, and
the first universal computer database that included the
retention indices of 25728 compounds on standard
nonpolar polydimethylsiloxane stationary phases ap-
peared only in 2005 [1]. Application of this approach
to previously uncharacterized compounds was consid-
ered inadmissible until recently.
such compounds with R
C3H7 are unknown [1].
At the same time, in organic analytical chemistry
there is a specific type of reactions for which isolation
of products is considered unnecessary in identification
of the starting compounds by chromatography spec-
trometry: derivatization reactions used to optimize the
conditions of chromatographic analysis of target ana-
lytes [3]. In this case, the reactions should be so spe-
cific that the structures of products, at known struc-
tures of the starting compounds, can be assumed with-
out additional proof. Furthermore, it can be noted that
the role of mass spectra in characterization of the
The same is true for many positional isomers of alkyl-
arenes themselves, polyhalo derivatives, etc. Several
important groups of ecotoxicants are so numerous that
synthesis or isolation of their individual representa-
tives is virtually impossible. For example, this prob-
lem was solved for all the 209 polychlorinated bi-
phenyls C12H10 xClx (1
tabolites, polychlorinated hydroxybiphenyls C12H9
x
10), but for their me-
x
(OH)Clx (1
x
9) it is unfeasible to synthesize or
isolate all the existing 839 congeners [2].
611

612
ZENKEVICH, MAKAROV
products thus obtained is minor, and for isomers hav-
ing identical mass spectra this method is useless. It
becomes particularly important to determine the chro-
matographic retention indices of such compounds.
methylation. In this case, it is basically unnecessary
to record the mass spectra of the products, because
compounds differing in the number of chloromethyl
groups can be readily distinguished by the chromato-
graphic retention parameters, and the mass spectra of
isomers with different positions of these groups are
virtually identical. This is illustrated in Fig. 1 by
the mass spectra of 1-methyl-2-(chloromethyl)benzene
and 1-methyl-3-(chloromethyl)benzene.
The use of unidimensional analytical parameters,
chromatographic retention indices, is generally insuf-
ficient for unambiguous identification. However, in
some particular cases it becomes possible, e.g., when
the level of a priori chemical information about the
samples being analyzed allows the number of alterna-
tive hypotheses about their component composition
to be substantially reduced [4]. In other words, identi-
fication of products of well-known organic reactions
solely on the basis of chromatographic data seems to
be quite possible.
The 14 alkylarenes C7 C12 whose chloromethyla-
tion products are considered in this paper are listed in
Table 1 in the order of increasing molecular weights
of the substrates. In addition, we included 1- and
2-methylnaphthalenes and three alkyl aryl ketones for
which the chromatographic analysis of chloromethyla-
tion products is of particular interest, because for, e.g.,
acetophenone these products were isolated previously
[6]. For the same purpose, we included cyclohexan-
one, because ketones also form products of chloro-
methylation at the -position to the carbonyl group.
For each of the starting compounds, we give the gas-
chromatographic retention indices (RIs), and the reac-
tion products are listed in the order of increasing
retention indices on a standard nonpolar polydimeth-
ylsiloxane stationary phase, OV-101. For each of the
products, we indicated their molecular weights (for
35Cl) and the differences between the retention indices
of the products and their precursors. In two cases, the
poly(chloromethyl) derivatives can be formed from
several precursors, and therefore for each of them we
give two RI values. Reference data on the retention
indices are known for only three compounds given in
Table 1: the simplest 1-methyl-4-(chloromethyl)ben-
zene and two products formed from acetophenone,
which clearly illustrates the existing level of chroma-
tographic characterization of compounds of this class
and the urgency of the problem under consideration.
Just this approach was used for identification of
products of radical chlorination of alkylarenes in vari-
ous positions of alkyl substituents [5]. However, com-
pounds of this class still remain insufficiently charac-
terized by chromatographic parameters and deserve
more detailed consideration. Among other synthetic
routes to these compounds, the well-known and com-
prehensively studied reaction of arene chloromethyla-
tion is of interest:
ArH + [CH2O] + HCl
[ArCH2OH]
ArCH2Cl + H2O.
(1)
The synthesis is usually performed with paraform,
by passing dry HCl through reaction mixtures contain-
ing as catalysts Lewis acids (AlCl3, ZnCl2, etc.) [6]
or nonvolatile inorganic acids (H2SO4, H3PO4) [7].
The reactant addition order can be inverse [6]. The
reaction can also be performed with aqueous HCl
solutions in the presence of phase-transfer catalysts
(e.g., cetyltrimethylammonium bromide) [8]. The by-
products are bis(chloromethyl) derivatives and, in
some cases, diarylmethanes ArCH2Ar formed by
alkylation of hydrocarbons ArH with the intermediate
carbinols ArCH2OH [6, 8].
The structures of chloromethylation products of
some alkylarenes are unambiguously determined by
the molecular structures of the starting compounds
and hence can be established unambiguously. For
example, durene and pentamethylbenzene can give a
single mono(chloromethylation) product each; mesi-
tylene can give one mono-, one bis-, and one tris-
(chloromethylation) products. Published data on isola-
tion of the main reaction products simplify the identi-
fication of the positional isomers of chloromethyl
derivatives of xylenes, 1,2,4-trimethylbenzene, etc.
[6]. The retention indices of the simplest mono(chlo-
romethyl) derivatives can be estimated with a fairly
high accuracy by an additive scheme from the reten-
tion indices of the corresponding alkylmethylarenes
and chromatographic increment of the reaction of
replacement of primary hydrogen atoms with chlorine
Chromatographic data on the retention indices of
(chloromethyl)arenes are limited. The simplest repre-
sentative of this series, benzyl chloride, has been
characterized in most detail [5, 9 12]. Data for iso-
meric (chloromethyl)toluenes are given in [12] and for
1,4-bis(chloromethyl)benzene, in [13]. The largest
number of chloromethyl derivatives have been charac-
terized in products of radical chlorination of methyl-
substituted arenes [5].
This paper deals with gas-chromatographic identi-
fication of (chloromethyl)arenes synthesized by
scheme (1) on the basis of their gas-chromatographic
retention indices and well-known features of chloro-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 4 2007

IDENTIFICATION OF ALKYLARENE CHLOROMETHYLATION PRODUCTS
613
(a)
105
100
50
140
51
77
39
103
97
27
63
142
89
86
125
74
15
69
0
10 20 30 40 50 60 70 80 90 100 110 120 130 140 150
m/z
(b)
105
100
50
0
140
51
77
39
103
97
27
63
142
65
89
86
125
74
15
69
10 20 30 40 50 60 70 80 90 100 110 120 130 140 150
m/z
Fig. 1. Illustration of the identity of the mass spectra of (a) 1-methyl-2-(chloromethyl)benzene and (b) 1-methyl-3-(chloro-
methyl)benzene (from the NIST database [1] with the permission of S. Stine, director).
(ArCH3
ArCH2Cl, RI 228 14) [14]. As a result,
16 units, which is a good result for our simple calcu-
lation scheme, confirming the correctness of identifi-
cation of all the chloromethylation products listed in
Table 2.
we obtain the estimates of the retention indices given
in Table 2. The mean deviation of the experimental
retention indices from the additive estimates is
5
Table 1. Retention indices (RIs) and results of identification of chloromethyl derivatives of alkylarenes and by-products
in reaction mixtures
RI of
product
Identification result
(molecuilar weight)
Starting compound (RI)
Toluene (760)
RIa
1096 4 1-Methyl-4-(chloromethyl)benzene (140) [1088]b
1412 3 1-Methyl-3,4-bis(chloromethyl)benzene (188)
1463 2 1-Methyl-2,4-bis(chloromethyl)benzene (188)
1616 3 4,4 -Dimethyldiphenylmethane (196) [1616]
1625 6 2,4 -Dimethyldiphenylmethane (196) [1622]
1636 5 2,2 -Dimethyldiphenylmethane (196) [1634]
336
316
367
c
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 4 2007

614
ZENKEVICH, MAKAROV
Table 1. (Contd.)
RI of
product
Identification result
(molecuilar weight)
Starting compound (RI)
RIa
Ethylbenzene (854)
1184 2 4-(Chloromethyl)-1-ethylbenzene (154)
330
366
368
1550 3 2,4-Bis(chloromethyl)-1-ethylbenzene (202)
1231 2 1,4-Dimethyl-2-(chloromethyl)benzene (154)
1518 4 Unidentified product of reaction of p-xylene with [CH2O]
[1518]
p-Xylene (863)
1544 3 1,4-Dimethyl-2,3-bis(chloromethyl)benzene (202)
1605 3 1,4-Dimethyl-2,6-bis(chloromethyl)benzene (202)
1618 3 1,4-Dimethyl-2,5-bis(chloromethyl)benzene (202)
1861 6 2,2 ,5,5 -Tetramethyldiphenylmethane (224) [1868]
2166 3 2,2 ,5,5 -Tetramethyl-x-(chloromethyl)diphenylmethane (272)
1207 1 1,3-Dimethyl-4-(chloromethyl)benzene (154)
1572 3 1,3-Dimethyl-4,6-bis(chloromethyl)benzene (202)
1808 3 2,3 ,4,5 -Tetramethyldiphenylmethane (224) [1806]
1823 3 2,2 ,4,4 -Tetramethyldiphenylmethane (224) [1822]
1953 3 1,3-Dimethyl-2,4,6-tris(chloromethyl)benzene (250)
2152 3 1,3-Dimethyl-2,4,5,6-tetrakis(chloromethyl)benzene (298)
1233 2 1,2-Dimethyl-4-(chloromethyl)benzene (154)
1520 3 Unidentified product of reaction of o-xylene with [CH2O]
[1519]
313
374
387
309
342
365
m-Xylene (865)
o-Xylene (885)
381
199
348
1542 2 1,2-Dimethyl-4,5-bis(chloromethyl)benzene (202)
1578 3 1,2-Dimethyl-3,4-bis(chloromethyl)benzene (202)
1600 5 1,2-Dimethyl-3,5-bis(chloromethyl)benzene (202)
1618 4 1,2-Dimethyl-3,6-bis(chloromethyl)benzene (202)
1863 3 3,3 ,4,4 -Tetramethyldiphenylmethane (224) [1868]
1926 5 1,2-Dimethyl-3,4,6-tris(chloromethyl)benzene (250)
2162 2 3,3 ,4,4 -Tetramethyl-x-(chloromethyl)diphenylmethane (272)
2198 3 1,2-Dimethyltetrakis(chloromethyl)benzene (298)
1312 3 1,3,5-Trimethyl-2-(chloromethyl)benzene (168)
1686 2 1,3,5-Trimethyl-2,4-bis(chloromethyl)benzene (216)
2073 2 1,3,5-Trimethyl-2,4,6-tris(chloromethyl)benzene (264)
1335 2 1,2,4-Trimethyl-5-(chloromethyl) and/or 1,2,4-trimethyl-6-
(chloromethyl)benzene (168)
309
345
367
385
395, 342
299
272
349
374
387
1,3,5-Trimethylbenzene (963)
1,2,4-Trimethylbenzene (984)
351
1392 3 1,2,4-Trimethyl-3-(chloromethyl)benzene (168)
1658 3 1,2,4-Trimethyl-5,6-bis(chloromethyl)benzene (216)
1710 2 1,2,4-Trimethyl-3,5-bis(chloromethyl) and/or 1,2,4-trimethyl-
3,6-bis-(chloromethyl)benzene (216)
1375 3 1,2,3-Trimethyl-4-(chloromethyl)benzene (168)
1478 3 1,2,4,5-Tetramethyl-3-(chloromethyl)benzene (182)
1867 3 1,2,4,5-Tetramethyl-3,6-bis(chloromethyl)benzene (230)
1517 3 1,2,3,4-Tetramethyl-5-(chloromethyl)benzene (182)
408
323
375
1,2,3-Trimethylbenzene (1011)d
1,2,4,5-Tetramethylbenzene
(1103)
364
375
389
380
1,2,3,4-Tetramethylbenzene
(1137)d
1-Methyl-4-(1-methylethyl)-
benzene (1013)
1328 2 1-Methyl-4-(1-methylethyl)-3-(chloromethyl)benzene (182)
1346 2 1-Methyl-4-(1-methylethyl)-2-(chloromethyl)benzene (182)
315
333
1670 2 1-Methyl-4-(1-methylethyl)-2,3-bis(chloromethyl)benzene (230) 342, 324
1696 2 1-Methyl-4-(1-methylethyl)-2,5-bis(chloromethyl)benzene (230)
1709 3 1-Methyl-4-(1-methylethyl)-2,6-bis(chloromethyl)benzene (230)
1660 3 Pentamethyl(chloromethyl)benzene (196)
350
363
391
346
Pentamethylbenzene (1269)d
1-Methyl-4-(1,1-dimethylethyl)-
benzene (1080)
1426 3 1-Methyl-4-(1,1-dimethylethyl)-2-chloromethylbenzene (196)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 4 2007

IDENTIFICATION OF ALKYLARENE CHLOROMETHYLATION PRODUCTS
Table 1. (Contd.)
Starting compound (RI)
615
RI of
product
Identification result
(molecuilar weight)
RIa
1,3,5-Trimethyl-2-(1-methylethyl)- 1602 3 1,3,5-Trimethyl-2-(1-methylethyl)-4-(chloromethyl)benzene
363
364
benzene (1239)
(210)
1966 2 1,3,5-Trimethyl-2-(1-methylethyl)-4,6-bis(chloromethyl)-
benzene (258)
1678 5 1-Methyl-4-(chloromethyl)naphthalene (190)
1654 2 2-Methyl-x-(chloromethyl)naphthalene (190)
2042 3, 1(2)-Methyl-x,y-bis(chloromethyl)naphthalenes (238)
2058 3,
1-Methylnaphthalene (1291)e
2-Methylnaphthalene (1282)
387
372
2070 2
Acetophenone (1050)
1147 2 1-Phenyl-2-propen-1-one (132) [1138]b
1378 4 1-Phenyl-3-chloro-1-propanone (168) [1390]b
1410 2 1-[4-(Chloromethyl)phenyl]ethanone (168)
1600 4 1-Phenyl-3-chloro-2-(chloromethyl)-1-propanone (216)
1462 6 3-Hydroxypropiophenone (150)
328
360
222
1814 3 1-Phenyl-3-chloro-2,2-bis(chloromethyl)-1-propanone (264)
1285 2 1-Phenyl-2-ethyl-2-propen-1-one (160)
1485 2 1-Phenyl-2-(chloromethyl)-1-butanone (196)
1540 6 1-Phenyl-2-ethyl-1-propanon-3-ol (178)
1586 3 1-[4-(chloromethyl)phenyl]-1-butanone (196)
1705 5 1-Phenyl-2,2-bis(chloromethyl)-1-butanone (244)
1351 2 1-Phenyl-2-(1-methylethyl)-2-propen-1-one (174)
1439 2 2,3-Dimethyl-1-phenyl-2-buten-1-one (174)
1549 2 3-Methyl-1-phenyl-2-(chloromethyl)-1-butanone (210)
1660 3 3-Methyl-1-[4-(chloromethyl)phenyl]-1-butanone (210)
1081 3 2-(Chloromethyl)cyclohexanone (146)
2024 4 2,2,6,6-Tetrakis(chloromethyl)cyclohexanone (290)
214
247
Butyrophenone (1238)
348
220
Isovalerophenone (1276)
273
384
208
Cyclohexanone (873)
a
b
RI values for chloromethylation products and their precursors (two figures correspond to two possible starting compounds). In
brackets are reference data or retention indices of specially synthesized compounds under the same conditions of analysis (printed
c
italic). Here and hereinafter, RI values are not given for chloromethylation by-products and for compounds that cannot be
identified unambiguously. Hydrocarbons present as impurities in the durene fraction. 1-Methylnaphthalene is an impurity in
a 2-methylnaphthalene sample. For each group of isomeric products, the retention indices of the major isomers are printed bold.
d
e
The most difficult is structural interpretation of the
chromatographic signals of several isomers differing
in the retention parameters; these differences can reach
50 70 units. The differences in the retention indices
of positional isomers of substituted arenes are asso-
ciated with the presence or absence of o-substituents
in their molecules. Using data from Table 1 for the
unambiguously identified chloromethylation products,
we can estimate the mean increments RI of chloro-
methyl groups in various positions of the molecules.
Position of CH2Cl group
RI
No o-substituents
339 9
369 18
300 30
225 15
One or two methyl groups in o-positions
One or two chloromethyl groups in o-positions (including CH3 + CH2Cl combination)
In alkyl fragments in -position relative to carbonyl group
Determination of such increments is equivalent to
the development and use of the simplest additive
scheme for estimating the retention indices. Their
more detailed structural differentiation is not approp-
riate, taking into account that the scheme itself is
approximate. However, the RI values obtained clear-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 4 2007

616
ZENKEVICH, MAKAROV
Table 2. Comparison of the retention indices (RIs) of the simplest (chloromethyl)arenes estimated by the additive scheme
(RIadd) using the increment of the reaction ArCH3 ArCH2Cl, RI 228 14, with the experimentally determined reten-
tion indices (RIexp) of components of reaction mixtures
Starting
RI
ArCH3 ArCH2Cl substitution product
RIadd
RIexp
alkylmethylarene
Toluene
760 Benzyl chloride
988
1091
1179
1212
1212
1212
1335
1331
1365
1365
1497
1497
986 7
1096 4
1184 2
1231 2
1207 2
1233 2
1312 3
1335 2
1392 3
1375 3
1478 3
1517 3
p-Xylene
863 1-Methyl-4-(chloromethyl)benzene
951 4-(Chloromethyl)-1-ethylbenzene
984 1,4-Dimethyl-2-(chloromethyl)benzene
1,3-Dimethyl-4-(chloromethyl)benzene
1,2-Dimethyl-4-(chloromethyl)benzene
1107 1,3,5-Trimethyl-2-(chloromethyl)benzene
1103 1,2,4-Trimethyl-5-(chloromethyl)benzene
1137 1,2,4-Trimethyl-3-(chloromethyl)benzene
1,2,3-Trimethyl-4-(chloromethyl)benzene
1269 1,2,4,5-Tetramethyl-3-(chloromethyl)benzene
1,2,3,4-Tetramethyl-5-(chloromethyl)benzene
RIexp), units
1-Methyl-4-ethylbenzene
1,2,4-Trimethylbenzene
1,2,3,5-Tetramethylbenzene
1,2,4,5-Tetramethylbenzene
1,2,3,4-Tetramethylbenzene
Pentamethylbenzene
Mean deviation, (RIadd
5 16
ly reflect the observed scatter of the retention indices
of isomeric (chloroalkyl)arenes depending on the posi-
tions of the other substituents and can be used for the
identification of these products. The results of apply-
ing this criterion to identification of alkyl(chlorometh-
yl)arenes in various groups of positional isomers are
given in Table 3. It can be noted that in some cases
this procedure allows unambiguous prediction of the
Table 3. Interpretation of the sequences of chromatographic elution of some isomeric alkyl(chloromethyl)arenes, based on
the mean increments RI and boiling points Tb estimated using ACD software
Starting
compound
RI of
product
Estimation Estimated
Component
by RI
Tb,
C
Toluene
1412 3 1-Methyl-3,4-bis(chloromethyl)benzene
1463 2 1-Methyl-2,4-bis(chloromethyl)benzene
1633 3 4,4 -Dimethyldiphenylmethane
1396
1465
264.8
273.4
286.0
298.5
284.8
289.9
291.5
285.8
288.1
293.3
297.3
304.5
1640 3 2,4 -Dimethyldiphenylmethane
p-Xylene
o-Xylene
1544 3 1,4-Dimethyl-2,3-bis(chloromethyl)benzene
1605 3 1,4-Dimethyl-2,6-bis(chloromethyl)benzene
1618 3 1,4-Dimethyl-2,5-bis(chloromethyl)benzene
1542 2 1,2-Dimethyl-4,5-bis(chloromethyl)benzene
1572 3 1,2-Dimethyl-3,4-bis(chloromethyl)benzene
1600 5 1,2-Dimethyl-3,5-bis(chloromethyl)benzene
1618 4 1,2-Dimethyl-3,6-bis(chloromethyl)benzene
1658 3 1,2,4-Trimethyl-5,6-bis(chloromethyl)benzene
1710 2 1,2,4-Trimethyl-3,5-bis(chloromethyl) and/or
1,2,4-trimethyl-3,6-bis(chloromethyl)benzene
1531
1600
1600
1533
1533
1602
1602
1635
1,2,4-Trimethylbenzene
1704
312.1
and 313.0
238.3
246.8
297.8
303.4
310.3
252.6
1-Methyl-4-(1-methyl-
ethyl)benzene
1328 2 1-Methyl-4-(1-methylethyl)-3-(chloromethyl)benzene
1346 2 1-Methyl-4-(1-methylethyl)-2-(chloromethyl)benzene
1670 2 1-Methyl-4-(1-methylethyl)-2,3-bis(chloromethyl)benzene
1696 2 1-Methyl-4-(1-methylethyl)-2,5-bis(chloromethyl)benzene
1709 3 1-Methyl-4-(1-methylethyl)-2,6-bis(chloromethyl)benzene
1351 2 2-(1-Methylethyl)-1-phenyl-2-propen-1-one
1313
1313
1697
1697
1697
Isovalerophenone
1439 2 2,3-Dimethyl-1-phenyl-2-buten-1-one
263.7
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 4 2007

IDENTIFICATION OF ALKYLARENE CHLOROMETHYLATION PRODUCTS
617
elution sequence for pairs (but not for larger groups)
of isomers, e.g., for pairs of bis(chloromethyl) deriva-
tives of toluene and pseudocumene, and hence their
identification. In more complex cases, the estimated
retention indices of several positional isomers are
equal, and more structurally specific criteria are re-
quired for their identification.
sequence of chromatographic elution of isomeric chlo-
romethyl derivatives.
Small difference in the estimated boiling points of
two bis(chloromethyl) derivatives of 1,2,4-trimethyl-
benzene, 312.1 and 313.0 C (Table 3), suggests joint
elution of these compounds; this assumption elimi-
nates the vagueness arising from the fact that there are
three expected reaction products but only two ob-
served chromatographic peaks.
Since the order of gas-chromatographic elution of
isomers belonging to the same series on stationary
phases of any polarity unambiguously corresponds to
the ascending order of their boiling points, the most
rational solution of the problem in hand is apparently
that based on estimation of the boiling points (Tb)
using the ACD software [15]. Although the accuracy
of Tb estimation by this method is relatively poor, it
can be assumed that, within a group of chemically
similar compounds, the errors should be comparable,
so that the relative order of Tb variation within a
group of isomers should be fairly reliable. The esti-
mated boiling points of isomers, arranged in Table 3
in ascending order within each group, are in all the
cases consistent with the two other criteria considered
above, which allows unambiguous prediction of the
The main side process accompanying the chloro-
methylation is the formation of substituted diphenyl-
methanes ArCH2Ar [6, 8]; for the majority of them,
data on the retention indices are also unknown. How-
ever, such products can be readily revealed in reaction
mixtures by theoretical estimation of their retention
indices using a version of the additive scheme [2]
involving construction of target molecules from
simpler precursors and calculation of the retention
indices without using any increments calculated be-
forehand. In accordance with this scheme, the reten-
tion index of 4,4 -dimethyldiphenylmethane (one of
by-products of toluene chloromethylation) can be esti-
mated from data for unsubstituted diphenylmethane,
p-xylene, and toluene as follows:
+ 2
2
=
1619 24
(1413 18)
+ 2(863 8)
2(760 8)
(experimental value 1616 3)
For 2,2 ,5,5 -tetramethyldiphenylmethane (by-prod-
uct of p-xylene chloromethylation), the scheme is as
follows:
In addition, the formation of all the diarylmethanes
detected was confirmed experimentally by performing
the reaction under similar conditions with H2SO4 used
instead of HCl, which excludes formation of the
chloromethylation products. For o- and p-xylenes,
other products of unknown chemical nature were addi-
tionally detected in the reaction mixtures; without
hypotheses on their structure, they cannot be identi-
fied using our approach. However, such products are
readily revealed by the retention indices and do not
interfere with the identification of the target compo-
nents.
+ 2
2
(1413 18)
+ 2(984 7)
2(760 8)
Among chloromethyl derivatives of methylnaph-
thalenes, only one component, the previously isolated
[6] 1-methyl-4-(chloromethyl)naphthalene, can be
identified. Ambiguous positions of the chloromethyl
= 1861 23
(experimental value 1857 6)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 4 2007

618
ZENKEVICH, MAKAROV
group and of several such groups in 2-methylnaphtha-
lene chloromethylation products cannot be determined
solely from the chromatographic data, and in this case
our approach is inapplicable also.
In the reaction mixture obtained with isovalerophen-
one, we additionally identified 2,3-dimethyl-1-phenyl-
2-buten-1-one formed by isomerization of the primary
product, 2-(1-methylethyl)-1-phenyl-2-propen-1-one.
In two cases (acetophenone and butyrophenone), the
chromatograms contained broad asymmetrical peaks
assignable to polar hydroxy ketones I. The product
of acetophenone chloromethylation at the -position
relative to the carbonyl group, 1-phenyl-3-chloro-1-
propanone, was identified by comparing its retention
index with the available reference value (Table 1), and
all the other -chloromethyl derivatives III and IV,
by the well reproducible increment RI equal to 222
15. With all the alkyl phenyl ketones, we detected
single products of chloromethylation of the aromatic
core, most probably at 4-position.
The following fact is worth noting. Instead of pure
1,2,4,5-tetramethylbenzene, we had at our disposal
only a durene fraction boiling in a relatively wide
range (180 210 C) and containing about 80% main
substances, with impurities of 1,2,3-trimethylbenzene,
1,2,3,4-tetramethylbenzene, and pentamethylbenzene.
Naturally, chloromethylation of this sample yielded
a multicomponent product mixture. However, this did
not preclude unambiguous identification of the prod-
ucts on the basis of the above-considered chromato-
graphic relationships of the reaction (the correspond-
ing data are included in Table 1). It follows from
these data that, first, chloromethylation cannot be
classed with derivatization reactions, because the fol-
lowing important criteria are not observed: short reac-
tion time, high degree of conversion (the conversion
is particularly low for monoalkyl-substituted arenes
and their derivatives containing acceptor substituents),
and formation of no more than one or two products.
However, on the other hand, just the latter feature
allows determination of the molecular structure of
positional isomers of alkylarenes, even present simul-
taneously, by chromatographic analysis of their chlo-
romethylation products, which is impossible using
other reactions of compounds of this class.
The mean value of RI = 222 15, determined for
alkyl phenyl ketones, allows identification of the
product of cyclohexanone chloromethylation at the
-position relative to the carbonyl group, 2-(chloro-
methyl)cyclohexanone ( RI = 1081
873 = 208).
In the region of the chromatogram corresponding to
bis- and tris(chloromethyl) derivatives, we observed
several peaks, which does not allow their unambigu-
ous assignment. However, in the region of the ex-
pected retention index of the exhaustive chloromethyl-
ation product, 2,2,6,6-tetrakis(chloromethyl)cyclohex-
anone, their is only one peak, so that its identification
can be considered as unambiguous.
Interpretation of the composition of chloromethyla-
tion products formed from alkyl phenyl ketones is
more difficult, because the substitution in the aromatic
core can be accompanied by reactions in the -posi-
tion relative to the carbonyl group:
Thus, determination of chromatographic retention
indices in combination with the a priori information
about the chloromethylation features allowed identifi-
cation of more than 50 chloromethyl derivatives of
alkylarenes and alkyl phenyl ketones and of about
ten by-products of this reaction. The suggested ap-
proach to identification of previously uncharacterized
products of comprehensively studied organic reactions
can also be applied to other processes.
ArCOCH2R + [CH2O] + HCl
[ArCOCH(CH2OH)R]
I
ArCOC(R)=CH2 + ArCOCH(CH2Cl)R
II
ArCOC(CH2Cl)2R.
IV
III
(2)
EXPERIMENTAL
To prepare chloromethyl derivatives, we used
available alkylarenes of pure or chemically pure
grade. Isopropylmesitylene (d240 0.890, nD20 1.5072)
from the collection of Prof. B.V. Ioffe was synthe-
sized by alkylation of mesitylene with isopropyl alco-
hol in the presence of H2SO4. Instead of pure durene
we used a durene fraction boiling in the range 180
210 C (main substance content about 80%, chromato-
graphic monitoring). Samples of butyrophenone (d420
0.987, n2D0 1.519) and isovalerophenone (d240 0.973,
n2D0 1.510) were kindly submitted by Cand. Sci.
(Chem.) L.M. Kuznetsova. All the starting com-
pounds were characterized by gas-chromatographic
Nevertheless, this problem can also be successfully
solved on the basis of chromatographic data. Virtually
all the anomalous products in the reaction mixtures
are readily revealed by their RI values differing from
those of the chloromethyl derivatives. For example,
, -unsaturated carbonyl compounds II were detected
with all alkyl phenyl ketones: acetophenone (retention
index 1147 2, identified by the reference value of the
retention index, 1138), butyrophenone (1285 2), and
isovalerophenone (1351 2). The RI values of these
products are considerably lower than those of the
chloromethyl derivatives: 97, 47, and 75, respectively.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 4 2007

IDENTIFICATION OF ALKYLARENE CHLOROMETHYLATION PRODUCTS
retention indices on a standard nonpolar phase; the ACKNOWLEDGMENTS
619
data obtained coincided with the reference data.
The study was financially supported by the Russian
Foundation for Basic Research (project no. 04-03-
32900).
Chloromethylation of alkylarenes was performed
by a simplified procedure (without using phase-trans-
fer catalysts). A 50-ml round-bottomed flask equipped
with a reflux condenser was charged with 2 ml of
alkylarene, 1.5 g of paraform, and 10 ml of concen-
trated HCl. The reaction mixture was refluxed for 2 h
on a sand bath. After cooling, the organic phase was
washed two times with 10 15 ml of water and ana-
lyzed. The degree of conversion for different alkyl-
arenes ranged from 10 to 50% (estimated from the
total areas of chromatographic peaks).
REFERENCES
1. NIST/EPA/NIH Mass Spectral Library/Software/Bi-
nary Version (NIST-05), June 2005, CD-ROM.
2. Zenkevich, I.G., Moeder, M., Koeller, G., and Schar-
der, S., J. Chromatogr. (A), 2004, vol. 2015, p. 227.
3. Zenkevich, I.G., Encyclopedia of Chromatography,
Cazes, J., Ed., New York: Taylor & Francis, 2005,
p. 427.
For additional identification of diarylmethanes in
reaction mixtures, the process was performed under
identical conditions but with HCl replaced with 10 ml
of 30% H2SO4.
4. Zenkevich, I.G., Zh. Anal. Khim., 2001, vol. 56, no. 9,
p. 915.
5. Zenkevich, I.G., Zh. Org. Khim., 2001, vol. 37, no. 2,
From unsubstituted benzene, benzyl chloride, and
4-chlorotoluene, no chloromethylation products were
obtained under these conditions. Anisole forms with
formaldehyde a polycondensation product, a white
resinous substance. Extensive tarring was observed
with cyclohexanone; the products were extracted from
the reaction mixture with chloroform (15 ml).
p. 283.
6. Fuson, R.C. and McKeever, C.H., Org. React., 1942,
vol. 1, p. 63.
7. Reagents for Organic Synthesis, Fieser, L.F., Ed.,
New York: Wiley, 1967 1979. Translated under the
title Reagenty dlya organicheskogo sinteza, Moscow:
Mir, 1971, vol. 4, p. 65.
Gas-chromatographic analysis of reaction mixtures
was performed on a Biokhrom-1 chromatograph
equipped with a flame ionization detector and a quartz
capillary column (25 m 0.20 mm, standard nonpolar
polydimethylsiloxane stationary phase OV-101) in the
linear programmed heating mode (from 60 to 240 C
8. Selva, M., Trotta, F., and Tundo, P., Synthesis, 1991,
no. 11, p. 1003.
9. Tiess, D. and Wiss, Z., Wilhelm-Piek-Univ. Rostok
Math. Naturwiss. Reihe, 1984, vol. 33, p. 6.
1
10. Gandhe, B.R., Malhotra, R.C., and Gutch, P.K.,
at a rate of 6 deg min ). The carrier gas was nitrogen;
1
linear velocity 25 cm 1 s , flow split ratio at sample
J. Chromatogr., 1989, vol. 479, p. 165.
injection (sample volume 0.5 1.0 l) 1 : 30. The line-
ar-logarithmic retention indices (RIs) were calculated
from the retention times by formula (3) using the
standard software (QBasic) [16]:
11. Dalluge, J., VanStee, L.L.P., Xu, X., Williams, J.,
Beens, J., Vreuls, R.J.J., and Brinkman, U.A.Th.,
J. Chromatogr. (A), 2002, vol. 974, p. 169.
12. Gautzsch, R. and Zinn, P., Chromatographia, 1996,
vol. 43, nos. 3 4, p. 163.
RI = RIn + (RIn+k
f (tR,n)]/[f (tR,n+k
RIn)[f (tR,x
f (tR,n)],
)
13. White, C.M., Hackett, J., Anderson, R.R., Kail, S.,
and Speck, P.S., J. High Res. Chromatogr., 1992,
vol. 15, no. 1, p. 105.
)
(3)
where RIx, RIn, and RIn +k are the retention indices
of the compound being characterized and reference
n-alkanes with the numbers of carbon atoms (n) and
(n + k) and retention times tR,x, tR,n, and tR,n + k, re-
spectively. The function f(tn) in the system of linear-
logarithmic indices has the form f(tR) = tR + qlog(tR),
where q is a variable coefficient calculated from the
retention times of three reference n-alkanes [16].
14. Zenkevich, I.G., Zh. Org. Khim., 1992, vol. 28, no. 9,
p. 1827.
15. Zenkevich, I.G., Zh. Fiz. Khim., 2003, vol. 77, no. 1,
p. 92.
16. Stolyarov, B.V., Savinov, I.M., Vitenberg, A.G., Kar-
tsova, L.A., Zenkevich, I.G., Kalmanovskii, V.I., and
Kalambet, Yu.A., Prakticheskaya gazovaya i zhid-
kostnaya khromatografiya (Practical Gas and Liquid
Chromatography), St. Petersburg: Sankt-Peterb. Gos.
Univ., 2002.
As a source of information on the gas-chromato-
graphic retention indices we used the NIST database
[1] and the database of one of the authors (I.Z.).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 4 2007