A SIMPLE EM00 FOR THE SYNTHESIS OF PERDEUTERATED

AROMATIC HYOROCARBONS AND HETEROCYCLIC COMPOUNDS

Steven B. Hawthorne, David J. Miller, Ted R. Aulich, and S yl vi a A. Farnum
Ul i vers i ty of North Dakota Energy Research Center
Box 8213, Uni vers i ty S tati on
&and Forks, North Dakota 58202
ABSTRACT
A general method has been developed f or the preparati on of deuterated
aromatic compounds that are useful f o r coal reacti on studi os and as i nternal
standards f or GC/MS anal ysi s. The method requi res l i t t l e s peci al i zed
equipment or synthesis expertise. A reacti on mi xture contai ni ng DC l , D2n, and
chromium i s used t o exchange deuterium f or aromatic hydrogens at temperatures
of ?Ono t o 300OC. A s i ngl e set of reacti on condi ti ons can he used t o prepare
a wide range of deuterated aromatics with nearl y complete exchange of aromatic
hydrogen f or deuterium and l i t t l e or no chemical degradation of the
reactant. When a 2D:l molar r ati o of deuterium t o aromatic hydrogen was used
the i s otopi c puri ty of most species tested i ncl udi ng phenanthrene ( i s otopi c
pur i ty of 94%), pyrene ( 95%) , phenol (96%), dibenzofuran (96%), carbazol e
(94x1, and di benzothiophene (939;), approached the H/D exchange equi 1 i brium of
95% i n two to f i f teen hours. The method al s o works wel l with complex mi xtures
as demonstrated by the deuterati on o f aromatics i n a coal - deri ved anthracene
o i l .
INTRODUCTION
The use of deuterated aromatic organi c compounds as i nternal standards f o r
the eval uati on of sample preparati on procedures and f o r the anal ysi s o f
complex samples usi ng gas chromatography coupled wi th mass spectrometry
(GC/MS) can greatl y increase the accuracy of anal yti cal res ul ts whi l e of ten
reducing the t i me requi red f or the anal ysi s. Deuterated compounds and
mi xtures are al so useful f or studying the f ate of organic compounds i n complex
systems such as coal conversion reacti ons. Unfortunatel y, the widespread use
of deuterated compounds i s l i mi ted by thei r hi gh cost and the l ack of
avai l abi l i ty o f many compound classes.
The purpose of t h i s paper i s to descri be a general method f or the
synthesis of deuterated species that i s appl i cabl e t o several classes o f
aromatic compounds, requi res minimal ti me and synthesi s experti se, yi el ds a
chemically and i s otopi cal l y pure product, uses simple and i nexpensi ve
equipment and reagents, and can he used with canplex mixtures. Thi s method
al so yi el ds products wi th mul ti pl e deuteri um which i s desi rabl e t o avoid the
overl ap i n the mass spectra that occurs from 13C i sotope peaks and (M-H)' i ons
when unlabeled and mnodeuteri o- l abel ed compounds occur i n the same sample
(1). The synthesis i s s i mi l ar t o the method of Werstiuk and Kadai (2-6) f o r
the H/D exchange of aromatic protons wi th D,o/DCl except that chromium i s
added t o increase the r ate of H/ D exchange. The a bi l i t y of t h i s method t o
provide chemically and i sotopi cal l y pure perdeuterated products was eval uated
471
f o r several aromatic hydrocarhons and 0-, S-, and N-containing aromatics. The
method was al so used t o produce perdeuterated deri vati ves of the components of
a coal-derived anthracene oi l .
EXPE RIME MAL
A l l reacti ons were performed i n 10 m 0.d. (8 mm i.d.) x approximately 8
cm long pyrex gl ass tubes. One end of the tube was sealed wi th a flame hefore
adding the reagents. The reacti on mi xture was then frozen i n l i qui d ni trogen,
the tube was evacuated usi ng a small l aboratory vacuum pump, and the tuhe was
sealed wi th a flame. This procedure f i l l e d approximately one-half of the tube
volume wi th reagents. The sealed tubes were then placed i nto a 1.3 cm 0.d. x
15 cm stai nl ess s teel pipe. Before capping the pi pe wi th "Swagelok" f i tti ngs ,
approximately 2 mL o f water was added so that the pressure i ns i de and outsi de
of the glass reacti on tube would be approximately equal duri ng heating. As a
safety measure, the s tai nl es s steel pi pe was placed i ns i de a containment
vessel made from a one-inch diameter thi ck- wal l ed i r on pi pe wi th threaded end
caps. A small hol e was dr i l l e d through one of the end caps t o avoid a
pressure increase i n the containment vessel. The enti re apparatus was then
heated t o 200-30O"C f or an appropri ate time peri od i n the oven of a gas
chromatograph. Caution: Since chl ori de i on degrades the strength of
s tai nl es s steel, the s tai nl es s steel pi pe shoul d be replaced i f a glass tube
breaks duri ng the reacti on. The deuterati on reagent consi sted o f 4% DC1 (by
wt. ) i n D?O (both > 99% i s otopi cal l y pure) wi th 10 mg/mL chromium metal.
Since the di s s ol uti on of the chromium metal evolves hydrogen gas, the addi ti on
of chromium was performed i n a venti l ated hood. Af ter the chromium had
di ssol ved (approximately one hour), the reagent mi xture was purged br i e f l y
wi th helium t o removed di ssol ved hydrogen. The reagent could then be stored
i ndef i ni tel y i n a desi ccator.
Unless otherwise noted, the deuterati on of the i ndi vi dual pure compounds
was performed usi ng a weighed amount of approximately 100 mg of tes t species
and an appropri ate volume of deuterati on reagent t o gi ve a 2O:l mol ar r ati o of
reagent deuterium to exchangeable protons. Each of the pure compounds was
reacted at 300C f o r 2 h r and/or 15 hr. If s i gni f i cant chemical degradation
occurred a t thi s temperature, an addi ti onal synthesi s was performed a t 200C
f or 2 hr. The deuterati on of the anthracene o i l was performed usi ng 50 mg of
sample wi th 1.0 mL of deuterati on reagent.
GC/MS anal ysi s of the deuterated products was performed wi th a Hewlett-
Packard model 59858 usi ng a 30 m x 0.32 mm i.d. (l um f i l m thi ckness) DB-5
fused s i l i c a capi l l ar y column ( J & W S ci enti f i c, Rancho Cordova, C.A.). A l l
analyses were performed i n the el ectron impact mode wi th 70 eV i oni zi ng
voltage. I s otopi c pur i ty of the products was cal cul ated from the resul tant
spectra. Gas chromatography wi th flame i oni zati on detecti on (FID) was
Performed on a Hewlett-Packard model 5890 GC wi th the same type o f
chromatographic column as used f or GC/MS. Chemical pur i ty of the s tar ti ng
materi al s and the products was deteni ned hy GC/FID anal ysi s using
gr avi mtr i cal l y prepared sol uti ons of standard and product species. Proton
NMR analyses of the deuterated oroducts were oerf oned on a Varian model XL-
200.
tetramethyl si l ane.
The deuterated products' were di ssol ved i n CD2C12 contai ni ng 0.25%
4 7 2
Since most of the tes t compounds (except the N-containing bases) were not
sol ubl e i n the reagent, quanti tati ve recovery of the products was eas i l y
attai ned by pi petti ng of f the l i qui d products or by removing the reagent from
the s ol i d products wi th a Pasteur pi pette. The s ol i d products were washed
wi th water and dri ed t o remove the resi dual reagent. The N-containing
aromatic bases ( ani l i ne and qui nol i ne) were removed from the reagent by making
the reacti on mi xture basi c wi th 2N NaOH and extracti ng wi th methylene
chl ori de. Since the purpose of t hi s synthesi s method was t o provide l abel ed
Products wi th deuterium s ubs ti tuti on i n chemically stabl e posi ti ons, the
hydroxyl deuterium on the two phenols, and the two amine deuteri um on ani l i ne
were exchanged for protons from H20 before being analyzed f or thei r i s otopi c
puri ty.
RESULTS AND DISCUSSION
The success of H/D exchange usi ng the DC1/D20/chromium reagent i n
synthesi zi ng perdeuterated aromatic canpounds fromseveral canpound classes i s
shown i n Table I . Mass spectra of several representati ve compounds before and
af ter deuterati on are shown i n F i gure 1. H/D exchanges wi th ethyl henzene,
phenanthrene, pyrene, perylene, biphenyl, phenol, dibenzofuran, ani l i ne,
carbazole, and dibenzothiophene a l l approached equi l i bri um with the deuterium
pool (assumed t o be 95% i s otopi c pur i ty based on the 20:l molar r ati o o f D/H)
i n ei ther two or 15 hours wi th no s i gni f i cant chemical degradation. The
i s otopi c puri ty of those species that attai n exchange equi l i bri um (95%
i s otopi c puri ty) can be improved, i f desired, hy i ncreasi ng the r ati o of
reagent D t o exchangeable H or by performing mul ti pl e exchange reacti ons.
Qui nol i ne al so showed no chemical degradation, but was onl y 73% i s otopi cal l y
pure af ter 15 hours. However, such products can s t i l l be useful f or i sotope
di l uti on analysis. F or example, the mass spectra of 73% i s otopi cal l y pure
qui nol i ne- d7 has a base peak o f 134 compared t o 129 f or undeuterated qui nol i ne
and, si nce no detectabl e overl ap i n t he i r mass spectra occurs i n the molecular
i on region, the 73% i s otopi cal l y pure product i s s t i l l useful as an i nternal
standard (F i gure 1). Longer reacti on times and/or hi gher reagent 0 t o
reactant H rati os coul d be used t o increase the i s otopi c puri ty.
Only three species, 2,4-dimethylphenol, ani sol e, and 2-methylthiophene,
showed enough degradation that the synthesis a t 300C was judged to be
unsuitable. Mi l der condi ti ons of 200C f o r 2 hr. were used f or each of these
species i n an attempt t o reduce degradation. Both 2,4-dimethylphenol and 2-
methylthiophene were reasonably stabl e under these condi ti ons and yi el ded
products wi th i s otopi c pur i ti es of 89% and 85%, respecti vel y (Table I ). The
methyl hydrogens of 2-methylthiophene exchanged readi l y and were i ncl uded i n
the cal cul ati on of i s otopi c puri ty. Anisole continued t o be converted t o
phenol even at these mi l der condi ti ons wi th onl y 43% o f the ori gi nal ani sol e
remaining af ter the reaction. Under these condi ti ons, onl y three pos i ti ons on
ani sol e underwent s i gni f i cant H/D exchange. These posi ti ons were shown by 200
MHz proton NMR t o be the ortho- and para- posi ti ons, as would be expected si nce
the methoxy group acti vates those posi ti ons f or el ectrophi l i c substi tuti on.
The same res ul t i s obtai ned when phenol undergoes the synthesis a t 20DY f o r 2
hr. These res ul ts i ndi cate that thi s method may be useful t o produce aromatic
compounds l abel ed at s peci f i c (ortho-, para- vs. meta-) posi ti ons by caref ul
sel ecti on of the reacti on temperature.
473
The use of t h i s synthesi s t o produce perdeuterated deri vati ves i n complex
mixtures was demonstrated wi th a coal deri ved anthracene o i l contai ni ng
predominantly aromatic hydrocarbons. F i gure 2 shows the res ul ts obtained when
the anthracene o i l underwent H/D exchange f o r 2 hours a t 300C. N3 detectabl e
chemical degradation of the sample occurred as determined by a canparison of
the GC/ F I D chromatograms of the o i l before and af ter the synthesis. The
molecular i on regi ons of the mass spectra ohtained before and af ter the
synthesis are shown f or several representati ve species (F i gure 2). The
i sotopi c puri ti es were naphthalene (97%), dihenzofuran (98%), dihenzothiophene
(99%), phenanthrene (96%), and pyrene (97%). Aromatic compounds having
al i phati c protons al s o showed nearl y quanti tati ve exchange of aromatic protons
f or deuterium, and some exchange of the al i phati c protons. For example, the
base peak f or 2-methylnaphthalene-d7 ( i f onl y aromatic protons exchanged f o r
D) would be a t m/z 149. The i ntense peaks a t m/z 151 and 152 show that some
al i phati c protons al so exchanged (F i gure 2).
The res ul ts of the perdeuterati on studi es of pure compounds (Table I ) and
the anthracene o i l demonstrate that the method presented here i s useful f or
synthesi zi ng perdeuterated aromatic compounds from several compound classes as
wel l as i n complex mixtures. A l l of the species that have been tested yi el d
products wi th both hi gh i s otopi c pur i ty and (except f or ani sol e) hi gh chemical
puri ty. The cost of the reagent i s low ( l es s than 20 dol l ars f o r thi s enti re
study) and the synthesi s i s simple t o perform.
CREDIT
The authors would l i ke t o thank the U.S. Department o f Energy for parti al
support of thi s work under contract number DE-FG22-86PC90911.
REFERENCES
1.
Blom, K.; Schuhardt, J . ; Munson, B. Anal. Chem. 1985, 57, 1986-1988.
2. Werstiuk, N.H.; Kadai, T. Can. J . Chem. 1973, 51, 1485-1486.
3. Werstiuk, N.H.; Kadai, T. Can. J. Chem. 1974, 52, 2169-2171.
4. Werstiuk, N.H.; Yadai, T. I n "Proceedings of the F i r s t I nternati onal
Conference on S tabl e I sotopes i n Chemistry, Bi ol ogy, and Medicine"; Kl ei n,
P.Y.; Peterson, S.V.; Eds; 1973, NT I S CONF-730525, pp. 13-19.
5.
6.
Werstiuk, N.H.; Timmins, G. Can. J . Chem. 1981, 59, 3218-3219.
Werstiuk, N.H.; Timmins, G. Can. J . Chem. 1981, 51, 1485-1486.
474
Table I
Synthesis of Perdeuterated Aromatic Compounds
ethyl benzene
phenanthrene
biphenyl
pyrene
peryl ene
phenol
2,4-dimethyl phenol
ani sole
dibenzofuran
ani l i ne
qui no1 i ne
car b azo 1 e
E-methyl t hi ophene
dibenzothi ophene
na
-
5
10
10
10
12
6
4
5
8
7
7
8
6b
8
I s otopi c P uri ty (%)
2 hr 15 hr 2 hrs
3o0c 3n0c mn0c
---
50 97
94 94
84 96
- 95
- 95
94 96 100'
89
- - 97c
52 96
95 96
29 73
93 94
- - 85b
95 93
Chemical P uri ty (%)
2 hr 15 hr 2 h r
3nnoc 3on0c 2nnoc
inn ino
ion inn
- - -
ion 95
- 100
- 100
88 39
100 99 100
<5d 493
i n0
100 7 J d
ion i on
94 89
99 99
e e 89
aThe number of exchangeable protons, n, i s used f or cal cul ati ng the
quanti ty of reagent requi red t o gi ve a D/H r a t i o o f 21131 i n the reacti on
mi x t ur e.
b A l l s i x of the protons on 2-methylthiophene exchanged readi l y so n=6 was
used t o determine the quanti ty of deuterati on reagent and f or the cal cul ati on
o f i sotopi c puri ty.
CI sotopi c puri ty was based on 3 rather than 5 H/D exchanges (see text).
dThe degradation product was phenol.
eNo 2-methylthiophene or i denti f i abl e degradation product was recovered.
475
Bef or e Deuterati on After Deuterati on
202
d,. -pyrene pyrene
40
20 20
106
:j, , , , 1 ~ , , , , , . , ;, , 11.. ,
0 0 . . . . : :I. . . . :. .
40 80 80 100 120 140 I60 180 200 220 10 60 80 100 120 140 160 80 ZOO 220
20
40 60 80 100 120 1 . 0
i i
40 I I II
2 12
192
I
100
(64
I d,-dibenzothiophene
C
-
100
dibenzothiophene
- . ; ii .,,,,, I.T., ;,, , , , , ,I,.< ; ; I , , , , ! , E ~ , ~ ~ , , , , ,,, ~ , , 1,.
152 18 160
a 2o
0
40 60 80 100 120 140 160 I60 200 40 60 80 100 120 140 160 180 200
1 : : 1 , d , , q; ; ; ,L , ,121 , , , . . , 6 1 , ~, , d,-quinoline ,dly- , ,;I , 1,. , , , ,
80
10
20
0
20
102
40 60 80 100 120 140 160 180 40 60 80 100 I20 140 160 160
i.1 , , carbazole : ,, , , , , , , , , ,!, , , , j ,
1 ; j i d. -carbazole
20 8. 138
145
10
0
40 60 80 100 120 140 160 I80 40 60 80 100 120 140 I60 180
ml z ml z
Fi g u r e 1:
El ec t r o n i mpact mass s pec t r a o f r e r es en t at i v e PAH and 0-, S-, and
N- c o n t ai n i n g ar omat i c s b ef o r e ( Pe f t s i d e of f i g u r e ) and a f t e r
( r i g h t s i d e) d eu t er at i o n f o r 15 hour s a t 300OC. I s o t o p i c and
chemi cal p u r i t i e s ar e gi ven i n Tab l e I .
476
!
! 0 , , I
m
120 140
C
0 136
.-
*
c :
a
0
n
i , , ,,I,, ,
T
120 140
140 160
150
160 180
I
I-L 1 0 2 0 0 170 190
J L 200 2 2 0
.I 200 220
/
L
I r
5 10 15 2 0
Retenti on Time (mi d
Fi g u r e 2: A compar i son of t h e mass s p ec t r al mol ec ul ar i o n r egi ons of
r ep r es en t at i v e s pec i es b ef o r e ( upper s p ec t r a) and a f t e r ( l o wer
s p ec t r a) d eu t er at i o n o f a c o al - d er i v ed ant hr acene oi l . Reac t i on
c o n d i t i o n s , i s o t o p i c p u r i t i e s , and gas chr omat ogr aphi c c o n d i t i o n s
a r e g i v en i n t h e t e x t .
477