Preparation and structure of some sulfanylpropenylidene derivatives of Meldrum's acid

Article abstract of DOI:10.1135/cccc2009020

Condensation of Meldrum's acid with the 3-sulfanylpropenal derivatives 7a and 7b gives the 3-sulfanylpropenylidene derivatives 2a and 2b, respectively. NMR and X-ray analysis of 2a and 2b show that the electron-donating group conjugates with the electron-

Full text of DOI:10.1135/cccc2009020

Sulfanylpropenylidene Derivatives of Meldrum’s Acid
995
PREPARATION AND STRUCTURE OF SOME
SULFANYLPROPENYLIDENE DERIVATIVES OF MELDRUM’S ACID
1
2,
Lynne A. CRAWFORD and Hamish McNAB *
School of Chemistry, The University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ, UK;
1
2
e-mail: crawford_lynne@hotmail.com, hmcn01@staffmail.ed.ac.uk
Received February 25, 2009
Accepted April 20, 2009
Publish ed on lin e Jun e 23, 2009
Dedicated, with greatest respect, to Dr. Alfred Bader – chemist, entrepreneur, art collector,
philanthropist – on the occasion of his 85th birthday.
Con den sation of Meldrum ’s acid with th e 3-sulfan ylpropen al derivatives 7a an d 7b gives th e
3-sulfan ylpropen yliden e derivatives 2a an d 2b, respectively. NMR an d X-ray an alysis of 2a
an d 2b sh ow th at th e electron -don atin g group con jugates with th e electron -with drawin g
dioxan edion e m oiety but th e effect is m uch less pron oun ced th an in an alogous dialkyl-
am in o derivatives 1. Th ere is little or n o con jugation of th e ortho-alkylsulfan yl group to th e
dioxan edion e m oiety in th e ben zyliden e derivatives 4a an d 4b.
Keyw ord s: Meldrum ’s acid; Sulfan ylpropen als; Push -pull con jugation ; X-ray diffraction ;
Dioxan es; Aldeh ydes; Kn oeven agel con den sation s.
We h ave previously reported th e syn th esis of a series of am in opropen yl-
iden e derivatives of Meldrum ’s acid (2,2-dim eth yl-1,3-dioxan e-4,6-dion e) by
con den sation of en am in als with Meldrum ’s acid in pyridin e solution 1. Th e
structural an d spectroscopic properties of th ese ‘push -pull’ com poun ds 1
(Fig. 1) are of in terest because th e stron gly electron don atin g am in o group
is directly con jugated to th e stron gly electron with drawin g dion e fun ction
of th e Meldrum ’s acid. In deed X-ray an alysis sh ows th at th e form al C–C
sin gle bon d in th e propen yliden e ch ain is sh orter th an th e adjacen t C=C
double bon ds2. In th is paper, we describe th e syn th esis of th io an alogues 2
of th ese com poun ds an d th e effect on th e spectroscopic an d structural
properties caused by replacin g th e n itrogen atom with a sulfur atom . Th e
bis(trifluoroacetyl) com poun d 3 is th e closest an alogue of th is series to h ave
been previously reported3. In addition , we probe th e effect on th e con ju-
gated system of th e sulfur series by a fused ben zen e rin g on th e propen yl-
iden e ch ain , as in com poun d 4; th e dialkylam in o an alogues of th e latter
Collect. Czech. Chem. Commun. 2009, Vol. 74, No. 6, pp. 995–1009
© 2009 Institute of Organic Chemistry and Biochemistry
doi:10.1135/cccc2009020

996
Crawford, McNab:
products can n ot be m ade because a low-en ergy ‘tertiary am in o’ rearran ge-
m en t4 takes place un der th e con dition s of th e Kn oeven agel con den sation 5.
3
3
FIG. 1
Som e ‘push -pull’ propen yliden es
RESULTS AND DISCUSSION
Preparation and Properties of the Aldehyde Starting Materials
3-(Alkylsulfan yl)propen als 7 are th e key startin g m aterials for th e syn th esis
of 2. Such com poun ds h ave been m ade but are m uch less well kn own th an
th eir 3-(dialkylam in o)propen al an alogues. A literature route6 to 3-(cyclo-
h exylsulfan yl)propen al 7a was used wh ich in volved reactin g cycloh exan e-
th iol (5) with propyn al (6) in ch loroform at 40 °C (Sch em e 1). Propyn al (6)
was syn th esised by flash vacuum pyrolysis (FVP) of diprop-2-yn yl eth er7.
Alth ough th e ben zyl com poun d 7b is kn own 8 th ere appears to be n o con -
ven ien t syn th etic m eth od. On ly un reacted th iol was obtain ed wh en th e
ch loroform route6 was applied, as above, but reaction of ph en ylm eth an e-
th iol (8) with propyn al (6) in m eth an ol in th e presen ce of trieth ylam in e
gave two products. Th e first was 3-(ben zylsulfan yl)propen al (7b) an d th e
secon d product was iden tified as com poun d 9, form ed by a subsequen t
con jugate addition process (Sch em e 1). Attem pts to preven t th is reaction by
addin g a dilute solution of base an d th iol to excess propyn al h ad n o effect
SCHEME 1
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Sulfanylpropenylidene Derivatives of Meldrum’s Acid
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on th e product ratio. It was also foun d th at th e base was n ecessary for th e
reaction to take place. However, th e two products 7b an d 9 could be sepa-
rated by dry flash ch rom atograph y in yields of 23 an d 20%, respectively.
Th e spectroscopic properties of 3-(alkylsulfan yl)propen al derivatives such
as 7 h ave n ot been studied system atically. Th e NMR ch em ical sh ifts of th e
con jugated system of 7 are easily assign ed by in spection , with th e aldeh yde
sign als (position 1) reson atin g aroun d δH 9.3 (δC 190), position 2 at aroun d
δH 6.1 (δC 125) an d position 3 at aroun d δH 7.5 (δC 156). Th ese sh ifts can be
ration alised by th e reson an ce structures sh own in Fig. 2 (X = S) wh ich dem -
on strate th at position s 1 an d 3 are electron -deficien t (con jugatin g to th e
carbon yl group) wh ereas position 2 is electron -rich (con jugatin g to th e
sulfur atom ). However, th e electron -don atin g effect of th e sulfur atom is
dram atically less th an th at of n itrogen in th e correspon din g en am in als
(e.g. 10); represen tative data (Table I) sh ow th at position 2 is sh ielded by
9
δH > 1 ppm (δC > 25 ppm ) in th e case of 10 .
As a con sequen ce, th e C(2)=C(3) bon d h as m uch m ore double bon d ch ar-
acter in th e sulfan ylpropen als 7 th an in th e am in opropen als (e.g. 10), as
3
3
reflected in th e couplin g con stan ts (7a, J2,3 = 15.2 Hz; 10, J2,3 = 12.6 Hz).
TABLE I
Com parison of selected NMR param eters of th e th iopropen al 7a an d th e en am in al 10
3
1
1
3
2
2
δH, ppm (J, Hz)
δC, ppm
Position
7a
10
7a
10
1
9.32, d
(7.6)
8.92, d
(8.3)
189.9
189.2
6.12, dd
(15.2, 7.6)
5.06, dd
(12.6, 8.3)
2
3
125.9
156.2
100.2
159.0
7.57, d
(15.2)
6.87, d
(12.6)
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3
1
2
FIG. 2
Reson an ce structures of 7 an d th e correspon din g en am in als
Th e aldeh ydes 11a an d 11b, precursors of th e Meldrum ’s acid derivatives
4, were syn th esised from 2-fluoroben zaldeh yde an d th e appropriate th iol,
in propan -2-ol, in 67 an d 49% yields, respectively (Fig. 3)10.
FIG. 3
Th e substituted ben zaldeh ydes 11
Synthesis and Properties of the Meldrum’s Acid Derivatives
Con den sation of 3-(cycloh exylsulfan yl)propen al 7a with Meldrum ’s acid in
toluen e in th e presen ce of a little piperidin ium acetate, a com m on m eth od
for aldeh yde substrates11, gave n o 2a, but th e piperidin o derivative 1a was
isolated by dry flash ch rom atograph y in 7% yield (Fig. 4). Th is suggests th at
th e catalytic am oun t of piperidin e can displace th e th iol group from th e
FIG. 4
Th e Meldrum ’s acid derivatives syn th esised
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Sulfanylpropenylidene Derivatives of Meldrum’s Acid
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sulfan ylpropen al 7a, an d th e resultin g en am in al 10 th en reacts with
Meldrum ’s acid. However, con den sation of 7a an d 7b with Meldrum ’s acid
in th e presen ce of titan ium tetrach loride (th e recipe m ore usually used for
keton es11) resulted in com poun ds 2a an d 2b in 36 an d 32% yields, respec-
tively (Fig. 4).
Th e exten t of delocalisation of th e sulfan ylpropen yliden e derivatives (e.g.
2a) was probed by NMR spectroscopy an d X-ray crystallograph y. Th e NMR
spectra sh ow sim ilar features to th ose of th e (alkylsulfan yl)propen als
(above), wh en com pared with th eir dialkylam in o an alogues (Table II). On ce
again , a desh ieldin g effect of ca. 20 ppm is observed at C(2) in 2a, wh en
com pared with 1a, th ough th e h eteroatom h as little effect on th e ch em ical
sh ifts of C(1) an d C(3) (Table II). Th e sh ift of th e quatern ary carbon C(5) of
th e Meldrum ’s acid rin g occurs in th e ran ge δC 104–106 ppm in th e th io
com poun ds 2a an d 2b wh ereas th e correspon din g carbon atom in th e
TABLE II
Com parison of selected NMR param eters of th e Meldrum ’s acid derivatives 2a, 2b an d 1a
1
1
1
2
2
2
3
3
3
δH, ppm (J, Hz)
δC, ppm
Position
2ba
1a
2a
1a
1
7.90, d
(11.8)
7.95, d
(13.2)
160.1b
161.2c
7.78, dd
(14.0, 11.8)
6.98, dd
(13.2, 12.1)
2
3
122.4
101.8
7.59, d
(14.0)
7.25, d
(12.1)
156.0b
158.7c
a
Data for 2b quoted because proton s H(1)–H(3) are n ot first order in th e spectrum of 2a
b
c
at 250 MHz. Assign m en t m ay be in terch an ged. Assign m en t m ay be in terch an ged.
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dialkylam in o com poun d 1a is sh ielded by >10 ppm at δC 93.7. In th e
1H NMR spectrum of com poun d 2b, sign ifican t desh ieldin g of proton H(2)
is observed, by com parison with th e correspon din g proton of th e dialkyl-
am in o an alogue 1a.
Th e structures of th e sulfan ylpropen yliden e derivatives 2a an d 2b
were con firm ed by X-ray crystallograph y as sh own in Fig. 5. Th e propen yl-
iden e ch ain is all-trans an d approxim ately coplan ar with th e dion e system
of th e Meldrum ’s acid un it in both cases (m ean deviation from th e
O(61)–C(6)–C(5)–C(4)–O(41)–C(1′)–C(2′)–C(3′)–S(1) plan e in com poun d 2a:
0.101 Å; in com poun d 2b: 0.096 Å; m axim um deviation from th is plan e in
com poun d 2a: 0.195 Å at O(61); in com poun d 2b: 0.188 Å at O(41)). In
com poun d 2b th e con figuration of th e ben zyl group is un expectedly
twisted towards th e Meldrum ’s acid m oiety, possibly to optim ise π–π stack-
in g in teraction s between th e ben zen e rin gs in th e crystal (sym m etry ele-
m en t –x, –y, 1 – z; cen troid to cen troid distan ce 4.6398(12) Å; dih edral
an gle between ben zen e plan es 0°; slippage 2.625 Å).
a
b
FIG. 5
Plot of th e Meldrum ’s acid derivative 2a (a) an d plot of 2b (b), both sh owin g th e crystallo-
graph ic n um berin g sch em e. Displacem en t ellipsoids are drawn at th e 30% probability level
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Sulfanylpropenylidene Derivatives of Meldrum’s Acid
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Bon d len gth s of th e con jugated system s of 2a, 2b, 1b an d th e aryl-
propen yliden e derivative12 12 are sh own in Fig. 6. Th ese param eters of 2a
an d 2b sh ow a h igh level of con sisten cy an d n o sign ifican t differen ces are
observed despite th e differen t con figuration s of th e sulfur substituen t.
Th ere are large differen ces between th e len gth s of th e form al C=C double
bon ds (1.348–1.366 Å) an d th e form al sin gle bon ds (both 1.418 Å) in th e
propen yliden e ch ain . Th e param eters of th e Meldrum ’s acid rin g are h igh ly
sym m etrical; th e carbon yl groups all h ave bon d len gth s in th e ran ge
1.203–1.209 Å an d th e correspon din g C(4)–C(5) an d C(5)–C(6) bon ds
(Fig. 6) lie between 1.462–1.471 Å (all stan dard deviation s 0.002 Å). All of
th ese param eters are very close in m agn itude to th ose of th e arylpropen yl-
iden e derivative12 12. On th e oth er h an d, th e differen ces between th e data
for com poun ds 2 an d th ose for th e dim eth ylam in o com poun d 1b are strik-
in g2. Th us, th e sh ortest bon d in th e propen yliden e ch ain of 1b is th e form -
al sin gle bon d (1.385 Å) an d all th e bon ds of th e ch ain are with in 0.024 Å
of on e an oth er. Th e bon d len gth s of th e carbon yl groups an d correspon d-
FIG. 6
2
12
Selected bon d len gth s of com poun ds 2a, 2b, 1b an d 12
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in g C–C bon ds of 1b are distorted. On e C=O bon d of 1b is sign ifican tly lon -
ger, at 1.225 Å, th an in 2b an d th e oth er is sh orter (1.193 Å), wh ereas th e
correspon din g C–C bon ds are 1.417 an d 1.449 Å, respectively2.
Th ese results con firm th at th e electron -don atin g ability of th e sulfur
atom in 2a an d 2b is in sufficien t to distort th e geom etry of th e propen yl-
iden e ch ain ; h en ce th e form al double an d sin gle bon ds h ave sign ifican tly
differen t len gth s. Sim ilarly th e carbon yl groups an d th e associated C–C
bon ds sh ow on ly m in im al eviden ce of ‘push -pull’ delocalisation sum m a-
rised by th e reson an ce structures sh own in Fig. 7. In con trast, th e am in o
com poun d 1b sh ows eviden ce of exten sive delocalisation , particularly to
th e trans-carbon yl group2.
FIG. 7
Reson an ce structures of propen yliden e derivatives of Meldrum ’s acid
In order to discover th e effect of a fused ben zen e rin g on th e delocal-
isation , th e con den sation products 4a an d 4b were first m ade (45 an d 56%
yields, respectively) by treatm en t of th e aldeh ydes 11a an d 11b with
Meldrum ’s acid overn igh t in pyridin e (Fig. 4). Th e quatern ary carbon C(5) of
th e Meldrum ’s acid rin g in 4a an d 4b occurs in th e ran ge δC 115–116 ppm ,
i.e. >10 ppm desh ielded by com parison with th e n on -an n elated an alogues
2a an d 2b. Th e correspon din g param eter of 5-ben zyliden e Meldrum ’s acid
itself13 is δC 114.75 wh ich suggests th at th e sulfur atom h as little role in
con jugation to th e Meldrum ’s acid rin g in com poun ds 4.
Th e crystal structure of 4b is sh own in Fig. 8. Un like th e structure of 2b,
th e S-ben zyl group is twisted away from th e Meldrum ’s acid rin g. Various
com pon en ts of th e poten tial con jugated system s are sign ifican tly n on -
plan ar relative to on e an oth er (Fig 8b). Key bon d len gth data are sum m a-
rised in Fig. 9.
All of th e structural param eters are con sisten t with even less delocal-
isation in th e an n elated derivative 4b com pared with its propen yliden e
an alogue 2b . Th us, all th e form al sin gle bon ds (C(4)–C(5), C(5)–C(6),
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Sulfanylpropenylidene Derivatives of Meldrum’s Acid
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a
b
FIG. 8
Plots of th e Meldrum ’s acid derivative 4b sh owin g th e crystallograph ic n um berin g sch em e (a).
Altern ative view of 4b sh owin g n on -plan arity of th e m olecule as a wh ole (b). Displacem en t el-
lipsoids are drawn at th e 30% probability level
C(7)–C(8)) are lon ger an d th e form al double bon ds (C(4)–O(4), C(6)–O(6),
C(5)–C(7)) are sh orter in 4b com pared with 2b (Fig. 9). Th is suggests th at
th e presen ce of th e ben zen e rin g in com poun d 4b blocks th e delocalisation
of th e sulfur lon e pair an d im plies th at som e delocalisation occurs in com -
poun ds 2a an d 2b th ough clearly n ot as m uch as in th e n itrogen an alogues
1. Com parison of th ese param eters of 4b with th ose of th e aryliden e deriva-
tives 13a an d 13b previously reported14 (Fig. 9) sh ows th at th ere is very
close structural correspon den ce with th e 4-n itro derivative 13a.
Flash vacuum pyrolysis (FVP) of th e am in opropen yliden e derivatives 1
provides a useful syn th etic route to azepin -3(2H)-on es by gen eration of a
m eth ylen eketen e followed by h ydrogen atom tran sfer an d electrocyclisat-
ion 1,15. In th e m ech an istically related form ation of pyrrol-3(2H)-on es15,16
an d th ioph en -3(2H)-on es15,17, from m eth ylen e Meldrum ’s acid derivatives,
th e h ydrogen atom tran sfer is particularly efficien t wh en it takes place from
a ben zyl substituen t. FVP reaction s of com poun ds 2a, 2b, 4a an d 4b were
carried out, but n o th iepin on es could be detected. FVP of 2a an d 4a at
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600 °C gave n o iden tifiable products an d startin g m aterial was recovered at
lower tem peratures. FVP of 2b an d 4b at 525–600 °C produced sign ifican t
quan tities of biben zyl, a com m on product of radical cleavage an d couplin g
un der FVP con dition s.
FIG. 9
14
14
Selected bon d len gth s of com poun ds 2b, 4b, 13a
an d 13b
In con clusion , we h ave reported th e successful syn th eses of 2a an d 2b,
represen tative exam ples of 3-(alkylsulfan yl)propen yliden e derivatives of
Meldrum ’s acid an d rare exam ples of sulfur-con tain in g push -pull con juga-
ted system s. Th e degree of con jugation is lim ited, as assessed by com parison
of NMR ch em ical sh ift an d bon d len gth data with appropriate m odel com -
poun ds. Un like th e related 3-(dialkylam in o)propen yliden e derivatives 1,
FVP of 2 did n ot give rise to cyclised products; reason s for th is beh aviour
will be addressed in a future publication .
EXPERIMENTAL
1H an d 13C NMR spectra were recorded at 250 an d 63 MHz, respectively, in CDCl3 solution s
un less oth erwise stated. 13C NMR sign als refer to on e CH reson an ce un less oth erwise stated;
th e term ‘quat’ refers to a quatern ary carbon atom . Ch em ical sh ifts (δ) are given in ppm rel-
ative to TMS; couplin g con stan ts (J) are quoted in Hz. Mass spectra were recorded un der
electron im pact con dition s. Wh ere h exan e–eth yl acetate m ixtures are used for dry-flash
ch rom atograph y, a gradien t elution m eth od was used in volvin g a 10% in crease in th e m ore
polar com pon en t every secon d fraction .
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Sulfanylpropenylidene Derivatives of Meldrum’s Acid
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3-(Cycloh exylsulfan yl)propen al (7a)
Cycloh exan eth iol (5; 0.35 g, 3 m m ol) an d propyn al (6; 0.22 g, 4 m m ol) were added to ch loro-
form (0.5 m l) with stirrin g at 20 °C. Th e tem perature was in creased to 40 °C for 2 h , th e sol-
ven t was rem oved un der reduced pressure an d th e resultin g 3-(cycloh exylsulfan yl)propen al
(7a; 64%) was purified by Kugelroh r distillation . 1H NMR (250 MHz): 9.32 d, 1 H, 3J = 7.6;
7.57 d, 1 H, 3J = 15.2; 6.12 dd, 1 H, 3J = 15.2, 7.6; 3.09 m , 1 H; 1.17–2.04 m , 10 H (com pati-
ble with publish ed data6). 13C NMR (63 MHz): 189.9, 156.2, 125.9, 45.3, 32.6 (2 CH2), 25.5
(2 CH2), 25.2 (CH2). EI-MS: 170 (31) [M+], 137 (8), 83 (57), 67 (30), 55 (100). HRMS: for
C9H14OS (M+) calculated 170.0762, foun d 170.0764. B.p. 140–142 °C/130 Pa.
3-(Ben zylsulfan yl)propen al (7b)
Trieth ylam in e (3 drops) was added to an ice-cooled solution of ph en ylm eth an eth iol (8; 0.25 g,
2 m m ol) an d propyn al (6; 0.12 g, 2.2 m m ol) in m eth an ol (10 m l) with stirrin g. Th e solution
was allowed to stir for 1 h an d th e solven t was rem oved un der reduced pressure. Th e result-
in g oil was subjected to dry flash ch rom atograph y on silica usin g h exan e–eth yl acetate as
eluen t to give 3-(ben zylsulfan yl)propen al (7b; 23%). 1H NMR (250 MHz): 9.35 d, 1 H, 3J =
7.6; 7.54 d, 1 H, 3J = 15.2; 7.25–7.36 m , 5 H; 6.17 dd, 1 H, 3J = 15.2, 7.6; 4.06 s, 2 H.
13C NMR (63 MHz): 189.7, 155.4, 134.6 (quat), 128.8 (2 CH), 128.6 (2 CH), 127.8, 126.2,
36.6 (CH2). EI-MS: 178 (11) [M+], 145 (2), 124 (9), 91 (100), 77 (6). HRMS: for C10H10OS
(M+) calculated 178.0452, foun d 178.0452. B.p. 107–109 °C/130 Pa (lit.8 107–112 °C/170 Pa).
Th e secon d fraction was 3,3-bis(ben zylsulfan yl)propan al (9; 20%). 1H NMR (250 MHz):
9.49 t, 1 H, 3J = 2.0; 7.24–7.36 m , 10 H; 4.02 t, 1 H, 3J = 7.2; 3.76–3.91 m , 4 H; 2.73 dd, 2 H,
3J = 7.2, 2.0. 13C NMR (63 MHz): 198.5, 137.2 (2 quat), 128.8 (4 CH), 128.5 (4 CH), 127.1
(2 CH), 48.4 (CH2), 43.5, 34.6 (2 CH2). EI-MS: 302 (1) [M+], 246 (11), 178 (15), 124 (11), 91
(100), 77 (12). HRMS: for C17H18OS2 (M+) calculated 302.0799, foun d 302.0799. M.p. 44–45 °C.
2-(Alkylsulfan yl)ben zaldeh yde Derivatives 11
2-Fluoroben zaldeh yde (2.5 g, 20 m m ol), th e appropriate th iol (20 m m ol) an d potassium car-
bon ate (3 g, 20 m m ol) were stirred un der reflux in propan -2-ol (35 m l) for 20 h 10. Th e solu-
tion was cooled an d poured in to water (100 m l), extracted with dich lorom eth an e (3 × 50 m l),
dried (an h ydrous MgSO4) an d th e solven t rem oved un der reduced pressure. Th e followin g
products were m ade by th is m eth od:
2-(Cyclohexylsulfanyl)benzaldehyde (11a). Com poun d 11a (49%) was m ade from cyclo-
h exan eth iol followin g th e gen eral procedure. 1H NMR (250 MHz): 10.55 s, 1 H; 7.25–7.88 m ,
4 H; 3.11 m , 1 H; 1.23–1.99 m , 10 H. 13C NMR (63 MHz): 192.1, 139.9 (quat), 135.8 (quat),
133.7, 132.5, 129.9, 126.6, 47.1, 33.0 (2 CH2), 25.8 (2 CH2), 25.5 (CH2) (NMR spectra con sis-
ten t with reported data18). EI-MS: 220 (46) [M+], 138 (100), 83 (29), 77 (12). HRMS: for
C
13H16OS (M+) calculated 220.0922, foun d 220.0922. B.p. 120–124 °C/110 Pa.
2-(Benzylsulfanyl)benzaldehyde (11b ). Com poun d 11b (67%) was m ade from ph en yl-
m eth an eth iol followin g th e gen eral procedure. 1H NMR (250 MHz): 10.24 s, 1 H; 7.22–7.82 m ,
9 H; 4.12 s, 2 H. 13C NMR (63 MHz): 191.3, 140.8 (quat), 136.0 (quat), 134.4 (quat), 133.8,
131.5, 129.7, 128.7, 128.5, 127.3, 125.9, 38.7 (CH2). M.p. 71–73 °C (lit.19 72–74 °C).
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Syn th esis of Meldrum ’s Acid Derivatives 2
A solution of titan ium tetrach loride (4 m m ol) in tetrach lorom eth an e (1 m l) was added drop-
wise to ice-cold tetrah ydrofuran (8 m l). Appropriate precaution s were taken wh en h an dlin g
th e toxic tetrach lorom eth an e. Th is was followed by slow addition of a solution of 2,2-
dim eth yl-1,3-dioxan e-4,6-dion e (2 m m ol) an d 3-(alkylsulfan yl)propen al (2 m m ol) in tetra-
h ydrofuran (2 m l), th en of a solution of pyridin e (0.8 m l) in tetrah ydrofuran (1 m l). Th e
stirrin g was con tin ued at 0 °C for 1 h an d at room tem perature overn igh t, after wh ich water
(10 m l) an d eth er (20 m l) were added. Th e organ ic layer was separated, wash ed with brin e
(2 × 20 m l), saturated aqueous sodium h ydrogen carbon ate (2 × 20 m l), dried (an h ydrous
MgSO4) an d th e solven t was rem oved un der reduced pressure. Th e residue was subjected to
dry flash ch rom atograph y on silica usin g h exan e–eth yl acetate as eluen t. Th e followin g
products were m ade by th is m eth od:
5-[3-(Cyclohexylsulfanyl)propenylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione (2a). Reaction of 7a
with Meldrum ’s acid usin g th e gen eral m eth od gave 5-[3-(cycloh exylsulfan yl)propen yliden e]-
2,2-dim eth yl-1,3-dioxan e-4,6-dion e (2a; 36%). 1H NMR (250 MHz): 7.92 m , 1 H; 7.72 m ,
2 H; 3.27 m , 1 H; 1.29–2.15 m , 10 H; 1.71 s, 6 H. 13C NMR (63 MHz): 163.5 (quat), 161.1
(quat), 160.1, 156.0, 122.4, 105.1 (quat), 104.3 (quat), 46.4, 32.8 (2 CH2), 27.4 (2 CH3), 25.5
(2 CH2), 25.2 (CH2). EI-MS: 296 (8) [M+], 269 (3), 238 (3), 181 (30), 123 (100), 115 (58),
83 (45). HRMS: for C15H20O4S (M+) calculated 296.1087, foun d 296.1085. M.p. 167–169 °C
(aceton itrile).
A suspen sion of Meldrum ’s acid (2 m m ol) an d 3-(cycloh exylsulfan yl)propen al (7a ;
2 m m ol) in toluen e (3 m l) was treated with acetic acid (4 drops) an d piperidin e (4 drops)
an d th e m ixture was stirred at room tem perature for 1 h . After rem oval of th e solven t un der
reduced pressure an d dry flash ch rom atograph y of th e residue on silica (usin g h exan e–eth yl
acetate as eluen t), th e on ly isolated product was 5-[3-(piperidin -1-yl)propen yliden e]-
2,2-dim eth yl-1,3-dioxan e-4,6-dion e (1a; 7%). 1H NMR (250 MHz): 7.95 d, 1 H, 3J = 13.2;
7.25 d, 1 H, 3J = 12.1; 6.98 dd, 1 H, 3J = 13.2, 12.1; 3.56–3.58 m , 4 H; 1.73 s, 6 H; 1.67 s,
6 H. 13C NMR (63 MHz): 165.4 (quat), 163.5 (quat), 161.2, 158.7, 103.0 (quat), 101.8, 93.7
(quat), 56.5 (CH2), 47.6 (CH2), 26.9 (2 CH3), 26.6 (CH2), 25.2 (CH2), 23.5 (CH2). For
C
14H19NO4 calculated: 62.55% C, 7.25% H, 5.2% N; foun d: 62.7% C, 7.2% H, 5.1% N. M.p.
166–167 °C.
5-[3-(Benzylsulfanyl)propenylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione (2b). Reaction of 7b
with Meldrum ’s acid usin g th e gen eral m eth od gave 5-[3-(ben zylsulfan yl)propen yliden e]-
2,2-dim eth yl-1,3-dioxan e-4,6-dion e (2b; 32%). 1H NMR (250 MHz): 7.90 d, 1 H, 3J = 11.8;
7.78 dd, 1 H, 3J = 14.0, 11.8; 7.59 d, 1 H, 3J = 14.0; 7.35–7.38 m , 5 H; 4.18 s, 2 H; 1.70 s,
6 H. 13C NMR (63 MHz): 163.3 (quat), 161.0 (quat), 158.4, 155.5, 134.5 (quat), 128.9 (2 CH),
128.9 (2 CH), 128.0, 122.2, 106.0 (quat), 104.3 (quat), 37.4 (CH2), 27.4 (2 CH3). EI-MS:
304 (14) [M+], 246 (34), 228 (5), 181 (91), 123 (81), 84 (100). For C16H16O4S calculated:
63.15% C, 5.25% H; foun d: 62.75% C, 5.0% H. HRMS: for C16H16O4S (M+) calculated
304.0775, foun d 304.0775. M.p. 101–102 °C (eth an ol).
5-[2-(Alkylsulfan yl)ben zyliden e]-2,2-dim eth yl-1,3-dioxan e-4,6-dion e Derivatives 4
Th e appropriate aldeh yde (5 m m ol) was dissolved in pyridin e (10 m l). Meldrum ’s acid (0.72 g,
5 m m ol) was added an d th e solution was stirred at room tem perature overn igh t. Th e m ix-
ture was added to eth er (30 m l) an d was wash ed with a copper(II) sulfate solution (3 × 30 m l),
th en with water (2 × 30 m l). Th e aqueous layers were th en com bin ed an d wash ed with eth er
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Sulfanylpropenylidene Derivatives of Meldrum’s Acid
1007
(2 × 30 m l). Th e com bin ed organ ic layers were dried (an h ydrous MgSO4) an d th e solven t re-
m oved un der reduced pressure. Th e followin g products were m ade by th is m eth od:
5-[2-(Cyclohexylsulfanyl)benzylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione (4a). Reaction of 11a
with Meldrum ’s acid gave com poun d 4a (45%). 1H NMR (250 MHz): 8.89 s, 1 H; 7.18–7.89 m ,
4 H; 3.10 m , 1 H; 1.22–2.16 m , 16 H. 13C NMR (63 MHz): 162.5 (quat), 159.5 (quat), 156.8,
138.4 (quat), 134.5 (quat), 132.0, 131.9, 131.1, 126.2, 115.9 (quat), 104.6 (quat), 48.2, 33.1
(2 CH2), 27.6 (2 CH3), 25.8 (2 CH2), 25.4 (CH2). EI-MS: 346 (4) [M+], 288 (3), 220 (61), 138
(100), 83 (78). HRMS: for C19H22O4S (M+) calculated 346.1239, foun d 346.1232. B.p.
140–144 °C/130 Pa.
5-[2-(Benzylsulfanyl)benzylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione (4b ). Reaction of 11b
with Meldrum ’s acid gave com poun d 4b (56%). 1H NMR (250 MHz): 8.70 s, 1 H; 7.18–7.68 m ,
9 H; 4.06 s, 2 H; 1.79 s, 6 H. 13C NMR (63 MHz): 162.3 (quat), 159.3 (quat), 156.3, 138.3
(quat), 136.5 (quat), 134.1 (quat), 132.0, 131.5, 130.9, 128.8 (2 CH), 128.5 (2 CH), 127.3,
126.5, 116.3 (quat), 104.6 (quat), 40.3 (CH2), 27.7 (2 CH3). EI-MS: 354 (0.4) [M+], 296 (7),
278 (1), 228 (68), 137 (87), 109 (56), 91 (100). For C20H18O4S calculated: 67.8% C, 5.05% H;
foun d: 67.75% C, 5.5% H. HRMS: for C20H18O4S (M+) calculated 354.0926, foun d 354.0929.
M.p. 85–86 °C (h exan e–eth yl acetate).
FVP Reaction s
Th e appropriate derivative was sublim ed un der vacuum th rough a silica furn ace tube (35 ×
2.5 cm ) an d th e product(s) were collected in a trap cooled by liquid n itrogen situated at th e
exit poin t of th e furn ace. Upon com pletion of th e pyrolysis, th e trap was allowed to warm
to room tem perature un der n itrogen atm osph ere. Th e en tire pyrolysate was dissolved in
solven t an d rem oved from th e trap. Pyrolysis con dition s are quoted as follows: substrate,
quan tity, furn ace tem perature (Tf), in let tem perature (Ti), pressure (P), pyrolysis tim e (t) an d
product(s). Th e followin g derivatives were pyrolysed:
Pyrolysis of 5-[3-(cyclohexylsulfanyl)propenylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione (2a).
FVP of 2a (0.30 g, Tf = 600 °C, Ti = 150 °C, P = 0.5 Pa, t = 30 m in ) gave n o products iden tifi-
able by 1H NMR spectroscopic an alysis of th e pyrolysate. Pyrolysis at h igh er an d lower tem -
peratures gave th e sam e result.
Pyrolysis of 5-[3-(benzylsulfanyl)propenylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione (2b). Th e 1H
NMR spectrum of th e products obtain ed by FVP of 2b (0.03 g, Tf = 600 °C, Ti = 150 °C, P =
0.5 Pa, t = 30 m in ) sh owed th e presen ce of biben zyl (32%). 1H NMR (200 MHz): 7.16–7.87
m , 10 H; 2.92 s, 4 H. 13C NMR (63 MHz): 129.3 (2 quat), 128.3 (4 CH), 128.2 (4 CH), 125.8
(2 CH), 37.8 (CH2) (NMR data con sisten t with publish ed values20) an d n o oth er iden tifiable
products.
Pyrolysis of 5-[2-(cyclohexylsulfanyl)benzylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione (4a). FVP
of 4a (0.3 g, Tf = 600 °C, Ti = 150 °C, P = 0.5 Pa, t = 30 m in ) gave n o iden tifiable products.
Pyrolysis at h igh er an d lower tem peratures gave th e sam e result.
Pyrolysis of 5-[(2-benzylsulfanyl)benzylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione (4b). The 1H NMR
spectrum of th e products obtain ed by FVP of 4b (0.03 g, Tf = 525 °C, Ti = 150 °C, P = 0.5 Pa,
t = 30 m in ) sh owed th e presen ce of biben zyl20 (46%). 1H NMR (200 MHz): 7.10–7.85 m , 10 H;
2.96 s, 4 H; an d n o oth er iden tifiable products. Pyrolysis at lower tem peratures gave on ly re-
covered startin g m aterial.
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1008
Crawford, McNab:
Crystallograph y
Diffraction data were collected usin g a Stoe Stadi-4 four-circle diffractom eter (2a an d 4b) or
a Bruker Sm art Apex CCD in strum en t (2b). Th e structures were solved by direct m eth ods
(SHELXS) an d refin ed by full m atrix least squares again st F2 (SHELXL). H-atom s attach ed to
m eth yl groups were located in differen ce m aps an d th e groups th ereafter treated as rotatin g
rigid groups; oth er H atom s were placed in idealised position s. All n on -H atom s were refin ed
with an isotropic displacem en t param eters. Crystal an d refin em en t data are sum m arised in
Table III. CCDC 275015 (2a), 610398 (2b ) an d 276770 (4b ) con tain th e supplem en tary
crystallograph ic data for th is paper. Th ese data can be obtain ed free of ch arge via www.
ccdc.cam .ac.uk/ con ts/retrievin g.h tm l (or from th e Cam bridge Crystallograph ic Data Cen tre,
12, Un ion Road, Cam bridge, CB2 1EZ, UK; fax: +44 1223 336033; or deposit@ccdc.cam .ac.uk).
TABLE III
Crystallograph ic data for 2a, 2b an d 4b
Crystal data
2a
2b
4b
Ch em ical form ula
Mr
C
15H20O4S
C16H16O4S
304.35
C20H18O4S
354.40
296.37
Cell settin gs
Space group
Tem perature, K
a, Å
m on oclin ic
P21/c
triclin ic
m on oclin ic
P21/n
P-1
150(2)
150(2)
220(2)
6.9480(9)
10.322(2)
21.304(4)
90.00
6.6366(7)
10.6039(10)
11.7281(12)
111.9440(10)
103.301(2)
90.298(2)
741.21(13)
2
9.5242(9)
16.2889(15)
11.4371(9)
90.00
b, Å
c, Å
α, °
β, °
96.417(14)
90.00
92.987(6)
90.00
γ, °
V, Å3
1518.3(5)
4
1771.9(3)
4
Z
Radiation type
Crystal form
Colour
CuKα
MoKα
MoKα
n eedle
tablet
block
red
oran ge
yellow
Crystal size, m m
R[F2 > 2σ(F2)]
wR(F2), S
0.51 × 0.35 × 0.27
0.042
0.62 × 0.40 × 0.22
0.036
0.58 × 0.39 × 0.39
0.031
0.113, 1.05
0.093, 1.05
0.078, 1.02
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Sulfanylpropenylidene Derivatives of Meldrum’s Acid
1009
W e are grateful to the Engineering and Physical Sciences Research Council (EPSRC) UK for
a research studentship to L. A. Crawford, to Dr. E. Stevenson for some preliminary experiments
and to Dr. A. Dawson and Prof. S. Parsons for the X-ray crystal structures.
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