Ultrasound Assisted Pictet–Spengler Synthesis of Tetrahydro‐β‐Carboline Derivatives

Abstract

The synthesis of twelve tetrahydro‐β‐carboline derivatives 3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h, 3i, 3j, 3k, 3l prepared via the Pictet–Spengler reaction is described. The reaction of tryptamine and a variety of arylaldehydes were carried out under ultrasonic irradiation and trifluoracetic acid catalysis at room temperature. These tetrahydro‐β‐carbolines have been synthesized in higher yields and shorter reaction times compared to the conventional method. Moreover, the reaction proceeded successfully even employing arylaldehydes with electron‐donating or electron‐attracting substituents which did not react under conventional method.

The Progress in Pictet‐Spengler β‐Carboline Synthesis under Green Conditions

“…The reaction was completed between 1-2 hours with good to excellent yield under ultrasonic irradiation conditions, while it extended to 24 to 48 hours with lower or similar yield under conventional conditions (Scheme 11). [33] Gomez et al [34] studied the one-pot Ugi-azide/Pictet-Spengler reaction assisted by ultrasound irradiation for the synthesis of a series of 2-tetrazolylmethyl-2,3,4,9-tetrahydro-1H-β-carbolines 59. The use of ultrasound irradiation and formaldehyde solution 56 led to shorten the time of the reaction with milder conditions and high yield 75% (Scheme 12).…”

“…The reaction was completed between 1–2 hours with good to excellent yield under ultrasonic irradiation conditions, while it extended to 24 to 48 hours with lower or similar yield under conventional conditions (Scheme 11). [33] …”

The use of ultrasound in the South Cone region. Advances in organic and inorganic synthesis and in analytical methods

“…Muscia et al . , an Argentinian group from Universidad de Buenos Aires [39] , developed a novel synthesis of twelve tetrahydro-β-carboline derivatives ( 104 ) prepared via the Pictet-Spengler reaction ( Scheme 28 ). The reaction of tryptamine ( 102 ) and a variety of arylaldehydes ( 103 ) was carried out under ultrasonic energy and trifluoracetic acid (TFA) catalysis at room temperature, giving good to excellent yields (47–87 %) in 1 or 2 h. These tetrahydro-β-carbolines were synthesized obtaining higher yields in shorter reaction times compared to the conventional method.…”

Synthesis of Tetrahydro-β-carboline Derivatives under Electrochemical Conditions in Deep Eutectic Solvents

“…The β-carboline ring is present in many naturally occurring alkaloids with variable biological activities such as anticancer, antimicrobial, anti-Alzheimer, antimalarial, anti-inflammatory, antihypertensive, analgesic, and vasorelaxant activities. − There is a wide interest in the development of novel synthetic approaches, , especially green methods for the preparation of β-carboline derivatives . The green methods used for the synthesis of β-carbolines include the use of microwave , and ultrasonic irradiation, as well as the use of various types of catalysts including heterogeneous, organometallic, , inorganic salts, organic, , natural, , and enzymatic catalysis . However, most of these methods require hazardous and corrosive reagents, long reaction times, expensive catalysts, or complicated apparatus.…”

“… 1 − 7 There is a wide interest in the development of novel synthetic approaches, 3 , 8 especially green methods for the preparation of β-carboline derivatives. 9 The green methods used for the synthesis of β-carbolines include the use of microwave 10 , 11 and ultrasonic irradiation, 12 as well as the use of various types of catalysts including heterogeneous, organometallic, 13 , 14 inorganic salts, 15 organic, 16 , 17 natural, 18 , 19 and enzymatic catalysis. 20 However, most of these methods require hazardous and corrosive reagents, long reaction times, expensive catalysts, or complicated apparatus.…”