The first 'alkane-like' functionalization of n-alkyl acetates: a new method for one-pot selective syntheses of bifunctional aliphatic compounds with an acetate group

Article abstract of DOI:10.1016/j.tetlet.2009.10.132

Selective one-pot functionalization of linear alkyl acetates C_nH_{2n + 1}OCOMe (n = 6, 8), with CO and various nucleophilic substrates (iso-propanol, morpholine, piperidine, and anisole) in the presence of the superelectrophilic system CBr₄·2AlBr₃ is performed for the first time.

Full text of DOI:10.1016/j.tetlet.2009.10.132

Tetrahedron Letters 51 (2010) 259–263
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Tetrahedron Letters
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The first ‘alkane-like’ functionalization of n-alkyl acetates: a new method
for one-pot selective syntheses of bifunctional aliphatic compounds with
an acetate group
*
Alexander V. Orlinkov, Nikolai D. Kagramanov, Pavel V. Petrovskii, Irena S. Akhrem
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Science, 119991, Moscow, GSP-1, 28 Vavilova Street, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
Selective one-pot functionalization of linear alkyl acetates CnH2n + 1OCOMe (n = 6, 8), with CO and various
nucleophilic substrates (iso-propanol, morpholine, piperidine, and anisole) in the presence of the super-
electrophilic system CBr4Á2AlBr3 is performed for the first time.
Received 30 July 2009
Revised 21 October 2009
Accepted 28 October 2009
Available online 31 October 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
n-Alkyl acetates
Functionalization
Superelectrophiles
Functionalized alkyl acetates
Selective one-pot C–H functionalization of monofunctional ali-
phatic compounds is an important goal opening the way to novel
bifunctional fine chemicals with desired properties that can be
used for the synthesis of biologically active compounds and mate-
rials for industrial use. However, finding reagents for such reac-
Reactions of alkanes and cycloalkanes with CO initiated by polyha-
lomethane-based superelectrophiles2 have made one-pot synthe-
ses of diverse carbonyl-containing products from readily
available raw materials possible. Some of the types of carbonyl-
containing compounds prepared by us from saturated hydrocar-
bons, CO and YH in the presence of CBr4Á2AlBr3 in a one-pot proce-
dure, are shown below (Scheme 1).2
tions presents
a considerable challenge, as most functional
groups have low tolerance to highly reactive systems that are capa-
ble of cleaving non-activated sp3 C–H bonds.
Evidently, the selective involvement of a functional group at a
sp3 C–H bond in aliphatic compounds bearing an acetate group
represents a more complicated problem compared to the func-
tionalization of alkanes. Indeed, the generation of a carbocation
in these ‘functionalized alkanes’ by a superelectrophile should
be hampered by both the deactivating effect of the electron-
withdrawing group and its ability to bond with the superelectro-
phile, resulting in diminished reactivity.4 In the case of alkyl ace-
tates, the possibility of cleavage of the ester bond by potent
superelectrophiles as well as isomerisation and cracking of the
carbocation, [CnH2n]+OCOMe, cannot be ruled out. Acid-catalyzed
ester cleavage has been extensively studied, and evidence has
emerged suggesting that protosolvation (or electrophilic solva-
tion) can play a role in this chemistry. Thus, methyl acetate is
found to be completely protonated at the acyl-oxygen in supe-
racidic FSO3H/SbF5/SO2 solution at low temperature. However,
even at À78 °C, protonated methyl acetate undergoes acyl-oxy-
gen cleavage to the acetyl cation and protonated methanol. This
suggests further protolytic activation of protonated methyl ace-
tate via the carboxonium dication.4
In this Letter we report a new approach to the one-pot synthesis
of novel bifunctional compounds from alkyl acetates, CnH2n + 1O-
COMe (n = 6, 8). It is important to mention that the functional
group present in the starting material remains intact during the
process, which occurs with good selectivity under extremely mild
conditions. Novel alkane-like methodology provides access to new,
very promising, and synthetically challenging functionalized alkyl
acetates with various functional groups.
Our strategy was based on the use of a new potent superelectr-
ophilic system CBr4Á2AlBr3 which can generate carbocations (R+)
effectively from saturated hydrocarbons (RH) under very mild con-
ditions.1,2 Generation of carbocations in the presence of superelec-
trophiles under a CO atmosphere results in the formation of
acylium cations (RCO+).3 The latter, in turn, can be converted into
carbonyl-containing derivatives of saturated hydrocarbons upon
treatment of the intermediates with various nucleophiles (YH).
* Corresponding author. Tel.: +1 7 495 1359329.
E-mail address: cmoc@ineos.ac.ru (I.S. Akhrem).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.10.132

260
A. V. Orlinkov et al. / Tetrahedron Letters 51 (2010) 259–263
RCOOR'
RCOR'
RCONR' 2
RH
+
CO
R
N
X
(X = CH2, O)
O
R
(X = O, S, NH)
X
O
-C H
,
C H ,
n-
5 12
C2H6, C3H8, n
4
10
RH =
R
(R = Me, Et)
Scheme 1. Examples of one-pot alkane functionalization.
O
O+H
O+H
H+
FSO3H- SbF5
SO2, -78 oC
Me
Me
MeCO+
+
MeO+H2
Me
+
Me
O
Me
O
Me
O
H
Examples of one-pot, selective C–H bond functionalizations of
phile with the acetate group are reversible, the C–H bond cleavage
followed by acylium cation formation under CO is virtually irre-
versible. As a result, the less nucleophilic center (C–H) can still re-
act with the superelectrophile even in the presence of the much
stronger CO donor.
monofunctional linear aliphatic compounds are very rare.5 Reac-
tions of aliphatic alcohols, ketones, and aldehydes with ozone in
magic acid in SO2ClF solution have been reported.5a Primary alco-
hols containing tertiary or secondary C–H bonds at the c-position
or more remote from the oxonium center have been shown to un-
dergo insertion reactions with protonated ozone to give oxidation
products in good yield. In contrast, secondary C–H bonds at the c-
position of aldehydes and ketones remain unreactive toward ozone
in SO2ClF at À40 °C. Such reactions with protonated ozone occur
only with higher ketone and aldehyde homologues.5a
These reactions proceeded with high regioselectivity, in each
case affording predominantly a single bifunctional product with
selectivities of 86–98% and, as a rule, in 72–85% yields. Conversions
of the initial n-alkyl acetates amounted to 80–98%. No products of
degradative functionalization containing a different number of car-
bon atoms in the alkyl group than in the initial alkyl acetates were
observed.
The direction of functionalization of n-hexyl acetate (Scheme 3)
depended on the temperature during carbonylation. At À20 °C,
functionalization with CO and nucleophiles (iso-propanol, morpho-
line, piperidine, and anisole) resulted in the formation of products
1, 2, 3, and 4 with a non-isomerized alkyl chain, in which the func-
tional group was located at the tertiary C-atom most distant from
the initial carbonyl group. The selectivities were 85% or higher. The
minor isomer formed had the neo-structure 5. In contrast, when
both the carbonylation of n-hexyl acetate and treatment of the
resultant carbonylation product with i-PrOH were carried out at
0 °C, neo-diester 5 was formed with a selectivity of 88%, while its
isomer 1 was produced as a minor component only.
The dependence of the outcome of the reaction on temperature
probably shows that the addition of a CO molecule to the second-
ary MeCO(CH2)4CH+Me cation proceeds more rapidly than its
isomerization into the tertiary cation and the subsequent addition
of CO to the sterically hindered cation. The selectivities and yields
of the products also depended on the nature of the nucleophile. In-
deed, reaction with morpholine proceeded selectively and led to
the corresponding product in high yield, while in the case of a
stronger nucleophile such as piperidine, both the selectivity and
yield were markedly lower.
Attempts to perform selective carbonylation of methyl-n-alkyl
ketones with CO in the presence of a proton superacid have been
unsuccessful.5b Over a wide temperature range and in the presence
of a large excess of HF–SbF5, the reactions either do not occur at all,
or have led to mixtures consisting predominantly of degradative
carbonylation products with smaller numbers of C-atoms in the al-
kyl group at the carbonyl than in the initial ketones, while the de-
sired products were formed in small amounts or not at all.5b Under
these conditions, only branched methyl alkyl ketones (n = 7–9)
having a tertiary C-atom at the end of their chains have been selec-
tively carbonylated with CO. However, conversions of the ketones
amounted to 16–66% only, although the reactions were carried out
in the presence of a 10-fold excess of HF–SbF5.5b Attempts to func-
tionalize esters have not been reported previously.
We found that at À20 °C or 0 °C under atmospheric CO pressure,
and in the presence of a 50–100% molar excess of the superelectr-
ophilic complex CBr4Á2AlBr3, effective carbonylation of n-alkyl ace-
tates, CnH2n + 1OCOMe (n = 6, 8) occurs. In situ treatment of the
carbonylation product with HNu nucleophilic agents (iso-propanol,
morpholine, piperidine, and anisole) led to the corresponding
bifunctional alkanes. Both carbonylations and subsequent reac-
tions with nucleophiles were carried out at the same temperature
and under a strictly maintained CO atmosphere (Scheme 2).
The carbonyl group is clearly a much stronger nucleophile than
an sp3 C–H bond. However, while interactions of the superelectro-
Functionalization of n-octyl acetate (Scheme 4) with CO and
nucleophiles (iso-propanol, morpholine, and anisole) afforded al-

A. V. Orlinkov et al. / Tetrahedron Letters 51 (2010) 259–263
261
O
E
O
CO
O
+
CnH2n+1
CnH2nCO+
CnH2n
O
O
O
E
E
2) H2O
O
1) HNu:
E = CBr4 2AlBr3
n = 6, 8
HNu: = ROH, R2NH, PhOMe
O
Nu
CnH2n
O
Scheme 2. One-pot functionalization of n-alkyl acetates.
CBr4 2AlBr3
oC
O
O
+
CO
CO+
0
O
O
- 20 o
C
iPrOH
0 o
C
CBr4 2AlBr3
O
O
O
O
O
CO+
O
5 (55%)
iPrOH
anisole
O
O
morpholine
piperidine
O
O
O
OiPr
O
O
O
O
1 (72%)
4 (73%)
O
O
O
O
N
N
O
2 (85%)
3 (42%)
Scheme 3. One-pot functionalization of n-hexyl acetate.
most exclusively the bifunctional products 6–8 of neo-structure.
The amounts of these neo-products were 95% or higher in the cor-
responding isomeric mixtures.
tures is of special interest because they display valuable properties,
such as enhanced thermal and chemical stabilities, and low freez-
ing points.6
The easier formation of the neo-products from n-octyl acetate
with a longer alkyl chain shows that the isomerization of a long-
chained cation generated from an alkyl acetate most likely pro-
ceeds more rapidly than with shorter homologues. The elaboration
of syntheses of bifunctional aliphatic compounds having neo-struc-
One-pot reactions of both n-hexyl and n-octyl acetates with CO
and anisole gave aromatic ketoacetates 4 or 8 in high yields and
selectivities with tert- or neo-alkyl groups, respectively.
Interestingly, the carbonylation and subsequent function-
alization of n-hexyl acetate (even at 0 °C) and its longer-chain
O
CBr4 2AlBr3
O
+
CO
CO+
- 20 o
Ñ
O
O
iPrOH
anisole
morpholine
O
O
OiPr
O
O
O
N
O
O
O
O
O
6 (77%)
O
8 (75%)
7 (80%)
Scheme 4. Selective one-pot functionalization of n-octyl acetate.

262
A. V. Orlinkov et al. / Tetrahedron Letters 51 (2010) 259–263
homologue n-octyl acetate occur with good regioselectivity, while
under the action of superacids, the corresponding C6 and C8 n-al-
kanes produced a mixture of isomers as well as products of their
degradative carbonylation, resulting in compounds with smaller
or larger numbers of C-atoms in the alkyl group at the carbonyl
than in the initial alkanes.7 The degradative carbonylation of C6 al-
kanes and their higher homologues C7–C10 does not occur in reac-
tions initiated by polyhalomethane-based superelectrophiles.8 In
this case, even at À40 °C, carbonylation of C6–C10 alkanes affords
exclusively, carbonyl-containing products with neo-alkyl substitu-
ents, that is, with a quaternary carbon atom at the carbonyl group.
These products were always represented by two dominating iso-
mers, AlkC(Me)2COOR and AlkC(Me)(Et)COOR.8
References and notes
1. Akhrem, I. S.; Orlinkov, A. V.; Vol’pin, M. E. J. Chem. Soc., Chem. Commun. 1993,
671.
2. Akhrem, I. S.; Orlinkov, A. V. Chem. Rev. 2007, 107, 2037. and references therein.
3. (a) Hogeveen, H.; Lukas, J.; Roobeck, C. F. J. Chem. Soc., Chem. Commun. 1969,
920; (b) Sommer, J.; Bukala, J. Acc. Chem. Res. 1993, 26, 370.
4. (a) Olah, G. A. Angew. Chem., Int. Ed. Engl. 1993, 32, 767; (b) Olah, G. A.; Klumpp,
D. A. Acc. Chem. Res. 2004, 37, 211; (c) Olah, G. A.; Hartz, N.; Rasul, G.;
Burrichter, A.; Prakash, G. K. S. J. Am. Chem. Soc. 1995, 117, 6421.
5. (a) Olah, G. A.; Yoneda, N.; Ohnishi, R. J. Am. Chem. Soc. 1976, 98, 7341; (b)
Yoneda, N.; Sato, H.; Fukuhara, T.; Takahashi, Y.; Suzuki, A. Chem. Lett. 1983, 19.
6. Fatty Acids in Industry; Johnson, R. W., Fritz, E., Eds.; Marcel Dekker: New York,
Basel, 1989; p 233. Chapter 11.
7. (a) Yoneda, N.; Fukuhara, T.; Takahashi, Y.; Suzuki, A. Chem. Lett. 1983, 17; (b)
Yoneda, N.; Takahashi, Y.; Fukuhara, T.; Suzuki, A. Bull. Soc. Chem. Jpn. 1986, 59,
2819.
As demonstrated in the present work, the aforementioned iso-
mers are produced in comparable amounts under conditions sim-
ilar to those for n-octyl acetate alkoxycarbonylation. Therefore, it
does not appear to be possible to obtain individual carbonyl-con-
taining products starting from C6–C10 alkanes.
8. Akhrem, I.; Afanas’eva, L.; Vitt, S.; Petrovskii, P. Mendeleev Commun. 2002, 180.
9. Rodd’s Chemistry of Carbon Compounds, Ansell, M. F.; Ed.; Amsterdam, 1973;
Vol. 1.
10. General procedure for compounds 1–4 and 6–8: At À20 °C, under atmospheric
CO pressure, n-alkyl acetate (1.6–1.9 mmol) was added to a stirred solution of
CBr4Á2AlBr3, freshly prepared from AlBr3 (6.50 mmol) and CBr4 (3.24 mmol) in
anhydrous CH2Br2 (2.5 mL) at room temperature. After stirring for 2.5 h at
The results of this work show that in the presence of the
acetoxy group, a single carbocation is generated selectively in
each case. Therefore, the corresponding acylium cation accumu-
lates in the reaction medium, allowing for regioselective func-
tionalization of the n-alkyl acetates. We believe that the site
for hydride abstraction from the alkyl acetate molecule is dic-
tated by two factors: (i) its remoteness from the already existing
functional group, and (ii) the stability of the carbocation to be
generated. For n-octyl acetate, the two requirements lead to a
compromise resulting in the formation of the most stable ter-
tiary cation separated from the functional group by five methyl-
enes. In the case of n-hexyl acetate, at a lower temperature
(À20 °C) the most distal yet less stable secondary cation is
formed, whereas at a higher temperature that favors isomeriz-
aton of the cations (0 °C), it is the more stable tertiary cation
that is produced, even though this cationic center is in proximity
to the functional group. The difference in the selectivities of the
carbonylation of n-octane and n-octyl acetate stems from the
fact that the former gives two cations that are rather similar
in stability, whereas the latter is transformed into an intermedi-
ate bearing the cationic center in the position that is most re-
mote from the ester group, Me2C+(C5H11).
À20 °C under
a CO atmosphere the nucleophile (iso-PrOH, morpholine,
piperidine, or anisole) was added to the in situ prepared carbonylation
intermediate strictly under CO. The mixture was stirred additionally for 10–
15 min at À20 °C and then left to warm to 0 °C over 20–30 min. Next, water
(10 mL) and CHCl3 (30 mL) were carefully added with stirring. The organic
layer was separated and the remaining aqueous layer was extracted with
CHCl3 (2 Â 20 mL). The combined organic extracts were dried over Na2SO4. The
structures of the products were established by 1H, 13C NMR11,12 and from GC–
MS spectra;13 conversions and isomeric ratios were determined by GC. The
yields of the obtained compounds were determined by 1H NMR11,12 with 1,3,5-
tribromobenzene as an internal standard.
Conditions and selected spectral data. All runs were carried out with 3.24 mmol
of CBr4Á2AlBr3.
Compound (1): 1.6 mmol of AcO-n-hexyl, 2.5 mL of iso-PrOH; yield 72% (86% as
an isomeric mixture); 1H NMR (400 MHz; CDCl3): d 1.19 (3H, d, JHH 9.1 Hz)
3
3
(see Ref. 11); 1.28 (6H, d, JHH 8.2 Hz); 1.35–1.75 (6H, m); 2.09 (3H, s); 2.50
(1H, m); 4.10 (2H, t, JHH 8.8 Hz); 5.06 (1H, sept, JHH 8.2 Hz). 13C NMR
(100 MHz, CDCl3): d 16.95; 21.62; 21.68; 24.19; 28.35; 33.20; 39.45; 64.18;
67.14; 171.05; 176.01. MS, m/z, (Irel, %): 230, M+ (0.5) (see Ref. 10); 171,
3
3
MÀOCOMe+ (14); 170, MÀAcOH+ (5); 129, PrOCOCH(Me)CH2 (96); 128 (65);
+
116, PrOC(OH)CHMe+ (64); 87 (27); 83 (44); 74 (79); 43 (100).
Compound (2): 1.6 mmol of AcO-n-hexyl, 6.5 mmol of morpholine; yield 85%
(90% as an isomeric mixture); 1H NMR (400 MHz; CDCl3): d 1.17 (3H, d, JHH
3
9.1 Hz); 1.30–1.80 (6H, m); 2.10 (3H, s); 2.69 (1H, m); 3.72 (8H, m); 4.10
3
(2H, t, JHH 8.8 Hz). 13C NMR (100 MHz, CDCl3): d 17.31; 20.66; 23.54; 28.39;
33.27; 34.75; 41.79; 45.74; 63.96; 66.52; 66.72; 170.77; 174.62.. MS, m/z, (Irel
,
%): 257, M+ (3); 242, (2); 214, MÀAc+ (17); 198, MÀOAc+ (26); 156,
morpholylCOCH(Me)CH2 (52); 143, morpholylC(OH)CHMe+ (100); 129 (27);
+
128 (28); 114, morpholylCO+ (22); 100 (21); 88 (72).
In contrast to
a-, b-, c-, or d-hydroxy acids and some of their
derivatives,9 whose syntheses, properties, applications in chemical
transformations, and practical use are well known, their long-
chained homologues and, in particular, compounds with branched
and neo-alkyl chains, are unavailable. Aromatic long-chain branched
and neo-ketoacetates have not been described earlier either.
In summary, an ‘alkane-like’ strategy has been used successfully
for the direct and simple one-pot functionalization of monofunc-
tional aliphatic compounds, namely n-hexyl and n-octyl acetates.
This approach has provided access to new, difficult to access
bifunctional aliphatic compounds with an acetate group, which
are of interest for the synthesis of biologically active compounds
and materials for industrial use. We believe that the field of ‘al-
kane-like’ reactions of monofunctional aliphatic compounds may
be expanded beyond the scope of alkyl acetates.
Compound (3): 1.6 mmol of AcO-n-hexyl, 6.5 mmol of piperidine; yield 42%
(85% as an isomeric mixture); 1H NMR (400 MHz; CDCl3): d 1.16 (3H, d, JHH
3
9.1 Hz); 1.30–1.40 (6H, br m); 1.60–1.75 (6H, m); 2.10 (3H, s); 2.73 (1H, m);
3.55 (4H, m); 4.10 (2H, t, JHH 8.8 Hz). 13C NMR (100 MHz, CDCl3): d 17.53;
3
20.75; 23.67; 24.44; 25.51; 28.48; 33.44; 34.91; 42.62; 46.32; 64.13; 170.78;
174.45. MS, m/z, (Irel, %): 255, M+ (3); 240, (2); 212, MÀAc+ (7); 196, MÀOAc+
(27); 154, piperidylCOCH(Me)CH2 (66); 141, piperidylCOCH(Me)+ (100).
+
Compound (4): 1.6 mmol of AcO-n-hexyl, 1.6 mmol of anisole; yield 73% (90%
as an isomeric mixture); 1H NMR (400 MHz; CDCl3): d 1.25 (3H, d, 3JHH 8.8 Hz);
3
1.3–1.9 (6H, m); 2.08 (3H, s); 3.48 (1H, m); 3.93 (3H, s); 4.09 (2H, t, JHH
8.8 Hz); 7.00 (2H, d, 3JHH 11.9 Hz); 8.00 (2H., d, 3JHH 11.9 Hz), (see Ref. 13). 13
C
NMR (100 MHz, CDCl3): d 17.38; 20.69; 23.57; 28.46; 33.07; 39.74; 55.16;
64.05; 113.53; 132.70; 161.82; 170.90; 202.36. MS, m/z, (Irel, %): 164,
MeOC6H4COCHMe+ (18); 135, MeOC6H4CO+ (100).
Procedure for compound (5): At 0 °C, under atmospheric CO pressure, n-hexyl
acetate (0.31 g, 2.17 mmol) was added to CBr4Á2AlBr3 (2.91 g, 3.34 mmol) in
CH2Br2 (2.5 mL), and the mixture was stirred over 1.5 h. Next, frozen iso-PrOH
(2.5 mL), at À20 °C, was added to the reaction mixture. After standard
treatment, a mixture of isomers 5 and 1 was obtained in a 10:1 ratio and a
total yield of 60%, the conversion of n-hexyl acetate was close to 100%. The
yield of 5 and ratio of isomers were determined by 1H NMR with 1,3,5-
tribromobenzene as an internal standard and by GC, respectively.
All the obtained products are novel and their structures were
confirmed by 1H and 13C NMR spectroscopy and mass-spectral
analysis. Typical experiments and selected spectral characteristics
are given.10
1H NMR (400 MHz; CDCl3): d 1.17 (6H, s) (see Ref. 12); 1.24 (6H, d, 3JHH 8.2 Hz);
3
3
1.35–1.75 (4H, m); 2.09 (3H, s); 4.10 (2H, t, JHH 8.8 Hz); 5.06 (1H, sept, JHH
8.2 Hz). 13C NMR (100 MHz, CDCl3): d 20.80; 21.56; 24.16; 24.88; 33.16; 36.48;
64.54; 67.23; 170.95; 176.86. MS, m/z, (Irel, %): 230, M+ (0.5); 171, MÀOAc+ (6);
170, MÀAcOH+ (19); 129, PrOCOCMe2+ (80); 128 (34); 83 (100); 55 (75); 43 (88).
Compound (6): 1.9 mmol of AcO-n-octyl, 2.0 mL of iso-PrOH; yield 77% (96% as an
isomeric mixture); 1H NMR (400 MHz; CDCl3): d 1.21 (6H, s) (see Ref. 12); 1.27
(6H, d, 3JHH 8.2 Hz); 1.50–1.75 (8H, m); 2.10 (3H, s); 4.10 (2H, t, 3JHH 8.8 Hz); 5.03
(1H, sept, 3JHH 8.2 Hz). 13C NMR (100 MHz, CDCl3): d 20.71; 21.48; 24.26; 24.84;
26.12; 28.18; 41.70; 64.16; 66.84; 170.71; 176.95. MS, m/z, (Irel, %): 259, M++H
Acknowledgments
We thank the Russian Foundation for Basic Research (Project
No. 09-03-00110) and the RAS Presidium Fund (Program 18P) for
financial support.

A. V. Orlinkov et al. / Tetrahedron Letters 51 (2010) 259–263
263
(5); 130, PrOCOCMe2+ (8); 111, (CH2)5CMe2+ (40); 88, PrOCOH+ (61); 69 (100); 67
(23); 55 (28).
d 20.57; 24.12; 26.15; 26.21; 27.98; 40.96; 47.07; 55.00; 64.03; 112.92;
130.20; 161.60; 170.64; 205.48. MS, m/z, (Irel
,
%): 250 (2); 178,
+
PhOC6H4C(OH)CMe2 (7); 135, PhOC6H4CO+ (100); 121 (2); 107, PhOC6H4
(12); 92 (3); 77 (20).
+
Compound (7):1.9 mmol of AcO-n-octyl, 5.7 mmol of morpholine; yield 80% (97%
as anisomeric mixture); 1H NMR (400 MHz; CDCl3):d1.30 (6H, s); 1.30–1.75 (8H,
3
3
m); 2.10 (3H, s); 3.70 (8H, m); 4.10 (2H, t, JHH 8.8 Hz). 13C NMR (100 MHz,
11. The presence of doublets (3H, d, JHH 9.1 Hz) at d 1.16–1.19 ppm and related
CDCl3): d 20.67; 24.43; 26.23; 26.60; 28.20; 38.45; 40.51; 42.13; 45.37; 64.06;
multiplets (1H) at 2.50–2.73 ppm in the1H NMR spectra proves that
66.61; 170.77; 175.27. MS, m/z, (Irel, %): 285, M+ (5); 242, MÀAc+ (10); 226,
compounds 1–3 contain non-branched alkyl chains CH2–CH–(COX)CH3.
MÀOAc+; 171, AcO(CH2)5CMe2 (9); 170, morpholylCOC(Me)2CH2 (16); 157,
morpholylC(OH)CMe2+ (47); 129, PrOCOCMe2+ (44); 114, morpholylCO+ (16); 88
(30); 69 (100).
Similarly, the structure of aromatic compound
4 was confirmed by the
+
+
presence of a doublet (3H) at 1.25 ppm and a deshielded multiplet (1H) at
3.48 ppm.
Compound (8): 1.9 mmol of AcO-n-octyl, 1.9 mmol of anisole; yield 75%
12. The presence of singlets (6H) at d 1.17–1.37 ppm establishes the neo-structure
for compounds 5–8.
13. Molecular ions are often absent in the MS of similar compounds, see: Pettersen,
J. E. Mass Spectrom. Ion Phys. 1983, 48, 129.
(98% as an isomeric mixture); 1H NMR (400 MHz; CDCl3): d 1.37 (6H, s);
3
1.30–1.85 (8H, m); 2.07 (3H, s); 3.90 (3H, s); 4.03 (2H, t, JHH 8.8 Hz); 6.93
3
3
(2H, d, JHH 11.9 Hz); 7.86 (2H, d, JHH 11.9 Hz). 13C NMR (100 MHz, CDCl3):