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Synthesis of Podands with Cyanurate or Isocyanurate Cores and Terminal Triple Bonds

PAPER 1639

Flavia Piron,a,b

Cornelia Oprea,a Crina Cisma ?,*a Anamaria Terec,a Jean Roncali,b Ion Grosu*a

Babes-Bolyai University, Organic Chemistry Department and CCOCCAN, Cluj-Napoca, 11 Arany Janos str., 400028 Cluj-Napoca, Romania b

University of Angers, CNRS, CIMA, Group Linear Conjugated Systems, 2 Bd Lavoisier, 49045 Angers, France Fax +40(264)590818.; E-mail: csocaci@chem.ubbcluj.ro; E-mail: igrosu@chem.ubbcluj.ro Received 11 February 2010

SYNTHESIS 2010, No. 10, pp 1639–1644Advanced online publication:06.04.2010

DOI: 10.1055/s-0029-1218724; Art ID:P01810SS ? Georg Thieme Verlag Stuttgart · New York

Abstract: The synthesis of podands with cyanuric or isocyanuric acid cores and oligoethyleneoxy pendant arms exhibiting terminal triple bonds or brominated triple bonds is reported. The starting ma-terial for cyanuric acid derived podands is commercially available cyanuric acid, while the isocyanuric derivatives are obtained by thermal isomerization of the corresponding cyanurates.

Key words: podands, cyanurates, alkynes, isomerization, heterocy-cles

In this work we have investigated the synthesis of tripo-dands with terminal triple bonds and cyanuric I or isocy-anuric acids II as cores, targeted to be useful intermediates for further functionalization in order to achieve a plethora of macromolecular or supramolecular compounds (Figure 1).1–9

Figure 1

The core of the two series of tripodands exhibit different properties: the 1,3,5-triazine unit I is an electron-poor het-eroaromatic system, while the isocyanurate core II can participate, via the oxygen atoms, as a donor for the for-mation of hydrogen bonds.10 The attachment of functional groups (X =Br) to the terminal triple bonds opens the way to many other possible synthetic approaches and makes these compounds important precursors for host mole-cules, macromolecules, and dendrimers with C 3 symme-try.

The investigated synthetic strategies utilize consecutive reactions, they are based on an inexpensive commercially available starting compound (cyanuric chloride), and the results have been compared with other methodologies,which failed or gave poor results.

Trialkoxycyanurates have long been known,11 their syn-thesis requires the reaction of silver cyanurates with alkyl halides, trimerization of imidates, and, most commonly used, the nucleophilic substitution of the chlorine in cya-nuric chloride with alkoxides.

Given the availability of cyanuric chloride, we focused our investigations on the possibility of obtaining com-pounds 2a –e (Scheme 1) by nucleophilic substitution of the chlorines of cyanuric chloride with alkoxides having oligoethyleneoxy chains and a terminal triple bond.

Scheme 1

The cyanurate 2a was previously synthesized 12 from cya-nuric chloride and propargyl alcohol in acetone using so-dium hydroxide as base. Compound 2a was later used as an intermediate for the construction of dendrimers.13 At-tempts to obtain 2a and other compounds 2 of the series

D o w n l o a d e d b y : I P -P r o x y U n i v e r s i t y o f M a s s a c h u s e t t s B o s t o n , U n i v e r s i t y o f M a s s a c h u s e t t s B o s t o n . C o p y r i g h t e d m a t e r i a l.

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using this reported procedure gave poor or moderate yields. The other procedures reported for the formation of trialkoxycyanurates starting from cyanuric chloride with alcohols use sodium hydride,14 sodium hydroxide, N ,N -diisopropylethylamine,15 or potassium tert -butoxide 16 as the base and require a large excess of alcohol. Due to the use of a large excess of alcohol, these procedures were considered unsuitable for the synthesis of 2a –e .The high yielding synthesis of trialkoxycyanurates start-ing from cyanuric chloride with alcohols using butyllithi-um as a base has been recently reported.17 We adapted this method for our target compounds and carried out the syn-thesis of 2a –e in tetrahydrofuran with stoichiometric amounts of the appropriate alcohol. The yields increased considerably (55–65%) when compared to other methods 12 and the separation and purification of the prod-ucts was substantially facilitated (Scheme 1).

The precursor alcohols 1b –e were synthesized using pro-cedures described in the literature 18 while propargyl alco-hol 1a is commercially available.

As shown in the literature, isocyanuric acid derivatives can be formed by trimerization of isocyanates,19 by substi-tution under harsh conditions at cyanuric acid,20 or by re-arrangement of the corresponding cyanurates.21,22

The hitherto unknown isocyanurate derivatives 3b –d (Scheme 2) were obtained by the rearrangement reaction from cyanurates 2b –d , in a process catalyzed by tetrabu-tylammonium bromide or tetrabutylphosphonium bro-mide at 120 °C without solvent. Even though there are reports that such thermal isomerizations occur using sol-vents at temperatures higher than 100 °C,22 the treatment of cyanurates 2 in toluene or xylene under reflux gave no isocyanurates 3. This type of reaction was previously de-scribed by Harrington et al.21 for the isomerization of oth-er 1,3,5-triazine derivatives.

Scheme 2

As an alternative route to the isocyanurate derivatives 3b –d , the alkylation of cyanuric acid with propargyloligo(eth-yleneoxy)ethyl halides 4b –d and 5b –d was attempted (Scheme 3). Despite the successful synthesis reported for 3a ,23 all attempts to alkylate cyanuric acid under various basic conditions (KOH, NaH)24 with the chlorides 4b –d or the iodides 5b –d failed.

Scheme 3

The chloro derivatives 4b and 4d are known com-pounds.25,26 The procedure reported for 4d 26 was used also for the synthesis of 4c , providing 4c ,d in good yields (70–85%) (Scheme 4). The iodo compounds 5b –d were syn-thesized (60–80% yields) by a standard procedure 27 for the halogen-exchange reaction (Scheme 4). Compounds 5c ,d have not been previously reported, while 5b was re-cently obtained by another procedure (using –OTs for I –exchange).28

Scheme 4

As another alternative synthetic route to isocyanuric acid derivatives 3, a side chain nucleophilic substitution of commercially available 1,3,5-tris(2-hydroxyethyl)cyanu-ric acid (6) with propargyl bromide and iodo derivatives 5b –d was considered. Only the reaction with propargyl bromide in the presence of sodium hydride (DMSO, 20°C) afforded the isocyanurate 3b , together with the ox-azolidone 7 (Scheme 5). In the other reactions (iodo deriv-atives 5b –d ), no isocyanurates were isolated from the reaction mixtures. The cleavage of the tris(2-hydroxyeth-yl)isocyanurate heterocycle involved in the formation of 7is likely to occur by nucleophilic attack of the deprotonat-ed side chain hydroxy group on the carbonyl site with in situ formation of the unsubstituted oxazolidone, which is further deprotonated and propargylated. Similar behavior,but without alkylation, was previously observed for 2-hy-droxyethyl isocyanurates on vacuum pyrolysis 29 and on heating in N ,N -dimethylformamide solution at high tem-peratures.30 In our case working at 35–40 °C gave the ox-azolidone 7 as the major product while the isocyanurate 3b was formed predominantly at room temperature (20°C).

The structures of the new cyanurates 2a –e and their iso-mers isocyanurates 3b –d were confirmed by NMR spec-troscopy. The main differences between the spectra of

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these two series were observed in the 13C NMR spectra where the quaternary C=O carbons in isocyanurates give signals at d =148–149 compared with C–O signals of the corresponding cyanurates which are considerably more deshielded (d =172–173). Similarly for the CH 2N carbon atoms of the isocyanurates 3 the 13C NMR signals are in the range d =41–42 (the corresponding protons show sig-nals at d =4.10–4.15), while the signals for the CH 2O moieties of cyanurates 2 are more deshielded (13C NMR,d =67–70 and 1H NMR, d =4.51–4.55).

In order to access C 3 podands with extended capacity for further applications (e.g., cross-coupling reactions), bro-mination of the terminal CH of the triple bonds in com-pounds 2a –c and 3a ,b was envisaged (Scheme 6). The reactions were carried out in fair to good yields (30–70%)with N -bromosuccinimide in the presence of silver nitrate.An excess of N -bromosuccinimide (250%) was used in or-der to enhance the ratio of triple substitution products.

Scheme 6

The structure of the brominated products 8a –c and 9a ,b was elucidated by NMR spectroscopy. Thus, the absence of signals for the protons of the terminal triple bonds in 1H NMR spectra, the upfield shift of the signals belonging to the sp carbon atoms in 13C NMR and the specific pattern for the tribrominated peaks in MS were noted (see exper-imental section).

An efficient synthesis of C 3 symmetry podands with pen-dant arms of different lengths (n =0–4) bearing at their extremities triple bonds, either brominated or not, and ex-hibiting 1,3,5-triazine or 1,3,5-triazinane-2,4,6-trione cores is reported. Starting from cyanuric chloride, an in-expensive commercially available compound, diverse po-dands could be obtained in a few consecutive steps. The compounds described in this paper represent promising versatile starting materials for functionalized podands and/or cryptands by subsequent reactions, such as copper-catalyzed [2+3] cycloaddition with azides or oxidative copper-catalyzed homocoupling, Sonogshira, and other palladium-catalyzed cross-coupling reactions.

H and 13C NMR spectra were recorded on a Bruker Avance 300spectrometer operating at 300 MHz (1H) and 75 MHz (13C) relative to TMS. MS were recorded on an ESI ion trap mass spectrometer (Agilent 6320) in positive mode and in EI mode (70eV) on a VG-Autospec mass spectrometer or in positive ionization on a Thermo-Finnigan MSQ mass spectrometer. Solvents were dried and distilled under argon using standard procedures before use. Chemicals of commercial grade were used without further purification. Melting points are uncorrected. Column chromatography purifications were carried out on Merck silica gel Si 60 (40–63 m m). TLC was carried out on aluminum plates coated with silica gel 60 F254 using UV lamp (254 nm) and KMnO 4 visualization.

Podands 2 with 1,3,5-Triazine Units; General Procedure

A soln of 15% n -BuLi in hexane (3.34 mL, 5.32 mmol) was slowly added to the soln of hydroxy alkyne 1b –e (5.32 mmol) in anhyd THF (40 mL) under an argon atmosphere at –78 °C. The lithium alkoxide soln was stirred at this temperature for 15 min and then cy-anuric chloride (327.2 mg, 1.77 mmol) in anhyd THF (10 mL) was added dropwise over 5 min. The mixture was stirred overnight at r.t.The solvent was removed and the residue was washed with H 2O (50mL), extracted with CH 2Cl 2, dried (Na 2SO 4), and concentrated.2,4,6-Tris(prop-2-ynyloxy)-1,3,5-triazine (2a)

Following the general procedure with purification by column chro-matography (silica gel, pentane–EtOAc, 9:1); white solid (65%);mp 69–70 °C (Lit.13 69–70 °C); R f =0.35 (pentane–EtOAc, 9:1).1H NMR (300 MHz, CDCl 3): d =2.53 (t, J =2.4 Hz, 3 H), 5.04 (d,J =2.4 Hz, 6 H).

13C NMR (75 MHz, CDCl 3): d =58.8 (CH 2), 75.8 (CH), 76.8 (C),172.3 (CO).

Anal. Calcd for C 12H 9N 3O 3: C, 59.26; H, 3.73; N, 17.28. Found: C,59.43; H, 3.58; N, 17.44.

2,4,6-Tris(3-oxahexa-5-ynyloxy)-1,3,5-triazine (2b)

Following the general procedure with purification by column chro-matography (silica gel, Et 2O–acetone–hexane, 4:1:1); white solid (63%); mp 96–97 °C; R f =0.35 (Et 2O–acetone–hexane, 4:1:1).1

H NMR (300 MHz, CDCl 3): d =2.43 (t, J =2.4 Hz, 3 H), 3.86 (t,J =4.8 Hz, 6 H), 4.21 (d, J =2.4 Hz, 6 H), 4.55 (t, J =4.8 Hz, 6 H).

Scheme 5

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C NMR (75 MHz, CDCl 3): d =58.4 (CH 2), 67.1, 67.2 (CH 2CH 2),74.8 (CH), 79.1 (C), 172.8 (CO).MS (ESI): m /z =376.1 [M + H]+.

Anal. Calcd for C 18H 21N 3O 6: C, 57.59; H, 5.64; N, 11.19. Found: C,57.37; H, 5.48; N, 11.35.

2,4,6-Tris(3,6-dioxanona-8-ynyloxy)-1,3,5-triazine (2c)

Following the general procedure with purification by column chro-matography (silica gel, Et 2O–acetone–hexane, 4:1:1); colorless liq-uid (63%); R f =0.35 (Et 2O–acetone–hexane, 4:1:1).

H NMR (300 MHz, CDCl 3): d =2.40 (t, J =2.4 Hz, 3 H), 3.65–3.67 (m, 12 H), 3.78–3.81 (m, 6 H), 4.16 (d, J =2.4 Hz, 6 H), 4.48–4.52 (m, 6 H).

13C NMR (75 MHz, CDCl 3): d =58.3 (CH 2), 67.3, 68.7, 68.9, 70.4(CH 2CH 2), 74.5 (CH), 79.4 (C), 172.8 (CO).

MS (ESI): m /z =508.2 [M + H]+.

Anal. Calcd for C 24H 33N 3O 9: C, 56.80; H, 6.55; N, 8.28. Found: C,56.96; H, 6.78; N, 8.19.

2,4,6-Tris(3,6,9-trioxadodeca-11-ynyloxy)-1,3,5-triazine (2d) Following the general procedure with purification by column chro-matography (silica gel, Et 2O–acetone–hexane, 4:1:1); colorless liq-uid (57%); R f =0.3 (Et 2O–acetone–hexane, 4:1:1).

H NMR (300 MHz, CDCl 3): d =2.42 (t, J =2.4 Hz, 3 H), 3.65–3.66 (m, 24 H), 3.76–3.82 (m, 6 H), 4.17 (d, J =2.4 Hz, 6 H), 4.49–4.52 (m, 6 H).

13C NMR (75 MHz, CDCl 3): d =58.3 (CH 2), 67.4, 68.8, 69.0, 70.4,70.5, 70.6 (CH 2CH 2), 74.4 (CH), 79.4 (C), 172.9 (C–O).

MS (ESI): m /z =640.3 [M + H]+, 662.3 [M + Na]+.

Anal. Calcd for C 30H 45N 3O 12: C, 56.33; H, 7.09; N, 6.57. Found: C,56.51; H, 6.98; N, 6.76.

2,4,6-Tris(3,6,9,12-tetraoxapentadec-14-ynyloxy)-1,3,5-triaz-ine (2e)

Following the general procedure with purification by column chro-matography (silica gel, Et 2O–acetone–hexane, 4:1:1); colorless liq-uid (55%); R f =0.35 (Et 2O–acetone–hexane, 4:1:1).

H NMR (300 MHz, CDCl 3): d =2.42 (t, J =2.4 Hz, 3 H), 3.64–3.67 (m, 36 H), 3.80–3.83 (m, 6 H), 4.18 (d, J =2.4 Hz, 6 H), 4.49–4.53 (m, 6 H).

13C NMR (75 MHz, CDCl 3): d =58.3 (CH 2), 67.4, 68.8, 69.1, 70.3,70.5 (3 C) (CH 2CH 2), 70.6 (CH 2), 74.4 (CH), 79.6 (C), 172.9 (CO).

MS (ESI): m /z =772.3 [M + H]+, 794.3 [M + Na]+.

Anal. Calcd for C 36H 57N 3O 15: C, 56.02; H, 7.44; N, 5.74. Found: C,55.88; H, 7.59; N, 5.57.

Isocyanurate Podands 3; General Procedure

Derivatives 2b –d (0.66 mmol) and Bu 4NBr (53 mg, 0.2 mmol) or Bu 4PBr (67.8 mg, 0.2 mmol) were stirred at 125 °C for 48 h. The mixture was extracted with CH 2Cl 2 and, after washing with H 2O,the organic layer was concentrated.

1,3,5-Tris(3-oxahexa-5-ynyl)-1,3,5-triazinane-2,4,6-trione (3b)Following the general procedure with purification by column chro-matography (silica gel, pentane–EtOAc, 1:2); colorless liquid (20%); R f =0.4 (EtOAc–pentane, 1:2).

H NMR (300 MHz, CDCl 3): d =2.42 (t, J =2.4 Hz, 3 H), 3.78 (t,J =5.4 Hz, 6 H), 4.13 (t, J =5.4 Hz, 6 H), 4.16 (d, J =2.1 Hz, 6 H).

13C NMR (75 MHz, CDCl 3): d =41.7 (NCH 2), 57.8 (OCH 2), 65.9(OCH 2), 74.7 (CH), 79.2 (C), 148.9 (C=O).

MS (APCI): m /z =376.3 [M + H]+.

Anal. Calcd for C 18H 21N 3O 6: C, 57.59; H, 5.64; N, 11.19. Found: C,57.80; H,5.41; N, 11.03.

1,3,5-Tris(3,6-dioxanona-8-ynyl)-1,3,5-triazinane-2,4,6-trione (3c)

Following the general procedure with purification by column chro-matography (silica gel, pentane–EtOAc, 1:1); yellow liquid (33%);R f =0.64 (EtOAc–pentane, 1:1).

H NMR (300 MHz, CDCl 3): d =2.42 (t, J =2.4 Hz, 3 H), 3.68 (m,12 H), 3.71 (t, J =4.5 Hz, 6 H), 4.10 (t, J =4.5 Hz, 6 H), 4.17 (d,J =2.1 Hz, 6 H).

13C NMR (75 MHz, CDCl 3): d =41.6 (NCH 2), 58.3 (OCH 2), 67.4(OCH 2), 69.0, 69.8 (CH 2CH 2), 74.5 (CH), 79.6 (C), 149.0 (C=O).

MS (ESI): m /z =508.4[M +H ]+, 530.4 [M + Na]+, 546.3 [M + K]+.Anal. Calcd for C 24H 33N 3O 9: C, 56.80; H, 6.55; N, 8.28. Found: C,56.65; H, 6.81; N, 8.39.

1,3,5-Tris(3,6,9-trioxadodeca-11-ynyl)-1,3,5-triazinane-2,4,6-trione (3d)

Following the general procedure with purification by column chro-matography (silica gel, pentane–EtOAc, 1:1); yellow liquid (20%);R f =0.5 (EtOAc–pentane, 1:1).

H NMR (300 MHz, CDCl 3): d =2.43 (t, J =2.4 Hz, 3 H), 3.61–6.71 (m, 30 H), 4.09 (t, J =4.5 Hz, 6 H), 4.19 (d, J =2.4 Hz, 6 H).13C NMR (75 MHz, CDCl 3): d =41.6 (NCH 2), 58.4 (OCH 2), 67.4,69.1, 69.9, 70.4, 70.6 (CH 2CH 2), 74.5 (CH), 149.0 (C=O).MS (ESI): m /z =640.4 [M + H]+.

Anal. Calcd for C 30H 45N 3O 12: C, 56.33; H, 7.09; N, 6.57. Found: C,56.29; H, 7.21; N, 6.51.

Chloroalkynes 4; General Procedure

Chloropoly(ethoxy)ethanol (20 mmol) was added dropwise to a soln of 95% NaH (0.97 g, 40 mmol) in anhyd THF (50 mL) at –20°C under an argon atmosphere. After 15 min at –78 °C, 80% prop-argyl bromide soln (2.97 g, 20 mmol) was added dropwise and the mixture was refluxed for 2 h. The mixture was concentrated by evaporation in vacuo, washed with H 2O (50 mL), and extracted with CH 2Cl 2. The organic layer was dried (Na 2SO 4) and concentrated and the resulting residue was purified by chromatography (silica gel, pentane–Et 2O, 4:1).

1-Chloro-3,6-dioxanona-8-yne (4c)

Following the general procedure; colorless liquid (70%); R f =0.56(pentane–Et 2O, 4:1).

1H NMR (300 MHz, CDCl 3): d =2.43 (t, J =2.1 Hz, 1 H), 3.61–3.77 (m, 8 H), 4.20 (d, J =2.4 Hz, 2 H).

13C NMR (75 MHz, CDCl 3): d =42.3 (ClC), 57.1 (OC), 68.5, 69.9,70.8 (CH 2CH 2), 74.3 (CH), 78.1 (C).

Anal. Calcd for C 7H 11ClO 2: C, 51.70; H, 6.82; Cl, 21.80. Found: C,51.98; H, 6.74; Cl, 21.93.

Iodoalkynes 5; General Procedure

Chloroalkynes 4b –d (17 mmol) and anhyd NaI powder (10.2 g, 68mmol) were refluxed in anhyd acetone (170 mL) for 48–68 h. The solvent was removed and the crude mixture was washed with H 2O and extracted with CH 2Cl 2. The organic layer was dried (Na 2SO 4)and the solvent removed under reduced pressure. The products were purified by chromatography (silica gel, pentane–Et 2O, 4:1).1-Iodo-3,6-dioxanona-8-yne (5c)

Following the general procedure; brown liquid (60%); R f =0.5(pentane–Et 2O, 4:1).

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H NMR (300 MHz, CDCl 3): d =2.42 (t, J =2.1 Hz, 1 H), 3.27 (t,J =6.9 Hz, 2 H), 3.65–3.76 (m, 6 H), 4.19 (d, J =2.4 Hz, 2 H).

13C NMR (75 MH z, CDCl 3): d =2.7 (ICH 2), 58.2 (OCH 2), 68.8,69.7, 71.7 (CH 2CH 2), 74.5 (CH), 79.3 (C).

Anal. Calcd for C 7H 11IO 2: C, 33.09; H, 4.36; I, 49.95. Found: C,33.27; H, 4.29; I, 50.11.

1-Iodo-3,6,9-trioxadodec-11-yne (5d)

Following the general procedure; brown liquid (79%); R f =0.38(pentane–Et 2O, 4:1).

H NMR (300 MHz, CDCl 3): d =2.42 (t, J =2.1 Hz, 1 H), 3.24 (t,J =6.6 Hz, 2 H), 3.64–3.76 (m, 10 H), 4.19 (d, J =2.4 Hz, 2 H).

13C NMR (75 MH z, CDCl 3): d =2.8 (ICH 2), 58.1 (OCH 2), 68.8,69.9, 70.2, 70.3, 71.6 (CH 2CH 2), 74.4 (CH), 79.4 (C).

Anal. Calcd for C 9H 15IO 3: C, 36.26; H, 5.07; I, 42.57. Found: C,36.61; H, 4.88; I, 42.69.

3-(Prop-2-ynyl)oxazolidin-2-one (7)

NaH 95% (1.72 g, 8.4 mmol) was slowly added to a soln of 1,3,5-tris(2-hydroxyethyl)cyanuric acid (6 g, 22.8 mmol) in anhyd DMSO (50 mL) under an argon atmosphere and cooling with ice,without freezing the solvent. The mixture was stirred at r.t. for 1 h and then 80% propargyl bromide in toluene (10.17 g, 68.4 mmol)was added dropwise at 35–40 °C and the mixture was stirred for 2h. The mixture was washed with H 2O (3×50 mL) and extracted with CH 2Cl 2. The organic layer was concentrated and the crude product was purified by column chromatography (silica gel,EtOAc–pentane, 1:2). The first collected fraction was compound 3b , colorless liquid (20%), R f =0.40 (EtOAc–pentane, 1:2), fol-lowed by compound 7, colorless liquid (31%), R f =0.30 (EtOAc–pentane, 1:2).

H NMR (300 MHz, CDCl 3): d =2.30 (t, J =2.4 Hz, 1 H), 3.62–3.89 (m, 2 H), 4.07 (d, J =2.4 Hz, 2 H), 4.33–4.38 (m, 2 H).

13C NMR (75 MHz, CDCl 3): d =34.0 (NCH 2), 43.8 (NCH 2), 61.9(OCH 2), 73.3 (CH), 76.81 (C), 157.8 (C=O).

Anal. Calcd for C 6H 7NO 2: C, 57.59; H, 5.64; N, 11.19. Found: C,57.77; H, 5.44; N,11.35.

Bromination Reaction; General Procedure

NBS (34.6 mmol) and AgNO 3 (4.9 mmol) were added to a soln of cyanurates 2 (3.3 mmol) or isocyanurates 3 (3.3 mmol) in degassed acetone (75 mL) under stirring at r.t. under an argon atmosphere.The mixture was stirred at r.t. overnight, extracted with CH 2Cl 2, and washed with brine. The oily crude product was purified by column chromatography (silica gel, toluene–acetone).

2,4,6-Tris(3-bromoprop-2-ynyloxy)-1,3,5-triazine (8a)

Following the general procedure with purification by column chro-matography (silica gel, toluene–acetone, 20:1); white solid (36%);mp 94–95 °C; R f =0.7 (toluene–acetone, 20:1).

H NMR (300 MHz, CDCl 3): d =5.05 (s, 6 H).

C NMR (75 MHz, CDCl 3): d =48.5 (CBr), 56.7 (CH 2), 73.3 (C),172.3 (CO).

MS (ESI): m /z (%)=477.9 (33), 479.9 (100), 481.8 (99), 483.8 (35)([M + H]+).

Anal. Calcd for C 12H 6Br 3N 3O 3: C, 30.03; H , 1.26; Br, 49.95; N,8.76. Found: C, 30.27; H, 1.42; Br, 50.15; N, 8.64.

2,4,6-Tris(6-bromo-3-oxahexa-5-ynyloxy)-1,3,5-triazine (8b)Following the general procedure with purification by column chro-matography (silica gel, toluene–acetone, 9:1); white solid (36%);mp 103–105 °C; R f =0.7 (toluene–acetone, 9:1).

H NMR (300 MHz, CDCl 3): d =3.86 (t, J =3.6 Hz, 6 H), 4.25 (s,6 H), 4.56 (t, J =3.6 Hz, 6 H).

C NMR (75 MH z, CDCl 3): d =46.6 (CBr), 59.4 (OCH 2), 67.1,67.4 (CH 2CH 2), 75.8 (C), 172.9 (CO).

MS (ESI): m /z (%)=610.0 (42), 612.0 (100), 614.0 (91), 616.0 (31)([M + H]+), 631.9 (19), 633.9 (53), 635.9 (54), 637.9 (18) ([M +Na]+).

Anal. Calcd for C 18H 18Br 3N 3O 6: C, 35.32; H, 2.96; Br, 39.16; N,6.87. Found: C, 35.17; H, 3.08; Br, 39.39; N, 6.93.

2,4,6-Tris(9-bromo-3,6-dioxanona-8-ynyloxy)-1,3,5-triazine (8c)

Following the general procedure with purification by column chro-matography (silica gel, toluene–acetone, 4:1); colorless liquid (20%); R f =0.31 (toluene–acetone, 4:1).

1H NMR (300 MHz, CDCl 3): d =3.68–3.71 (m, 12 H), 3.82–3.84(m, 6 H), 4.22 (s, 6 H), 4.53–4.55 (m, 6 H).

13C NMR (75 MH z, CDCl 3): d =46.1 (CBr), 59.4 (OCH 2), 67.4,68.8, 69.2, 70.5 (CH 2CH 2), 76.1 (C), 172.9 (CO).

MS (ESI): m /z (%)=742.1 (35), 744.0 (100), 746.0 (90), 747.9 (31)([M + H]+), 763.9 (6), 765.9 (10), 767.9 (11), 770.0 (3) [M + Na]+.Anal. Calcd for C 24H 30Br 3N 3O 9: C, 38.73; H, 4.06; Br, 32.21; N,5.65. Found: C, 38.55; H, 4.19; Br, 32.34; N, 5.49.

1,3,5-Tris(3-bromoprop-2-ynyl)-1,3,5-triazinane-2,4,6-trione (9a)

Following the general procedure with purification by column chro-matography (silica gel, toluene–acetone, 9:1); white solid (45%);mp 79–81 °C; R f =0.6 (toluene–acetone, 9:1).

1H NMR (300 MHz, CDCl 3): d =4.70 (s, 6 H).

C NMR (75 MHz, CDCl 3): d =33.5 (NCH 2), 44.8 (CBr), 72.8 (C),147.1 (C=O).

MS (ESI): m /z (%)=477.9 (29), 479.9 (100), 482.0 (95), 483.9 (27)[M + H]+.

Anal. Calcd for C 12H 6Br 3N 3O 3: C, 30.03; H , 1.26; Br, 49.95; N,8.76. Found: C, 30.16; H, 1.34; Br, 49.77; N, 8.81.

1,3,5-Tris(6-bromo-3-oxahexa-5-ynyl)-1,3,5-triazinane-2,4,6-trione (9b)

Following the general procedure with purification by column chro-matography (silica gel, toluene–acetone, 4:1); white solid (73%);R f =0.56 (toluene–acetone, 4:1).

H NMR (300 MHz, CDCl 3): d =3.77 (t, J =4.2 Hz, 6 H), 4.13 (t,J =4.2 Hz, 6 H), 4.20 (s, 6 H).

13C NMR (75 MH z, CDCl 3): d =41.8 (NCH 2), 46.3 (CBr), 58.9(OCH 2), 66.1 (CH 2), 75.9 (C), 148.9 (C=O).

MS (ESI): m /z (%)=610.0 (37), 611.9 (96), 613.9 (100), 615.9 (34)([M + H]+).

Anal. Calcd for C 18H 18Br 3N 3O 6: C, 35.32; H, 2.96; Br, 39.16; N,6.87. Found: C, 35.40; H, 3.09; Br, 39.02; N, 6.73.

Acknowledgment

We are grateful to Professor Jürgen Liebscher from Humboldt Uni-versity, Berlin for fruitful discussions. We acknowledge the finan-cial support of this work by PNCDI II program (UEFISCSU;projects IDEAS 570/2007 and 2358/2008 and TD82).

1644 F. Piron et al.PAPER

Synthesis 2010, No. 10, 1639–1644? Thieme Stuttgart ·New York

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