WO2016113764A1 - One step process for the synthesis of azido alcohols from alkene - Google Patents

One step process for the synthesis of azido alcohols from alkene Download PDF

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WO2016113764A1
WO2016113764A1 PCT/IN2016/050020 IN2016050020W WO2016113764A1 WO 2016113764 A1 WO2016113764 A1 WO 2016113764A1 IN 2016050020 W IN2016050020 W IN 2016050020W WO 2016113764 A1 WO2016113764 A1 WO 2016113764A1
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azido
methoxyphenyl
temperature ranging
nmr
afford
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PCT/IN2016/050020
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French (fr)
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WO2016113764A4 (en
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Arumugam Sudalai
Pragati Kishore PRASAD
Rambabu REDDI
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Council Of Scientific & Industrial Research
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C247/00—Compounds containing azido groups
    • C07C247/02—Compounds containing azido groups with azido groups bound to acyclic carbon atoms of a carbon skeleton
    • C07C247/08—Compounds containing azido groups with azido groups bound to acyclic carbon atoms of a carbon skeleton being unsaturated
    • C07C247/10—Compounds containing azido groups with azido groups bound to acyclic carbon atoms of a carbon skeleton being unsaturated and containing rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C247/00—Compounds containing azido groups
    • C07C247/02—Compounds containing azido groups with azido groups bound to acyclic carbon atoms of a carbon skeleton
    • C07C247/04—Compounds containing azido groups with azido groups bound to acyclic carbon atoms of a carbon skeleton being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C247/00—Compounds containing azido groups
    • C07C247/14—Compounds containing azido groups with azido groups bound to carbon atoms of rings other than six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane

Definitions

  • the present invention relates to one step room temperature process for the synthesis of 1,2-azido alcohols from alkenes. More particularly, I 2 catalysed a regio and diastereo selective one step room temperature process for the synthesis of 1,2- azido alcohols from alkenes.
  • 1,2-Azido alcohols have been widely employed in organic synthesis for the regioselective preparation of 1,2-amino alcohols and highly oxygenated compounds such as carbohydrates and nucleosides. They are also useful intermediates for the preparation of several target compounds such as triazoles, triazole-fused dihydrooxazinones, 2-oxazolidinones, 1,4-oxazepines and 1,3-oxazines, oxazaborolidines, 1,3-oxazolidines, and in the chemistry of peptidomimetics and pseudopeptides. Selective olefin difunctionalization with an azido and an oxygen based group is an important transformation for organic synthesis because vicinal azido alcohol derivatives are widely present in synthetically valuable molecules.
  • Ring-opening of oxiranes with phenoxides or sodium azide is investigated under different reaction conditions affording nonracemic 1,2-hydroxy ethers and 1,2-azido alcohols with excellent enantioselectivity (99% ee) and in good to high chemical yield.
  • the main objective of the present invention is to provide one step room temperature process for the synthesis of 1,2-azido alcohols from alkenes with high regioselectivity as well as diastereoselectivity.
  • Another objective of the present invention is to provide metal free process for the synthesis of 1,2-azido alcohols from alkenes.
  • Still another objective of the present invention is to provide high yield process for the synthesis of 1,2-azido alcohols from alkenes.
  • the present invention provides one step room temperature process for the synthesis of 1,2-azido alcohol from alkenes including the steps: (a) adding halogen source to a stirred solution of alkene substrate in a solvent system followed by addition of co-oxidant at 0°C to -5°C; (b) adding base to reaction mixture of step (a) followed by addition of azide source at a temperature ranging between 0°C to -5°C; (c) stirring the reaction mixture of step (b) at a temperature ranging between 25 to 30°C for 8-12 hours to afford 1 ,2-azidoalcohols .
  • the present invention provides I 2 catalysed a regio and diastereo selective one step room temperature process for the synthesis of 1,2-azido alcohol from alkenes.
  • I 2 catalysed a regio and diastereo selective one step room temperature process for the synthesis of azido alcohols from alkenes comprising treating alkenes with azide source in presence of base in a solvent system with the use of a co-oxidant to afford azido alcohol.
  • said azide source is sodium azide.
  • said base may be selected from triethylamine (Et 3 N), potassium carbonate (K 2 C0 3 ), potassium tert-butoxide (K'OBu), sodium hydride (NaH), l,8-diazabicycloundec-7-ene (DBU).
  • Et 3 N triethylamine
  • K 2 C0 3 potassium carbonate
  • K'OBu potassium tert-butoxide
  • NaH sodium hydride
  • DBU l,8-diazabicycloundec-7-ene
  • said suitable solvents may be selected from water, acetonitrile, ethylacetate and Ci to C 3 alcohols, dimethylsulfoxide (DMSO), dimethyl formamide (DMF), acetone, dioxane, tetrahydrofuran (THF), N,N-dimethylacetamide (DMA) or combinations thereof.
  • said solvent system that works effectively for the process of invention comprises DMSO and DMF in a ratio of 1 : 1.
  • said co-oxidant may be selected from anhydrous tert-butyl hydroperoxide (TBHP) or 30%-50% aq. H 2 0 2 .
  • TBHP tert-butyl hydroperoxide
  • said alkenes may be selected from the group consisting of mono, di or tri substituted alkenes.
  • Iodine source is selected from Iodine solution, tetra-n-butylammonium iodide, sodium iodide, potassium iodide.
  • the present disclosure also relates to a process for preparation of chloramphenicol from 1 ,2-azidoalcohol comprising the steps of: (a) adding 20% palladium hydroxide on carbon to a stirred solution of azidoalcohol in methanol under H2 atmosphere at a temperature ranging between 25 °C to afford aminodiol; (b) adding methyl dichloroacetate into aminodiol of step (a) and heating the solution at a temperature ranging between around 90°C for 1 hour to afford crude product; (c) adding crude product of step (b) into nitrating mixture at a temperature ranging between around -20°C; (d) stirring the solution of step c at a temperature of 0°C for 1 hour to afford chloramphenicol.
  • said 1,2-azidoalcohol is Syn-2-azido-l- phenylpropane- 1 ,3-diol.
  • said nitrating mixture of step (c) is mixture of nitric acid and sulphuric acid.(conc. HN0 3 : cone. H 2 S0 4 (1: 1)).
  • the present discosure also relates to a process for preparation of tert-butyl anti- 2,3-dihydroxy- 1 -(4-methoxyphenyl)propyl)carbamate from 1 ,2-azidoalchohol comprising the steps of: (a) adding 20% palladium hydroxide on carbon to a stirred solution of azidoalcohol in solvent under H2 atmosphere at a temperature ranging between 25 °C for 12 hours to afford aminodiol; (b) adding Boc anhydride ((Boc)20) and triethyl amine (Et3N) to a stirred solution of step (a) in dicholoromethane and allowing stirring at a temperature ranging from 25 °C for 2 hours to afford tert-butyl anti-2,3-dihydroxy- 1 -(4-methoxyphenyl)propyl)carbamate.
  • said 1 ,2-azidoalcohol is 3-
  • the present discosure also relates to a process for preparation of (4R,5R)-5- (hydroxymethyl)-4-(4-methoxyphenyl) oxazolidin-2-one from Terttert-butyl anti-2,3- dihydroxy- 1 -(4-methoxyphenyl)propyl)carbamate comprising adding sodium hydride to a solution of Terttert-butyl anti-2,3-dihydroxy-l-(4- methoxyphenyl)propyl)carbamate in dry THF under nitrogen temperature at a temperature ranging from 25°C to 30°C, stirring continued for 3-3.5 hours to afford (4R,5R)-5-(hydroxymethyl)-4-(4-methoxyphenyl) oxazolidin-2-one.
  • the present invention provides one step room temperature process for the synthesis of 1,2-azido alcohol from alkenes.
  • the present invention provides I 2 catalysed a regio and diastereo selective one step room temperature process for the synthesis of 1,2-azido alcohol from alkenes.
  • I 2 catalysed a regio and diastereo selective one step room temperature process for the synthesis of 1,2-azido alcohol from alkenes comprising treating alkenes with azide source in presence of base in a solvent system with the use of a co-oxidant to afford 1,2-azido alcohol.
  • said azide source is sodium azide.
  • said base may be selected from triethylamine (Et 3 N), potassium carbonate (K 2 CO 3 ), potassium tert-butoxideCK'OBu), sodium hydride (NaH), l,8-diazabicycloundec-7-ene (DBU).
  • said suitable solvents may be selected from water, acetonitrile, ethylacetate and Ci to C 3 alcohols, dimethylsulfoxide (DMSO), dimethyl formamide (DMF), acetone, dioxane, tetrahydrofuran (THF), N,N-dimethylacetamide (DMA) or combinations thereof.
  • DMSO dimethylsulfoxide
  • DMF dimethyl formamide
  • THF tetrahydrofuran
  • DMA N,N-dimethylacetamide
  • said solvent system that works effectively for the process of invention comprises DMSO and DMF in a ratio of 1 : 1.
  • said co-oxidant may be selected from anhydrous tert-butyl hydroperoxide (TBHP) or 30% -50% aq. 3 ⁇ 4(3 ⁇ 4 at ambient temperature.
  • TBHP tert-butyl hydroperoxide
  • the ambient temperature for the purpose of the invention is 25 °C to 35 °C.
  • said alkenes are selected from the group consisting of mono, di or tri substituted alkenes.
  • Iodine source is selected from Iodine solution, tetra-n-butylammonium iodide, sodium iodide, potassium iodide.
  • R Alkyl (linear or alicyclic) , aryl group with various substitutions like alkyl, N0 2 , - Oalkyl, halo, at any position on the armatic ring,
  • R Alkyl (linear or alicyclic) , aryl group with various substitutions like alkyl, N0 2 , - Oalkyl, halo, at any position on the armatic ring, H
  • Novel regio and diastereo 1 ,2-azidoalcohols are included 2-azido-l-(2- bromophenyl)ethan- 1 -ol, 1 -azido-2-phenylpropan-2-ol, 1 -azido-4-(benzyloxy)-2- methylbutan-2-ol, 3-azido-4-(benzyloxy)-2-methylbutan-2-ol, Syn-2-azido-l- phenylpropane- 1 ,3-diol, 2-azido- 1 -(4-methoxyphenyl)propane- 1 ,3-diol, 2-azido-2- phenylethan-l-ol, 2-azido-2-(p-tolyl)ethan-l-ol, 2-azido-2-(2-bromophenyl)ethan-l-ol, 2-azido-2-(3
  • Solvents were purified and dried by standard procedures before use; petroleum ether of boiling range 60-80 °C was used. Melting points are uncorrected and recorded on a

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  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The present invention relates to one step room temperature process for the synthesis of azido alcohols from alkenes. More particularly, I2 catalysed a regio and diastereo selective one step room temperature process for the synthesis of 1,2-azido alcohols from alkenes.

Description

ONE STEP PROCESS FOR THE SYNTHESIS OF AZIDO ALCOHOLS FROM
ALKENE
FIELD OF THE INVENTION:
[001] The present invention relates to one step room temperature process for the synthesis of 1,2-azido alcohols from alkenes. More particularly, I2 catalysed a regio and diastereo selective one step room temperature process for the synthesis of 1,2- azido alcohols from alkenes.
BACKGROUND OF THE INVENTION:
[002] 1,2-Azido alcohols have been widely employed in organic synthesis for the regioselective preparation of 1,2-amino alcohols and highly oxygenated compounds such as carbohydrates and nucleosides. They are also useful intermediates for the preparation of several target compounds such as triazoles, triazole-fused dihydrooxazinones, 2-oxazolidinones, 1,4-oxazepines and 1,3-oxazines, oxazaborolidines, 1,3-oxazolidines, and in the chemistry of peptidomimetics and pseudopeptides. Selective olefin difunctionalization with an azido and an oxygen based group is an important transformation for organic synthesis because vicinal azido alcohol derivatives are widely present in synthetically valuable molecules.
[003] The osmium-based Sharpless aminohydroxylation continues to be a prevalent stereospecific method for olefin amino-oxygenation. This pioneering method has also inspired extensive efforts for the development of alternative approaches to improve upon a broader substrate scope and a better regioselectivity. Among these approaches, non-precious metal catalyzed processes emerge with increasing interests.
[004] Article titled "Stereoselective radical azido oxygenation of alkenes" by Bo Zhang and Armido Studer et al. published in Organic Letter, 2013, 15, pp 4548-4551 reports a readily prepared N3-iodine(III) reagent acts as a clean N3-radical precursor in a radical azido oxygenation of various alkenes in the presence of TEMPONa as a mild organic reducing reagent. The C-radical generated after N3-radical addition is efficiently trapped by in situ generated TEMPO.
[005] Article titled "I2-catalyzed regioselective oxo- and hydroxy-acyloxylation of alkenes and enol ethers: a facile access to a-acyloxyketones, esters, and diol derivatives" by Rambabu N. Reddi et al. published in Organic Letter, 2014, 16 (21), pp 5674-5677 reports I2-catalyzed oxo-acyloxylation of alkenes and enol ethers with carboxylic acids providing for the high yield synthesis of a-acyloxyketones and esters is described. This unprecedented regioselective oxidative process employs TBHP and Et3N in stoichiometric amounts under metal-free conditions in DMSO as solvent. Additionally, I2-catalysis allows the direct hydroxy-acyloxylation of alkenes with the sequential addition of ΒΗ3· SMe2 leading to monoprotected diol derivatives in excellent yields.
[006] Article titled "Efficient catalytic synthesis of optically pure 1,2-azido alcohols through enantioselective epoxide ring opening with HN3" by Santosh Singh Thakur et al. published in Journal of Molecular Catalysis A: Chemical, 2006, 259(1-2), pp 116— 120 reports chiral binuclear Co(salen) complexes bearing Lewis acid of group 13 metal chlorides show very high catalytic activity and enantioselectivity for the ring opening of epoxides using HN3 as azide source. It provides a facile and practical synthetic route to a wide range of chiral nonracemic 1,2-azido alcohols and related compounds in one-pot synthesis with excellent selectivity (92.0-99.6% e.e.) under mild conditions. The presence of Lewis acid of group 13 shows a strong synergistic effect.
[007] Article titled "Chiral epoxides via borane reduction of 2-haloketones catalyzed by spiroborate ester: application to the synthesis of optically pure 1,2-hydroxy ethers and 1,2-azido alcohols" by Kun Huang et al. published in Journal of Organic Chemistry, 2011, 76 (6), pp 1883-1886 reports an enantioselective borane-mediated reduction of a variety of 2-haloketones with 10% spiroaminoborate ester 1 as catalyst is described. By a simple basic workup of 2-halohydrins, optically active epoxides are obtained in high yield and with excellent enantiopurity (up to 99% ee). Ring-opening of oxiranes with phenoxides or sodium azide is investigated under different reaction conditions affording nonracemic 1,2-hydroxy ethers and 1,2-azido alcohols with excellent enantioselectivity (99% ee) and in good to high chemical yield.
[008] Article titled "Nucleophilic ring opening of 1,2-epoxides in aqueous medium" by David Amantini et al. published in ARKIVOC 2002(11) 293-311 reports Nucleophilic ring opening of 1,2-epoxides in aqueous medium in the presence and absence of metal salts is reviewed. Azidolysis, hydrolysis, iodolysis and thiolysis are the reactions mainly investigated. The pH of the reaction medium controls the reactivity and regioselectivity of the process. By working at suitable pH values, even salts such as A1C13, SnCLt and T1CI4 are active catalysts.
[009] Despite these and other excellent discoveries, a direct organocatalytic route for the synthesis of 1,2 azidoalcohols from alkenes is still desirable. Further, it is desirable that the direct route of synthesis provides good selectivity towards regio and diastereo isomers of 1,2-azidoalcohols.
OBJECTIVE OF THE INVENTION:
[010] The main objective of the present invention is to provide one step room temperature process for the synthesis of 1,2-azido alcohols from alkenes with high regioselectivity as well as diastereoselectivity.
[011] Another objective of the present invention is to provide metal free process for the synthesis of 1,2-azido alcohols from alkenes.
[012] Still another objective of the present invention is to provide high yield process for the synthesis of 1,2-azido alcohols from alkenes.
SUMMARY OF THE INVENTION:
[013] Accordingly, the present invention provides one step room temperature process for the synthesis of 1,2-azido alcohol from alkenes including the steps: (a) adding halogen source to a stirred solution of alkene substrate in a solvent system followed by addition of co-oxidant at 0°C to -5°C; (b) adding base to reaction mixture of step (a) followed by addition of azide source at a temperature ranging between 0°C to -5°C; (c) stirring the reaction mixture of step (b) at a temperature ranging between 25 to 30°C for 8-12 hours to afford 1 ,2-azidoalcohols .
[014] More particularly, the present invention provides I2 catalysed a regio and diastereo selective one step room temperature process for the synthesis of 1,2-azido alcohol from alkenes.
[015] In an embodiment, I2 catalysed a regio and diastereo selective one step room temperature process for the synthesis of azido alcohols from alkenes comprising treating alkenes with azide source in presence of base in a solvent system with the use of a co-oxidant to afford azido alcohol.
[016] The above process is shown in scheme 1 below:
90%
Figure imgf000005_0001
Scheme 1
[017] In another embodiment, said azide source is sodium azide.
[018] Still another embodiment, said base may be selected from triethylamine (Et3N), potassium carbonate (K2C03), potassium tert-butoxide (K'OBu), sodium hydride (NaH), l,8-diazabicycloundec-7-ene (DBU).
[019] Yet another embodiment, said suitable solvents may be selected from water, acetonitrile, ethylacetate and Ci to C3 alcohols, dimethylsulfoxide (DMSO), dimethyl formamide (DMF), acetone, dioxane, tetrahydrofuran (THF), N,N-dimethylacetamide (DMA) or combinations thereof. [020] Still yet another embodiment, said solvent system that works effectively for the process of invention comprises DMSO and DMF in a ratio of 1 : 1.
[021] Still yet another embodiment, said co-oxidant may be selected from anhydrous tert-butyl hydroperoxide (TBHP) or 30%-50% aq. H202.
[022] Still yet another embodiment, said alkenes may be selected from the group consisting of mono, di or tri substituted alkenes.
[023] Still yet another embodiment, Iodine source is selected from Iodine solution, tetra-n-butylammonium iodide, sodium iodide, potassium iodide.
[024] The present disclosure also relates to a process for preparation of chloramphenicol from 1 ,2-azidoalcohol comprising the steps of: (a) adding 20% palladium hydroxide on carbon to a stirred solution of azidoalcohol in methanol under H2 atmosphere at a temperature ranging between 25 °C to afford aminodiol; (b) adding methyl dichloroacetate into aminodiol of step (a) and heating the solution at a temperature ranging between around 90°C for 1 hour to afford crude product; (c) adding crude product of step (b) into nitrating mixture at a temperature ranging between around -20°C; (d) stirring the solution of step c at a temperature of 0°C for 1 hour to afford chloramphenicol.
[025] Still yet another embodiment, said 1,2-azidoalcohol is Syn-2-azido-l- phenylpropane- 1 ,3-diol.
[026] Still yet another embodiment, said nitrating mixture of step (c) is mixture of nitric acid and sulphuric acid.(conc. HN03: cone. H2S04 (1: 1)).
[027] The present discosure also relates to a process for preparation of tert-butyl anti- 2,3-dihydroxy- 1 -(4-methoxyphenyl)propyl)carbamate from 1 ,2-azidoalchohol comprising the steps of: (a) adding 20% palladium hydroxide on carbon to a stirred solution of azidoalcohol in solvent under H2 atmosphere at a temperature ranging between 25 °C for 12 hours to afford aminodiol; (b) adding Boc anhydride ((Boc)20) and triethyl amine (Et3N) to a stirred solution of step (a) in dicholoromethane and allowing stirring at a temperature ranging from 25 °C for 2 hours to afford tert-butyl anti-2,3-dihydroxy- 1 -(4-methoxyphenyl)propyl)carbamate. [028] Still yet another embodiment, said 1 ,2-azidoalcohol is 3-azido-3-(4- methoxyphenyl)propane- 1 ,2-diol.
[029] The present discosure also relates to a process for preparation of (4R,5R)-5- (hydroxymethyl)-4-(4-methoxyphenyl) oxazolidin-2-one from Terttert-butyl anti-2,3- dihydroxy- 1 -(4-methoxyphenyl)propyl)carbamate comprising adding sodium hydride to a solution of Terttert-butyl anti-2,3-dihydroxy-l-(4- methoxyphenyl)propyl)carbamate in dry THF under nitrogen temperature at a temperature ranging from 25°C to 30°C, stirring continued for 3-3.5 hours to afford (4R,5R)-5-(hydroxymethyl)-4-(4-methoxyphenyl) oxazolidin-2-one.
DETAILED DESCRIPTION OF THE INVENTION:
[030] The invention will now be described in detail in connection with certain preferred and optional embodiments, so that various aspects thereof may be more fully understood and appreciated.
[031] In view of above, the present invention provides one step room temperature process for the synthesis of 1,2-azido alcohol from alkenes.
[032] More particularly, the present invention provides I2 catalysed a regio and diastereo selective one step room temperature process for the synthesis of 1,2-azido alcohol from alkenes.
[033] In an embodiment, I2 catalysed a regio and diastereo selective one step room temperature process for the synthesis of 1,2-azido alcohol from alkenes comprising treating alkenes with azide source in presence of base in a solvent system with the use of a co-oxidant to afford 1,2-azido alcohol.
The above process is shown in scheme 1 below:
90%
Figure imgf000007_0001
Scheme 1
[034] In another embodiment, said azide source is sodium azide.
[035] Still another embodiment, said base may be selected from triethylamine (Et3N), potassium carbonate (K2CO3), potassium tert-butoxideCK'OBu), sodium hydride (NaH), l,8-diazabicycloundec-7-ene (DBU).
Yet another embodiment, said suitable solvents may be selected from water, acetonitrile, ethylacetate and Ci to C3 alcohols, dimethylsulfoxide (DMSO), dimethyl formamide (DMF), acetone, dioxane, tetrahydrofuran (THF), N,N-dimethylacetamide (DMA) or combinations thereof.
[036] Still yet another embodiment, said solvent system that works effectively for the process of invention comprises DMSO and DMF in a ratio of 1 : 1.
[037] Still yet another embodiment, said co-oxidant may be selected from anhydrous tert-butyl hydroperoxide (TBHP) or 30% -50% aq. ¾(¾ at ambient temperature. The ambient temperature for the purpose of the invention is 25 °C to 35 °C.
[038] Still yet another embodiment, said alkenes are selected from the group consisting of mono, di or tri substituted alkenes.
[039] Still yet another embodiment, Iodine source is selected from Iodine solution, tetra-n-butylammonium iodide, sodium iodide, potassium iodide.
[040] In another embodiment, the scope of this reaction is further explored to include di and trisubstituted alkenes which resulted in an oxidant directed (TBHP/ aq. ¾(¾) highly diastereoselective reaction (Scheme 2).
sy
Figure imgf000009_0001
pto >99
R = Alkyl (linear or alicyclic) , aryl group with various substitutions like alkyl, N02, - Oalkyl, halo, at any position on the armatic ring,
R =Alkyl (linear or alicyclic) , aryl group with various substitutions like alkyl, N02, - Oalkyl, halo, at any position on the armatic ring, H
Scheme 2
[041] Variously substituted aryl, heteroaryl and aliphatic substrates are found compatible with the reaction conditions employed in the instant method. The products were obtained in good to excellent yields and with high diastereoselectivity. The yield of the process is in the range of 70-95%.
[042] Following Scheme 3 shows I2 catalyzed azidihydroxylation of styrene
Figure imgf000009_0002
Scheme 3
Following table 1 shows I2-catalyzed regiodivergent azidohydroxylation of
styrene: optimization studies
Table 1
Figure imgf000009_0003
3 h TBHP Et3N CH3CN+DMF 48
4 h TBHP Et3N CH2C12+DMF 18
5 h TBHP Et3N DMSO+ DMF
90,38
6 h TBHP K2C03 DMSO+ DMF 18
7 h TBHP K'OBu DMSO+ DMF 44
8 h TBHP NaH DMSO+ DMF 32
9 TBHP DBU DMSO+ DMF 65
10 "Bu4NI TBHP Et3N DMSO+ DMF 5
11 Nal TBHP Et3N DMSO+ DMF 11
12 KI TBHP Et3N DMSO+ DMF 14
13 i2 50% aq.H202 Et3N DMSO+ DMF 82
14 I2 30 % aq.H202 Et3N DMSO+ DMF 78
The representative examples are shown in Table 2 below. Reaction conditions are same as Scheme 1.
Table
Following scheme 4 shows I2-catalyzed regio- and stereodivergent azidohydroxylation of alkenes
Figure imgf000010_0001
Scheme 4
Following table 2 shows some examples of using reaction condition of scheme 4.
Figure imgf000011_0001
Figure imgf000012_0001
Table 2
[043] Novel regio and diastereo 1 ,2-azidoalcohols are included 2-azido-l-(2- bromophenyl)ethan- 1 -ol, 1 -azido-2-phenylpropan-2-ol, 1 -azido-4-(benzyloxy)-2- methylbutan-2-ol, 3-azido-4-(benzyloxy)-2-methylbutan-2-ol, Syn-2-azido-l- phenylpropane- 1 ,3-diol, 2-azido- 1 -(4-methoxyphenyl)propane- 1 ,3-diol, 2-azido-2- phenylethan-l-ol, 2-azido-2-(p-tolyl)ethan-l-ol, 2-azido-2-(2-bromophenyl)ethan-l-ol, 2-azido-2-(3-nitrophenyl)ethan-l-ol, 2-azido-4-(benzyloxy)-2-methylbutan-l-ol, 3- azido-l-(benzyloxy)-3-methylbutan-2-ol, 3-azido-3-(4-methoxyphenyl)propane-l,2- diol [044] The following examples, which include preferred embodiments, will serve to illustrate the practice of this invention, it being understood that the particulars shown are by way of example and for purpose of illustrative discussion of preferred embodiments of the invention.
[045] EXAMPLES:
Solvents were purified and dried by standard procedures before use; petroleum ether of boiling range 60-80 °C was used. Melting points are uncorrected and recorded on a
Buchi B-542 instrument. 1 H NMR and 13 C NMR spectra were recorded on Brucker AC-200 spectrometer unless mentioned otherwise. Deuterated solvent CDCI3+ CCI4
(70:30) were used as internal standard and singlet at 96.1 ppm in 13 C NMR corresponds to carbon of CCI4. Elemental analysis was carried out on a Carlo Erba CHNS-0 analyzer. HRMS data were recorded on a Waters SYNAPT G2 High Definition Mass Spectrometry System. Purification was done using column chromatography (230-400 mesh). The compounds 5a-n and TBHP (5-6 M solution in decane: <4% water) are commercially available and were procured from Sigma Aldrich (used as such without any further purification). The relative configuration of diastereomers was determined by comparison of their 1HNMR spectra with literature data.
[046] Example 2:
General experimental procedure for the preparation of vicinal azido alcohols (6a- n)
To a stirred solution of alkene (1 mmol) in DMSO: DMF (4 mL: 4 mL) at 0 °C was added I2 (10 mol %) followed by dropwise addition of 5- 6 M TBHP in decane (2 mmol, 0.360 mL). The addition of Et3N (1 mmol, 0.140 mL) was then done slowly (slow decolorisation of reaction mixture was observed) and finally sodium azide (2 mmol, 130 mg) was added pinchwise. The reaction mixture was then allowed to stir at room temperature (25 °C) for 8 hours (monitored by TLC). After completion, the reaction mixture was then cooled to 0 °C excess sodium azide was quenched with water. Organic layer was diluted with EtOAc. The organic layer was separated and the aqueous layer was extracted with EtOAc (3 x 20 mL). The combined organic extracts were repeatedly washed with saturated brine solution, dried over anhyd. Na2S04 and concentrated under reduced pressure to give crude products which were purified by column chromatography [silica gel (230-400 mesh)] using petroleum ether: EtOAc (8:2) as an eluent to afford corresponding vicinal azido alcohol (6a-n) in 74-90% yield.
Spectroscopic data of examples of 1,2- azido alcohols products:
The chemical structures are presented in Table 2.
1) 2-azido-l-phenylethan-l-ol (6a)
Yield: 90% (146 mg); Colorless viscous liquid; Rf = 0.40 (Pet ether: EtOAc = 8: 2); IR (CHCls, cm"1) vmax 1031, 1101, 1247, 2103, 2847, 2933, 3356; 1H NMR (400 MHz,CDCl3): δ 2.61 (br. s, 1H), 3.41 (dd, / = 3.7, 12.4, 1H), 3.47 (dd, / = 8.2, 12.4, 1H,), 4.85 (dd, = 8.2, 3.9 Hz, 1H), 7.30 - 7.39 (m, 5H); 13C NMR (50 MHz, CDC13) 558.1, 73.4, 125.9, 128.3, 128.7, 140.6; HRMS calcd for [(C8H9N30+Na)+] 186.0638; found: 186.0640.
2) 2-azido-l-(p-tolyl)ethan-l-ol (6b)
Yield: 88% (155 mg); Colorless gum; Rf = 0.40 (Pet ether: EtOAc = 8: 2); IR (CHC13, cm"1) vmax 750, 1222, 2095, 2950, 3020, 3412; 1H NMR (200 MHz,CDCl3) δ 2.34 (s, 3H), 2.63 (br. s., 1H), 3.32 - 3.51 (m, 2H), 4.81 (dd, = 7.6, 4.4 Hz, 1H), 7.17 (d, = 8.1 Hz, 2H), 7.24 (d, = 8.2 Hz, 2H); 13C NMR (50 MHz, CDC13) δ 21.1, 58.0, 73.2, 125.8, 129.3, 137.6, 138.1; HRMS calcd for [(C9HnN30+Na)+] : 200.0794; found: 200.0793.
3) 4-(2-azido-l-hydroxyethyl)phenol (6c)
Yield: 76% (135 mg); Colorless liquid; Rf = 0.40 (Pet ether: EtOAc = 7: 3); IR (CHC13, cm"1) vmax 1247,1607, 2103, 2923, 3356; 1H NMR (200 MHz,CDCl3) δ 3.41 - 3.46 (m, 2H), 4.32 - 4.36 (m, 1H), 4.81 (dd, = 7.7, 4.5 Hz, 1H), 6.81 (d, 2H, = 8.5 Hz), 7.24 (d, 2H, = 8.4 Hz), 7.97 (s, D20 exchangeable, 1H); "C NMR (50 MHz,CDCl3) δ 58.1, 73.1, 115.6, 127.5, 128.6, 155.8; HRMS calcd for [(C8H9N302+Na)+] 202.0587 found 202.0579.
4) 2-azido-l-(2-bromophenyl)ethan-l-ol (6d)
Yield: 82% (196 mg); Colorless liquid; Rf = 0.40 (Pet ether: EtOAc = 8: 2); IR (CHC13, cm"1) vmax 761, 1012, 1214, 2103, 2724, 3018; 1H NMR (500 MHz, CDC13) δ 2.46 (d, = 3.4 Hz, 1H), 3.35 (dd, = 12.6, 8.2 Hz, 1H), 3.60 (dd, = 12.6, 2.9 Hz, 1H), 5.26 (dt, 3.0 Hz, 1H), 7.19 (t, = 8.5 Hz, 1H), 7.38 (t, = 8.5 Hz, 1H), 7.54 (d, = 8.8 Hz, 1H), 7.64 (d, = 9.1 Hz, 1H); 13C NMR (125 MHz,CDCl3) δ 56.5, 72.4, 121.7, 127.8, 127.9, 129.7, 132.8, 139.5; HRMS calcd for [(C8H8BrN30+Na)+] 263.9743 found 263.9738.
5) 2-azido-l-(3-nitrophenyl)ethan-l-ol (6e)
Yield: 77% (160 mg): Colorless liquid; Rf = 0.40 (Pet ether: EtOAc = 8: 2); IR (CHCI3, cm"1) vmax 1211, 1350, 1531, 2104, 3438; 1H NMR (200 MHz, CDC13) δ 2.59 (s, 1H), 3.52 - 3.56 (m, 2H), 5.01 (t, = 5.9 Hz, 1H), 7.58 (t, = 7.9 Hz, 1H), 7.75 (d, = 7.8 Hz, 1H), 8.19 - 8.30 (m, 2H); 13C NMR (101 MHz, CDC13) δ 57.9, 72.3, 121.0, 123.2, 129.6, 132.0, 142.6, 148.4. HRMS calcd for [(C8H8N404+H)+] 209.0674 found 209.0673.
6) l-azido-2-phenylpropan-2-ol (6f)
Yield: 78% (140 mg); Colorless gum; Rf = 0.40 (Pet ether: EtOAc = 8: 2); IR (CHC13, cm"1) vmax 761, 1272, 2096, 2828, 2950, 3020, 3422 ; 1H NMR (500 MHz, CDC13) δ 1.61 (s, 3H), 2.36 (s, 1H), 3.45 (d, = 12.3 Hz, 1H), 3.61 (d, = 12.3 Hz, 1H), 7.29 - 7.32 (m, 1H), 7.37 - 7.40 (m, 2H), 7.45 - 7.47 (m, 2H); 13C NMR (125 MHz, CDC13) δ 27.1, 62.2, 74.5, 124.8, 127.5, 128.5, 144.7; HRMS calcd for [(C9HnN30 +Na)+] 200.0794; found: 200.0794.
7) l-azidooctan-2-ol (6g)
Yield: 79% (135 mg); Colorless liquid; Rf = 0.60 (Pet ether: EtOAc = 8: 2); IR (CHC13, cm"1) vmax 759, 1261, 2104, 2937, 3404 ; 1H NMR (200 MHz,CDCl3) δ 0.82 (t, / = 6.2 Hz, 3H), 1.23 (br. s., 7H), 1.38 (br. s., 3H), 1.97 (br. s., 1H), 3.18 - 3.34 (m, 2H), 3.67 (br. s., 1H); 13C NMR (50 MHz,CDCl3) δ 14.1, 22.6, 25.4, 29.2, 31.8, 34.3, 57.2, 70.8; HRMS calcd for [(C8Hi7N30+Na)+] 194.1264; found: 194.1263.
8) l-azido-4-(benzyloxy)-2-methylbutan-2-ol (6h)
Yield: 84% (196 mg); Colorless liquid; Rf = 0.50 (Pet ether: EtOAc = 8: 2); IR (CHC13, cm"1) vmax 705, 1082, 1274, 1717, 2106, 2926, 2974, 3412; 1H NMR (400 MHz,CDCl3) δ 1.35 (s, 3H), 1.82 - 1.99 (m, 2H), 2.59 (d, = 4.9 Hz, 1H), 2.70 (d, = 4.9 Hz, 1H), 3.53- 3.62 (m, 2H), 4.50 (s, 2H), 7.28 - 7.37 (m, 5H); 13C NMR (100 MHz, CDC13) 521.6, 36.6, 53.9, 55.4, 66.6, 73.0, 127.6, 128.4, 138.3; HRMS calcd for [(Ci2Hi7N302+Na)+] 258.1213; found: 258.1209.
9) 3-azido-4-(benzyloxy)-2-methylbutan-2-ol (6i)
Yield: 74% (175 mg); Colorless liquid; Rf = 0.50 (Pet ether: EtOAc = 8: 2); IR (CHC13, cm"1) vmax 705, 765, 1082, 1274, 1377, 1612, 1717, 2106, 2926, 2974, 3412; 1H NMR (200 MHz,CDCl3) δ 1.27 (s, 3H), 1.35 (s, 3H), 2.98 (t, = 5.4 Hz, 1H), 3.51 - 3.69 (m, 2H), 4.49 - 4.67 (m, 2H), 7.30 - 7.36 (m, 5H); 13C NMR (50 MHz,CDCl3) δ 18.9, 24.7, 57.5, 61.9, 68.8, 73.2, 127.8, 128.4, 137.9; HRMS calcd for [(Ci2Hi7N302+Na)+] 258.1213; found: 258.1210.
10) SjH-2-azidocyclohexan-l-ol (6j)
Yield: 87% (122 mg); Colorless liquid; Rf = 0.40 (Pet ether: EtOAc = 9: 1); IR (CHC13, cm"1) vmax 760, 1259, 2102, 2937, 3403; 1H NMR (400 MHz,CDCl3) δ 1.28 - 1.34 (m, 3H), 1.37 - 1.56 (m, 1H), 1.83 - 1.90 (m, 1H), 2.00 - 2.16 (m, 2H), 2.34 (d, = 2.3 Hz, 1H), 2.45 - 2.51 (m, 1H), 3.66 (td, = 9.8, 3.9 Hz, 1H), 4.05 (ddd, = 12.4, 9.8, 4.4 Hz, 1H); 13C NMR (50 MHz, CDC13) δ 24.4, 28.0, 33.6, 38.6, 43.5, 76.0; HRMS calcd for [(C6HnN30+Na)+] 164.0794; found: 164.0794.
11) 5jH-2-azido-2,3-dihydro-lH-inden-l-ol (6k)
Yield: 87% (152 mg); Colorless liquid; Rf = 0.50 (Pet ether: EtOAc = 8: 2); IR (CHC13, cm"1) vmax 770, 1219, 2097, 2916, 3356; 1H NMR (500 MHz,CDCl3) δ 2.39 (d, = 5.2 Hz, 1H), 3.14 -3.22 (m, 2H), 4.35 (q, = 5.2 Hz, 1H), 5.16 (s, 1H), 7.28 - 7.34 (m, 3H), 7.45 - 7.47 (m, 1H); 1JC NMR (125 MHz, CDC13) δ 35.2, 65.7, 76.4, 124.7, 125.1, 127.6, 129.0, 139.0, 141.9; HRMS calcd for [(C9H9N30+Na)+] 198.0638; found: 198.0640.
12) Sjra-2-azido-l-phenylpropan-l-ol (61)
Yield: 88% (155 mg); Colorless gum; Rf = 0.40 (Pet ether: EtOAc = 8: 2); IR (CHC13, cm"1) vmax 771, 1229, 1605, 2101, 2926, 3013, 3346; 1H NMR (400 MHz, CDC13) δ 1.58 (d, = 6.1 Hz, 3H), 4.56 - 4.66 (m, 1H), 5.12 (d, = 7.8 Hz, 1H), 7.31 - 7.45 (m, 5H); 13C NMR (100 MHz, CDC13) δ 18.4, 80.6, 84.8, 126.0, 129.2, 129.8, 135.2; HRMS calcd for [(C9HnN30+Na)+] 200.0794; found: 200.0788;
13) 5jH-2-azido-l-phenylpropane-l,3-diol (6m)
Yield: 80% (115 mg); colorless gum; Rf = 0.30 (Pet ether: EtOAc = 6: 4); IR (CHC13, cm"1) vmax 761, 1219, 1605, 2105, 2893, 2933, 3013, 3416; 1H NMR (200 MHz, CDC13) δ 2.64 (br. s., 1H), 2.70 (br. s, 1H), 3.51 - 3.73 (m, 2H), 3.83 (d, = 4.7 Hz, 1H), 4.85 (t, = 6.5 Hz, 1H), 7.34-7.43 (m, 5 H); 13C NMR (125 MHz, CDC13) δ 62.8, 67.0, 74.0, 126.5, 127.8, 128.9, 136.2; HRMS calcd for [(C9HnN302+Na)+] 216.0749 found: 216.0736.
14) 2-azido-l-(4-methoxyphenyl)propane-l,3-diol (6n)
Yield: 82% (182 mg); colorless gum: Rf = 0.30 (Pet ether: EtOAc = 6: 4); IR (CHC13, cm"1) vmax 754, 1222, 2103, 2822, 2937, 3397; 1H NMR (200 MHz, CDC13) 53.51 - 3.90 (m, 6H), 4.78 (t, = 5.56 Hz, 1H), 6.88- 6.95 (m, 2H), 7.29- 7.35 (m, 2H). 13C NMR (100 MHz,) CDC13 δ 55.3, 62.7, 69.1, 74.4, 114.1, 127.6, 132.2, 159.7; HRMS calcd for [(Ci0H13N3O3+H)+] 224.1035 found: 224.1033.
[047] Example 3:
Experimental procedure for the preparation of Syra-2-azido-l-phenylpropane-l,3- diol (6m):
To a stirred solution of alkene (10 mmol, 1.34 g) in DMSO: DMF (40 mL: 40 mL) at 0 °C was added I2 (10 mol %, 0.253 g) followed by dropwise addition of 5- 6 M TBHP in decane (20 mmol, 3.60 mL). The addition of Et3N (10 mmol, 1.3 mL) was then done slowly (slow decolorisation of reaction mixture was observed) and finally sodium azide (20 mmol, 1.28 g) was added pinchwise. The reaction mixture was then allowed to stir at room temperature (25 °C) for 8 hours (monitored by TLC). After completion, the reaction mixture was then cooled to 0 °C and excess sodium azide was quenched with water. Organic layer was diluted with EtOAc. The organic layer was separated and the aqueous layer was extracted with EtOAc (3 x 100 mL). The combined organic extracts were repeatedly washed with saturated brine solution, dried over anhyd. Na2S04 and concentrated under reduced pressure to give crude products which were purified by column chromatography [silica gel (230-400 mesh)] using petroleum ether: EtOAc (8:2) as an eluent to afford corresponding vicinal azido alcohol (6m) in 88% (1.7 g) yield.
[048] Example 4:
Synthesis of Chloramphenicol (8):
To a stirred solution of Specific compound name need to be provided (6m) (1.5 g, 7.7 mmol ) in methanol (40 ml) was added 20% Pd(OH)2/C (50 mg) carefully at room temperature (25°C to 30°C) and a H2 balloon was kept to provide hydrogen atmosphere. After the completion of the reaction as monitored by TLC, it was filtered over celite and the filtrate was concentrated under reduced pressure to give aminodiol, which was added methyl dichloroacetate (3 mL) and heated at a temperature ranging between 90 °C- 100°C for 1-1.5 hours. The excess ester was removed under reduced pressure to give the crude product. To a stirred solution of cone. HN03: cone. H2S04 (1: 1) (5 mL) was added the crude product at a temperature ranging between -20 °C to - 30°C, the resulting solution was stirred for 1.5 h at 0 °C. After the completion of the reaction as monitored by TLC, it was poured into water and extracted with diethylether (3x50 mL), washed with water, brine and dried over anhydrous Na2S04 and concentrated under reduced pressure to give crude product which were purified by column chromatography [silica gel (230-400 mesh)] using petroleum ether: EtOAc (6:4) as an eluent to afford chloramphenicol (8) in 71% yield. Yield: 71% (1.8g); colorless gum; Rf = 0.40 (Pet ether: EtOAc = 7: 3); IR (CHC13, cm" *) vmax 850, 1049, 1216, 1348, 1416, 1454, 1523, 1604, 1686, 2929, 3020, 3420; 1H NMR (400 MHz, acetone- d6) δ 3.58 - 3.88 (m, 2H), 4.09 - 4.17 (m, 1H), 4.52 (br. s., 3H), 5.25 (s, 1H), 6.10 (s, 1H), 7.60 (d, = 8.5 Hz, 2H), 8.09 (d, = 8.5 Hz, 2H); 13C NMR (100 MHz, acetone- d6) δ 55.9, 60.6, 65.7, 69.6, 122.3, 126.3, 146.3, 149.2, 163.4; HRMS calcd for [(CnHi2Cl2N205+Na)+] 345.0015; found: 345.0009.
[049] Example 5:
General experimental procedure for the preparation of vicinal azido alcohols (7a- n):
To a stirred solution of alkene (1 mmol) in DMSO: DMF (4 ml: 4 ml) at 0 °C was added I2 (10 mol %) followed by dropwise addition of 50% aqueous H202 (2 mmol, 0.140 mL). The addition of Et3N (1 mmol, 0.140 mL) was then done slowly (vigorous decolorisation of reaction mixture was observed) and finally sodium azide (2 mmol, 130 mg) was added pinch wise. The reaction mixture was then allowed to stir at room temperature for 8 hours (monitored by TLC). Organic layer was diluted with EtOAc. The organic layer was separated and the aqueous layer was extracted with EtOAc (3 x 20 mL). The combined organic extracts were repeatedly washed with saturated brine solution, dried over anhyd. Na2S04 and concentrated under reduced pressure to give crude products which were purified by column chromatography [silica gel (230-400 mesh)] using petroleum ether: EtOAc (8:2) as an eluent to afford corresponding vicinal azido alcohol (7a-n) in 74-92% yield.
1) 2-azido-2-phenylethan-l-ol (7a)
Yield: 82% (150 mg); Colorless liquid; Rf = 0.35 (Pet ether: EtOAc = 8: 2); IR (CHC13, cm"1) vmax 1026, 1105, 1227, 2106, 2847, 2933, 3416; 1H NMR (400 MHz,CDCl3) δ 2.02 (s, 1H), 3.74 (t, = 5.6 Hz, 2H), 4.68 (t, = 6.4 Hz, 1H), 7.33 - 7.41 (m, 5H); 13C NMR (50 MHz,CDCl3) δ 66.3, 67.7, 127.1, 128.6, 128.8, 136.2 ; HRMS calcd for [(C8H9N30 +Na)+] 186.0638; found: 186.0640.
2) 2-azido-2-(p-tolyl)ethan-l-ol (7b) Yield: 89% (158 mg); Colorless liquid; Rf = 0.35 (Pet ether: EtOAc = 8: 2); IR (CHCls, cm"1) vmax 752, 1232, 2104, 2893, 2950, 3021, 3382; 1H NMR (200 MHz, CDCI3) δ 2.35 (s, 3H), 3.69 (d, = 6.4 Hz, 2H), 4.60 (t, = 6.4 Hz, 1H), 7.19 (s, 4H ); 13C NMR (50 MHz, CDC13) δ 21.1, 66.3, 67.6, 127.1, 129.5, 133.2, 138.4; HRMS calcd for [(C9H11N3O +Na)+] 200.0794; found: 200.0793;
Data of 7(c) need to be included
3) 2-azido-2-(2-bromophenyl)ethan-l-ol (7d)
Yield: 86% (205 mg); Colorless liquid; Rf = 0.35 (Pet ether: EtOAc = 8: 2); IR (CHCI3, cm"1) vmax 761, 1032, 1255, 2103, 2931, 3367; 1H NMR (500 MHz,CDCl3) δ 2.24 (br. s., 1H), 3.63 (t, = 9.6 Hz, 1H), 3.87 (d, = 11.0 Hz, 1H), 5.18 (dd, / = 8.1, 3.7 Hz, 1H), 7.19 - 7.22 (m, 1H), 7.37 (t, = 7.3 Hz, 1H), 7.46 (d, = 7.6 Hz, 1H), 7.59 (d, = 7.9 Hz, 1H); 13C NMR (125 MHz,CDCl3) δ 65.4, 66.7, 123.1, 128.0, 128.5, 129.9, 133.1, 135.8; HRMS calcd for [(C8H8BrN30 +Na)+] 263.9743; found: 263.9739.
4) 2-azido-2-(3-nitrophenyl)ethan-l-ol (7e)
Yield: 76% (158 mg); Colorless liquid; Rf = 0.35 (Pet ether: EtOAc = 8: 2); IR (CHCI3, cm"1) vmax 757, 1350, 1530, 1631, 2107, 2925, 3085, 3413; 1H NMR (500 MHz, CDCI3) δ2.81 (dd, = 5.4, 2.5 Hz, 1H), 3.24 (dd, / = 5.4, 4.0 Hz, 1H), 3.98 (dd, = 3.9, 2.5 Hz, 1H), 7.55 (t, = 7.6 Hz, 1H), 7.62 (d, = 7.6 Hz, 1 H), 8.17 - 8.19 (m, 2H); 13C NMR (125 MHz, CDC13) δ51.4, 76, 120.7, 123.1, 129.6, 131.4, 140.1 ; HRMS calcd for [(C8H8N404+H)+] 209.0674 found 209.0670.
5) 2-azido-2-phenylpropan-l-ol (7f)
Yield: 83% (146 mg); Colorless liquid; Rf = 0.35 (Pet ether: EtOAc = 8: 2); IR (CHCI3, cm"1) vmax 1H NMR (200 MHz,CDCl3) δ 1.43 (s, 3H), 2.32 (s, 1H), 3.50 (d, = 11.3 Hz, 1H), 3.67 (d, 7 = 11.3 Hz, 1H), 7.21 - 7.37 (m, 5H); 13C NMR (50 MHz, CDCI3) δ 26.0, 70.9, 74.8, 125.1, 127.1, 128.4, 145.0; HRMS calcd for [(C9H11N3O +Na)+] 200.0794; found: 200.0794.
6) 2-azidooctan-l-ol (7g) Yield: 83% (142 mg); Colorless liquid; Rf = 0.50 (Pet ether: EtOAc = 8: 2); IR (CHC13, cm"1) vmax 1H NMR (200 MHz,CDCl3) δ 0.87 - 0.93 (m, 3H), 1.30 (br. s., 8H), 1.50 (d, = 5.2 Hz, 2H), 1.95 (br. s., 1H), 3.41 - 3.60 (m, 2H), 3.62 - 3.76 (m, 1H); 13C NMR (50 MHz, CDC13) δ 14.1, 22.6, 26.0, 29.1, 30.6, 31.7, 64.5, 65.2; HRMS calcd for [(C8Hi7N30+Na)+] 194.1264; found: 194.1263.
7) 2-azido-4-(benzyloxy)-2-methylbutan-l-ol (7h)
Yield: 74% (172 mg); Colorless liquid; Rf = 0.45 (Pet ether: EtOAc = 8: 2); IR (CHC13, cm"1) vmax 744, 1104, 1292, 2102, 2867, 2926, 3460; 1H NMR (400 MHz,CDCl3) δ 1.25 (s, 3H), 1.64 (s, 1H), 1.74 - 1.81 (m, 1H), 1.92 - 1.99 (m, 1H), 3.24 (s, 2H), 3.58 (s, 1H), 3.70 - 3.76 (m, 2H), 4.55 (s, 2H), 7.31 - 7.40 (m, 5H); 13C NMR (100 MHz,CDCl3) δ 25.0, 37.5, 60.5, 66.9, 72.8, 73.4, 127.8, 127.9, 128.5, 137.4; HRMS calcd for [(Ci2Hi7N302+Na)+] 258.1213; found: 258.1209.
8) 3-azido-l-(benzyloxy)-3-methylbutan-2-ol (7i)
Yield: 78% (185 mg); Colorless liquid; Rf = 0.45 (Pet ether: EtOAc = 8: 2); IR (CHC13, cm"1) vmax 771,1077, 1456, 2121, 2924, 3416; 1H NMR (500 MHz,CDCl3) δ 1.17 (s, 3H), 1.23 (s, 3H), 2.16 (s, 1H), 3.55 - 3.59 (m, 2H), 3.64 (d, = 8.2 Hz, 1H), 4.54 (dd, = 12.2, 4.6 Hz, 2H), 7.31 - 7.38 (m, 5H); 13C NMR (125 MHz, CDC13) δ25.2, 26.6, 71.5, 71.8, 73.7, 75.6, 127.8, 128.0, 128.5, 137.5; HRMS calcd for [(Ci2Hi7N302+Na)+] 258.1213; found: 258.1210.
9) AHti-2-azidocyclohexan-l-ol (7j)
Yield: 92% (130 mg); Colorless liquid; Rf = 0.35 (Pet ether: EtOAc = 9: 1); IR (CHC13, cm"1) vmax 764, 1285,1455, 2100, 3410; 1H NMR (400 MHz,CDCl3) δ 1.25 - 1.33 (m, 4H), 1.65 - 1.8 (br. s, 2H), 1.97- 2.04 (m, 2H), 2.76 (br. s., 1H), 3.12 - 3.18 (m, 1H), 3.35 (dt, = 9.6, 4.5 Hz, 1H); 13C NMR (100 MHz,CDCl3) δ 23.8, 24.1, 29.7, 33.0, 66.9, 73.4; HRMS calcd for [(C6HnN30 +Na)+] 164.0794; found: 164.0794.
10) Anti -2-azido-2,3-dihydro-lH-inden-l-ol (7k)
Yield: 82% (144 mg); Colorless liquid; Rf = 0.40 (Pet ether: EtOAc = 8: 2); IR (CHC13, cm"1) vmax 761, 1219, 2098, 2844, 2926, 3366; 1H NMR (400 MHz,CDCl3) δ 2.86 (dd, / = 16.0, 5.9 Hz, 1 H), 3.28 (dd, / = 16.0, 6.7 Hz, 1H), 3.44 (br. s, 1H), 4.46 (q, = 5.9 Hz, 1H), 4.65 (d, = 4.9 Hz, 1H), 7.29-7.39 (m, 4H); 13C NMR (100 MHz,CDCl3) δ 35.2, 65.7, 76.4, 124.7, 125.1, 127.6, 129.0, 139.0, 141.9; HRMS calcd for [(C9H9N30+Na)+] 198.0638; found: 198.0640.
11) Arati'-l-azido-l-phenylpropan-2-ol (71)
Yield: 86% (152 mg); Colorless liquid Rf = 0.35 (Pet ether: EtOAc = 8: 2); IR (CHC13, cm"1) vmax 759, 1269, 2109, 2829, 2950, 3020, 3322; 1H NMR (200 MHz,CDCl3) δ 1.11 (d, = 6.2 Hz, 3H), 1.63 (br. s., 1H), 3.88 (quin, = 6.1 Hz, 1H), 4.38 (d, = 5.8 Hz, 1H), 7.23 - 7.35 (m, 5H); 13C NMR (50 MHz,CDCl3) δ 18.6 , 70.6, 71.6, 127.8, 128.6, 128.9, 136.3; HRMS calcd for [(C9HnN30 +Na)+] 200.0794; found: 200.0794.
12) Arati'-3-azido-3-phenylpropane-l,2-diol (7m)
Yield: 78% (112 mg); Colorless liquid; Rf = 0.25 (Pet ether: EtOAc = 6: 4); IR (CHC13, cm"1) vmax 777, 1309, 1604, 2107, 2933, 3014, 3389; 1H NMR (400 MHz,CDCl3) δ 2.68 (br. s., 2 H), 3.61 - 3.71 (m, 2H), 3.80 (td, = 6.4, 3.3 Hz, 1H), 4.59 (d, = 7.1 Hz, 1H), 7.34 - 7.44 (m, 5H); 13C NMR (100 MHz, CDC13) δ 62.8, 67.1, 74.0, 127.8, 128.8, 129.0, 136.2; HRMS calcd for [(C9HnN302+Na)+] 216.0749 found: 216.0745.
13) 3-azido-3-(4-methoxyphenyl)propane-l,2-diol (7n)
Yield: 80% (890 mg); colorless liquid; Rf = 0.25 (Pet ether: EtOAc = 6: 4); IR (CHC13, cm"1) vmax 1035, 1195, 1513, 1616, 2100, 2920, 3050, 3368 (broad); 1H NMR (200 MHz,CDCl3) δ 2.73 (br. s., 1H), 3.21 - 3.68 (m, 2H), 3.74 - 3.82 (m, 4H), 4.52 (d, = 7.2 Hz, 1 H), 6.92 (d, = 8.7 Hz, 2 H), 7.27 (d, = 8.7 Hz, 2 H); 13C NMR (101 MHz, CDC13) δ 55.2, 63.0, 66.4, 73.9, 114.3, 128.0, 129.1, 159.8; HRMS calcd for [(CioH13N303+H)+] 224.1035 found: 224.1036.
[050] Example 6: Synthesis of Tert-butyl arati-2,3-dihydroxy-l-(4-methoxyphenyl)propyl)carbamate
(9):
Figure imgf000023_0001
To a stirred solution of azidoalcohol 7n (0.5g, 2.2 mmol ) in MeOH (20 mL) was added 20% Pd(OH)2/C (25 mg) carefully at room temperature and a H2 balloon was kept to provide hydrogen atmosphere. After the completion of the reaction as monitored by TLC, it was filtered over celite and the filtrate was concentrated under reduced pressure to give aminodiol, which was added (Boc)20 (2.4 m mol, 0.487 g) and Et3N (4.4 mmol, 0.44 g) and allowed to stir at a temperature ranging from 25 °C for 2 hours. After the completion of the reaction as monitored by TLC, it was poured into water and extracted with diethylether (3x50 mL), washed with water, brine and dried over anhydrous Na2S04 and concentrated under reduced pressure to give crude product which were purified by column chromatography [silica gel (230-400 mesh)] using petroleum ether: EtOAc (6:4) as an eluent to afford compound 9 in 76% yield (496 mg).
Yield: 76% (496 mg); colorless liquid; Rf = 0.25 (Pet ether: EtOAc = 5: 5); mp: 114- 116 °C, (lit.67 mp: 116-118 °C); IR (CHC13, cm"1) vmax 669, 757, 831, 927, 1035, 1167, 1216, 1368, 1585, 1612, 1701, 2400, 2839, 2981, 3019, 3438, 3682; 1H NMR (500 MHz, CDC13) δ 1.34 (br. s., 10H), 3.01 - 3.25 (m, 1H), 3.54 (br. s., 2H), 3.71 (s, 4H), 4.55 (br. s., 1H), 5.29 (br. s., 1H), 6.78 (d, = 5.5 Hz, 2H), 7.15 (d, = 6.7 Hz, 2H): 13C NMR (126 MHz, CDC13) δ 28.3, 55.2, 56.1, 63.2, 74.1, 76.7, 77.3, 80.1, 96.1, 114.2, 128.5, 131.1, 156.2, 159.2; HRMS calcd for [(Ci5H24N05+H)+] 298.1654 found: 298.1650.
[051] Example 7:
Synthesis of (4R,5R)-5-(hydroxymethyl)-4-(4-methoxyphenyl) oxazolidin-2-one
(10):
Figure imgf000024_0001
9 <76 %> (i) cytoxazone
To a solution of anti-3 -amino- 1,2-diol 9 (0.3 g, 1.0 mmol) in dry THF ( 10 mL) was added NaH (0.05 g, 60% w/w, 2.0 mmol) at a temperature ranging from 25 °C, and the mixture was stirred under nitrogen atmosphere for 3 hours. The reaction mixture was concentrated and the resulting mixture was extracted with EtOAc (3 x 10 mL), washed with saturated aq. NH4C1 (5 mL) and brine solution (5 mL). The organic layers were separated, dried over anhyd. Na2S04, and concentrated to give the crude product, which was then purified by column chromatography over silica gel using pet. ether:EtOAc (60:40) as am eluent to give 10 (0.2 g) as a colorless solid.
Yield: 90% (335 mg); colorless solid; mp: 116-1 18 °C, (lit.67 mp: 119-121 °C); Rf = 0.25 (Pet ether: EtOAc = 7: 3); IR (CHC13, cm"1) vmax 769, 843, 1028, 1248, 1395, 1513, 1610, 1733, 2580, 2924, 3272; 1H NMR (500 MHz, DMSO-d6) δ 3.00 - 3.03 (m, 2H), 3.26 (t, = 3.7 Hz, 2H), 3.77 (s, 3H), 4.69- 4.71 (m, 2H), 4.88 (d, = 8.2 Hz, 1H), 6.89 (dd, = 8.4, 2.0 Hz, 2H), 7.15 (d, = 8.5 Hz, 2H), 7.98 (br. s., 1H): 13C NMR (126 MHz, DMSO-d6) δ 39.0, 39.2, 39.3, 39.7, 39.8, 40.0, 54.8, 56.3, 60.9, 78.4, 78.6, 78.9, 80.0, 95.5, 113.4, 127.8, 129.0, 158.6, 158.9. HRMS calcd for [(CiiH13N04+H)+] 224.0922; found: 224.0920.
[052] Example 8:
Synthesis of 2-azido-2phenylethan-l-ol (lsO-7a): + ph 3OH
Figure imgf000024_0002
7a-180 (78%)
25 °C, 8 h
18
To a stirred solution of styrene (0.5 mmol) in DMSO: O-DMF (which was purified
18 and prepared by dimethylaminomethylene dimethylamm-onium chloride) and lo0-H20 (>97%-180) heating in 110 °C for 12 hours) (0.5 ml: 0.5 ml) at 0 °C was added I2 (10 mol %) followed by dropwise addition of 50% aqueous H202 (1 mmol). The addition of Et3N (0.5 mmol) was then done slowly (vigorous decolorisation of reaction mixture was observed) and finally sodium azide (1 mmol) was added pinchwise. The reaction mixture was then allowed to stir at room temperature for 8 hours (monitored by TLC). Organic layer was diluted with EtOAc. The organic layer was separated and the aqueous layer was extracted with EtOAc (3 x 8 mL). The combined organic extracts were repeatedly washed with saturated brine solution, dried over anhyd. Na2S04 and concentrated under reduced pressure to give crude products which were purified by column chromatography [silica gel (230-400 mesh)] using petroleum ether: EtOAc (8:2) as an eluent to afford corresponding vicinal azido alcohol (lsO-7a) in 78% yield and (lsO-6a) in 6% yield. The ^NMR and 13C NMR data was in well agreement as 7a and 6a compounds. HRMS calcd for [(C8H9N30+H)+] 166.0861 ; found: 166.0860.
[054] ADVANTAGES OF THE INVENTION:
• Cheaper Oxidising system, High regio selectivity as well as diastereoselectivity
• Metal free process
• Room Temperature process
• High yield

Claims

WE CLAIM:
1. A one step room temperature process for the selective synthesis of regio and diastereo 1,2-azidoalcohols from alkenes comprising
a. adding halogen source to a stirred solution of alkene substrate in a solvent system followed by addition of co-oxidant at 0°C to - 5°C;
b. adding base to reaction mixture of step (a) followed by addition of azide source at a temperature ranging between 0°C to -5°C; c. stirring the reaction mixture of step (b) at a temperature ranging between 25 to 30°C for 8-12 hours to afford 1,2-azidoalcohols.
2. The process as claimed in claim 1, wherein said azide source is sodium azide.
3. The process as claimed in claim 1, wherein said halogen source is iodine solution, tetra-n-butylammonium iodide, sodium iodide, potassium iodide.
4. The process as claimed in claim 1, wherein said base is selected from triethylamine (Et3N), potassium carbonate (K2CO3), potassium tert-butoxide (K'OBu), sodium hydride (NaH), l,8-Diazabicycloundec-7-ene (DBU).
5. The process as claimed in claim 1, wherein said solvent is selected from water, acetonitrile, ethylacetate and Ci to C3 alcohols, dimethylsulfoxide (DMSO), dimethyl formamide (DMF), acetone, dioxane, tetrahydrofuran (THF), N,N- dimethylacetamide (DMA) or combinations thereof.
6. The process as claimed in claim 1, wherein said solvent system is DMSO and DMF in a ratio of 1 : 1 (volume/volume).
7. The process as claimed in claim 1, wherein said co-oxidant is selected from anhydrous tert-butyl hydroperoxide (TBHP) or 30%-50% aq. H2O2 at the temperature ranging from 25°C to 35°C.
8. The process as claimed in claim 1, wherein yield of said process is in the range of 70-95%.
9. The process as claimed in claim 1, wherein said process is metal free.
10. Novel regio and diastereo 1,2-azidoalcohols are included 2-azido-l-(2- bromophenyl)ethan- 1 -ol, 1 -azido-2-phenylpropan-2-ol, 1 -azido-4-(benzyloxy)- 2-methylbutan-2-ol, 3-azido-4-(benzyloxy)-2-methylbutan-2-ol, Syn-2-azido- 1 -phenylpropane- 1 ,3-diol, 2-azido- 1 -(4-methoxyphenyl)propane- 1 ,3-diol, 2- azido-2-phenylethan- 1 -ol, 2-azido-2-(p-tolyl)ethan- 1 -ol, 2-azido-2-(2- bromophenyl)ethan- 1 -ol, 2-azido-2-(3-nitrophenyl)ethan- 1 -ol, 2-azido-4- (benzyloxy)-2-methylbutan-l-ol, 3-azido-l-(benzyloxy)-3-methylbutan-2-ol, 3- azido-3-(4-methoxyphenyl)propane- 1 ,2-diol.
11. A process for preparation of chloramphenicol from 1 ,2-azidoalcohol of claim 1 comprising the steps of:
a) adding 20% palladium hydroxide on carbon to a stirred solution of azidoalcohol in methanol under H2 atmosphere at a temperature ranging between 25 °C to afford aminodiol;
b) adding methyl dichloroacetate into aminodiol of step (a) and heating the solution at a temperature ranging around 90°C for 1 hour to afford crude product;
c) Adding crude product of step (b) into nitrating mixture at a temperature ranging around -20 °C;
d) Stirring the solution of step c at a temperature of 0°C for 1 hour to afford chloramphenicol.
12. The process as claimed in claim 11, wherein said 1 ,2-azidoalcohol is Syn-2- azido- 1 -phenylpropane- 1 ,3-diol.
13. The process as claimed in claim 11, wherein said nitrating mixture of step (c) is mixture of nitric acid and sulphuric acid.(conc. HN03: cone. H2SO4 (1: 1)).
14. A process for preparation of tert-butyl anti-2,3-dihydroxy-l-(4- methoxyphenyl)propyl)carbamate from 1 ,2-azidoalchohol of claim 1 comprising the steps of: a) adding 20% palladium hydroxide on carbon to a stirred solution of azidoalcohol in solvent under H2 atmosphere at a temperature ranging between 25 °C for 12 hours to afford aminodiol;
b) adding Boc anhydride ((Boc)20) and triethyl amine (Et3N) to a stirred solution of step (a) in dicholorome thane and allowing stirring at a temperature ranging from 25°C for 2 hours to afford Tert-butyl anti-2,3- dihydroxy- 1 -(4-methoxyphenyl)propyl)carbamate .
15. The process as claimed in claim 14, wherein said 1 ,2-azidoalcohol is 3-azido-3- (4-methoxyphenyl)propane- 1 ,2-diol.
16. A process for preparation of (4R,5R)-5-(hydroxymethyl)-4-(4-methoxyphenyl) oxazolidin-2-one from tert-butyl anti-2,3-dihydroxy-l-(4- methoxyphenyl)propyl)carbamate comprising adding sodium hydride to a solution of tert-butyl anti-2,3-dihydroxy-l-(4- methoxyphenyl)propyl)carbamate in dry THF under nitrogen temperature at a temperature ranging from 25°C to 30°C, stirring continued for 3-3.5 hours to afford (4R,5R)-5-(hydroxymethyl)-4-(4-methoxyphenyl) oxazolidin-2-one.
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