NH4SCN

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Chinese Chemical Letters 23 (2012) 77–80 www.elsevier.com/locate/cclet

Phosphine-free conversion of alcohols into alkyl thiocyanates using trichloroisocyanuric acid/NH4SCN Roya Azadi *, Babak Mokhtari, Mohamad-Ali Makaremi Department of Chemistry, College of Science, Shahid Chamran University, Ahvaz 61357-43337, Iran Received 13 July 2011 Available online 8 November 2011

Abstract A convenient and efficient phosphine-free procedure for the one-pot conversion of primary, secondary and tertiary alcohols into the corresponding alkyl thiocyanates or alkyl isothiocyanates is described using trichloroisocyanuric acid/NH4SCN. # 2011 Roya Azadi. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. Keywords: Phosphine-free; Alcohol; Thiocyanate; Trichloroisocyanuric acid; Thiocyanation

Trichloroisocyanuric acid [1,3,5-trichoro-1,3,5-triazine-2,4,6-(1H,3H,5H)-trione or TCCA] belongs to the large group of N-chloroimides and amides which is a subgroup of the more general N-chloroamines [1]. This reagent has been previously applied for organic transformation include chlorination of alkenes [2], ketones [3], sulfides [4], cyclic ethers [5], N-heterocycles [6], and alcohols [7]; conversion of carboxylic acids to amides or esters [8]; dehydrogenation of amines [9]; oxidation of ethers [10], thioethers [11], aldehydes [12], acetals, [13] alcohols [14], and hydroxylamines [15]. Alkyl thiocyanate constitutes an important class of organic compounds which have been widely used in biology, synthetic and polymer chemistry. Due to such biological, medicinal and industrial importance, the preparation of alkyl thiocyanates has received considerable attention in the literature [16]. The general method employed for their preparation include using alkyl halides (or tosylates) and alcohols as alkylating agents. Despite the simplicity of conversion of alkyl halides into alkyl thiocyanates, the conversion of alcohols into alkyl thiocyanates is more difficult and requires in situ activation of the hydroxyl group of alcohol toward nucleophilic substitution using phosphine-based reagents. These reagents include Ph3P(SCN)2 [17], Ph3P(Br)2/NH4SCN [18], trichloroisocyanuric acid/PPh3/NaSCN [19], Ph3P/diethylazo dicarboxylate/NH4SCN [20], Ph3P/dichlorodicyanoquinone/Bu4NSCN [21], diphenylphosphinite ionic liquid (IL-OPPh2)/Br2/NH4SCN [22]. One of the major disadvantages often encountered with these systems is the difficulty of removing by-products, in particular, phosphine oxides. In continuation of our ongoing program to develop new reagents and synthetic procedures for the thiocyanation of alcohols [23,24], we report here, a new, mild and efficient phosphine-free procedure for the one-pot conversion of primary, secondary and tertiary alcohols into their corresponding alkyl thiocyanates or alkyl isothiocyanates using TCCA/NH4SCN in acetonitrile at room temperature (Scheme 1).

* Corresponding authors. E-mail addresses: [email protected] (R. Azadi), [email protected] (B. Mokhtari). 1001-8417/$ – see front matter # 2011 Roya Azadi. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. doi:10.1016/j.cclet.2011.09.022

78

R. Azadi et al. / Chinese Chemical Letters 23 (2012) 77–80 O Cl O

ROH

N

N N Cl

Cl O

+ NH4SCN

CH3CN, r. t.

RSCN if R = 1o and 2o alkyl RNCS if R = 3o alkyl

Scheme 1. Conversion of alcohols into alkyl thiocyanates or isothiocyanates.

Table 1 Optimized conditions for thiocyanation of 1 mmol of benzyl alcohol with 1 mmol of TCCA and different amounts of NH4SCN in acetonitrile. Entry

Molar ratio of TCCA/NH4SCN

Time (h)

T (8C)

Conversion (%) a

1 2 3 4

1:2 1:3 1:4 1:5

24 15 8 1.5

rt rt rt rt

40 80 100 100

a

Isolated yield.

In order to optimize the reaction conditions, the benzyl alcohol was selected as a model compound and the reaction of 1 mmol of it with 1 mmol of TCCA and different amounts of NH4SCN (2–5 mmol) was studied in detail. The results are summarized in Table 1. As clear from Table 1 the best results obtained when reaction was performed at molar ratio is 1:1:5 for benzyl alcohol/TCCA/NH4SCN respectively (Table 1, entry 4). In addition, the order of reagent addition is very important and the alcohol must be added after the precipitation of NH4Cl resulted from the reaction between TCCA and NH4SCN. Simultaneous addition of reagents dramatically lowered the yield of thiocyanation reaction and increased the oxidation product. Having optimized conditions in hand, structurally diverse alcohols were subjected to this reaction and the results are shown in Table 2. As it is demonstrated in Table 2, benzylic alcohols either carrying electron-withdrawing or electron-donating groups are successfully converted to their corresponding alkyl thiocyanates (Table 2, entries 2–6). In the case of pmethoxybenzyl alcohol carrying an electron-donating group, the reaction occurs rapidly (1 h) (Table 2, entry 2) while the presence of electron-withdrawing groups such as –Cl or –NO2 in the substrates increases the reaction time (Table 2, entries 3–6). 1-Octanol and 2-octanol are converted into their corresponding alkyl thiocyanates with this reagent in

Table 2 Conversion of alcohols into alkyl thiocyanates or isothiocyanates with TCCA and NH4SCN in acetonitrile at room temperature. Entry

Alcohol

Time (h)

RSCN/RNCS (%)a

Yield (%) b

Refd

1 2 3 4 5 6 7 8 9 10 11 12 13 14

Benzyl alcohol 4-Methoxy benzyl alcohol 4-Nitro benzyl alcohol 4-Chloro benzyl alcohol 2-Nitro benzyl alcohol 2-Chloro benzyl alcohol 2-Phenyl ethanol 1-Octanol 2-Octanol Cyclohexanol 1-Phenyl ethanol Diphenylmethanol Dimethyl phenyl methanol Triphenylcarbinol

1.5 1 12 12 12 12 8 7 8 10 8 12 10 10

100/0 100/0 100/0 100/0 100/0 100/0 100/0 100/0 100/0 100/0 100/0 84/16 10/90 0/100

95 90 50 57 45 52 95 92 80 82 83 72 c 75 c 60

18 18 20 18 23 23 17 21 21 17 17 20 20 24

a b c d

NMR yield. Isolated pure product. A mixture of thiocyanate and isothiocyanate was obtained. All the products are known compounds and were identified by comparison of their physical and spectral data with those of authentic samples.

R. Azadi et al. / Chinese Chemical Letters 23 (2012) 77–80

O

O

N

O N

Cl

NH4SCN

O

N Cl

-NH4Cl

SCN or Cl

N

O

N

SCN

:

Cl

79

ROH

N O Cl or SCN I

O NCS ro Cl O

N

NH O N Cl or SCN

+

ROSCN

NH4SCN

RSCN if R = 1o, 2o alkyl RNCS if R = 3o alkyl

Scheme 2. Suggested mechanism for the formation of alkyl thiocyanates and isothiocyanates.

high yields (Table 2, entries 8 and 9). As a model compound for tertiary alcohols, dimethyl phenyl methanol (1 mmol) was subjected to TCCA and NH4SCN in acetonitrile at room temperature. The obtained result is 75% yield of alkyl isothiocyanate as a major product after 10 h (Table 2, entry 13). Furthermore, the reaction of trityl alcohol (Table 2, entry 14) with this reagent gave only triphenyl methyl isothiocyanates which can be attributed to the high stability of its carbocation. Based on these results and previous report [24], the following mechanism was suggested for this reaction (Scheme 2). Nucleophilic attack of the alcohol on the sulfur of thiocyanated TCCA (I) produces ROSCN which in the presence of NH4SCN can produce the desired alkyl thiocyanate or alkyl isothiocyanate by nucleophilic substitution. In the case of primary alcohols, mechanism of the last step is SN2 and thiocyanate ion attack from softer sulfur atom into ROSCN and for tertiary alcohols, its mechanism is SN1 and SCN attack by the harder nitrogen terminus and alkyl isothiocyanate was formed as a major product. Systematic studies on alkylation of thiocyanate ions had shown that attack at the sulfur atom is approximately 102–103 times faster than at the nitrogen atom in SN2-type reactions, while the S/N ratio decreased in SN1-type reactions [25]. In summary, the present investigation has demonstrated that the use of trichloroisocyanuric acid with ammonium thiocyanate offers a simple, novel, and convenient method for the one-pot conversion of primary, secondary and tertiary alcohols into corresponding alkyl thiocyanates or isothiocyanates. Typical procedure for the conversion of benzyl alcohol into benzyl thiocyanate: To a flask containing TCCA (0.232 g, 1 mmol) was added CH3CN (5–7 mL) followed by NH4SCN (0.38 g, 5 mmol) at room temperature. The reaction mixture was left to stir for 30 min to form a white solid. Then benzyl alcohol (0.1 mL, 1 mmol) was added into the reaction mixture. TLC of the reaction mixture showed the completion of the reaction after 30 min. After evaporation of acetonitrile, water was added to flask and benzyl thiocyanate was extracted with diethyl ether (3  5 mL). Evaporation of the ether and chromatography on a short silica gel column using n-hexane/ethyl acetate (5/ 1) as eluent gave benzyl thiocyanate in 95% yield. IR (–SCN) in CCl4 2150 cm 1; 1H NMR (400 MHz, CDCl3): d 4.12 (2H, s), 7.33–7.47 (5H, m); 13C NMR (100 MHz, CDCl3): d 135.22, 133.60, 129.70, 129.45, 111.35, 38.70. Acknowledgment We thank Shahid Chamran University Research Council, Ahvaz, for financial support of this investigation. References [1] U. Tilstam, H. Weinmann, Org. Process Res. Dev. 6 (2002) 384. [2] (a) K. Ziegler, A. Spa¨th, E. Schaaf, W. Schumann, E. Winkelmann, Anal. Chem. 551 (1942) 80; (b) A.J. Mura Jr., D.A. Bennett, T. Cohen, Tetrahedron Lett. 50 (1975) 4433. [3] H. Suzuki, Japanese Patent 09067359 A2, Chem. Abstr. 126 (1997) 277382. [4] L. Muthusubramanian, R.B. Mitra, V.S.S. Rao, K.V. Raghavan, Indian J. Chem. Sect. B 35 (1996) 1331. [5] E.C. Juenge, P.L. Spangler, W.P. Duncan, J. Org. Chem. 31 (1966) 3836.

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