Generation of cyclic ketene-N,X-acetals (X = O, S) from 2-alkyl-1,3-oxazolines and 2-alkyl-1,3-thiazolines. Reactions with acid chlorides, 1,3-diacid chlorides and N-(chlorocarbonyl) isocyanate

Article abstract of DOI:10.1055/s-2005-918499

2-Alkyl-1,3-oxazolines, 2-alkyl-1,3-thiazolines, and the corresponding cyclic ketene-N,X-acetals (X = O, S) derived from them were reacted with monoacid chlorides, diacid chlorides, triacid chlorides. A series of these carbon-carbon bond-forming reactions and cyclizations to both substituted 2,3-dihydrooxazolo[3,2-a]pyridine-5,7-diones and 2,3-dihydrothiazolo[3,2-a] pyridine-5,7-diones proceeded under mild reaction conditions. Cyclic ketene-N,X-acetal intermediates play important roles in all these reactions. Related cyclizations with N-(chlorocarbonyl) isocyanate formed substituted 2,3-dihydrooxazolo[3,2-c]pyrimidine-5,7-diones and 2,3-dihydrothiazolo[3,2-c] pyrimidine-5,7-diones. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-918499

PAPER
37
Generation of Cyclic Ketene-N,X-Acetals (X = O, S) from 2-Alkyl-1,3-oxazo-
lines and 2-Alkyl-1,3-thiazolines. Reactions with Acid Chlorides, 1,3-Diacid
Chlorides and N-(Chlorocarbonyl) Isocyanate
G
eneration and Re
i
actions
h
of Cyclic
K
u
etene-
N
,
X
-A
a
cetals(X
=
O,
S) Zhou,* Charles U. Pittman Jr.*
Department of Chemistry, Mississippi State University, Starkville, MS 39762, USA
Fax +1(662)3257611; E-mail: zhou_aihua@yahoo.com, cpittman@ra.msstate.edu
Received 31 March 2005; revised 15 July 2005
Abstract: 2-Alkyl-1,3-oxazolines, 2-alkyl-1,3-thiazolines, and the
corresponding cyclic ketene-N,X-acetals (X = O, S) derived from
them were reacted with monoacid chlorides, diacid chlorides, tri-
acid chlorides. A series of these carbon–carbon bond-forming reac-
tions and cyclizations to both substituted 2,3-dihydrooxazolo[3,2-
a]pyridine-5,7-diones and 2,3-dihydrothiazolo[3,2-a]pyridine-5,7-
diones proceeded under mild reaction conditions. Cyclic ketene-
N,X-acetal intermediates play important roles in all these reactions.
Related cyclizations with N-(chlorocarbonyl) isocyanate formed
substituted 2,3-dihydrooxazolo[3,2-c]pyrimidine-5,7-diones and
2,3-dihydrothiazolo[3,2-c]pyrimidine-5,7-diones.
Figure 1 Resonance structures of N-methyl cyclic ketene-N,X-ace-
tals
Cyclic ketene-N,X-acetals can now be easily made from
2-alkyl-1,3-oxazolines 3 and 2-alkyl-1,3-thiazolines
4.17,18 Oxazolines and thiazolines have been employed in
organic synthesis for about 70 years.19–32 Herein, amino
alcohols were used as starting materials for 2-alkyl-1,3-
oxazolines 3 and 2-alkyl-1,3-thiazolines 4 (Scheme 1),
which were converted to cyclic ketene-N,X-acetals.1–3,17,18
Key words: 2-alkyl-1,3-oxazolines, 2-alkyl-1,3-thiazolines, cyclic
ketene-N,O-acetals, cyclic ketene-N,S-acetal, cyclization reaction
Cyclic ketene acetals have attracted interest due to their
nucleophilic reactions with electrophilic compounds1–9
and their ability to undergo rapid cationic homo- and co-
polymerization.10–16 Cyclic ketene-N,X-acetals (X = O, S)
1 and 2 contain extremely electron-rich double bonds,
negatively polarized at their exocyclic carbons. They ex-
hibit high nucleophilicity, exerted through resonance be-
tween the exo-methylene group and the two adjacent
heteroatoms (N, O or S) (Figure 1). Acetals 1 and 2 con-
tain two nucleophilic contributions within the same func-
tional group, in the form of enamines and vinyl (thio)ether
functions. This suggests that they should be explored
more thoroughly as a class of carbon nucleophiles for car-
bon–carbon bond-forming reactions. Heretofore, they
have been employed rather sporadically because of their
highly reactive and unstable nature.
Amino alcohols reacted with carboxylic acids to afford 2-
alkyl-1,3-oxazolines 3 in 60–80% yield. Amino alcohols
reacted with acid chlorides plus triethylamine in CH2Cl2
for one hour to afford hydroxyamides. Treatment with ei-
ther Lawesson’s reagent in refluxing toluene, or P2S5 in
mineral oil at 140 °C generated 2-alkyl-1,3-thiazolines 4.
N-Methylation of either 3 or 4 with iodomethane in dry ni-
tromethane afforded N-methyl-2-methyl-1,3-oxazolinium
iodides 5 and N-methyl-2-methyl-1,3-thiazolinium io-
dides 6. Sodium hydride in THF converted 5 and 6 to N-
methyl cyclic ketene-N,X-acetals 1 and 2. Compounds 1
and 2 are extremely sensitive to acids, acidic surfaces, and
water, so isolation requires basic media or base-treated
glassware surfaces.
1) R4CHCOCl
Et3N, CH2Cl2
R4
R4
R4
X
2) P2S5, PhCH3
H2N
OH
CH3
CH3
CH3I
NaH
THF
N
X
N
N
X
I
R1 R2 R3
CH3NO2
R1 R2 R3
R1 R2 R3
R4CHCOOH
reflux, 24 h
R1 R2 R3
1 X = O
2 X = S
5 X = O
6 X = S
3 X = O
4 X = S
Scheme 1 Synthesis of N-methyl cyclic ketene-N,X-acetals
SYNTHESIS 2006, No. 1, pp 0037–0048
x
x
.
x
x
.2
0
0
5
Advanced online publication: 24.11.2005
DOI: 10.1055/s-2005-918499; Art ID: M01705SS
© Georg Thieme Verlag Stuttgart · New York

38
A. Zhou, C. U. Pittman Jr.
PAPER
Table 1 Reactions of 2-Alkyl-1,3-oxazolines (or 2-Alkyl-1,3-thiazolines) with Acid Chloridesa
Entry
X
Substituents in 3 and 4
R in RCOCl Product
Yield (%)b
R1
R2
R3
H
R4
H
3a
3b
3c
3d
4a
4b
4c
4d
4e
4f
O
O
O
O
S
CH3
CH3
CH3
CH3
H
CH3
CH3
CH3
CH3
H
C6H5
9a
9b
91
90
83
88
92
88
85
90
93
85
H
CH3
Et
H
C6H5
H
C6H5
9c
H
(CH3)3C
C6H5
9d
H
H
10a
10b
10c
10d
10e
10f
S
H
H
CH3
H
H
C6H5
S
Et
H
H
C6H5
S
CH3
H
CH3
H
H
H
C6H5
S
H
H
(CH3)3C
(CH3)3C
S
H
H
CH3
H
a The ratio of 3 (or 4)/acid chloride/Et3N = 1:2.2:3.
b All yields are isolated yields.
2-Methyl-1,3-oxazolines react with two equivalents of an tons produced ketenes whose further reactions were not
acid chloride, without a-protons, to afford N-acyl-b-keto studied.
cyclic ketene-N,O-acetals as shown by Tohda et al.33 Cy-
Next, we investigated whether heterocycles 3 and 4 would
clic ketene-N,O-acetals were recently shown to be inter-
undergo cyclization through their intermediate N-acyl cy-
mediates in that reaction.17 We now extend this chemistry
to 2-alkyl-1,3-thiazolines and other 2-alkyl-1,3-oxazo-
lines (alkyl = ethyl and propyl) upon their reactions with
mono-, di-, and triacid chlorides which have no a-protons.
Thus, 3 and 4 reacted with acid chloride (2.2 equivalents)
and triethylamine (3 equivalents) in refluxing acetonitrile
clic ketene-N,X-acetals, when reacted with diacid chlo-
rides which have no a-protons. Could ring closure occur,
placing the second keto function cis to N and trans to O?
Indeed, the consumption of one acid chloride function of
the diacid chloride in the presence of triethylamine gener-
ated the expected reactive intermediate N-acyl cyclic
ketene-N,X-acetals 11 and 12 (Table 2). Rapid intramo-
to generate N-acyl-b-keto cyclic ketene-N,X-acetals 7 and
8 in excellent yields (Table 1).
lecular nucleophilic attack by the acetal’s nucleophilic
Consumption of one equivalent of acid chloride generates carbon on the second acid chloride function generated the
reactive N-acyl cyclic ketene-N,X-acetal intermediates 7 6/5-fused ring 2,3-dihydrooxazolo[3,2-a]pyridine-5,7-di-
and 8. Subsequent nucleophilic attack by these intermedi- ones 13 and 2,3-dihydrothioazolo-[3,2-a]pyridine-5,7-di-
ate N-acyl cyclic ketene-N,X-acetals 7 and 8 on a second ones 14, respectively. For example, one equivalent of a,a-
equivalent of acid chloride generates the N-acyl-b-keto disubstituted malonyl dichloride reacted with one equiva-
cyclic ketene-N,X-acetals 9 and 10, where the b-keto lent of 2-alkyl-1,3-oxazolines 3 or 2-alkylthiazolines 4
group was always cis to the oxygen or sulfur, and R4 was (Table 2) in refluxing acetonitrile for three hours to give
cis to nitrogen (demonstrated by NOESY experiments). excellent yields of 13a–g and 14a–g, respectively. This
High yields of 9 and 10 were achieved when benzoyl and facile cyclization is an extremely efficient way to prepare
trimethylacetyl chlorides were used. In contrast, the use of the ring systems 2,3-dihydrooxazolo[3,2-a]pyridine-5,7-
propionyl chloride or isobutyryl chloride, which have a- diones 13 and 2,3-dihydrothioazolo[3,2-a]pyridine-5,7-
protons, did not produce the corresponding N-acyl-b-keto diones 14 with a variety of substituents at the 2-, 3-, 6-,
cyclic ketene-N,X-acetals. Competing base-catalyzed and 8-positions.
elimination of HCl from acid chlorides containing a-pro-
Synthesis 2006, No. 1, 37–48 © Thieme Stuttgart · New York

PAPER
Generation and Reactions of Cyclic Ketene-N,X-Acetals (X = O, S)
39
Table 2 The Reactions of 2-Alkyl-1,3-oxazolines 3 (or 2-Alkyl-1,3-thiazolines 4) with a,a-Disubstituted Malonyl Diacid Chloridesa
Entry
X
Substituents in 3 and 4
R in RCOCl Product
Yield (%)b
R1
R2
R3
H
R4
3f
O
O
O
O
O
O
O
S
H
H
H
CH3
13a
13b
13c
13d
13e
13f
95
94
92
90
92
92
89
94
92
92
91
90
91
93
3e
3f
H
H
H
CH3
H
CH3
H
H
H
Et
3e
3f
H
H
H
CH3
H
Et
H
H
H
-(CH2)3-
-(CH2)3-
-(CH2)3-
CH3
3e
3d
4a
4b
4g
4a
4h
4a
4h
H
H
CH3
H
CH3
H
CH3
H
CH3
H
13g
14a
14b
14c
14d
14e
14f
H
H
S
H
H
CH3
CH3
H
H
CH3
S
H
H
CH3
H
CH3
S
H
H
Et
S
H
H
H
CH3
H
Et
S
H
H
H
-(CH2)3-
-(CH2)3-
S
H
H
H
CH3
14g
a The ratio of 3 (or 4)/acid chloride/Et3N = 1:1:3.
b All yields are isolated yields.
The facile synthesis of ring system 14 reported here is of has been reported on 2-cyanomethylbenzothiazole in tri-
special interest due to the known biological activities of ethylamine–dioxane at ambient temperature with N-(chlo-
35
some of these derivatives. Some 2,3-dihydrothiazolo[3,2- rocarbonyl) isocyanate. We are continuing to explore
a]pyridine-5,7-diones are known to generate pronounced these cyclizations on 2-alkyl-1,3-oxazolines, 2-alkyl-1,3-
increases of HDL cholesterol and marked decreases of thiazolines, and 2-alkyl-1,3-oxazines and 2-alkyl-1,3-thi-
LDL and VLDL cholesterol, when administered in vivo to azines without electron-withdrawing substituents on the
rats.34
2-alkyl group.36
To expand the scope of this cyclization, N-(chlorocarbon- The facile synthesis of 17 and 18 is of special interest be-
yl) isocyanate was used as the dielectrophile in place of cause biological activity has been demonstrated for deriv-
a,a-disubstituted diacid chlorides. N-Acylation should atives of the latter. They are claimed to be useful for
easily occur. Consumption of one equivalent of acid chlo- prevention and treatment of diseases involving c-Jun N-
ride generated reactive N-acyl cyclic ketene-N,X-acetal terminal kinase (JNK), e.g. cardiac failure, hypertension,
intermediates 15 and 16 upon reaction with 3 and 4, re- rheumatoid arthritis, Alzheimer’s disease, etc.37 JNK is a
spectively. Rapid intramolecular nucleophilic attack by signaling protein that is capable of initiating the apoptotic
the reactive exocyclic b-carbon of intermediates 15 and cell death process. 38,39
16 on the isocyanate carbon then generated the highly
Oxalyl chloride and phthaloyl dichloride (no a-protons)
functionalized ring systems of 2,3-dihydrooxazolo[3,2-
did not undergo analogous cyclizations with 2-alkyl-1,3-
c]pyrimidine-5,7-diones 17 and 2,3-dihydrothiazolo[3,2-
oxazolines 3 or 2-alkyl-1,3-thiazolines 4 to generate the
corresponding 5/5- or 7/5-ring fusions (Scheme 2). Simi-
c]pyrimidine-5,7-diones 18 (Table 3). These reactions all
proceed in excellent yields. A single similar cyclization
larly, phosgene failed to convert 2-alkyloxazolines or 2-
Synthesis 2006, No. 1, 37–48 © Thieme Stuttgart · New York

40
A. Zhou, C. U. Pittman Jr.
PAPER
Replacement of the N-acyl function with a methyl group
in reaction intermediates 7/8, 11/12, and 15/16 should in-
crease the b-carbon’s nucleophilicity. Thus, N-methyl cy-
clic ketene-N,X-acetals 1 and 2 were synthesized
(Scheme 1) and reacted with acid chlorides. N-Methyl cy-
clic ketene-N,X-acetals 1 and 2 were used immediately af-
ter being prepared and characterized. They reacted with
acid chlorides in THF at room temperature in the presence
of triethylamine to form the corresponding N-methyl-b-
keto cyclic ketene-N,X-acetals 22 and 23 in good isolated
yields (Table 4).
Table 3 Preparation of 2,3-Dihydrooxazolo[3,2-c]pyrimidine-5,7-
diones 17 and 2,3-Dihydrothiazolo[3,2-c]pyrimidine-5,7-diones 18a
Entry
X
Substituents in 3 or 4
Pro-
duct
Yield
(%)b
Table 4 The Reaction of N-Methyl Cyclic Ketene-N,X-acetals with
R1
R2
R3
R4
Acid Chloridesa
3e
3d
4h
4g
4d
O
O
S
H
H
H
CH3
H
17a
17b
18a
18b
18c
90
86
94
92
92
CH3
H
CH3
H
H
H
CH3
CH3
H
S
H
H
CH3
S
CH3
CH3
H
a The ratio of 3 (or 4)/N-(chlorocarbonyl)isocyanate/Et3N = 1:1:2.
b All yields are isolated yields.
Entry
X
Substituents in 1 and 2 R4 in
Pro- Yield
duct (%)b
R4COCl
R1
CH3
CH3
CH3
CH3
H
R2
CH3
CH3
CH3
CH3
H
R3
1a
1a
1a
1a
2a
2b
2c
2d
2a
2b
2c
2d
2a
2a
2a
2a
2a
2a
O
O
O
O
S
S
S
S
S
S
S
S
S
S
S
S
S
S
H
C6H5
22a
22b
70
73
64
59
78
75
71
74
81
76
68
69
82
77
74
79
alkylthiazolines to their corresponding 4/5-ring-fusion
products (Scheme 2). The failure of oxalyl chloride to
generate 20 was disappointing in view of the successful
cyclization of oxalyl chloride on a 2-carbethoxythiazoline
derivative reported by Shane et al.40 at room temperature
in CH2Cl2. Oxalyl chloride reacted extremely rapidly and
exothermically with 3 and with 4 in acetonitrile, THF,
CH2Cl2, or acetone, generating black solutions and black
residues. Dropwise additions of oxalyl chloride at 0 °C or
–23 °C failed to produce 20. An electron-withdrawing R4
function on 3 or 4 may play a crucial role in this reaction.
H
(CH3)3C
H
CH3(CH2)2 22c
(CH3)2CH 22d
H
H
C6H5
23a
23b
23c
23d
23e
23f
23g
23h
23i
H
H
CH3
H
C6H5
Et
H
C6H5
CH3
H
CH3
H
H
C6H5
H
(CH3)3C
(CH3)3C
(CH3)3C
(CH3)3C
CH3
H
H
CH3
H
Et
H
CH3
H
CH3
H
H
H
H
H
H
CH3CH2
23j
H
H
H
CH3(CH2)2 23k
(CH3)2CH 23l
H
H
H
H
H
H
CH3(CH2)3 23m 75
CH3(CH2)6 23n 75
H
H
H
a The ratio of 1 (or 2)/acid chloride/Et3N = 1:2:2.5.
b All yields are isolated yields.
Scheme 2 Reaction of 2-alkylthiazolines and 2-alkyloxazolines with
oxalyl chloride, phthaloyl chloride, and phosgene
Synthesis 2006, No. 1, 37–48 © Thieme Stuttgart · New York

PAPER
Generation and Reactions of Cyclic Ketene-N,X-Acetals (X = O, S)
41
Acid chlorides, with or without a-protons, could be em-
ployed in the synthesis of 22 and 23. This demonstrates
the much higher nucleophilic reactivity of these cyclic
ketene-N,X-acetals 1 and 2, versus intermediates 7/8, 11/
12 and 15/16. The latter could not compete with ketene
generation when reacted with acid chlorides. However, 1
and 2 reacted more rapidly with acid chlorides than acid
chlorides react with triethylamine to generate ketenes, al-
lowing the use of ambient temperature and shorter reac-
tion times. The reactions to generate 22 and 23 reached
completion at room temperature within ten minutes. The
successful conversion of 1 and 2 to the corresponding N-
methyl-b-keto cyclic ketene-N,X-acetals 22 and 23, using
acid chlorides containing a-protons (Table 4), contrasts
sharply with the failure to convert 3 and 4 to products 9
and 10 with a-proton-containing acidic chlorides. Table 1
contains no reactions with acid chlorides that have a-pro-
tons. N-Methyl cyclic ketene-N,X-acetals 1 and 2 are
clearly stronger carbon nucleophiles than their respective
N-acyl analogues, 7/8, 11/12, and 15/16.
Scheme 3 Reaction of N-methyl cyclic ketene-N,X-acetals 1 and 2
When 2.5 equivalents of either N-methyl cyclic ketene-
N,X-acetals 1 or 2 were reacted with one equivalent of a
diacid chloride having no a-protons (a,a-disubstituted
malonyl dichloride or p-terephthalic chloride), bis-a,b-
unsaturated ketones 24 and 25 were formed in high yields
(Table 5). These reactions were carried out at ambient
temperature in THF. However, when diacid chlorides
with a-protons (succinyl chloride and glutaryl dichloride)
were used, the analogous products were not produced. In-
stead, extremely rapid reactions occurred in THF, gener-
ating black solutions and black residues. Lowering the
reaction temperature to –20 °C still did not afford prod-
ucts 24 or 25.
with 1,3,5-benzenetricarbonyl chloride
Cyclization reactions using 2,4,5-trimethyloxazole 28, 2-
methylbenzothiazole 30, and 1,2-dimethylimidazole 32
with diethylmalonyl dichloride failed to form 29, 31, and
33, respectively (Scheme 4). Instead, 28, 30, and 32 were
recovered. Each of these heterocyclic compounds are aro-
matic. Therefore, it may be more difficult to produce the
corresponding nonaromatic, 7-p-electron 1,3-heteroatom
cyclic ketene acetals 29, 31, and 33.
Reactions of 1 and 2 with 1,3,5-benzenetricarbonyl chlo-
ride generated the tris-a,b-unsaturated ketones 26 and 27
in high isolated yields (Scheme 3).
Table 5 Reaction of N-Methyl Cyclic Ketene-N,X-acetals 1 and 2
with Diacid Chloridesa
Substituents in 1 and 2
Entry
X
R
Pro-
duct
Yield
(%)b
R1
CH3
H
R2
CH3
H
R3
H
H
H
H
1a
2a
2c
2a
O
S
S
S
p-C6H4
24a
85
88
79
80
>C(CH3)2 25a
>C(CH3)2 25b
Scheme 4 Reactions of 2,4,5-trimethyloxazole (28), 2-methylben-
zothiazole (30) and 1,2-dimethylimidazole (32) with diethylmalonyl
dichloride
Et
H
H
H
p-C6H4
25c
a The ratio of 1 (or 2)/diacid chloride/Et3N = 2.5:1:3.
b All yields are isolated yields.
Synthesis 2006, No. 1, 37–48 © Thieme Stuttgart · New York

42
A. Zhou, C. U. Pittman Jr.
PAPER
IR (film): 3062, 2967, 1741, 1675, 1643, 1598, 1562, 1414, 1329,
1284, 1022, 900, 727, 698 cm–1.
alkyl-1,3-thiazolines, and N-methyl cyclic ketene-N,X- 1H NMR (300 MHz, CDCl3): d = 7.18–7.74 (m, 10 H), 5.04 (s, 1 H),
In summary, we have successfully demonstrated C–C
bond-forming reactions of 2-alkyl-1,3-oxazolines, 2-
4.35 (s, 2 H), 1.64 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 186.4, 168.5, 161.1, 139.8, 134.4,
132.4, 130.9, 128.7, 128.6, 127.7, 126.8, 85.5, 79.5, 62.5, 22.5.
acetals with monoacid chlorides, reactions of N-methyl
cyclic ketene-N,X-acetals with di-, and triacid chlorides.
Cyclization reactions of 2-alkyl-1,3-oxazolines and 2-
alkyl-1,3-thiazolines with diacid chlorides generated ex-
cellent isolated yields of 2,3-dihydrooxazolo[3,2-a]pyri-
dine-5,7-diones 13 and 2,3-dihydrothioazolo[3,2-a]py-
ridine-5,7-diones 14, respectively. Analogous cycliza-
tions of N-(chlorocarbonyl) isocyanate generated the
corresponding 2,3-dihydrooxazolo[3,2-c]pyrimidine-5,7-
diones 17 and 2,3-dihydrothiazolo[3,2-c]pyrimidine-5,7-
diones 18. These four classes of 5/6-fused ring systems
are highly functionalized. These reactions permit a great
deal of structural diversity, since the substituents at the 2-,
3-, 6-, and 8-positions can be readily varied (the acidic NH
at position 6 in 17 and 18 can be functionalized after cy-
clization). These carbon–carbon bond-forming reactions
proceed under mild conditions with very good yields. Fur-
ther applications of these reactions in diversity-oriented
synthesis are being investigated in our lab. For example,
2-alkyl-1,3-oxazines and 2-alkyl-1,3-thiazines can be
converted to 6/6-fused ring-systems when treated with
1,3-diacid chlorides or N-(chlorocarbonyl) isocyanate36 in
close analogy to the reactions reported here.
2-(3-Benzoyl-4,4-dimethyloxazolidin-2-ylidene)-1-phenylpro-
pan-1-one (9b)
White solid; yield: 132 mg (90%); mp 120–122 °C.
IR (film): 3060, 2965, 2926, 2889, 1786, 1735, 1654, 1523, 1450,
1359, 1175, 1092, 972, 773, 706 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.31–8.11 (m, 10 H), 3.80 (s, 2 H),
2.14 (s, 3 H), 1.21 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 186.0, 164.5, 161.6, 134.9, 132.8,
129.7, 128.8, 128.5, 128.0, 127.9, 126.5, 78.4, 66.4, 53.5, 27.8,
16.5.
2-(3-Benzoyl-4,4-dimethyloxazolidin-2-ylidene)-1-phenylbu-
tan-1-one (9c)
White solid; yield: 127 mg (83%); mp 122–124 °C.
IR (film): 3060, 2966, 2930, 2873, 1786, 1735, 1648, 1451, 1356,
1238, 1103, 1065, 972, 773, 706 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.34–8.10 (m, 10 H), 3.81 (s, 2 H),
2.51 (q, J = 7.4 Hz, 2 H), 1.27 (s, 6 H), 1.17 (t, J = 7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 185.0, 164.4, 160.7, 134.9, 132.9,
129.8, 128.9, 128.3, 128.2, 128.1, 128.0, 126.5, 78.3, 66.7, 27.9,
23.4, 13.4.
Melting points were recorded with a Mel-Temp apparatus
and are uncorrected (a heating rate of 2 °C/min near the
1-[3-(2,2-Dimethylpropionyl)-4,4-dimethyloxazolidin-2-
ylidene]-3,3-dimethylbutan-2-one (9d)
mp was used). The IR spectra were recorded on a Midac White solid; yield: 108 mg (88%); mp 59–60 °C.
FT infrared spectrometer as films on KBr plates. The 1H
IR (film): 2967, 2929, 2870, 1758, 1677, 1644, 1481, 1360, 1106,
and 13C NMR spectra were recorded using a Bruker model
AMX-300 spectrometer operating at 300 MHz for proton
and 75 MHz for carbon. Chemical shifts are reported in
ppm downfield from Me4Si used as the internal standard.
All reactions were carried out under a dried nitrogen at-
mosphere. MeCN and Et3N were distilled from calcium
1000, 838 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.80 (s, 1 H), 3.88 (s, 2 H), 1.31
(s, 9 H), 1.27 (s, 6 H), 1.13 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 174.7, 163.9, 159.6, 102.0, 78.3,
66.1, 39.1, 37.3, 28.1, 27.4, 27.2.
hydride under nitrogen. CH2Cl2 and MeNO2 were pre- 2-(3-Benzoylthiazolidin-2-ylidene)-1-phenylethanone (10a)
Yellow solid; yield: 125 mg (92%); mp 123–125 °C.
dried with CaCl2 and then distilled from CaH2 under nitro-
gen. THF was distilled from Na metal/benzophenone
ketyl. All other commercially obtained reagents were used
as received. The silica gel used for the column chromatog-
raphy was purchased from Aldrich Company (70–230
mesh, 60 Å).
IR (film): 3057, 2962, 2868, 1665, 1511, 1354, 1224, 1157, 1021,
780, 699 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.04–7.62 (m, 10 H), 7.04 (s, 1 H),
4.16 (t, J = 6.9 Hz, 2 H), 3.06 (t, J = 6.9 Hz, 2 H).
13C NMR (75 MHz, CDCl3) d = 187.7, 169.2, 159.4, 138.3, 135.2,
131.7, 131.5, 128.3, 128.2, 127.7, 127.3, 103.4, 52.5, 27.6.
2-(3-Benzoyl-4,4-dimethyloxazolidin-2-ylidene)-1-phenyleth-
anone (9a); Typical Procedure
MS (EI, 70 eV): m/z (%) = 309 [M+], 308, 204, 105 (100), 77, 51.
Benzoyl chloride (137 mg, 0.97 mmol) was added dropwise to a
stirred soln of 2,4,4-trimethyl-2-oxazoline (3a) (50 mg, 0.44 mmol)
and Et3N (133 mg, 1.32 mmol) in MeCN (20 mL) at r.t. Then this
soln was refluxed for 3 h and the solvent was removed by rotary
evaporation. H2O (20 mL) was added to the residue, followed by ex-
traction with CH2Cl2 (2 × 25 mL). The organic layer was washed
with 10% aq Na2HCO3 soln (20 mL), then with H2O (15 mL), and
dried over Na2SO4. The solvent was removed by rotary evaporation
and the residue was purified by column chromatography with silica
gel (hexane–EtOAc, 1:1) to give 9a. The preparation of 9b–d and
10a–f is the same as this procedure.
2-(3-Benzoyl-5-methylthiazolidin-2-ylidene)-1-phenylethanone
(10b)
Yellow solid; yield: 125 mg (88%); mp 107–110 °C.
IR (film): 3056, 2962, 2869, 1664, 1624, 1597, 1510, 1488, 1327,
1296, 1227, 1172, 1010, 912, 777, 698 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.30–7.63 (m, 10 H), 7.03 (s, 1 H),
4.20 (dd, J = 6.1, 10.1 Hz, 1 H), 3.80 (dd, J = 6.9, 11.1 Hz, 1 H),
3.57 (m, 1 H), 1.41 (d, J = 6.7 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 187.6, 169.2, 159.3, 138.3, 135.1,
131.6, 131.3, 128.5, 128.0, 127.5, 127.2, 103.0, 58.8, 37.7, 18.7.
White solid; yield: 158 mg (91%); mp 119–120 °C.
Synthesis 2006, No. 1, 37–48 © Thieme Stuttgart · New York

PAPER
Generation and Reactions of Cyclic Ketene-N,X-Acetals (X = O, S)
43
MS (EI, 70 eV): m/z (%) = 323 [M+], 322, 250, 218, 105 (100), 77,
White solid; yield: 142 mg (95%); mp 98–99 °C.
51.
IR (film): 2982, 2935, 2866, 1703, 1376, 1229, 1136, 993, 836, 726
cm–1.
1H NMR (300 MHz, CDCl3): d = 5.13 (s, 1 H), 4.71 (t, J = 7.0 Hz,
2 H), 4.07 (t, J = 7.0 Hz, 2 H), 1.42 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 196.6, 174.5, 164.9, 81.7, 68.4,
50.9, 41.9, 24.4.
2-(3-Benzoyl-4-ethylthiazolidin-2-ylidene)-1-phenylethanone
(10c)
Yellow solid; yield: 126 mg (85%); mp 100–102 °C.
IR (film): 3050, 2964, 1625, 1597, 1489, 1345, 1283, 1231, 1175,
1053, 924, 778, 699 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.25–7.59 (m, 10 H), 6.76 (s, 1 H),
4.79 (m, 1 H), 3.31 (dd, J = 6.5, 11.4Hz, 1 H), 2.88 (d, J = 11.4 Hz,
1 H), 1.78 (m, 2 H), 0.97 (t, J = 7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 187.3, 168.0, 159.0, 138.2, 134.8,
131.6, 131.1, 128.5, 128.0, 127.8, 127.1, 104.6, 63.5, 31.1, 24.3,
10.2.
6,6,8-Trimethyl-2,3-dihydrooxazolo[3,2-a]pyridine-5,7-dione
(13b)
White solid; yield: 108 mg (94%); mp 99–101 °C.
IR (film): 2974, 2926, 2867, 1702, 1436, 1375, 1227, 1175, 984,
938, 679 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.62 (t, J = 7.8 Hz, 2 H), 4.00 (t,
J = 7.8 Hz, 2 H), 1.67 (s, 3 H), 1.32 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 196.5, 174.2, 161.4, 88.9, 68.0,
50.6, 42.2, 24.6, 6.7.
2-(3-Benzoyl-4,4-dimethylthiazolidin-2-ylidene)-1-phenyleth-
anone (10d)
Yellow solid; yield: 133 mg (90%); mp 118–120 °C.
IR (film): 3055, 2969, 1626, 1597, 1509, 1367, 1305, 1240, 1170,
1058, 922, 763, 694 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.21–7.77 (m, 10 H), 6.00 (s, 1 H),
3.31 (s, 2 H), 1.68 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 186.9, 170.5, 162.7, 138.6, 135.0,
132.6, 131.4, 129.1, 128.8, 128.0, 127.0, 102.6, 67.7, 42.2, 24.4.
6,6-Diethyl-2,3-dihydrooxazolo[3,2-a]pyridine-5,7-dione (13c)
White solid; yield: 106 mg (92%); mp 91–92 °C.
IR (film): 2969, 2935, 1697, 1618, 1445, 1434, 1372, 1200, 1146,
943, 779 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.27 (s, 1 H), 4.72 (t, J = 8.0 Hz,
2 H), 4.10 (t, J = 8.0 Hz, 2 H), 1.82–2.05 (m, 4 H), 0.77 (t, J = 7.4
Hz, 6 H).
13C NMR (75 MHz, CDCl3): d = 196.3, 173.7, 165.4, 85.1, 68.3,
61.6, 41.6, 32.7, 9.4.
1-[3-(2,2-Dimethylpropionyl)thiazolidin-2-ylidene]-3,3-dimeth-
ylbutan-2-one (10e)
Yellow solid; yield: 110 mg (93%); mp: 125–127 °C.
MS (EI, 70 eV): m/z (%) = 210 (M+ + H, 100), 181, 166, 112, 83, 55.
IR (film): 2967, 2867, 1807, 1760, 1680, 1647, 1303, 1087, 1000,
884, 825, 738 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.58 (s, 1 H), 4.18 (t, J = 6.5 Hz,
2 H), 2.97 (t, J = 6.5 Hz, 2 H), 1.38 (s, 9 H), 1.19 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 204.5, 177.0, 158.3, 103.7, 51.5,
42.5, 41.5, 28.3, 27.8, 26.9.
MS (EI, 70 eV): m/z (%) = 269 [M+ + H], 212, 184 (100), 170, 128,
199, 177, 157, 142, 115, 85, 73, 57.
6,6-Diethyl-8-methyl-2,3-dihydrooxazolo[3,2-a]pyridine-5,7-di-
one (13d)
White solid; yield: 111 mg (90%); mp 93–95 °C.
IR (film): 2967, 2935, 2877, 1692, 1669, 1605, 1444, 1378, 1203,
1162, 951, 901 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.70 (t, J = 8.0 Hz, 2 H), 4.10 (t,
J = 8.0 Hz, 2 H), 2.05 (m, 4 H), 1.78 (s, 3 H), 0.72 (t, J = 8.0 Hz, 6
H).
1-[3-(2,2-Dimethylpropionyl)-5-methylthiazolidin-2-ylidene]-
3,3-dimethylbutan-2-one (10f)
13C NMR (75 MHz, CDCl3): d = 196.1, 173.2, 161.9, 92.4, 68.0,
61.4, 42.0, 32.9, 9.4, 6.5.
Yellow solid; yield: 105 mg (85%); mp 120–121 °C.
IR (film): 2961, 2866, 1676, 1634, 1509, 1316, 1090, 1010, 892,
823 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.60 (s, 1 H), 4.18 (dd, J = 5.7,
10.7 Hz, 1 H), 3.87 (dd, J = 6.1, 10.7 Hz, 1 H), 3.45 (m, 1 H), 1.38
(s, 9 H), 1.25 (d, J = 12.2 Hz, 3 H), 1.19 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 204.6, 177.2, 158.4, 103.5, 57.9,
42.6, 41.5, 38.0, 28.0, 26.9, 18.5.
6-(1,1-Cyclobutane)-2,3-dihydrooxazolo[3,2-a]pyridine-5,7-di-
one (13e)
White solid; yield: 105 mg (92%); mp 150–152 °C.
IR (film): 2950, 1695, 1605, 1473, 1441, 1354, 1241, 1131, 927,
818, 582 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.09 (s, 1 H), 4.72 (t, J = 8.0 Hz,
2 H), 4.09 (t, J = 8.0 Hz, 2 H), 2.45–2.61 (m, 4 H), 2.13–2.24 (m, 2
H).
6,6-Dimethyl-2,3-dihydrooxazolo[3,2-a]pyridine-5,7-dione
(13a); Typical Procedure
13C NMR (75 MHz, CDCl3): d = 194.5, 172.9, 165.1, 81.5, 68.4,
Dimethylmalonyl chloride (100 mg, 0.59 mmol) was added drop-
wise to a stirred soln of 2-methyloxazoline (3) (50 mg, 0.59 mmol)
and Et3N (178 mg, 1.77 mmol) in MeCN (40 mL) at r.t. Then this
soln was refluxed for 3 h and the solvent was removed by rotary
evaporation. H2O (20 mL) was added to the residue, followed by ex-
traction with CH2Cl2 (2 × 25 mL). The organic layer was washed
with 10% aq NaHCO3 soln (20 mL), then with brine (20 mL), and
dried over Na2SO4. The solvent was removed by rotary evaporation
and the residue was purified by column chromatography with silica
gel (hexane–EtOAc, 1:1) to give 13a. The preparation of 13b–g and
14a–g followed the same procedure, except 2-substituted thiazo-
lines were employed with 14a–g.
53.8, 41.8, 29.7, 15.3.
6-(1,1-Cyclobutane)-8-methyl-2,3-dihydrooxazolo[3,2-a]pyri-
dine-5,7-dione (13f)
White solid; yield: 120 mg (92%); mp 152–154 °C.
IR (film): 2954, 1694, 1666, 1609, 1438, 1378, 1225, 1206, 1150,
950, 938, 735 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.69 (t, J = 8.0 Hz, 2 H), 4.08 (t,
J = 8.0 Hz, 2 H), 2.44–2.61 (m, 4 H), 2.13–2.25 (m, 2 H), 1.76 (s, 3
H).
Synthesis 2006, No. 1, 37–48 © Thieme Stuttgart · New York

44
A. Zhou, C. U. Pittman Jr.
PAPER
13C NMR (75 MHz, CDCl3): d = 194.6, 172.8, 161.6, 89.1, 68.1,
53.6, 42.2, 30.0, 15.4, 6.7.
1H NMR (300 MHz, CDCl3): d = 4.32 (t, J = 7.2 Hz, 2 H), 3.33 (t,
J = 7.2 Hz, 2 H), 1.82–1.99 (m, 4 H), 1.99 (s, 3 H), 0.73 (t, J = 7.4
Hz, 6 H).
6-(1,1-Cyclobutane)-3,3-dimethyl-2,3-dihydrothiazolo[3,2-
a]pyridine-5,7-dione (13g)
White solid; yield: 116 mg (89%); mp 144–145 °C.
13C NMR (75 MHz, CDCl3): d = 194.4, 173.6, 157.2, 108.5, 61.5,
49.0, 32.9, 27.4, 12.2, 9.4.
IR (film): 2953, 1698, 1651, 1429, 1367, 1186, 946, 808 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.06 (s, 1 H), 4.31 (s, 2 H), 2.44–
2.62 (m, 4 H), 2.13–2.21 (m, 2 H), 1.68 (s, 6 H).
6-(1,1-Cyclobutane)-2,3-dihydrothiazolo[3,2-a]pyridine-5,7-di-
one (14f)
Yellow solid; yield: 112 mg (91%); mp 144–145 °C.
IR (film): 3064, 2951, 1687, 1620, 1571, 1401, 1343, 1310, 1117,
833 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.60 (s, 1 H), 4.26 (t, J = 7.2 Hz,
2 H), 3.38 (t, J = 7.2 Hz, 2 H), 2.53 (t, J = 8.3 Hz, 4 H), 2.10–2.22
(m, 2 H).
13C NMR (75 MHz, CDCl3): d =194.4, 173.3, 165.8, 81.6, 80.6,
60.9, 55.1, 29.2, 23.5, 15.1.
6,6-Dimethyl-2,3-dihydro-oxazolo[3,2-a]pyridine-5,7-dione
(14a)
Yellow solid; yield: 112 mg (94%); mp 105–106 °C.
13C NMR (75 MHz, CDCl3): d = 193.0, 173.1, 160.8, 98.1, 54.1,
48.5, 29.5, 27.4, 15.0.
IR (film): 3069, 2869, 1687, 1631, 1579, 1391, 1334, 1172, 1039,
815, 733 cm–1.
6-(1,1-Cyclobutane)-8-methyl-2,3-dihydrothiazolo[3,2-a]pyri-
dine-5,7-dione (14g)
Yellow solid; yield: 122 mg (93%); mp 145–146 °C.
1H NMR (300 MHz, CDCl3): d = 5.62 (s, 1 H), 4.24 (t, J = 7.1 Hz,
2 H), 3.36 (t, J = 7.1 Hz, 3 H), 1.42 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 195.1, 174.8, 160.6, 98.3, 51.3,
48.8, 27.4, 24.3.
MS (EI, 70 eV): m/z (%) = 197 (100) [M+], 182, 169, 154, 128, 70,
60.
IR (film): 3004, 2951, 1682, 1630, 1592, 1401, 1379, 1285, 1176,
1017, 853 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.27 (t, J = 7.2 Hz, 2 H), 3.37 (t,
J = 7.2 Hz, 2 H), 2.53 (t, J = 8.0 Hz, 4 H), 2.12–2.25 (m, 2 H), 1.85
(s, 3 H).
13C NMR (75 MHz, CDCl3): d = 192.7, 173.1, 156.8, 105.7, 54.2,
49.2, 29.9, 27.5, 15.2, 12.4.
2,6,6-Trimethyl-2,3-dihydrothiazolo[3,2-a]pyridine-5,7-dione
(14b)
Yellow solid; yield: 118 mg (92%); mp 107–108 °C.
IR (film): 3048, 2973, 2870, 1687, 1634, 1579, 1398, 1322, 1260,
1197, 1163, 1025, 846, 723 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.59 (s, 1 H), 4.31 (dd, J = 5.7,
10.9 Hz, 1 H), 3.85–3.99 (dd, J = 5.7, 10.9 Hz, 1 H), 3.85–3.99 (m,
1 H), 1.54 (d, J = 6.3 Hz, 3 H), 1.42 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 195.0, 174.7, 160.7, 98.2, 55.3,
51.2, 39.3, 24.1, 19.8.
8-Methyl-2,3-dihydrooxazolo[3,2-c]pyrimidine-5,7-dione(17a);
Typical Procedure
N-(Chlorocarbonyl) isocyanate (220 mg, 2.1 mmol) was added
dropwise to a stirred soln of 2-ethyloxazoline 3 (210 mg, 2.1 mmol)
and Et3N (422 mg, 4.20 mmol) in THF (20 mL) at r.t. Then this soln
was refluxed for 2 h and the solvent was removed by rotary evapo-
ration. H2O (20 mL) was added to the residue, followed by extrac-
tion with CH2Cl2 (2 × 25 mL). The organic layer was washed with
10% aq NaHCO3 soln (20 mL), H2O (15 mL), and dried over
Na2SO4. The solvent was removed by rotary evaporation and the
residue was purified by column chromatography with silica gel
(hexane–EtOAc, 1:1) to give 17a. The preparation of 17b and 18a–
c followed the same procedure.
2,6,6,8-Tetramethyl-2,3-dihydrothiazolo[3,2-a]pyridine-5,7-di-
one (14c)
Yellow solid; yield: 125 mg (92%); mp 105–107 °C.
IR (film): 2975, 2871, 1694, 1639, 1597, 1458, 1404, 1258, 1176,
1038, 767 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.33 (m, 1 H), 3.87–3.98 (m, 1 H),
3.87–3.98 (m, 1 H), 1.81 (s, 3 H), 1.54 (d, J = 6.3 Hz, 3 H), 1.39 (s,
3 H), 1.38 (s, 3 H).
White solid; yield: 0.39 g (90%); mp >250 °C.
IR (KBr): 3500–3200, 2940, 2669, 1679, 1644, 1472, 1188, 764
cm–1.
1H NMR (300 MHz, DMSO): d = 10.90 (s, 1 H), 4.69 (t, J = 7.8 Hz,
2 H), 4.00 (t, J = 7.8 Hz, 2 H), 1.64 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 194.1, 174.2, 156.7, 105.0, 55.6,
50.8, 38.9, 24.2, 19.7, 12.1.
13C NMR (75 MHz, DMSO): d = 165.3, 159.0, 147.4, 81.6, 69.3,
6,6-Diethyl-2,3-dihydrothiazolo[3,2-a]pyridine-5,7-dione (14d)
Yellow solid; yield: 124 mg (91%); mp 95–97 °C.
42.6, 6.8.
MS (EI, 70 eV): m/z (%) = 168 (100) [M+], 140, 125, 97, 83, 67, 53.
IR (film): 2966, 2935, 1687, 1632, 1579, 1457, 1396, 1293, 1232,
1147 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.73 (s, 1 H), 4.29 (t, J = 7.2 Hz,
2 H), 3.36 (t, J = 7.2 Hz, 2 H), 1.83–2.02 (m, 4 H), 0.77 (t, J = 7.4
Hz, 6 H).
13C NMR (75 MHz, CDCl3): d = 195.0, 173.9, 161.1, 101.2, 61.7,
48.4, 32.7, 27.3, 9.3.
3,3-Dimethyl-2,3-dihydrooxazolo[3,2-c]pyrimidine-5,7-dione
(17b)
White solid; yield: 303 mg (86%); mp >250 °C.
IR (KBr): 3500–3200, 2938, 2675, 1677, 1648, 1469, 1190, 760
cm–1.
1H NMR (300 MHz, CDCl3): d = 11.40 (s, 1 H), 4.91 (s, 1 H), 4.22
(s, 2 H), 1.53 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 165.5, 162.8, 147.5, 81.2, 76.4,
45.7, 23.8.
6,6-Diethyl-8-methyl-2,3-dihydrothiazolo[3,2-a]pyridine-5,7-
dione (14e)
Yellow solid; yield: 130 mg (90%); mp 97–98 °C.
IR (film): 2970, 2935, 1682, 1622, 1586, 1456, 1378, 1263, 1243,
1036, 754 cm–1.
8-Methyl-2,3-dihydrothiazolo[3,2-c]pyrimidine-5,7-dione (18a)
Yellow solid; yield: 363 mg (94%); mp >250 °C.
Synthesis 2006, No. 1, 37–48 © Thieme Stuttgart · New York

PAPER
Generation and Reactions of Cyclic Ketene-N,X-Acetals (X = O, S)
45
IR (KBr): 3400–3200, 3035, 2826, 1715, 1665, 1468, 1374, 1241,
1129, 890, 749 cm–1.
1H NMR (300 MHz, DMSO): d = 11.10 (s, 1 H), 4.16 (t, J = 7.2 Hz,
2 H), 3.43 (t, J = 7.2 Hz, 2 H), 1.73 (s, 3 H).
13C NMR (75 MHz, DMSO): d = 162.8, 153.5, 148.6, 99.8, 49.7,
28.2, 12.2.
N-Methyl-2-methylthiazolinium iodide 6 (13.7 g, 94%) was ob-
tained after filtration, washing with dry Et2O (3 × 50 mL), and dry-
ing under vacuum. No further purification was performed. This
iodide salt was used directly for the synthesis of 3-methyl-2-meth-
ylenethiazolidine (2a).
Dried THF (80 mL) was added to a three-neck round-bottom flask
equipped with a magnetic stirrer, a stopper, and a condenser with a
nitrogen inlet on its top. NaH (1.50 g, 60% in mineral oil, 37.5
mmol) was added to the THF. N-methyl-2-methylthiazolinium io-
dide (6) (6.00 g, 24.7 mmol) was added in small portions to the sus-
pension of NaH in THF at r.t. Hydrogen evolution was observed
during the addition of N-methyl-2-methylthiazolinium iodide. After
the addition of 6 the reaction mixture was stirred for an additional 3
h. Anhyd petroleum ether (200 mL) was added. The reaction mix-
ture separated into a liquid and a solid phase. The clear liquid on the
top was transferred to another flask. Distillation of this clear solu-
tion gave 3-methyl-2-methylenethiazolidine (2a).
2,8-Dimethyl-2,3-dihydrothiazolo[3,2-c]pyrimidine-5,7-dione
(18b)
Yellow solid; yield: 382 mg (92%); mp >250 °C.
IR (KBr): 3400–3200, 3032, 2828, 1715, 1669, 1470, 1376, 1244,
893, 752 cm–1.
1H NMR (300 MHz, DMSO): d = 11.10 (s, 1 H), 4.24 (dd, J = 6.6,
11.1 Hz, 1 H), 4.04 (m, 1 H), 3.85 (dd, J = 5.7, 11.1 Hz, 1 H), 1.71
(s, 3 H), 1.40 (d, J = 6.6 Hz, 3 H).
13C NMR (75 MHz, DMSO): d = 162.7, 153.2, 148.7, 99.9, 55.9,
40.3, 19.9, 12.2.
Colorless liquid; yield: 2.01 g (70%); bp 78 °C (20 mmHg).
1H NMR (300 MHz, pyridine-d5): d = 3.86 (d, J = 6.1 Hz, 2 H), 3.20
(t, J = 6.0 Hz, 2 H), 2.90 (t, J = 5.9 Hz, 2 H), 2.58 (s, 3 H).
MS (EI, 70 eV): m/z (%) = 198 (100) [M+], 183, 127, 95, 74.
13C NMR (75 MHz, pyridine-d5): d = 151.9, 73.8, 57.64, 35.6, 27.9.
3,3-Dimethyl-2,3-dihydrothiazolo[3,2-c]pyrimidine-5,7-dione
(18c)
Yellow solid; yield: 382 mg (92%); mp >250 °C.
3,5-Dimethyl-2-methylenethiazolidine (2b)
Colorless liquid; yield: 2.2 g (68%); bp 82–83 °C (20 mmHg).
IR (KBr): 3400–3200, 3032, 2825, 1715, 1441, 1385, 1177, 870,
758 cm–1.
1H NMR (300 MHz, DMSO): d = 10.97 (s, 1 H), 5.58 (s, 1 H), 3.31
(s, 2 H), 1.59 (s, 6 H).
1H NMR (300 MHz, pyridine-d5): d = 3.88 (d, J = 4.8 Hz, 2 H), 3.49
(m, 1 H), 3.28 (dd, J = 6.1, 9.2 Hz, 1 H), 2.85 (dd, J = 6.5, 9.2 Hz,
1 H), 2.58 (s, 3 H), 1.23 (d, J = 6.7 Hz, 3 H).
13C NMR (75 MHz, pyridine-d5): d = 152.5, 73.7, 64.7, 38.8, 35.5,
20.3.
13C NMR (75 MHz, DMSO): d = 162.3, 158.1, 148.8, 93.1, 68.5,
41.1, 24.2.
4-Ethyl-3-methyl-2-methylenethiazolidine (2c)
Colorless liquid; yield: 2.1 g (64%); bp 93–94 °C (20 mmHg).
1H NMR (300 MHz, pyridine-d5): d = 3.82 (s, 2 H), 3.20 (m, 1 H),
3.22 (dd, J = 6.1, 10.3 Hz, 1 H), 2.68 (dd, J = 6.1, 10.3 Hz, 1 H),
2.56 (s, 3 H), 1.56 (m, 1 H), 1.35 (m, 1 H), 0.76 (t, J = 7.4 Hz, 3 H).
13C NMR (75 MHz, pyridine-d5): d = 151.8, 73.0, 68.3, 33.5, 32.2,
24.6, 10.1.
3,4,4-Trimethyl-2-methyleneoxazolidine (1a)
Dried THF (80 mL) was added to a three-neck round-bottom flask
equipped with a magnetic stirrer, a stopper, and a condenser with a
nitrogen inlet on its top. NaH (1.50 g, 60% in mineral oil, 37.5
mmol) was added to the THF. 2-Methyloxazolinium iodide (6.00 g,
23.1 mmol) was added in small portions to the suspension of NaH
in THF at r.t. H2 evolution was observed.
The reaction mixture was stirred for an additional 3 h. Anhyd petro-
leum ether (200 mL) was added. The reaction mixture separated
into a liquid and a solid phase. The clear liquid on the top was trans-
ferred to another flask. Distillation of this clear solution gave 3,4,4-
trimethyl-2-methyleneoxazolidine (1a).
3,4,4-Trimethyl-2-methylenethiazolidine (2d)
Colorless liquid; yield: 2.3 g (69%); bp 94–95 °C (20 mmHg).
1H NMR (300 MHz, pyridine-d5): d = 3.89 (d, J = 18.9 Hz, 2 H),
2.79 (s, 2 H), 2.43 (s, 3 H), 1.06 (s, 6 H).
13C NMR (75 MHz, pyridine-d5): d = 151.3, 73.8, 65.2, 41.3, 30.0,
23.3.
Colorless liquid; yield: 2.0 g (70%); bp 55–56 °C (9 mmHg).
1H NMR (300 MHz, CDCl3): d = 3.80 (s, 2 H), 3.48 and 2.85 (d,
J = 3.5 Hz, 2 H), 2.24 (s, 3 H), 1.09 (s, 6 H).
1-Phenyl-2-(3,4,4-trimethyloxazolidin-2-ylidene)ethanone
(22a); Typical Procedure
3-Methyl-2-methylenethiazolidine (2a)
AcCl (6.41 g, 81.9 mmol) was added dropwise to a stirred soln of
ethanolamine (5.00 g, 81.9 mmol) and Et3N (9.98 g, 98.1 mmol) in
CH2Cl2 (150 mL) at 0 °C for 60 min. A Büchner funnel was used to
remove solid from the solution. The solvent was then removed by
rotary evaporation. The N-acylaminoalcohol residue was not puri-
fied further for the next step. The N-acylaminoalcohol residue was
dissolved in mineral oil (or toluene) (200 mL), followed by the ad-
dition of P2S5 (25.0 g, 11.0 mmol) or Lawesson’s reagent (33.1 g,
81.9 mmol). This mixture was heated at 130 °C (or refluxed, in the
case of toluene) under nitrogen for 120 min. The product mixture
was poured, without cooling, into 1 N KOH soln (200 mL) slowly,
then was extracted with Et2O (2 × 150 mL). After removal of Et2O
by rotary evaporation, distillation gave 2-methylthiazoline 4a (5.4
g, 65%). MeI (8.40 g, 59.2 mmol) was added dropwise to a soln of
2-methylthiazoline 4a (5.00 g, 49.5 mmol) in dry MeNO2 (60 mL).
The mixture was stirred at r.t. for 12 h, followed by the addition of
anhyd Et2O (200 mL) to precipitate the corresponding iodide salts.
Benzoyl chloride (450 mg, 3.2 mmol) in THF was added dropwise
to the soln of 3,4,4-trimethyl-2-methyleneoxazolidine (1a) (200
mg, 1.6 mmol) and Et3N (400 mg, 4.0 mmol) in THF at r.t. The mix-
ture was stirred for 20 min. The solid was filtered and the solvent
was evaporated. Then the residue was purified by column chroma-
tography with silica gel (hexane–EtOAc, 1:1) to give 22a. The same
procedure was used for 22b–f and 23a–o.
White solid; yield: 300 mg (70%); mp 111–113 °C.
IR (film): 3057, 2970, 2900, 1627, 1579, 1530, 1435, 1209, 1158,
1018, 914, 864, 733 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.36–7.87 (m, 5 H), 5.10 (s, 1 H),
4.24 (s, 2 H), 2.73 (s, 3 H), 1.24 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 185.5, 165.5, 141.6, 129.6, 127.4,
126.5, 78.5, 72.7, 59.8, 26.2, 22.6.
Synthesis 2006, No. 1, 37–48 © Thieme Stuttgart · New York

46
A. Zhou, C. U. Pittman Jr.
PAPER
MS (EI, 70 eV): m/z (%) = 231 [M+], 214, 202, 147 (100), 105, 77,
H), 2.78 (dd, J = 4.2, 11.4 Hz, 1 H), 1.60 (m, 2 H), 0.89 (t, J = 7.25
51.
Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 185.5, 166.4, 139.9, 130.2, 127.7,
3,3-Dimethyl-1-(3,4,4-trimethyloxazolidin-2-ylidene)butan-2-
one (22b)
White solid; yield: 246 mg (73%); mp 106–107 °C.
IR (film): 2956, 1634, 1546, 1445, 1260, 1172, 1019, 936, 723 cm–1.
126.8, 86.9, 67.2, 33.7, 31.0, 23.5, 9.2.
MS (EI, 70 eV): m/z (%) = 247 [M+], 230, 218, 170, 105 (100), 77,
51.
1H NMR (300 MHz, CDCl3): d = 4.66 (s, 1 H), 4.21 (s, 2 H), 2.71
(s, 3 H), 1.28 (s, 6 H), 1.15 (s, 9 H).
1-Phenyl-2-(3,4,4-trimethylthiazolidin-2-ylidene)ethanone
(23d)
White solid; yield: 292 mg (74%); mp 120–122 °C.
13C NMR (75 MHz, CDCl3): d = 200.8, 165.7, 78.7, 71.0, 59.7, 42.2,
27.9, 26.4, 23.0.
IR (film): 2967, 2927, 1707, 1596, 1571, 1489, 1421, 1336, 1212,
1153, 892, 735, 708 cm–1.
1-(3,4,4-Trimethyloxazolidin-2-ylidene)pentan-2-one (22c)
White solid; yield: 201 mg (64%); mp 107–110 °C.
IR (film): 2953, 1734, 1558, 1447, 1167, 1022 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.21 (s, 1 H), 2.69 (s, 2 H), 2.35
(t, J = 7.8 Hz, 2 H), 1.65 (m, 2 H), 1.28 (s, 3 H), 0.94 (t, J = 7.5 Hz,
3 H).
13C NMR (75 MHz, CDCl3): d = 200.8, 164.7, 78.7, 71.0, 60.0, 44.6,
26.5, 23.0, 19.5, 14.0.
1H NMR (300 MHz, CDCl3): d = 7.92 (m, 2 H), 7.40 (m, 3 H), 5.99
(s, 1 H), 2.91 (s, 2 H), 2.85 (s, 3 H), 1.32 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 185.9, 166.5, 140.1, 130.3, 127.8,
126.9, 87.7, 66.0, 40.7, 30.5, 23.7.
MS (EI, 70 eV): m/z (%) = 247 [M+], 216 (100), 156 (71.2), 128
(23.6), 105 (35.5), 85 (18.7), 77 (86.3).
3,3-Dimethyl-1-(3-methylthiazolidin-2-ylidene)butan-2-one
(23e)
3-Methyl-1-(3,4,4-trimethyloxazolidin-2-ylidene)butan-2-one
(22d)
White solid; yield: 186 mg (59%); mp 104–106 °C.
IR (film): 2957, 1733, 1555, 1451, 1019 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.46 (s, 1 H), 4.21 (s, 2 H), 2.71
(s, 3 H), 1.29 (s, 6 H), 1.08 (d, J = 7.0 Hz, 6 H).
White solid; yield: 258 mg (81%); mp 62–63 °C.
IR (film): 2952, 2900, 2863, 1619, 1524, 1466, 1358, 1301, 1119,
949, 886 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.58 (s, 1 H), 3.60 (t, J = 7.6 Hz,
2 H), 3.00 (t, J = 7.4 Hz, 2 H), 2.97 (s, 3 H), 1.17 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 200.8, 165.8, 86.2, 55.3, 41.2, 35.1,
27.5, 30.5.
13C NMR (75 MHz, CDCl3): d = 199.6, 164.8, 78.5, 74.4, 59.7, 39.7,
26.3, 22.8, 19.6.
MS (EI, 70 eV): m/z (%) = 200 [M+ + H], 142 (100), 82, 57.
2-(3-Methylthiazolidin-2-ylidene)-1-phenylethanone (23a)
White solid; yield: 273 mg (78%); mp 112–113 °C.
1-(3,5-Dimethylthiazolidin-2-ylidene)-3,3-dimethylbutan-2-one
(23f)
IR (film): 3062, 2940, 2854, 1608, 1573, 1512, 1465, 1424, 1217,
1062, 942, 867, 736, 659 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.91 (m, 2 H), 7.41 (m, 3 H), 6.06
(s, 1 H), 3.63 (t, J = 7.6 Hz, 2 H), 3.04 (t, J = 7.6 Hz, 2 H), 3.01 (s,
3 H).
13C NMR (75 MHz, CDCl3): d = 185.7, 167.1, 140.0, 130.5, 127.9,
127.0, 87.5, 55.6, 35.3, 27.2.
White solid; yield: 259 mg (76%); mp 63–64 °C.
IR (film): 2953, 2900, 2862, 1609, 1509, 1425, 1351, 1284, 1125,
945, 766 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.55 (s, 1 H), 3.69 (dd, J = 7.3, 9.9
Hz, 1 H), 3.51 (m, 1 H), 3.23 (dd, J = 6.1, 9.9 Hz, 1 H), 2.96 (s, 3
H) 1.38 (d, J = 6.5 Hz, 3 H), 1.17 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 201.1, 165.9, 86.1, 62.4, 41.4, 37.4,
35.3, 27.6, 19.8.
MS (EI, 70 eV): m/z (%) = 219 [M+], 202, 142, 105, 77, 51.
MS (EI, 70 eV): m/z (%) = 214 [M+ + H], 156 (100), 72, 57.
2-(3,5-Dimethylthiazolidin-2-ylidene)-1-phenylethanone (23b)
White solid; yield: 280 mg (75%); mp 114–116 °C.
1-(4-Ethyl-3-methyl-1-thiazolidin-2-ylidene)-3,3-dimethyl-
butan-2-one (23g)
White solid; yield: 247 mg (68%); mp 70–71 °C.
IR (film): 2961, 2921, 1596, 1572, 1463, 1423, 1288, 1216, 1060,
934, 831, 735, 705 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.92 (m, 2 H), 7.37 (m, 3 H), 5.98
(s, 1 H), 3.63 (dd, J = 7.6, 10.3 Hz, 1 H), 3.43 (m, 1 H), 3.12 (dd,
J = 6.5, 10.3 Hz, 1 H), 2.86 (s, 3 H), 1.26 (d, J = 6.9 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 184.3, 166.1, 139.2, 129.6, 127.2,
126.1, 86.1, 61.5, 36.7, 34.4, 19.0.
IR (film): 2962, 2875, 1619, 1509, 1426, 1353, 1117, 919, 768 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.52 (s, 1 H), 3.60 (m, 1 H), 3.15
(dd, J = 7.6, 11.1 Hz, 1 H), 2.94 (s, 3 H), 2.77 (dd, J = 4.6, 11.1 Hz,
1 H), 1.63–1.76 (m, 2 H), 1.17 (s, 9 H), 0.93 (d, J = 7.6 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 200.9, 165.3, 85.9, 67.1, 41.3, 33.7,
31.2, 27.6, 23.6, 9.4.
MS (EI, 70 eV): m/z (%) = 233 [M+], 216 (100), 156, 128, 105, 85,
77.
MS (EI, 70 eV): m/z (%) = 228 [M+ + H], 170 (100), 82, 57.
2-(4-Ethyl-3-methylthiazolidin-2-ylidene)-1-phenylethanone
(23c)
White solid; yield: 281 mg (71%); mp: 117–119 °C.
3,3-Dimethyl-1-(3,4,4-trimethylthiazolidin-2-ylidene)butan-2-
one (23h)
White solid; yield: 251 mg (69%); mp 68–70 °C.
IR (film): 2963, 2933, 1710, 1608, 1596, 1508, 1423, 1349, 1210,
1060, 912, 733, 709 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.93 (m, 2 H), 7.39 (m, 3 H), 6.00
(s, 1 H), 3.71 (m, 1 H), 3.16 (dd, J = 8.0, 11.4 Hz, 1 H), 2.96 (s, 3
IR (film): 2966, 2866, 1620, 1505, 1424, 1365, 1338, 1157, 1122,
925 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.50 (s, 1 H), 2.87 (s, 2 H), 2.80
(s, 3 H), 1.33 (s, 6 H), 1.17 (s, 9 H).
Synthesis 2006, No. 1, 37–48 © Thieme Stuttgart · New York

PAPER
Generation and Reactions of Cyclic Ketene-N,X-Acetals (X = O, S)
47
13C NMR (75 MHz, CDCl3): d = 201.5, 165.5, 87.0, 65.7, 41.5, 41.0,
30.5, 27.8, 23.9.
IR (film): 2924, 2853, 1624, 1522, 1467, 1426, 1356, 1299, 1204,
1140, 1074, 730 cm–1.
MS (EI, 70 eV): m/z (%) = 228 [M+ + H], 170 (100), 128, 82.
1H NMR (300 MHz, CDCl3): d = 5.40 (s, 1 H), 3.60 (t, J = 7.4 Hz,
2 H), 3.02 (t, J = 7.4 Hz, 2 H), 2.95 (s, 3 H), 2.32 (t, J = 7.4 Hz, 2
H), 1.62 (m, 2 H), 1.28–1.29 (m, 8 H), 0.87 (t, J = 6.9 Hz, 3 H).
1-(3-Methylthiazolidin-2-ylidene)propan-2-one (23i)
Sticky oil; yield: 206 mg (82%).
13C NMR (75 MHz, CDCl3): d = 195.3, 164.5, 90.3, 55.2, 42.1, 35.0,
IR (film): 2940, 2852, 1623, 1522, 1467, 1425, 1348, 1208, 966
cm–1.
1H NMR (300 MHz, CDCl3): d = 5.40 (s, 1 H), 3.62 (t, J = 7.4 Hz,
2 H), 3.03 (t, J = 7.4 Hz, 2 H), 2.95 (s, 3 H), 2.10 (s, 3 H).
31.4, 29.2, 28.9, 27.1, 25.5, 22.3, 13.8.
MS (EI, 70 eV): m/z (%) = 241 [M+], 199, 177, 157, 142 (100), 115,
82, 74.
2-(3,4,4-Trimethyloxazolidin-2-ylidene)-1-{4-[2-(3,4,4-trimeth-
yloxazolidin-2-ylidene)acetyl]phenyl}ethanone (24a); Typical
Procedure
13C NMR (75 MHz, CDCl3): d = 191.9, 164.5, 90.6, 55.1, 34.9, 28.8,
27.0.
MS (EI, 70 eV): m/z (%) = 157 [M+], 142 (100), 114, 82, 58.
Terephthaloyl chloride (0.35 g, 1.7 mmol) in THF (60 mL) was add-
ed dropwise to the soln of 3,4,4-trimethyl-2-methyleneoxazolidine
1a (0.53 g, 4.2 mmol) and Et3N (0.51 g, 5.1 mmol) in THF at r.t. The
mixture was stirred for 20 min. The solid was filtered from the re-
action soln and solvent was evaporated. Then the residue was puri-
fied by column chromatography with silica gel (hexane–EtOAc,
1:1) to give 24a. The same procedure was applied for the prepara-
tion of 25a–c, 26, and 27.
1-(3-Methylthiazolidin-2-ylidene)butan-2-one (23j)
Sticky oil; yield: 211 mg (77%).
IR (film): 2967, 2871, 1622, 1524, 1467, 1427, 1354, 1299, 1141,
1049, 945 cm–1.
1H NMR (300 MHz, CDCl3): = d 5.40 (s, 1 H), 3.61 (t, J = 7.4 Hz,
2 H), 3.03 (t, J = 7.4 Hz, 2 H), 2.95 (s, 3 H), 2.37 (q, J = 7.7 Hz, 2
H), 1.11 (t, J = 7.4 Hz, 3 H).
White solid; yield: 0.65 g (85%); mp 238–239 °C.
13C NMR (75 MHz, CDCl3): d = 185.9, 164.4, 89.6, 66.0, 34.9, 34.7,
27.0, 9.3.
IR (neat): 2964, 1612, 1548, 1441, 1227, 1171, 1007, 899, 857, 742
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.87 (s, 4 H), 5.13 (s, 2 H), 4.28
(s, 4 H), 2.78 (s, 6 H), 1.28 (s, 12 H).
MS (EI, 70 eV): m/z (%) = 171 [M+], 142 (100), 82, 58.
13C NMR (75 MHz, CDCl3): d = 185.2, 165.7, 143.0, 126.4, 78.7,
73.1, 60.0, 26.3, 22.9.
1-(3-Methylthiazolidin-2-ylidene)pentan-2-one (23k)
Sticky oil; yield: 219 mg (74%).
MS (EI, 70 eV): m/z (%) = 384 [M+], 230 (100), 214, 202, 147, 105,
77, 51.
IR (film): 2957, 2870, 1622, 1525, 1467, 1427, 1356, 1300, 1145,
1061, 962, 736 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.40 (s, 1 H), 3.61 (t, J = 7.7 Hz,
2 H), 3.02 (t, J = 7.7 Hz, 2 H), 2.95 (s, 3 H), 2.32 (t, J = 7.7 Hz, 2
H), 1.65 (m, 2 H), 0.93 (t, J = 7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 195.0, 164.4, 90.2, 55.1, 44.0, 34.9,
27.0, 18.8, 13.7.
3,3-Dimethyl-1,5-bis-(3-methylthiazolidin-2-ylidene)pentane-
2,4-dione (25a)
Yellow solid; yield: 488 mg (88%); mp 165–167 °C.
IR (film): 2927, 2855, 1604, 1515, 1462, 1422, 1350, 1300, 1102,
1074, 945, 879, 730 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.44 (s, 2 H), 3.60 (t, J = 7.4 Hz,
4 H), 3.05 (t, J = 7.4 Hz, 4 H), 2.92 (s, 6 H), 1.41 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 195.8, 165.4, 88.8, 57.8, 55.6, 35.5,
27.4, 23.1.
MS (EI, 70 eV): m/z (%) = 185 [M+], 142 (100), 115, 82.
3-Methyl-1-(3-Methylthiazolidin-2-ylidene)butan-2-one (23l)
Sticky oil; yield: 234 mg (79%).
IR (film): 2961, 2865, 1625, 1524, 1469, 1427, 1357, 1299, 1202,
1128, 1070, 955, 763 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.42 (s, 1 H), 3.61 (t, J = 7.7 Hz,
2 H), 3.02 (t, J = 7.7 Hz, 2 H), 2.96 (s, 3 H), 2.55 (m, 1 H), 1.11 (d,
J = 6.9 Hz, 6 H).
13C NMR (75 MHz, CDCl3): d = 198.9, 164.9, 88.5, 55.1, 39.3, 34.9,
26.9, 19.2.
1,5-Bis-(4-ethyl-3-methylthiazolidin-2-ylidene)-3,3-dimethyl-
pentane-2,4-dione (25b)
Yellow solid; yield: 513 mg (79%); mp 173–175 °C.
IR (film): 2963, 2932, 2876, 1605, 1498, 1422, 1348, 1097, 913,
728 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.34 (s, 2 H), 3.73 (m, 2 H), 3.17
(dd, J = 8.8, 11.1 Hz, 2 H), 2.87 (s, 6 H), 2.79 (dd, J = 4.2, 11.1 Hz,
2 H), 1.62 (m, 4 H), 1.35 (s, 6 H), 0.93 (t, J = 7.3 Hz, 6 H).
13C NMR (75 MHz, CDCl3): d = 195.0, 164.1, 87.4, 66.5, 56.7, 33.3,
30.7, 23.2, 22.6, 8.9.
MS (EI, 70 eV): m/z (%) = 185 [M+], 142 (100), 82, 58.
1-(3-Methylthiazolidin-2-ylidene)hexan-2-one (23m)
Sticky oil; yield: 239 mg (75%).
IR (film): 2955, 2870, 1623, 1524, 1467, 1427, 1356, 1300, 1143,
1069, 958, 736 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.40 (s, 1 H), 3.60 (t, J = 7.4 Hz,
2 H), 3.02 (t, J = 7.4 Hz, 2 H), 2.95 (s, 3 H), 2.34 (t, J = 7.4 Hz, 2
H), 1.60 (quin, J = 7.4 Hz, 2 H), 1.60 (sext, J = 7.4 Hz, 2 H), 0.93
(t, J = 7.4 Hz, 3 H).
2-(3-Methylthiazolidin-2-ylidene)-1-{4-[2-(3-methylthiazolidin-
2-ylidene)acetyl]phenyl}ethanone (25c)
Yellow solid; yield: 490 mg (80%); mp 262–265 °C.
IR (KBr): 2925, 2859, 1587, 1523, 1466, 1430, 1224, 748 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.95 (s, 4 H), 6.10 (s, 2 H), 3.69
(t, J = 7.7 Hz, 4 H), 3.10 (t, J = 7.4 Hz, 4 H), 3.07 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 195.1, 164.4, 90.2, 55.1, 41.7, 34.9,
27.5, 27.0, 22.2, 13.6.
13C NMR (75 MHz, CDCl3): d = 195.8, 165.4, 88.8, 57.8, 55.6, 35.5,
27.4, 23.1.
1-(3-Methylthiazolidin-2-ylidene)nonan-2-one (23n)
Sticky oil; yield: 289 mg (75%).
Synthesis 2006, No. 1, 37–48 © Thieme Stuttgart · New York

48
A. Zhou, C. U. Pittman Jr.
PAPER
MS (EI, 70 eV): m/z (%) = 360 [M+], 218 (100), 202, 142, 105, 77,
51.
(13) Liu, Y.; Pittman, C. U. Jr. J. Polym. Sci., Polym. Chem. Ed.
1997, 35, 3655.
(14) Zhu, P. C.; Lin, J.; Pittman, C. U. Jr. J. Org. Chem. 1995, 60,
5729.
(15) Wu, Z.; Stanley, R. R.; Pittman, C. U. Jr. J. Org. Chem.
1999, 64, 8386.
1-{3,5-Bis-[2-(3,4,4-trimethyloxazolidin-2-ylidene)acetyl]phe-
nyl}-2-(3,4,4-trimethyloxazolidin-2-ylidene)ethanone (26)
White solid; yield: 721 mg (79%); mp 252–255 °C.
(16) Fukuda, H.; Oda, M.; Endo, T. Macromol. Chem., Rapid
Commun. 1998, 19, 149.
(17) Zhou, A. H.; Pittman, C. U. Jr. Tetrahedron Lett. 2004, 45,
IR (film): 2932, 2857, 1587, 1515, 1452, 1351, 1195, 738 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.45 (s, 3 H), 5.28 (s, 3 H), 4.31
(s, 6 H), 2.80 (s, 9 H), 1.31 (s, 18 H).
13C NMR (CDCl3): d = 185.8, 166.2, 141.4, 127.7, 79.1, 73.7, 60.3,
26.7, 23.2.
8899.
(18) Li, H. M.S. Thesis; Mississippi State University: USA, 2000.
(19) Dreme, M.; Brunel, S.; Liauro, M. F. Tetrahedron 1984, 40,
349.
(20) Leffler, M. T.; Adams, R. J. Am. Chem. Soc. 1937, 59, 2252.
(21) Mitchell, M. A.; Benicewicz, B. C. Synthesis 1994, 675.
(22) Busacca, C. A.; Yong, D.; Spinelli, E. M. Tetrahedron Lett.
1996, 37, 2935.
(23) Wipf, P.; Wang, X. J. Comb. Chem. 2002, 4, 656.
(24) Robbe, Y.; Fernandez, J. P.; Chapat, J. P.; Sentenac-
Roumanou, H. Eur. J. Med. Chem. 1985, 20, 16.
(25) Pickaert, G.; Ziessel, R. Synthesis 2004, 2716.
(26) Katritzky, A. R.; Donkor, A.; Fang, Y. J. Org. Chem. 2001,
66, 4041.
1-{3,5-Bis-[2-(3-methylthiazolidin-2-ylidene)acetyl]phenyl}-2-
(3-methylthiazolidin-2-ylidene)ethanone (27)
Yellow solid; yield: 749 mg (88%); mp 282–285 °C.
IR (film): 2960, 1603, 1540, 1436, 1172, 1011, 926, 738 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.68 (s, 3 H), 6.29 (s, 3 H), 3.71
(t, J = 7.7 Hz, 6 H), 3.12 (t, J = 7.7 Hz, 6 H), 3.09 (s, 9 H).
13C NMR (75 MHz, DMSO): d = 183.0, 167.2, 140.2, 127.0, 86.7,
55.3, 35.2, 26.7.
(27) Hong, S.; Tian, S.; Metz, M. V.; Marks, T. J. J. Am. Chem.
Soc. 2003, 125, 14768.
(28) Basil, L. F.; Meyers, A. I.; Hassner, A. Tetrahedron 2002,
58, 207.
(29) Poindexter, G. S. Synthesis 1981, 541.
(30) Nishio, T. Tetrahedron Lett. 1995, 3, 6113.
(31) Nishio, T.; Konno, Y.; Ori, M.; Sakamoto, M. Eur. J. Org.
Chem. 2001, 3553.
(32) Singh, H.; Sarin, R. Tetrahedron 1986, 42, 1449.
(33) Tohda, Y.; Toshihide, K.; Masahiro, A.; Ryohei, A.;
Hiroshi, S.; Yutaka, M. Bull. Chem. Soc. Jpn. 1984, 57,
2329.
References
(1) Meyers, A. I.; Nazarenko, N. J. Am. Chem. Soc. 1972, 94,
3243.
(2) Fukuda, H.; Oda, M.; Endo, T. Macromolecules 1996, 29,
3043.
(3) Klemm, E.; Letsch, J. J. Polym. Sci., Part A: Polym. Chem.
1994, 32, 2867.
(4) (a) Kurth, M. J.; Decker, O. H.; Hakon, H.; Yanuck, K. D. J.
Am. Chem. Soc. 1985, 107, 443. (b) Kurth, M. J.; Decker, O.
H. Tetrahedron Lett. 1983, 24, 4535.
(5) Fukuda, H.; Oda, M.; Endo, J. Polym. Sci., Part A: Polym.
Chem. 1999, 37, 699.
(6) McElvain, S. M.; Degginger, E. R.; Behun, J. D. J. Am.
Chem. Soc. 1954, 76, 5736.
(7) Banville, J.; Grandmaison, J. L.; Lang, G. Can. J. Chem.
1974, 52, 80.
(34) Furrer, H.; Granzer, E.; Wagner, R. Eur. J. Med. Chem.
1994, 29, 819.
(35) Elgemeie, G. H.; El-Ezbany, S. R.; Ali, H. A. Synth.
Commun. 2001, 31, 3459.
(36) Njogu, M. M.S. Thesis; Mississippi State University: USA,
2005.
(8) Bellus, D. J. Org. Chem. 1979, 44, 1208.
(9) Hayes, R.; Li, K.-D.; Leeming, P.; Wallace, T. W.;
Williams, R. C. Tetrahedron 1999, 55, 12907.
(10) Wu, Z.; Cao, L.; Pittman, C. U. Jr. Recent Res. Dev. Polym.
Sci. 1998, 2, 467.
(11) Cao, L. Ph.D. Dissertation; Mississippi State University:
USA, 1998.
(37) Ito, F.; Kumura, H.; Ikata, H.; Kitamura, S.; Kawamoto, T.;
Abe, H. Jpn. Kokai Tokyo Koho 2004, 117.
(38) Bozyczko-Coyn, D.; Saporito, M. S.; Hudkins, R. L. Curr.
Drug Targets: CNS Neurol. Disord. 2002, 1, 31.
(39) Kuan, C. Y.; Burke, R. E. Curr. Drug Targets: CNS Neurol.
Disord. 2005, 4, 63.
(40) Bhattia, S. H.; Davies, G. M.; Hitchcock, P. B.; Loakes, D.;
Young, D. W. J. Chem. Soc., Perkin Trans. 1 1999, 2449.
(12) Zhu, P. C.; Pittman, C. U. Jr. J. Polym. Sci., Polym. Chem.
Ed. 1996, 34, 169.
Synthesis 2006, No. 1, 37–48 © Thieme Stuttgart · New York