The synthesis and crystal structure of (4E)-5-(3-chlorophenyl)-N-(4- chlorophenyl)-2-diazo-3-oxopent-4-enoic acid amide

Article abstract of DOI:10.1007/s10870-005-5135-7

(4E)-5-(3-Chlorophenyl)-N-(4-chlorophenyl)-2-diazo-3-oxopent-4-enoic acid amide (5) was synthesized from p-chloroaniline to N-(4-chlorophenyl)-2-diazo-3- oxo-butyramide (4) with 3-chlorobenzaldehyde. The yielded product 5 was investigated with X-ray crystallographic, NMR, MS, and IR techniques. Compound 5 (C₁₇H₁₁Cl₂N₃O₂, Formula wt = 360.19), crystallizes in the monoclinic space group P21/c with unit cell parameters a = 10.516(2), b = 17.996(4), c = 8.902(2) A, α = 90.00, β = 105.36(3), γ = 90.00°. V = 1624.5(6) A³, Z = 4, D_x = 1.473Mg m^-3. The final R was 0.0511.

Full text of DOI:10.1007/s10870-005-5135-7

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Journal of Chemical Crystallography, Vol. 35, No. 11, November 2005 ( 2005)
DOI: 10.1007/s10870-005-5135-7
The synthesis and crystal structure of (4E)-5-
(3-chlorophenyl)-N-(4-chlorophenyl)-2-diazo-
3-oxopent-4-enoic acid amide
Dong Heng-Shan,(1)∗ Wang Dong-Dong,(1) and Jin Chi-Qiong(1)
Received December 19, 2004; accepted April 11, 2005
(4E)-5-(3-Chlorophenyl)-N-(4-chlorophenyl)-2-diazo-3-oxopent-4-enoic acid amide (5)
was synthesized from p-chloroaniline to N-(4-chlorophenyl)-2-diazo-3-oxo-butyramide (4)
with 3-chlorobenzaldehyde. The yielded product 5 was investigated with X-ray crystallo-
graphic, NMR, MS, and IR techniques. Compound 5 (C17H11Cl2N3O2, Formula wt =
360.19), crystallizes in the monoclinic space group P21/c with unit cell parameters
◦
˚
a = 10.516(2), b = 17.996(4), c = 8.902(2) A, α = 90.00, β = 105.36(3), γ = 90.00 .
V = 1624.5(6) A , Z = 4, Dx = 1.473 Mg m−3. The final R was 0.0511.
3
˚
KEY WORDS: Crystal structure; diazodicarbonyl compound; 2-diazo-3-oxopent-4-enoic acid amide; synthesis;
ethyl (acetoketal)acetate; (2-methyl-[1,3]dioxolan-2-yl)acetic acid ethyl ester.
Introduction
show various biological effects, such as anti-HIV
activity.9,20 For this reason, the heterocyclic
In recent years in various publications,
derivatives containing two 1,2,3-triazoles, and
pyrone nucleus are very interesting, we also
demonstrated that the new title compounds of
pyrono[3,2-d]1,2,3-triazole containing more
heterocycles can be studied, but their properties
have not been published in the literature till
now. We have reported the crystalline structure
of 5-[5-amino-1-(4-chlorophenyl)-1,2,3-triazol-
4-yl]-2-(3-bromoanilino)-1,3,4-thiadiazole and
their derivatives,21–23 the crystalline structure of
3-[5-methyl-1-(4-methylphenyl)-1,2,3-triazol-4-
yl]-s-triazolo[3,4-b]-1,3,4-thiadiazole.24 When
we concentrate on synthesis of 4-acetyl-1-
(p-chlorophenyl)-5-hydroxyl-1,2,3-triazole by
reaction of p-chlorophenyl azide with ethyl
(acetoketal)acetate or (2-methyl-[1,3]-dioxolan-
2-yl)-acetic acid ethyl ester, N-(4-chlorophenyl)-
2-diazo-3-oxo-butyramide is obtained. In
subsequent reaction of the compound with
certain compounds having a 1,2,3-triazole
nucleus have been reported as antibacterials,1
antifungals,2 antivirals,3 anti-inflammatories and
analgesics.4 Recently, some new 1,3,4-triazole
derivatives have been synthesized as possible
anticonvulsants5 and plant growth regulators6;
and 1,2,3-triazole derivatives have been synthe-
sized to inhibit tumor proliferation, invasion,
metastasis,7 and have shown anti-HIV activity.8–13
Likewise, the pyrone nucleus derivatives have
been synthesized which have shown anti-HIV
activity.14–19 The fused benzopyrone derivatives
(1) State Key Laboratory of Applied Organic Chemistry, Institute of
Organic Chemistry, College of Chemistry and Chemical Engi-
neering, Lanzhou University, Lanzhou, Gansu 730000, People’s
Republic of China.
∗To whom correspondence should be addressed; e-mail: dongheng
shan@lzu.edu.cn.
897
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1074-1542/05/1100-0897/0 2005 Springer Science+Business Media, Inc.

898
Dong, Wang, and Jin
point apparatus. IR spectra were obtained in
KBr discs on a Nicolet 170SX FT-IR spectrom-
eter. MS were performed on an HP-5988A spec-
3-chlorobenzaldehydes, we obtained (4E)-5-
(3-chlorophenyl)-N-(4-chlorophenyl)-2-diazo-3-
oxopent-4-enoic acid amide which resulted
in the triazole ring opened in acidic water.
A great deal of interest has been focused on
the α-diazocarbonyl compounds.25 When pro-
perly substituted, they can be useful materials
for photoresist. This has inspired us to extend
our work on α-diazodicarbonyl compounds N-
(4-chlorophenyl)-2-diazo-3-oxobutyramide with
heterocyclic opening in order to study the
synthesis and potential applications of (4E)-5-
(3-chlorophenyl)-N-(4-chlorophenyl)-2-diazo-3-
oxopent-4-enoic acid amides.
1
trometer (EI at 70 eV). H NMR spectroscopy
(CDCl3) were recorded on an Avance Mercury
plus-300 MHz instrument with TMS as an inter-
nal standard.
2-(Methyl-[1,3]-dioxolan-2-yl)-acetic acid
ethyl ester (1) was prepared following the method
reported in the literature.26
A mixture of ethyl acetoacetate (13.0 g,
0.1 mol), ethylene glycol (50 mL), PTS (50 mg)
and benzene (100 mL) was refluxed with con-
tinuous removal of water azeotropically for 8 h.
The reaction mixture was cooled and neutralized
with aqueous K2CO3 (5 mL). The reaction mix-
ture was diluted with water (100 mL) and benzene
layer was separated. The aqueous phase was ex-
tracted with benzene (2 × 100 mL), the obtained
benzene layers were combined, dried (Na2SO4),
and distilled. The obtained residue was distilled
under reduced pressure to give as viscous col-
orless liquid (in 90% yield).1H NMR δH: 4.04–
4.16 (q, 2H, J = 7.2 Hz, OCH2CH3); 3.93 (s, 4H,
In this paper, we report the synthesis and
crystalline structure of (4E)-5-(3-chlorophenyl)-
N-(4-chlorophenyl)-2-diazo-3-oxopent-4-enoic
acid amide (5).
The route of synthesis is shown in Scheme 1.
Experimental section
Melting points were uncorrected and de-
termined on an XT4-100× microscopic melting
---
---
---
---
OCH2CH2O ); 2.62 (s, 2H, CCH2CO2 );
---
1.46 (s, 3H, CH3 ); 1.19–1.26 (t, 3H, J =
---
7.2 Hz, CH2 CH3) ppm.
N-(4-Chlorophenyl)-2-diazo-3-oxobutyra-
mide was prepared from p-chloroaniline follo-
wing the method reported in the literature.27
The solution of sodium ethoxide (3.5 g,
0.15 mol of sodium in 50 mL of ethanol) was
added to a solution of 15.3 g (0.1 mol) p-
chlorophenyl azide and 12.0 mL (0.1 mol) ethyl
(acetoketal)acetate (1) in 80 mL absolute ethanol
in one portion under ice bath. Then, the reaction
mixture was heated under refluxed for 48 h. The
solution was cooled to room temperature, and the
solvent was removed in vacuo to give a syrup mix-
ture. This mixture was dissolved in 100 mL water
and acidified to pH = 1∼2 with hydrochloric acid
(4 M). After stirring in an ice-bath for 1 h, the
resulting precipitate was filtered off and washed
with water and recrystalized from ethanol to give
16 g compound 4. Yield 65%, mp 145–146◦C
(Lit. 143◦C), IRυmax: 3236, (b, N H), 3069
--- ---
Scheme 1.

2-Diazo-3-oxopent-4-enoic acid amide
899
---
and data collection were performed with MoKα
(Ar H), 3027, 2938, (w, CH3), 2125(s, diazo),
˚
---
---
---
radiation (λ = 0.71073 A) on an Enraf–Nonius
1670, 1638 (s, C O, CONH ), 1596, 1548,
---
CAD4 computer-controlled kappa axis diffrac-
tometer operating in the ω/2θ scanning mode.
The structure was determined by direct meth-
ods (SHELXS-97)28 and refined by full covari-
ance matrix methods (SHELXL-97).29 The crystal
data, data collection and the refinement parameter
for the structure are given in Table 1.
1488 (s, Ar−),1 953, 841, 820 (m, Ph-1,2H), 722
1
---
(C Cl) cm . H NMR δH : 10.22 (b, 1H, NH);
7.52–7.55 (d, 2H, J = 7.2 Hz, Ph-2,6H); 7.30–
7.27 (d, 2H, J = 7.2 Hz, Ph-3,5H); 2.43 (s, 3H,
+
·
---
CH3 ) ppm. MS m/z: 237 (M , 21), 239 (M+2,
7), 194(4), 181(9), 167(10), 153(6), 138(54),
127(14), 111(28), 99(21), 83(44), 75(28), 69
(5), 63(19), 55(14), 50(11), 43(100), 39(10).
(4E)-5-(3-chlorophenyl) - N -(4-chlorophen-
yl)-2-diazo-3-oxopent-4-enoic acid amide (5)
was prepared by the following method.
The structure of the title compound is shown
in Fig. 1. Selected bond lengths and angles are
given in Table 2. The geometric calculations were
performed using the program SHELX-97.
Compound 4 (1.5 g) was added to a solu-
tion of sodium hydroxide (0.8 g) and 20 mL
50% ethanol (V/V), then 3-chlorobenzaldehyde
was added dropwise to the solution with con-
tinuous stirring at room temperature. The re-
action mixture was stirred at room tempera-
ture for 8 h, acidified to pH = 7∼8 with HCl
(4M), the deposit was filtered and recrystalized
from ethanol to give 5. Yield 87%, mp 159–
Results and discussion
The structure of the title compound 5 is
shown in Fig. 1. In recent years, the synthesis and
Table 1. Crystal Data and Summary of Data Collection and Structure
Refinement
160◦C, IRυmax: 3224, (b, N H), 3179, 3110
--- ---
Compound
CCDC deposit no.
Color
Formula weight
Temperature (K)
Crystal system
Space group
C17H11Cl2N3O2
250506
Colorless
360.19
20(293)
Monoclinic
P21/c
---
(Ar H), 3060, 2938, (w, CH3), 2120 (s, di-
---
---
---
azo), 1668, 1641 (s, C O, CONH ), 1576,
---
1543, 1490 (s, Ar), 975, 830 (m, Ph-1, 2H), 925,
789, 789 (−m1, chlorophyl 1H or 3H), 738, 692
1
---
(C Cl)cm . H NMR δH: 10.58 (b, 1H, NH);
Unit cell dimensions
---
7.72–7.77 (d, 1H, J = 15 Hz, C11 H); 7.29–
˚
a (A)
10.516(2)
17.996(4)
8.902(2)
1624.5(6)
˚
---
b (A)
7.55 (m, 8H, Ar H); 6.88–6.89 (d,+1H, J =
˚
c (A)
Volume (A )
·
---
15 Hz, C10 H) ppm. MS m/z: 359 (M , 15.3%),
361(M+2, 10.2%), 278(0.4), 276(0.8), 274(1.9),
233(3), 207(3), 205(9), 195(2.5), 193(7), 182(2),
180(7), 178(16), 167(20), 165(52), 151(21),
149(52), 131(21), 127(47), 125(24), 115(54), 111
(50), 91(16), 77(18), 69(70), 57(93), 43(100).
The purified product was dissolved in a mix-
ture of ethyl acetate, petroleum ether solvent. The
crystal was obtained after 10 day by evaporation
of the solvent.
3
˚
Z
4
Dcalc (g/cm3)
1.473
736
0.414
F(000)
Absorption coefficient (mm−1
Diffractometer/scan
)
Enraf–Nonius CAD4, ω/2θ
kα (graphite monochromator)/
0.71073
5.98–25.03
2997
1593
2810/0/218
F2
˚
Radiation/λ (A)
θmin, θmax (◦)
Reflections measured
Independent/observedreflections
Data/restraints/parameters
Refinement method Full-matrix
least-squares on
Goodness-of-fit on F2
Shift/su max
Crystal structure determinations
and refinement
1.028
0.094
Final R indices
R1 = 0.0511, wR2 = 0.1184
R1 = 0.1171, wR2 = 0.1340
0.218 and −0.184
R indices [I > 2σ(I)]
Largest diff. peak and hole (eA
Single crystals were selected and mounted on
the tip of a glass fiber. Preliminary examination
−3
˚
)

900
Dong, Wang, and Jin
◦
˚
Table 2. Selected Bond Lengths (A) and Angles ( )
Angle (◦)
˚
Atoms
Length (A)
Atoms
----
Cl1 C16
---- ----
C7 N1 C6
1.737(6)
1.755(5)
1.206(6)
1.238(6)
1.356(6)
1.404(6)
1.116(6)
1.326(7)
1.370(7)
1.374(7)
1.360(8)
1.360(8)
1.372(7)
1.376(7)
1.484(7)
1.443(8)
1.465(7)
1.309(7)
1.460(7)
1.380(7)
1.381(8)
1.391(7)
1.371(8)
1.358(8)
1.366(7)
127.0(4)
175.4(5)
120.5(5)
119.0(5)
122.2(5)
119.0(4)
118.8(5)
118.0(5)
121.5(5)
118.8(5)
124.3(5)
116.9(4)
127.0(5)
120.7(5)
112.3(4)
118.4(5)
110.9(4)
130.6(5)
118.7(5)
121.0(5)
120.3(5)
121.1(5)
128.4(5)
118.2(5)
123.2(5)
118.5(5)
121.1(5)
119.1(5)
119.5(5)
121.9(5)
118.6(4)
119.5(4)
120.0(5)
----
---- ----
Cl2 C3
N3 N2 C8
----
O1 C7
---- ----
C6 C1 C2
----
---- ----
O2 C9
C3 C2 C1
----
N1 C7
---- ----
C2 C3 C4
----
---- ----
N1 C6
C2 C3 Cl2
----
N2 N3
---- ----
C4 C3 Cl2
----
---- ----
N2 C8
C3 C4 C5
----
C1 C6
---- ----
C4 C5 C6
----
---- ----
C1 C2
C1 C6 C5
----
C2 C3
---- ----
C1 C6 N1
----
---- ----
C3 C4
C5 C6 N1
----
C4 C5
---- ----
O1 C7 N1
----
---- ----
C5 C6
O1 C7 C8
----
C7 C8
---- ----
N1 C7 C8
----
---- ----
C8 C9
N2 C8 C9
----
C9 C10
---- ----
N2 C8 C7
----
---- ----
C10 C11
C9 C8 C7
----
C11 C12
---- ----
O2 C9 C8
----
---- ----
C12 C17
O2 C9 C10
Fig. 1. ORTEP drawing of the title compound 5 showing the
atom numbering scheme (ellipsoids: 50% probability).
----
C12 C13
---- ----
C8 C9 C10
----
----
----
C13 C14
C11 C10 C9
---- ----
----
C14 C15
C10 C11 C12
---- ----
----
C15 C16
C17 C12 C13
---- ----
characteristics of 5-amino-1-(4-chlorophenyl)-1,2,
3-triazol-4-yl and 5-methyl-1-(4-methylphenyl)-
1,2,3-triazol-4-yl derivatives have been inves-
tigated.21–24 These heterocyclic compounds
contain 1,2,3-triazole ring, and they was a se-
ries stable compounds. In order to continuate
our studies, we now report the crystal structure
of (4E)-5-(3-chlorophenyl)-N-(4-chlorophenyl)-
2-diazo-3-oxopent-4-enoic acid amide (5).
We isolated compound 4 that was formed
from the ring opening product using 4-acetyl-
1-(4-chlorophenyl)-5-hydroxy-1, 2, 3 -triazole in
acid medium. We claim that the reaction mech-
anism is the following formation under the reac-
tion conditions in Scheme 2. The reaction mecha-
nism is in agreement with literature that reported
the reaction mechanism.27,30 We have known
that the structure has something to do with the
medium.
----
C16 C17
C17 C12 C11
---- ----
C13 C12 C11
---- ----
C12 C13 C14
---- ----
C15 C14 C13
---- ----
C16 C15 C14
---- ----
C15 C16 C17
---- ----
C15 C16 Cl1
---- ----
C17 C16 Cl1
---- ----
C16 C17 C12
1,2,3-triazole ring. The bond length is shorter than
˚
˚
---
---
---
N N [N1 N2 1.361(5) A; N2 N3 1.295(5) A]
---
in 1,2,3-triazole ring.
Identified as a diazo compound showing
strong IR absorption at 2125 cm−1 of 4 and
2120 cm−1 of 5, there is no 1,2,3-triazole ring sys-
tem in molecular structure of compounds.27 The
˚
---
bond length of N2 N3 (1.116(6) A) in compound
5 are not in agreement with the values reported for
Scheme 2.

2-Diazo-3-oxopent-4-enoic acid amide
901
14. Romines, K.R.; Watenpaugh, K.D.; Howe, W.J.; Tomich, P.K.;
Lovasz, K.D.; Morris, J.K.; Janakiraman, M.N.; Lynn, J.C.;
Horng, M.-M.; Chong, K.-T.; Hinshaw, R.R.; Dolak, L.A. J.
Med. Chem. 1995, 38, 4463.
15. Romines, K.R.; Morris, J.K.; Howe, W.J.; Tomich, P.K.;
Horng, M.-M.; Chong, K.-T.; Hinshaw, R.R.; Anderson, D.J.;
Strohbach, J.W.; Turner, S.R.; Mizsak, S.A. J. Med. Chem. 1996,
39, 4125.
16. Skulnick, H.I.; Johnson, P.D.; Aristoff, P.A.; Morris, J.K.;
Lovasz, K.D.; Howe, W.J.; Watenpaugh, K.D.; Janakiraman,
M.N.; Anderson, D.J.; Reischer, R.J.; Schwartz, T.M.; Banitt,
L.S.; Tomich, P.K.; Lynn, J.C.; Horng, M.-M.; Chong, K.-T.;
Hinshaw, R.R.; Dolak, L.A.; Seest, E.P.; Schwende, F.J.; Rush,
B.D.; Howard, G.M.; Toth, L.N.; Wilkinson, K.R.; Kakuk, T.J.;
Johnson, C.W.; Cole, S.L.; Zaya, R.M.; Zipp, G.L.; Possert,
P.L.; Dalga, R.J.; Zhong, W.-Z.; Williams, M.G.; Romines, K.R.
J. Med. Chem. 1997, 40, 1149.
17. Gupta, S.P.; Babu, M.S.; Kaw, N. J. Tetrahedron 1999, 14, 109.
18. Tait, B.D.; Hagen, S.; Domagala, J.M.; Ellsworth, E.L.; Gajda,
C.; Hamilton, H.W.; Vara Prasad, J.V. N.; Ferguson, D.;
Graham, N.; Hupe, D.; Nouhan, C.; Tummino, P.J.; Humblet,
C.; Lunney, E.A.; Pavlovsky, A.; Rubin, J.; Gracheck, S.J.;
Baldwin, E.T.; Bhat, T.N.; Erickson, J.W.; Gulnik, S.V.; Liu, B.
J. Med. Chem. 1997, 40, 3781.
The ring system and all of atoms are in the
plane in intramolecular, so there is the conjugate
---
of the π π. It is shown in Fig. 1.
These are the interactions of hydrogen
---
bond on the molecular stacking [N1 H1A 0.90
˚
---
H1A· · ·O2 1.95 N1 H1A· · ·O2 2.697(5) A
◦
---
N1 H1A· · ·O2 139.7( )].
Acknowledgments
The authors would like to acknowledge the
NNSFC (chuangxin qunti) and Lanzhou Univer-
sity SKLAOC for their support.
References
1. Zhang, Z.-Y.; Liu, Y.; Yang, S.-Y. Pharm Sin. 1991, 26(11),
809.
2. Abdou, N.A.; Soliman, S.N.; Abou Sier, A.H. Bull. Fac. Pharm.
1990, 28(2), 29 (Chem. Abstr. 1992, 117, 69793n).
3. Srivastava, A.J.; Swarup, S.; Saxena, V.K.; Chowdhury, B.L. J.
Indian Chem. Soc. 1991, 68(2), 103.
4. Cooper, K.; Steele, J.; Richardson, K. EP 329357 (Chem. Abstr.
1990, 112, 76957u).
5. Husain, M.I.; Mohd, A. J. Indian Chem. Soc. 1986, 63, 317.
6. Elliott, R.; Sunley, R.L.; Griffin, D.A. GB 2,175, 301 (Chem.
Abstr. 1987, 107, 134310n).
19. Vara Prasad, J.V.N.; Para, K.S.; Tummino, P.J.; Ferguson, D.;
Mcquade, E.J.; Lunney, E.A.; Rapundalo, S.T.; Batley, B.L.;
Hingorani, G.; Domagala, J.M.; Gracheck, S.J.; Bhat, T.N.;
Liu, B.; Baldwin, E.T.; Erickson, J.W.; Sawyer, T.K. J. Med.
Chem. 1995, 38, 898.
20. Raghavan, K.; Buolamwini, J.K.; Fesen, M.R.; Pommier, Y.;
Kohn, K.W.; Weinstein, J.N. J. Med. Chem. 1995, 38, 890.
21. Zhang, Z.-Y.; Dong, H.-S.; Zhu, Y. Acta Chim. Sin. 1996, 54,
1054.
22. Zhang, Z.-Y.; Dong, H.-S.; Guan, Z.-W.; Yang, S.-Y. Chem.
Res. Chin. Univ. 1997, 13, 27.
7. Kohn, E.C.; Liotta, L.A. U.S. 637145 (Chem. Abstr. 1991, 115,
248099w).
23. Zhang, Z.-Y.; Dong, H.-S.; Yang, S.-Y. Org. Chem. 1996, 16,
430; 1998, 18, 253.
8. Alvarez, R.; Velazquez, S.; San-Felix, A.; Aquaro, S.; De
Clercq, E.; Perno, C.F.; Karlsson, A.; Balzarini, J.; Camarasa,
M.J. J. Med. Chem. 1994, 37, 4185.
24. Dong, H.-S.; Quan, B.; Zhu, D.W.; Li, W.D. J. Mol. Struct.
2002, 613, 1–5.
25. Ye, T.; McKervey, M.A. Chem. Rev. 1994, 94, 1091.
26. Ayyangar, N.R.; Mehendale, A.R.; Argade, A.B. Synth. Com-
mun. 1987, 17, 1959–1964.
27. Olesen, P.H.; Nielsen, F.E.; Pedersen, E.B.; Becher, J. J. Hetro-
cyclic Chem. 1984, 21, 1603–1608.
28. Sheldrick, G.M. SHELXS-97, Program for Structure Solution:
Acta Crystallogr. Sect. A 1990, 46, 467.
9. De Clercq, E. Medicinal Research Reviews, 2002, 22(6), 531.
10. Saito, Y.; Escuret, V.; Durantel, D.; Zoulim, F.; Schinazi, R.F.;
Agrofoglio, L.A. Bioorg. Med. Chem. 2003, 11(17), 3633.
11. Himanshu; Tyagi, R.; Olsen, C.E.; Errington, W.; Parmar, V.S.;
Prasad, A.K. Bioorg. Med. Chem. 2002, 10(4), 963.
12. Velazquez, S.; Alvarez, R.; Perez, C.; Gago, F.; De, C.;
Balzarini, J.; Camarasa, M.J. Antivir. Chem. Chemoter. 1988,
9, 481.
29. Sheldrick, G.M. SHELXL-97, Program for Crystal Structure
Refinement; Universita¨t Go¨ttingen: Germany, 1997.
30. Maier, D.; Maas, G. Zh. Org. Khim. 1994, 30(9), 1391–1397.
13. Garanti, L.; Molteni, G. Tetrahedron Lett. 2003, 44(6), 1133.