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Reaction of 2-amino-2-deoxy-d -glucose with aryl and acyl isothiocyanates, and aryl isocyanates: structure of the intermediate products
125
Carbohydrate Research, 210 (1991) 125%L43 Elsevier Science Publishers B.V., Amsterdam
Reaction of 2-amino-2-deoxy-D-glucose with aryl and acyl isothiocyanates, and aryl isocyanates: structure of the intermediate products Jo& FernBndez-Bolafios
Guzmhn*, Salud Garcia Rodriguez, Josh: Fernhndez-Bolaiios,
Departumento de Quimica Oryrinica. Facultad de Quimica, Universidad de Sevilla. 41071 Sevillu (Spain)
M”. J&us Dianez, and Amparo L6pez-Castro lnstiiutn de Ciencius de Materiales de Sevillrr. C.S.I.C., Universidad de &villa. 41071 Sevillu (Spain) (Received April 30th, 1990; accepted for publication,
July 12th, 1990)
ABSTRACT
The structure of(4R)-l-aryl-5-hydroxy-4-(o-arahino-tetritol-l-yI)imidazolidine-2-thiones (l-3), obtained by reaction of 2-amino-2-deoxy-D-glucose with aryl isothiocyanates. has been confirmed by ‘H-and ‘%-n.m.r. spectroscopy. Likewise, the structures of 2-(3-benzoyhhioureido)-2-deoxy-D-glucopyranose and 2-deoxy-2-(3-phenylureido)-D-glucopyranose, prepared by reaction of 2-amino-2-deoxy-D-glucose with benzoyl isothiocyanate and phenyl isocyanate, respectively, were also established. An X-ray analysis of l-5R (aryl = phenyl) has been carried out and its conformation in the solid state is one of the preponderant conformations in solution.
INTRODUCTlON
The reaction of amino sugars with isothiocyanates and isocyanates has been studied extensively’“. The structure of 2-(3-arylthioureido)-2-deoxy-D-glucopyranose was proposeds.6 for the first isolable products of the reaction of aryl isothiocyanates with 2-amino-2-deoxy-D-glucose. The same structrure was given’ to the products obtained by 0-deacetylation of I ,3,4,6-tetra-O-acetyI-2-(3-arylthioureido)-2-deoxy-~-D-glucopyranose. The suggestion8 that 2-deoxy-2-thioureidoaldoses are reactive and cyclise to 5-hydroxyimidazolidine-2-thiones was based on the results of electrophoresis in borate and tungstate buffers, and U.V.and i.r. spectroscopy of the isolated products. However, the stabilities of 2-deoxy-2-ureidoaldoses and 2-acylthioureido-2-deoxyaldoses were not studied. We now report on the structure of the first isolable compounds in the reaction of 2-amino-2-deoxy-D-glucose with aryl isothiocyanates, benzoyl isothiocyanate, and phenyl isocyanate, based mainly on ‘H- and ‘3C-n.m.r. data.
* Author for correspondence. 0008-6215/91/$03.50
@ 1991 ~ Elsevier Science Publishers B.V.
fi(.O!i
i:ti2CH
QH
1
5 1:
k
!: ,.
REACTION
OF AMINO
SUGARS
WITH
ISOTHIOCYANATES
AND
ISOCYANATES
127
’ Ill I) 0
” Ill <‘l),OI)
REACTION
OF AMINO SUGARS
WITH
ISOTHIOCYANATES
AND ISOCYANATES
129
TABLE
IV
Bond lengths (A) and angles ~____
( ) for I-5R
1.697(1X) 1.3X6(30) I .430( ISI 1.431(21) I .436(‘11 1419(143 1.335(?3) 1.437(1’)1 1.445(15, 1.337(1”) 1455(1~ l.ZlO(lhi 1.519(151 1.197(X) I .14X( IX) I .i7X(!31 1.360(X) ! .396(x!) 1,3h7(21) l.5i4(lh)
I .5I ‘( 1xi I 54’7(IXJ
The value of 1.697(18) ,h observed ofthe values for single (1.8 I A) and double character
is a
normal
for the length
of the
S C bond is intermediate
bonds (I .56 A). and this partial double-bond
feature of these compounds.
The average distances
(C-2 N- 1 and
REACTION OF AMINO SUGARS WITH ISOTHIOCYANATES
AND ISOCYANATES
131
of 1.336(23), C-4-N-3 and C-5-N- 1 of 1.446( l9), and the C-5-C-4 distance of 1.5 10( 16) A agree well with the mean values reported for analogous compounds’3.‘4. The average angles C-N-C and N-CC are 11 l( 1) and 103(l)“, respectively, and the N-C-N angle is 109(l)‘. The exocyclic bonds C-5-O-5, N-l-C-l”, and C-4-C-l’ are 1.386(20), 1.455(15), and 1.529( 15) A, respectively. The imidazolidine ring is planar [maximum deviation from the best plane is O.O88(12)A]. The Satom is in thisplane with adeviationof -0.016(4) A, but C-l’, C-l”, and O-5 are out of this plane, at - 0.879( 11) - 0.174(11), and 0.923(9) A, respectively. The corresponding bonds are bent by 42(l), 14(l), and -52(l)“. The mean value of the C-C bond length in the phenyl ring is 1.374(20) 8, and the mean C-H bond length is 1.09 (2) A. The N substituent is at -0.108( 16) A from the least squares calculated plane. The polyhydroxyalkyl chain C-l’/4 is nearly planar [maximum deviation from the least squares plane, 0.034(14) A]. Th e average C-C and C-O bond lengths of 1.524(17) and 1.431(18) A, respectively, and the average bond angles C-CC and C-C-O of 113(l) and 109( 1)“, respectively, are normal. The Newman projections along the backbone carbons, shown in Fig. 2, accord with a 3,Gi conformation, one of the conformers found in solution. According to the Klyne and Prelog rules’5, the configuration for the chiral centres C-5, C-4, C-l’, C-2, and C-3’ are R, R, R, S, and R, respectively. C-2-N-3
c-1’ c-4-c-5
H-5 c-l-c-4
c-2’-
C-l’
Fig. 2. Newman projections along the carbon backbone of l-5R
The dihedral angles between the phenyl and imidazolidine ring and between the sugar-chain plane and the imidazolidine ring are 44.4(8) and 88.7(6)“, respectively. The molecules in the crystal were closely stacked through van der Waals forces and there were three possible hydrogen bonds:
.-
6.5 6.3 6.1
described
13 14 15
’ Conditions
’ Assignments
94.7 89.7
13 15
’ In (CD,),SO.
in Table V.
2.2 2.0 2.1
J,, 8.6 8.9 8.2
J,,
4.10 dd 4.14 dd 4.07 dd
H-3
73.9 74.2
c-3
5.6 5.6 5.4
J5.f
79.4 79.4
c-4
43.9 63.9
C-6
11.2 11.0 11.1
Jo,.
3.72 dtd 3.71 dtd 3.76 dtd
H-5
68.3 68.7
c-5
for 13 and 15
2.6 2.0 2.6
J,,
3.64 dd 3.62 dd 3.72 dd
H-4
for 13-15
may be interchanged
65.2 60.6
C-2
shift data” (8, 50.3 MHz)
C-l
chemical
-0 -0 -0
J>j
Compound
“C-N.m.r.
VJJ
J,,,
Compound
TABLE
4.15 d 4.17d 4.00 dd
(Hz) for 13-15
Jvalues”
‘H-N.m.r.
TABLE VI
’ In (CD,),SO.
15
5.91 d
5.97 d 5.97 d
13
14
H-2
shift data” (6. 200 MHz)
H-l
chemical
Compound
‘H-N.m.r.
TABLE V
1.3
5.0 4.8 4.7
181.2
c=s
5.8 5.6 5.6
Jm
3.39 dt 3.35 dt 3.40 dt
H-6’
J,,,,
157.3
c=o
JwH
3.56 ddd 3.56 ddd 3.58 ddd
H-6
136.4* 139.4
C-l
127.1 119.3
129.0 128.7
c-3,5
136.0” 123.0
c-4
4.77 d 5.10d 4.74 d
1.14~7.32 m 5.36 d 7.42-7.54 m 5.58 d 7.00-7.63 m 5.31 d
C-2,6
OH-5
OH-3
Aromatic
Aromatic
5.6 5.7 5.5
J, o,,
9.08 s 9.28 s 7.53 d
NH
20.8
Ml>
4.55 t 4.59 t 4.50 t
OH-6
2.30 s
Me
I
HtOH
nI: aIi
I
/ CN,OH
CH20H
16
R':
19
R'= ti-6, I$: H-6',
OH , R'T "-6 ( 123: H-6'
.
,3= oi_,
the b anomers 22 and 24 obtained from 1.3,4.6-tetra-U-acctyi-l-amino-7-deox~-i-r~glucopyranose by reaction with benzoyl isothiocyanate and phenyl iwc~an;ite”. resprctivcly. CLDeacetylation of’24 in methanolic sodium methoxide gave the giucot‘uranoimidazolidin-3--one 15 instead of the expected 12. Conventional acetylation of 2 ga\e a mixture of at least three compounds. in which 20 was not detected. Treatment ofthe mixture with silica geiin rzfluuing toluens” followed by O-deacetylation gave 17. presumably through the tctra-acct:\te ot’17 ‘T‘hts method is a new route to tetritol-I -yidihydroinlid~~role-7-t.h~(~r?es.
REACTION OF AMINO SUGARS WITH ISOTHIOCYANATES
AND ISOCYANATES
135
REACTION
OF AMINO
SUGARS
WITH
ISOTHIOCYANATES
AND ISOCYANATES
137
TARLE ‘H-N.m.r.
x J \aiues” (Hz) for 21-24
REACTION
OF AMINO
SUGARS
WITH
ISOTHIOCYANATES
139
AND ISOCYANATES
solidified on treatment with ether. The solid was washed with aqueous 90% ethanol, to give a 3:2 mixture [130 mg, 20%; m.p. 180” (dec.)] of 2-5R and 2-5S, as deduced from the ‘H-n.m.r. spectrum of a solution in DzO recorded immediately. After 4 h, the ratio had become 9: I. (4R)-I-p-Chlorophenyl-5-hydroxy-4-(D-arabino-tetritol-I-yl)imidrrzolidine2-thione (3). -
A mixture of Zamino-2-deoxy-D-glucose (180 mg) andp-chlorophenyl isothiocyanate (255 mg) was treated as described for the preparation of 1, to give 3 (294 mg, 84%), m.p. 144148”; [a]: +42”, [or]& + 45, [a]& + 50”, [XI:!, + 92” (c 1, pyridine) 5:l); {lit.’ m.p. 144147”, [a],, +30” (ethanol)}; R, 0.52 (dichloromethane-methanol, nig 236 nm (E,,,~ 19.5); v,,, 3360 (NH, OH), 1450 (NH). 1260 (C = S), 1495, 1450, and 830 cm-’ (aryl, p-substituted). Mass spectrum: m/z 330 (M+ -H,O, 8%), 228 (M+ -C,H,O,, 3), 212 (C,H, 37ClN,S+, 36), 211 (C7H637C1N2S+,47), 210 (B+ + H, 90) 209 (B’, 100, where B = I-p-chlorophenyl-2-thioxo-imidazolinyl), 178 (Bf + H-S, 68), and 169 (ClC,H,NCS+, 40). The ‘H- and ‘3C-n.m.r. data are given in Tables I-III. Anal. Calc. for C,,H,,ClN,O,S: C, 44.76; H, 4.91; Cl, 10.16; N, 8.03. Found: C, 44.48; H, 4.90; Cl, 10.00; N, 8.01. I-p-Tolyl-((1,2-dideoxy-a-D-glucofurano)[2,1-d
Jimidazolidine-2-thione
(13).
~
Compound 2 (100 mg) was heated for 20 min at 155-l 60’. Crystallisation of the product from aqueous 50% ethanol gave 13 (58 mg, 61%) Recrystallisation from aqueous 95% ethanol gave material having m.p. 242-244” (dec.); [a]: + 64”, [XI& -i-68”, [a]:& + 76”, [a& + 111” (c 1, pyridine) {lit.6 m.p. 239-240’, [a]: + 64” (pyridine)}; R, 0.68 (dichloromethane-methanol, 5:l); v,,, 3430, 3355, 3205, 3150 (NH, OH), 1480 (NH), 1235 (C = S), 1580, 1515. 1445, and 820 cm-’ (aryl, p-substituted). Mass spectrum: m/z 310 (Mj, 17%),309(M+-H,7),292(M+-Hz0,2),208(M+-CC4Hh03, 15) 19O(B++ H, 95) 189 (B+, 100, where B = I-p-tolyl-2-thioxo-imidazolinyl), 149 (CH,C,H,NCS+, 5), and 91 (C7H7+, 15). The ‘H- and 13C-n.m.r. data are given in Tables V-VII. Z-p-Chlorophenyl-(l,2-dideoxy-a-r>-glucofurano)[2,1-d]imidazolidine-2-thione (14). -- Compound 3 (100 mg) was heated for 10 min at 155-l 60”. Crystallisation of the product from aqueous 50% ethanol gave 14 (60 mg, 63%) m.p. 24@241” (lit.35 m.p. 250”), R, 0.65 (dichloromethane-methanol, 5: 1); v,,, 3430,3355,3210 (NH, OH), 1495, 1430, 830 (aryl, p-substituted), 1480 (NH), and 1235 cm-’ (C = S). The ‘H-n.m.r. data are given in Tables V and VI. 2-(3-Benzoylthioureidoj-2-deoxy-D-glucopyranose (11). - A stirred mixture of ammonium thiocyanate (200 mg, 2.6 mmol) and benzoyl chloride (0.3 mL, 2.6 mmol) in acetone (2.5 mL) was boiled for 15 min under reflux, then filtered, and added to a solution of 2-amino-2-deoxy-D-glucose (0.45 g, 2.5 mmol) in water (0.75 mL). The mixture was kept for 24 h at NO”, then concentrated. Preparative t.1.c. (dichloromethane-methanol, 5: 1) of the syrupy residue and crystallisation from ethanol gave 11 (0.45 g, 53%), m.p. 188-190” (dec.); [CL]:+ 80”, [E]& + 83”, [a]& + 90”,[a]::, + 126”(c 1, pyridine) {lit.” m.p. 185”, [a]: +82.7” (pyridine)]; R, 0.72 (dichloromethane-methanol, 5:l); v,,, 3480, 3395, 3225, 3170 (NH, OH), 1650 (C=O), 1600, 1455, 725, 690 (phenyl), 1535, 1470 (NH), and 1275 cm-’ (C=S). Mass spectrum: m/z 194 (PhCONHCSNHCH,, 16%), 122 (PhCONH,, 14) 121 (PhCONH,, 33) 106 (PhCbH,
REACTION OF AMINO SUGARS WITH ISOTHIOCYANATES AND ISOCYANATES
1,3,4,6-Tetra-O-acetyl-2-deoxy-2-(3-phenylureido)-a-
141
(23) and P-D-glucopyrano-
se (24). -Conventional
acetylation of 12 (40 mg, 0.13 mmol) with acetic anhydride (0.3 mL) in pyridine (0.3 mL) gave a 3:2 mixture (59 mg, 94%) of 23 and 24, as deduced from the ‘H- and “C-n.m.r. spectra, R, 0.79 for 23 and 0.71 for 24 (dichloromethanemethanol, 4O:l). Signal assignments of the mixture were facilitated by the ‘H- and 13C-n.m.r. spectra of 24 obtained as described”. 4-(~-arabino-Tetritol-l-yl)-I-p-toI_~l-4-imidazoline-2-thione (17). -Conventional acetylation of 2 (380 mg, 1.16 mmol) with acetic anhydride (2 mL) in pyridine (2 mL) gave a mixture of three main compounds, R, 0.77, 0.64, and 0.45 (t.1.c.; ether-hexane, 10: 1); 20 was not detected. To a solution of the mixture in toluene ( 10 mL) was added Silica Gel 60 (Merck, 1 g) and the stirred mixture was boiled for 1 h under reflux, then filtered. The filtrate, which gave one main spot in t.1.c. (R, 0.45; ether-hexane, 10: l), was concentrated. A solution of the residue in methanolic 0.1% sodium methoxide (10 mL) was deionised with Amberlite IR-120 (H+) resin and concentrated. The syrupy residue was crystallised from aqueous 95% ethanol to give 17 (121 mg, 34%). Recrystallisation from ethanol gave material with m.p. 210-212”, [XI: - 30”, [tl]$, - 3 l”, [XI& - 36”, [c(]i:, - 68” (c 2, pyridine) {lit.h m.p. 21 l-212”, [cx], - 30” (pyridine)}. Crystal analysis*. - Compound l-5R crystallised as colourless prisms. Rather poor crystals were obtained with approximate dimensions 0.39 x 0.42 x 0.20 mm, which belonged to the monoclinic system with systematic absences consistent with P2,. Accurate cell dimensions and crystal orientation matrix, determined on a CAD-4 diffractometer by a least-squares treatment of the setting angles of 25 reflections in the range 2 < 0 < 14”, were a 6.978(9), b 7.125(2), c 14.694(5)& and p 94.4(3)“. The unit-cell volume (v) was 728.3(4)A3, and the absorption coefficient (p) was 0.23 mm-‘. An Enraf-Nonius CAD-4 diffractometer was used with monochromated MO-K, radiation (0.7107A), the w/20 mode, and 20,,, = 50” (0 < h d 8,0 < li < 8, - 17 < 1d 17). Two reference reflections were measured every hour to monitor crystal stability, and were re-centred after every hundred measured reflections in order to monitor crystal orientation. No significant changes in the intensities were noted. From 1435 measured reflections, 1042 were observed with 13 20(I); F(OOO) = 332. Corrections were made for Lorentz-polarisation effects, but not for extinction and absorption. The last effect was not taken into account because the crystal absorption with MO radiation was negligible. The structure was solved by direct methods with the MULTAN-80 program36, and 234 reflections with IE] > 1.62 and 5 reflections in the starting set were used to determine the structure. The initial E map revealed most of the non-hydrogen atoms and the remainder were located from subsequent electron-density maps. After anisotropic refinement by full-matrix least squares of all the 21 non-hydrogen atoms in the asymmetric unit, the hydrogen atoms were located at geometrical positions and were
* Lists of the observed and calculated structure factors, the anisotropic thermal parameters, and nonhydrogen and hydrogen atomic co-ordinates are deposited with, and can be obtained from, Elsevier Science Publishers B.V., BBA Data Deposition, P.O. Box 1527, Amsterdam. The Netherlands. Reference should be made to No. BBA/DD/451 Carbohydr. Res., 210(1991) 125-143.
We thank (PB88-0268). de Ahorros
de &villa
Laboratory. program.
the Direccibn
Denmark) and Profeswr
REFERLNC‘ES
General
and the Junta de Andalucia
de Investigaclbn for tinancial
Cicntitica support.
is thanked
for a grant (to S.G.R.1,
tar
(to J.F,-B.G.)
facilities
.I. b~uentes Mota for valuable
y Tt;cnica
forn grant
Monte de Piedad ) C-‘:lj;k
Professor
K. Bock (Carisbc‘rg
for the USC oi‘ the ?,L..C’t-IEML’ discu~~ir~ns.
REACTION OF AMINO SUGARS WITH ISOTHIOCYANATES
19 20 21 22 23
24 25 26
AND ISOCYANATES
143
P. N. Preston, Condensed Imidasoles, WileyyInterscience, 1986, p. 136. F. Kruger and H. Rudy, Justus Liebigs Ann. Chem., 696 (1966) 214-220. F. Micheel and W. Lengsfeld, Chem. Ber,, 89 (1956) 12461253. D. Horton, W. Priebe, and M. Sznaidman, Carhohydr. Res., 187 (1989) 145%148. F. Duus, in D. Barton and W. D. Ollis (Ed%), Comprehensive Organic Chemistry, Vol. 3, Pergamon, 1979, p. 456. A. F. Hegarty, in D. Barton and W. D. Ollis (Eds.), Comprehensice Organic Chemikfry, Vol. 2, Pergamon, 1979, p. 1094. J. Fuentes Mota, M. A. Pradera Adrian, C. Ortiz Mellet. J. M. Garcia Fernandez, R. Babiano Caballero, and J. A. Galbis Perez, Carbohydr. Res., 173 (1988) I-16. J. Fuentes Mota, J. M. Garcia Fernandez, C. Ortiz Mellet, M. A. Pradera Adrian, and R. Babiano,
Carhohydr. Res., 193 (1989) 314-321. 27 K. Hofmann, Imidazole and Its Deriaatiues, Interscience,
London. 1953, pp. 78-79. 28 M. Avalos Gonzalez, J. Fuentes Mota, I. M. Gomez Monterrey, J. L. Jimenez Requejo, J. C. Palacios Albarran, and M. C. Ortiz Mellet, Carbohydr. Res., 154 (1986) 49-62. 29 M. Avalos Gonzalez, J. L. Jimenez Requejo, J. C. Palacios Albarran, F. Rebolledo Vicente, and J. Fuentes Mota, Carbohydr Res., 197 (1990) 31&317. 30 E. Moreno, M. Garcia Gea, and V. Hernandez Montis, Crysf. Sfruct. Commun., 5 (1976) 369.-372. 31 A. Conde, F. Bernier, and R. Marquez, Actu Crysrullogr., Sect. B, 36 (1980) 3048%3051. 32 R. Jimenez-Garay, A. Lopez-Castro and R. Marquez, Acta Cr.ysta/logr., Sect. B, 32 (1976) 2115-2118. 33 M. D. Estrada, A. Conde, and R. Marquez, Acta Crystallogr., SW/. C, 39 (1983) 141&1421; 43 (1987) 1134-1138. 34 S. L. Patt and J. M. Shoolery, J. Magn. Reson., 46 (1982) 536539. 35 J. Fernandez-Bolafios and J. Fuentes Mota, An. Quim., Ser. C, 72 (1976) 79-80.
36 P. Main, S. J. Fiske, S. E. Hull, L. Lessinger, G. Germain, J. P. Declerq, and M. M. Woolfson, MULTAN-80, A System of Computer Programsfor Automatic Solulion q/Crystal Structuresfrom X-Ray Di@acrion Duta, Universities of York (Great Britain) and Louvain (Belgium), 1980. 37 International Tablesfor X-Ray Crystallography, Vol. III, Kynoch Press, Birmingham, 1962. 38 J. M. Stewart, F. A. Kundell, and J. C. Baldwin. The X-Ray 70 System, Computer Science Center, University of Maryland, 1970. 39 M. Nardelli, Comput. Chem., 7 (1983) 95-98.
Carbohydrate Research, 210 (1991) 125%L43 Elsevier Science Publishers B.V., Amsterdam
Reaction of 2-amino-2-deoxy-D-glucose with aryl and acyl isothiocyanates, and aryl isocyanates: structure of the intermediate products Jo& FernBndez-Bolafios
Guzmhn*, Salud Garcia Rodriguez, Josh: Fernhndez-Bolaiios,
Departumento de Quimica Oryrinica. Facultad de Quimica, Universidad de Sevilla. 41071 Sevillu (Spain)
M”. J&us Dianez, and Amparo L6pez-Castro lnstiiutn de Ciencius de Materiales de Sevillrr. C.S.I.C., Universidad de &villa. 41071 Sevillu (Spain) (Received April 30th, 1990; accepted for publication,
July 12th, 1990)
ABSTRACT
The structure of(4R)-l-aryl-5-hydroxy-4-(o-arahino-tetritol-l-yI)imidazolidine-2-thiones (l-3), obtained by reaction of 2-amino-2-deoxy-D-glucose with aryl isothiocyanates. has been confirmed by ‘H-and ‘%-n.m.r. spectroscopy. Likewise, the structures of 2-(3-benzoyhhioureido)-2-deoxy-D-glucopyranose and 2-deoxy-2-(3-phenylureido)-D-glucopyranose, prepared by reaction of 2-amino-2-deoxy-D-glucose with benzoyl isothiocyanate and phenyl isocyanate, respectively, were also established. An X-ray analysis of l-5R (aryl = phenyl) has been carried out and its conformation in the solid state is one of the preponderant conformations in solution.
INTRODUCTlON
The reaction of amino sugars with isothiocyanates and isocyanates has been studied extensively’“. The structure of 2-(3-arylthioureido)-2-deoxy-D-glucopyranose was proposeds.6 for the first isolable products of the reaction of aryl isothiocyanates with 2-amino-2-deoxy-D-glucose. The same structrure was given’ to the products obtained by 0-deacetylation of I ,3,4,6-tetra-O-acetyI-2-(3-arylthioureido)-2-deoxy-~-D-glucopyranose. The suggestion8 that 2-deoxy-2-thioureidoaldoses are reactive and cyclise to 5-hydroxyimidazolidine-2-thiones was based on the results of electrophoresis in borate and tungstate buffers, and U.V.and i.r. spectroscopy of the isolated products. However, the stabilities of 2-deoxy-2-ureidoaldoses and 2-acylthioureido-2-deoxyaldoses were not studied. We now report on the structure of the first isolable compounds in the reaction of 2-amino-2-deoxy-D-glucose with aryl isothiocyanates, benzoyl isothiocyanate, and phenyl isocyanate, based mainly on ‘H- and ‘3C-n.m.r. data.
* Author for correspondence. 0008-6215/91/$03.50
@ 1991 ~ Elsevier Science Publishers B.V.
fi(.O!i
i:ti2CH
QH
1
5 1:
k
!: ,.
REACTION
OF AMINO
SUGARS
WITH
ISOTHIOCYANATES
AND
ISOCYANATES
127
’ Ill I) 0
” Ill <‘l),OI)
REACTION
OF AMINO SUGARS
WITH
ISOTHIOCYANATES
AND ISOCYANATES
129
TABLE
IV
Bond lengths (A) and angles ~____
( ) for I-5R
1.697(1X) 1.3X6(30) I .430( ISI 1.431(21) I .436(‘11 1419(143 1.335(?3) 1.437(1’)1 1.445(15, 1.337(1”) 1455(1~ l.ZlO(lhi 1.519(151 1.197(X) I .14X( IX) I .i7X(!31 1.360(X) ! .396(x!) 1,3h7(21) l.5i4(lh)
I .5I ‘( 1xi I 54’7(IXJ
The value of 1.697(18) ,h observed ofthe values for single (1.8 I A) and double character
is a
normal
for the length
of the
S C bond is intermediate
bonds (I .56 A). and this partial double-bond
feature of these compounds.
The average distances
(C-2 N- 1 and
REACTION OF AMINO SUGARS WITH ISOTHIOCYANATES
AND ISOCYANATES
131
of 1.336(23), C-4-N-3 and C-5-N- 1 of 1.446( l9), and the C-5-C-4 distance of 1.5 10( 16) A agree well with the mean values reported for analogous compounds’3.‘4. The average angles C-N-C and N-CC are 11 l( 1) and 103(l)“, respectively, and the N-C-N angle is 109(l)‘. The exocyclic bonds C-5-O-5, N-l-C-l”, and C-4-C-l’ are 1.386(20), 1.455(15), and 1.529( 15) A, respectively. The imidazolidine ring is planar [maximum deviation from the best plane is O.O88(12)A]. The Satom is in thisplane with adeviationof -0.016(4) A, but C-l’, C-l”, and O-5 are out of this plane, at - 0.879( 11) - 0.174(11), and 0.923(9) A, respectively. The corresponding bonds are bent by 42(l), 14(l), and -52(l)“. The mean value of the C-C bond length in the phenyl ring is 1.374(20) 8, and the mean C-H bond length is 1.09 (2) A. The N substituent is at -0.108( 16) A from the least squares calculated plane. The polyhydroxyalkyl chain C-l’/4 is nearly planar [maximum deviation from the least squares plane, 0.034(14) A]. Th e average C-C and C-O bond lengths of 1.524(17) and 1.431(18) A, respectively, and the average bond angles C-CC and C-C-O of 113(l) and 109( 1)“, respectively, are normal. The Newman projections along the backbone carbons, shown in Fig. 2, accord with a 3,Gi conformation, one of the conformers found in solution. According to the Klyne and Prelog rules’5, the configuration for the chiral centres C-5, C-4, C-l’, C-2, and C-3’ are R, R, R, S, and R, respectively. C-2-N-3
c-1’ c-4-c-5
H-5 c-l-c-4
c-2’-
C-l’
Fig. 2. Newman projections along the carbon backbone of l-5R
The dihedral angles between the phenyl and imidazolidine ring and between the sugar-chain plane and the imidazolidine ring are 44.4(8) and 88.7(6)“, respectively. The molecules in the crystal were closely stacked through van der Waals forces and there were three possible hydrogen bonds:
.-
6.5 6.3 6.1
described
13 14 15
’ Conditions
’ Assignments
94.7 89.7
13 15
’ In (CD,),SO.
in Table V.
2.2 2.0 2.1
J,, 8.6 8.9 8.2
J,,
4.10 dd 4.14 dd 4.07 dd
H-3
73.9 74.2
c-3
5.6 5.6 5.4
J5.f
79.4 79.4
c-4
43.9 63.9
C-6
11.2 11.0 11.1
Jo,.
3.72 dtd 3.71 dtd 3.76 dtd
H-5
68.3 68.7
c-5
for 13 and 15
2.6 2.0 2.6
J,,
3.64 dd 3.62 dd 3.72 dd
H-4
for 13-15
may be interchanged
65.2 60.6
C-2
shift data” (8, 50.3 MHz)
C-l
chemical
-0 -0 -0
J>j
Compound
“C-N.m.r.
VJJ
J,,,
Compound
TABLE
4.15 d 4.17d 4.00 dd
(Hz) for 13-15
Jvalues”
‘H-N.m.r.
TABLE VI
’ In (CD,),SO.
15
5.91 d
5.97 d 5.97 d
13
14
H-2
shift data” (6. 200 MHz)
H-l
chemical
Compound
‘H-N.m.r.
TABLE V
1.3
5.0 4.8 4.7
181.2
c=s
5.8 5.6 5.6
Jm
3.39 dt 3.35 dt 3.40 dt
H-6’
J,,,,
157.3
c=o
JwH
3.56 ddd 3.56 ddd 3.58 ddd
H-6
136.4* 139.4
C-l
127.1 119.3
129.0 128.7
c-3,5
136.0” 123.0
c-4
4.77 d 5.10d 4.74 d
1.14~7.32 m 5.36 d 7.42-7.54 m 5.58 d 7.00-7.63 m 5.31 d
C-2,6
OH-5
OH-3
Aromatic
Aromatic
5.6 5.7 5.5
J, o,,
9.08 s 9.28 s 7.53 d
NH
20.8
Ml>
4.55 t 4.59 t 4.50 t
OH-6
2.30 s
Me
I
HtOH
nI: aIi
I
/ CN,OH
CH20H
16
R':
19
R'= ti-6, I$: H-6',
OH , R'T "-6 ( 123: H-6'
.
,3= oi_,
the b anomers 22 and 24 obtained from 1.3,4.6-tetra-U-acctyi-l-amino-7-deox~-i-r~glucopyranose by reaction with benzoyl isothiocyanate and phenyl iwc~an;ite”. resprctivcly. CLDeacetylation of’24 in methanolic sodium methoxide gave the giucot‘uranoimidazolidin-3--one 15 instead of the expected 12. Conventional acetylation of 2 ga\e a mixture of at least three compounds. in which 20 was not detected. Treatment ofthe mixture with silica geiin rzfluuing toluens” followed by O-deacetylation gave 17. presumably through the tctra-acct:\te ot’17 ‘T‘hts method is a new route to tetritol-I -yidihydroinlid~~role-7-t.h~(~r?es.
REACTION OF AMINO SUGARS WITH ISOTHIOCYANATES
AND ISOCYANATES
135
REACTION
OF AMINO
SUGARS
WITH
ISOTHIOCYANATES
AND ISOCYANATES
137
TARLE ‘H-N.m.r.
x J \aiues” (Hz) for 21-24
REACTION
OF AMINO
SUGARS
WITH
ISOTHIOCYANATES
139
AND ISOCYANATES
solidified on treatment with ether. The solid was washed with aqueous 90% ethanol, to give a 3:2 mixture [130 mg, 20%; m.p. 180” (dec.)] of 2-5R and 2-5S, as deduced from the ‘H-n.m.r. spectrum of a solution in DzO recorded immediately. After 4 h, the ratio had become 9: I. (4R)-I-p-Chlorophenyl-5-hydroxy-4-(D-arabino-tetritol-I-yl)imidrrzolidine2-thione (3). -
A mixture of Zamino-2-deoxy-D-glucose (180 mg) andp-chlorophenyl isothiocyanate (255 mg) was treated as described for the preparation of 1, to give 3 (294 mg, 84%), m.p. 144148”; [a]: +42”, [or]& + 45, [a]& + 50”, [XI:!, + 92” (c 1, pyridine) 5:l); {lit.’ m.p. 144147”, [a],, +30” (ethanol)}; R, 0.52 (dichloromethane-methanol, nig 236 nm (E,,,~ 19.5); v,,, 3360 (NH, OH), 1450 (NH). 1260 (C = S), 1495, 1450, and 830 cm-’ (aryl, p-substituted). Mass spectrum: m/z 330 (M+ -H,O, 8%), 228 (M+ -C,H,O,, 3), 212 (C,H, 37ClN,S+, 36), 211 (C7H637C1N2S+,47), 210 (B+ + H, 90) 209 (B’, 100, where B = I-p-chlorophenyl-2-thioxo-imidazolinyl), 178 (Bf + H-S, 68), and 169 (ClC,H,NCS+, 40). The ‘H- and ‘3C-n.m.r. data are given in Tables I-III. Anal. Calc. for C,,H,,ClN,O,S: C, 44.76; H, 4.91; Cl, 10.16; N, 8.03. Found: C, 44.48; H, 4.90; Cl, 10.00; N, 8.01. I-p-Tolyl-((1,2-dideoxy-a-D-glucofurano)[2,1-d
Jimidazolidine-2-thione
(13).
~
Compound 2 (100 mg) was heated for 20 min at 155-l 60’. Crystallisation of the product from aqueous 50% ethanol gave 13 (58 mg, 61%) Recrystallisation from aqueous 95% ethanol gave material having m.p. 242-244” (dec.); [a]: + 64”, [XI& -i-68”, [a]:& + 76”, [a& + 111” (c 1, pyridine) {lit.6 m.p. 239-240’, [a]: + 64” (pyridine)}; R, 0.68 (dichloromethane-methanol, 5:l); v,,, 3430, 3355, 3205, 3150 (NH, OH), 1480 (NH), 1235 (C = S), 1580, 1515. 1445, and 820 cm-’ (aryl, p-substituted). Mass spectrum: m/z 310 (Mj, 17%),309(M+-H,7),292(M+-Hz0,2),208(M+-CC4Hh03, 15) 19O(B++ H, 95) 189 (B+, 100, where B = I-p-tolyl-2-thioxo-imidazolinyl), 149 (CH,C,H,NCS+, 5), and 91 (C7H7+, 15). The ‘H- and 13C-n.m.r. data are given in Tables V-VII. Z-p-Chlorophenyl-(l,2-dideoxy-a-r>-glucofurano)[2,1-d]imidazolidine-2-thione (14). -- Compound 3 (100 mg) was heated for 10 min at 155-l 60”. Crystallisation of the product from aqueous 50% ethanol gave 14 (60 mg, 63%) m.p. 24@241” (lit.35 m.p. 250”), R, 0.65 (dichloromethane-methanol, 5: 1); v,,, 3430,3355,3210 (NH, OH), 1495, 1430, 830 (aryl, p-substituted), 1480 (NH), and 1235 cm-’ (C = S). The ‘H-n.m.r. data are given in Tables V and VI. 2-(3-Benzoylthioureidoj-2-deoxy-D-glucopyranose (11). - A stirred mixture of ammonium thiocyanate (200 mg, 2.6 mmol) and benzoyl chloride (0.3 mL, 2.6 mmol) in acetone (2.5 mL) was boiled for 15 min under reflux, then filtered, and added to a solution of 2-amino-2-deoxy-D-glucose (0.45 g, 2.5 mmol) in water (0.75 mL). The mixture was kept for 24 h at NO”, then concentrated. Preparative t.1.c. (dichloromethane-methanol, 5: 1) of the syrupy residue and crystallisation from ethanol gave 11 (0.45 g, 53%), m.p. 188-190” (dec.); [CL]:+ 80”, [E]& + 83”, [a]& + 90”,[a]::, + 126”(c 1, pyridine) {lit.” m.p. 185”, [a]: +82.7” (pyridine)]; R, 0.72 (dichloromethane-methanol, 5:l); v,,, 3480, 3395, 3225, 3170 (NH, OH), 1650 (C=O), 1600, 1455, 725, 690 (phenyl), 1535, 1470 (NH), and 1275 cm-’ (C=S). Mass spectrum: m/z 194 (PhCONHCSNHCH,, 16%), 122 (PhCONH,, 14) 121 (PhCONH,, 33) 106 (PhCbH,
REACTION OF AMINO SUGARS WITH ISOTHIOCYANATES AND ISOCYANATES
1,3,4,6-Tetra-O-acetyl-2-deoxy-2-(3-phenylureido)-a-
141
(23) and P-D-glucopyrano-
se (24). -Conventional
acetylation of 12 (40 mg, 0.13 mmol) with acetic anhydride (0.3 mL) in pyridine (0.3 mL) gave a 3:2 mixture (59 mg, 94%) of 23 and 24, as deduced from the ‘H- and “C-n.m.r. spectra, R, 0.79 for 23 and 0.71 for 24 (dichloromethanemethanol, 4O:l). Signal assignments of the mixture were facilitated by the ‘H- and 13C-n.m.r. spectra of 24 obtained as described”. 4-(~-arabino-Tetritol-l-yl)-I-p-toI_~l-4-imidazoline-2-thione (17). -Conventional acetylation of 2 (380 mg, 1.16 mmol) with acetic anhydride (2 mL) in pyridine (2 mL) gave a mixture of three main compounds, R, 0.77, 0.64, and 0.45 (t.1.c.; ether-hexane, 10: 1); 20 was not detected. To a solution of the mixture in toluene ( 10 mL) was added Silica Gel 60 (Merck, 1 g) and the stirred mixture was boiled for 1 h under reflux, then filtered. The filtrate, which gave one main spot in t.1.c. (R, 0.45; ether-hexane, 10: l), was concentrated. A solution of the residue in methanolic 0.1% sodium methoxide (10 mL) was deionised with Amberlite IR-120 (H+) resin and concentrated. The syrupy residue was crystallised from aqueous 95% ethanol to give 17 (121 mg, 34%). Recrystallisation from ethanol gave material with m.p. 210-212”, [XI: - 30”, [tl]$, - 3 l”, [XI& - 36”, [c(]i:, - 68” (c 2, pyridine) {lit.h m.p. 21 l-212”, [cx], - 30” (pyridine)}. Crystal analysis*. - Compound l-5R crystallised as colourless prisms. Rather poor crystals were obtained with approximate dimensions 0.39 x 0.42 x 0.20 mm, which belonged to the monoclinic system with systematic absences consistent with P2,. Accurate cell dimensions and crystal orientation matrix, determined on a CAD-4 diffractometer by a least-squares treatment of the setting angles of 25 reflections in the range 2 < 0 < 14”, were a 6.978(9), b 7.125(2), c 14.694(5)& and p 94.4(3)“. The unit-cell volume (v) was 728.3(4)A3, and the absorption coefficient (p) was 0.23 mm-‘. An Enraf-Nonius CAD-4 diffractometer was used with monochromated MO-K, radiation (0.7107A), the w/20 mode, and 20,,, = 50” (0 < h d 8,0 < li < 8, - 17 < 1d 17). Two reference reflections were measured every hour to monitor crystal stability, and were re-centred after every hundred measured reflections in order to monitor crystal orientation. No significant changes in the intensities were noted. From 1435 measured reflections, 1042 were observed with 13 20(I); F(OOO) = 332. Corrections were made for Lorentz-polarisation effects, but not for extinction and absorption. The last effect was not taken into account because the crystal absorption with MO radiation was negligible. The structure was solved by direct methods with the MULTAN-80 program36, and 234 reflections with IE] > 1.62 and 5 reflections in the starting set were used to determine the structure. The initial E map revealed most of the non-hydrogen atoms and the remainder were located from subsequent electron-density maps. After anisotropic refinement by full-matrix least squares of all the 21 non-hydrogen atoms in the asymmetric unit, the hydrogen atoms were located at geometrical positions and were
* Lists of the observed and calculated structure factors, the anisotropic thermal parameters, and nonhydrogen and hydrogen atomic co-ordinates are deposited with, and can be obtained from, Elsevier Science Publishers B.V., BBA Data Deposition, P.O. Box 1527, Amsterdam. The Netherlands. Reference should be made to No. BBA/DD/451 Carbohydr. Res., 210(1991) 125-143.
We thank (PB88-0268). de Ahorros
de &villa
Laboratory. program.
the Direccibn
Denmark) and Profeswr
REFERLNC‘ES
General
and the Junta de Andalucia
de Investigaclbn for tinancial
Cicntitica support.
is thanked
for a grant (to S.G.R.1,
tar
(to J.F,-B.G.)
facilities
.I. b~uentes Mota for valuable
y Tt;cnica
forn grant
Monte de Piedad ) C-‘:lj;k
Professor
K. Bock (Carisbc‘rg
for the USC oi‘ the ?,L..C’t-IEML’ discu~~ir~ns.
REACTION OF AMINO SUGARS WITH ISOTHIOCYANATES
19 20 21 22 23
24 25 26
AND ISOCYANATES
143
P. N. Preston, Condensed Imidasoles, WileyyInterscience, 1986, p. 136. F. Kruger and H. Rudy, Justus Liebigs Ann. Chem., 696 (1966) 214-220. F. Micheel and W. Lengsfeld, Chem. Ber,, 89 (1956) 12461253. D. Horton, W. Priebe, and M. Sznaidman, Carhohydr. Res., 187 (1989) 145%148. F. Duus, in D. Barton and W. D. Ollis (Ed%), Comprehensive Organic Chemistry, Vol. 3, Pergamon, 1979, p. 456. A. F. Hegarty, in D. Barton and W. D. Ollis (Eds.), Comprehensice Organic Chemikfry, Vol. 2, Pergamon, 1979, p. 1094. J. Fuentes Mota, M. A. Pradera Adrian, C. Ortiz Mellet. J. M. Garcia Fernandez, R. Babiano Caballero, and J. A. Galbis Perez, Carbohydr. Res., 173 (1988) I-16. J. Fuentes Mota, J. M. Garcia Fernandez, C. Ortiz Mellet, M. A. Pradera Adrian, and R. Babiano,
Carhohydr. Res., 193 (1989) 314-321. 27 K. Hofmann, Imidazole and Its Deriaatiues, Interscience,
London. 1953, pp. 78-79. 28 M. Avalos Gonzalez, J. Fuentes Mota, I. M. Gomez Monterrey, J. L. Jimenez Requejo, J. C. Palacios Albarran, and M. C. Ortiz Mellet, Carbohydr. Res., 154 (1986) 49-62. 29 M. Avalos Gonzalez, J. L. Jimenez Requejo, J. C. Palacios Albarran, F. Rebolledo Vicente, and J. Fuentes Mota, Carbohydr Res., 197 (1990) 31&317. 30 E. Moreno, M. Garcia Gea, and V. Hernandez Montis, Crysf. Sfruct. Commun., 5 (1976) 369.-372. 31 A. Conde, F. Bernier, and R. Marquez, Actu Crysrullogr., Sect. B, 36 (1980) 3048%3051. 32 R. Jimenez-Garay, A. Lopez-Castro and R. Marquez, Acta Cr.ysta/logr., Sect. B, 32 (1976) 2115-2118. 33 M. D. Estrada, A. Conde, and R. Marquez, Acta Crystallogr., SW/. C, 39 (1983) 141&1421; 43 (1987) 1134-1138. 34 S. L. Patt and J. M. Shoolery, J. Magn. Reson., 46 (1982) 536539. 35 J. Fernandez-Bolafios and J. Fuentes Mota, An. Quim., Ser. C, 72 (1976) 79-80.
36 P. Main, S. J. Fiske, S. E. Hull, L. Lessinger, G. Germain, J. P. Declerq, and M. M. Woolfson, MULTAN-80, A System of Computer Programsfor Automatic Solulion q/Crystal Structuresfrom X-Ray Di@acrion Duta, Universities of York (Great Britain) and Louvain (Belgium), 1980. 37 International Tablesfor X-Ray Crystallography, Vol. III, Kynoch Press, Birmingham, 1962. 38 J. M. Stewart, F. A. Kundell, and J. C. Baldwin. The X-Ray 70 System, Computer Science Center, University of Maryland, 1970. 39 M. Nardelli, Comput. Chem., 7 (1983) 95-98.