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1 

Guilherme Silva Torrezan 

Uso do glicerol, glicerol bruto da produção do 
biodiesel e outros solventes próticos na síntese de 

cetonas (E)-α,β-insaturadas 

São José do Rio Preto  

   2018 



2 

Uso do glicerol, glicerol bruto da produção do 
biodiesel e outros solventes próticos na síntese de 

cetonas (E)-α,β-insaturadas 

Orientador: Prof. Dr. Luis Octavio Regasini  

Co-orientador: Prof. Dr. Marcelo Freitas Lima 

São José do Rio Preto 

2018 

Dissertação apresentada como parte dos requisitos 

para obtenção do título de Mestre em Química, 

junto ao Programa de Pós-Graduação em Química, 

do Instituto de Biociências, Letras e Ciências 

Exatas da Universidade Estadual Paulista “Júlio de 

Mesquita Filho”, Campus de São José do Rio Preto. 

Guilherme Silva Torrezan 





3 

Uso do glicerol, glicerol bruto da produção do biodiesel 
e outros solventes próticos na síntese de cetonas (E)-

α,β-insaturadas

BANCA EXAMINADORA 

Prof. Dr. Luis Octavio Regasini 

Universidade Estadual Paulista “Júlio de Mesquita Filho” – UNESP 

Prof. Dr. Luiz Carlos da Silva Filho 

Universidade Estadual Paulista “Júlio de Mesquita Filho” – UNESP, Campus Bauru 

Profa. Dr. Daniel Rinaldo 

Universidade Estadual Paulista “Júlio de Mesquita Filho” – UNESP, Campus Bauru 

São José do Rio Preto

29 de março de 2018 

Dissertação apresentada como parte dos requisitos 

para obtenção do título de Mestre em Química, 

junto ao Programa de Pós-Graduação em Química, 

do Instituto de Biociências, Letras e Ciências 

Exatas da Universidade Estadual Paulista “Júlio de 

Mesquita Filho”, Campus de São José do Rio Preto. 

Guilherme Silva Torrezan 



         AGRADECIMENTOS 
Agradeço a Deus, primeiramente, pela vida, pela saúde, por tantas outras bênçãos 

recebidas. Também pelas oportunidades que me concedeu, pelos amigos que colocou em 
meu caminho e por nunca me desamparar. 

A meus pais, Jácomo e Débora, e a minha irmã, Ingrid, que, mesmo em meio a 
lutas e dificuldades, sempre me apoiaram. Agradeço especialmente pela paciência, pelos 
conselhos, pelo apoio, e por todo amor. Essa vitória também é de vocês. 

A meu querido mestre, “pai científico” e amigo Prof. Dr. Luis Octavio Regasini, 
também pela paciência, pelos ensinamentos, pelas correções na vida e na ciência e por 
sempre acreditar e confiar em mim e no meu trabalho. Serei sempre grato pelas lições de 
química e da vida. Obrigado por tudo. 

A meu grande amigo e co-orientador do meu trabalho, Prof. Dr. Marcelo Freitas 
Lima, também pelos ensinamentos da vida, da ciência e colaboração. Sem você este 
trabalho não iria ser completo. 

A minha Namorada Ester Paula que me ajudou e me aconselhou nos momentos 
bons e ruins dessa caminhada. Essa vitória também é sua. 

A meu grande amigo Carlos Roberto Polaquini, também pelos ensinamentos da 
vida e da ciência. 

A minha grande amiga Mariana Bastos, também pelos ensinamentos da vida e da 
ciência. 

Aos meus grandes amigos do Laboratório de Química Verde & Medicinal por 
tornar o ambiente de trabalho um dos melhores lugares em que eu poderia estar. Obrigado 
pela amizade, pelos conselhos, pelos momentos de descontração e pelo auxílio com o 
trabalho. 

Ao Laboratório de bioquímica e microbiologia aplicada – Instituto de Biociências, 
Letras e Ciências Exatas - UNESP/São José do Rio Preto e ao Diego Alves Monteiro, pela 
colaboração. 

Ao Laboratório de Análise Térmica Ivo Giolito – Instituto de Química – 
UNESP/Araraquara e ao José Augusto Teixeira, pela colaboração. 

Aos meus queridos amigos Diogo, Matheus, Luís Felipe, Afonso, Fernando, 
Rodolfo, Cézar, Nicolas, Vitor, Renan, Caio, Leonardo, Erick, Fagner, Guilherme Neves, 
Luciano, Gabriel e Hugo  por se tornarem como uma família para mim, me ajudando com 
palavras de carinho, com momentos de diversão e por estarem sempre presentes. 

E, por fim, agradeço a todos que, direta ou indiretamente, contribuíram para o bom 
andamento desse trabalho e também a todos que estiveram presentes e me ajudaram de 
alguma forma a chegar até aqui.  



 

     Resumo 

O glicerol é o principal co-produto da produção de biodiesel e vem sendo considerado 

como um solvente verde. Neste trabalho, utilizamos o glicerol e o glicerol bruto 

proveniente da produção de biodiesel para a síntese das cetonas α,β-insaturadas (2E, 4E) 

-1,5-difenilpenta-2,4-dien-1-ona (1)  e (2E, 6E) -2,6-dibenzilidenociclohexanona (2),

utilizando reações aldólicas mono- e dicondensadas, respectivamente. As cetonas 1 e 2 

sintetizadas em glicerol e glicerol bruto forneceram rendimentos superiores aos outros 

solventes próticos, incluindo etanol, metanol, PEG-400 e água. Para investigar as razões 

que justificariam a eficiência do glicerol, foram realizados os cálculos computacionais 

usando a teoria do funcional da densidade, que validou o mecanismo E1cB, assim como 

uma barreira de energia de ativação que favorece a rota sintética usando o glicerol. Além 

disso, o glicerol bruto de óleo de milho e girassol foram utilizados na síntese de 1 e 2 

durante quatro reciclos, demonstrando rendimentos finais de 59,0 e 48,2%, 

respectivamente. 

Palavras-chave: glicerol, solventes próticos, cetonas, Condensação aldólica, Biodiesel, 

Química Verde   



6

Abstract 

Glycerol is main co-product from biodiesel production and has been recognized as green 

solvent. Herein, we used glycerol and crude glycerol for synthesis of α,β-unsaturated 

ketones: (2E,4E)-1,5-diphenylpenta-2,4-dien-1-one (1) and (2E,6E)-2,6-

dibenzylidenecyclohexanone (2), using mono- and dicondensation aldol reactions, 

respectively. Glycerol and crude glycerol were able to furnish 1 and 2 in yields higher 

than other protic solvents, including ethanol, methanol, PEG-400 and water. In order to 

investigate reasons for efficiency glycerol, we performed computational calculations 

using Density Functional Theory, which has validated E1cB mechanism, as well as 

favorable enegy barrier using glycerol. In addition, crude glycerol from corn and 

sunflower oils were used in synthesis of 1 and 2 for four recycles, displaying final yields 

of 59.0 and 48.2%, respectively. 

Keywords: glycerol, protic solvents, ketones, Aldol condensation, Biodiesel 

,Green chemistry  



7 

LISTA DE FIGURAS 

Figure 1. Structures of ketones 1 and 2…………………………………………….13 

Figure 2. Synthesis of reference samples of ketones 1 and 2……………………...16 

Figure 3. Simultaneous TG-DSC curves in dynamic dry air atmosphere of reference 

samples of ketones 1 and 2…………………………………………………………21 

Figure 4. Free energy (kcal mol -1) of determining step of synthesis of ketone 1 via E1cB 

mechanism in water and glycerol…………………………………………………..23 

Figure 5. Gravimetry and Chromatography yields of re-use investigations............ 25         



8 

LISTA DE TABELAS 

Table 1. Gravimetry and chromatography yields of synthesis of ketones 1 and 2 in 

glycerol and other protic solvents …………………………………………….22 

Table 2.  Gravimetry and chromatography yields of synthesis of ketones 1, 2  and 2.a in 

crude glycerol from oils ……………………....................................................24 



9 

SUPPLEMENTARY MATERIALS (Lista de Anexos) 

Anexo 1. 1H NMR Spectrum of reference sample of ketone 1…………………..........32 

Anexo 2.  Expansion of 1H NMR spectrum of reference sample of ketone 1………...32 

Anexo 3. 13C NMR spectrum of reference sample of ketone 1……………………….33 

Anexo 4. Expansion of 13C NMR spectrum of reference sample of ketone 1………...33 

Anexo 5. 1H NMR spectrum of reference sample of ketone 2………………………..34 

Anexo 6. Expansion of 1H NMR spectrum of reference sample of ketone 2…………34 

Anexo 7. 13C NMR spectrum of reference sample of ketone 2……………………….35 

Anexo 8. Expansion of 13C NMR spectrum of reference sample of ketone 2………..35 

Anexo 9. Mass spectrum (MS) of reference sample of ketone 1……………………..36 

Anexo 10. Mass spectrum (MS/MS), precursor ion m/z 235.04 [M + H]+ of reference 

sample of ketone 1………………………………………………………………….....36 

Anexo 11. Mass spectrum (MS) of reference sample of ketone 2…………………….37 

Anexo 12. Mass spectrum (MS/MS), precursor ion m/z 275.09 [M + H]+ of reference 

sample of ketone 2…………………………………………………………………….37 

Anexo 13. Chromatogram of reference sample of ketone 1…………………………..38 

Anexo 14. Chromatogram of reference sample of ketone 2…………………………..38 

Anexo 15. Analytical curve of reference sample of ketone 1…………………………39 

Anexo 16. Analytical curve of reference sample of ketone 2…………………………39 

Anexo 17. UV-Vis spectra of reference samples of ketones 1 e 2 from HPLC-PAD 

experiment………………………………………………………………………….....40 

Anexo 18. Expansion of 1H NMR spectrum of ketone 1 synthesized in glycerol……41 

Anexo 19. Chromatogram of ketone 1 synthesized in glycerol……………………....41 

Anexo 20. Expansion of 1H NMR spectrum of ketone 1 synthesized in ethanol….....42 

Anexo 21. Chromatogram of ketone 1 synthesized in ethanol………………………42 

Anexo 22. Expansion of 1H NMR spectrum of ketone 1 synthesized in methanol.....43 

Anexo 23. Chromatogram of ketone 1 synthesized in methanol………………….....43 

Anexo 24. Expansion of 1H NMR spectrum of ketone 1 synthesized in PEG-400.....44 

Anexo 25. Chromatogram of ketone 1 synthesized in PEG-400………………….....44 

Anexo 26. Expansion of 1H NMR spectrum of ketone 1 synthesized in water……...45 

Anexo 27. Chromatogram of ketone 1 synthesized in water…………………….......45 

Anexo 28. Expansion of 1H NMR spectrum of ketone 2 synthesized in glycerol…..46 

Anexo 29. Chromatogram of ketone 2 synthesized in glycerol……………………..46 

Anexo 30. Expansion of 1H NMR spectrum of ketone 2 synthesized in ethanol…...47 

 



10 

Anexo 31. Chromatogram of ketone 2 synthesized in ethanol…………………....47 

Anexo 32. Expansion of 1H NMR spectrum of ketone 2 synthesized in methanol..48 

Anexo 33. Chromatogram of ketone 2 synthesized in methanol………………......48 

Anexo 34. Expansion of 1H NMR spectrum of ketone 2 synthesized in PEG-400....49 

Anexo 35. Chromatogram of ketone 2 synthesized in PEG-400…………………..49 

Anexo 36. Expansion of 1H NMR spectrum of ketone 2 synthesized in water…....50 

Anexo 37. Chromatogram of ketone 2 synthesized in water……………………....50 

Anexo 38. Expansion of 1H NMR spectrum of ketone 1 synthesized in crude glycerol 

from castor oil……………………………………………………………………...51 

Anexo 39. Chromatogram of ketone 1 synthesized in crude glycerol from castor 

oil…………………………………………………………………………………..51 

Anexo 40. Expansion of 1H NMR spectrum of ketone 1 synthesized in crude glycerol 

from corn oil……………………………………………………………………….52 

Anexo 41. Chromatogram of ketone 1 synthesized in crude glycerol from corn 

oil…………………………………………………………………………………..52 

Anexo 42. Expansion of 1H NMR spectrum of ketone 1 synthesized in crude glycerol 

from soybean oil…………………………………………………………………...53 

Anexo 43. Chromatogram of ketone 1 synthesized in crude glycerol from soybean 

oil…………………………………………………………………………………..53 

Anexo 44. Expansion of 1H NMR spectrum of ketone 1 synthesized in crude glycerol 

from sunflower oil……………………………………………………………….....54 

Anexo 45. Chromatogram of ketone 1 synthesized in crude glycerol from sunflower 

oil…………………………………………………………………………………...54 

Anexo 46. Expansion of 1H NMR spectrum of ketone 2 synthesized in crude glycerol 

from castor oil……………………………………………………………………...55 

Anexo 47. Chromatogram of ketone 2 synthesized in crude glycerol from castor 

oil…………………………………………………………………………………..55 

Anexo 48. Expansion of 1H NMR spectrum of ketone 2 synthesized in crude glycerol 

from corn oil…………………………………………………………………….....56 

Anexo 49. Chromatogram of ketone 2 synthesized in crude glycerol from corn 

oil…………………………………………………………………………………..56 

Anexo 50. Expansion of 1H NMR spectrum of ketone 2 synthesized in crude glycerol 

from soybean oil…………………………………………………………………....57 



11 

Anexo 51. Chromatogram of ketone 2 synthesized in crude glycerol from soybean 

oil…………………………………………………………………………………..57 

Anexo 52. Expansion of 1H NMR spectrum of ketone 2 synthesized in crude glycerol 

from sunflower oil…………………………………………………………………58 

Anexo 53. Chromatogram of ketone 2 synthesized in crude glycerol from sunflower 

oil………………………………………………………………………………….58 

Anexo 54. Chromatogram of ketone 1 synthesized in crude glycerol from corn oil (Cycle 

1, 344 nm)………………………………………………………………………….59 

Anexo 55. Chromatogram of ketone 1 synthesized in crude glycerol from corn oil (Cycle 

2, 344 nm)…………………………………………………………………………..59 

Anexo 56. Chromatogram of ketone 1 synthesized in crude glycerol from corn oil (Cycle 

3, 344 nm)…………………………………………………………………………..60 

Anexo 57. Chromatogram of ketone 1 synthesized in crude glycerol from corn oil (Cycle 

4, 344 nm)…………………………………………………………………………..60 

Anexo 58. Chromatogram of ketone 1 synthesized in crude glycerol from corn oil (Cycle 

5, 344 nm)…………………………………………………………………………..61 

Anexo 59. Chromatogram of ketone 2 synthesized in crude glycerol from corn oil (Cycle 

1, 328 nm)…………………………………………………………………………..61 

Anexo 60. Chromatogram of ketone 2 synthesized in crude glycerol from corn oil (Cycle 

2, 328 nm)…………………………………………………………………………..62 

Anexo 61. Chromatogram of ketone 2 synthesized in crude glycerol from corn oil (Cycle 

3, 328 nm)…………………………………………………………………………..62 

Anexo 62. Chromatogram of ketone 2 synthesized in crude glycerol from corn oil (Cycle 

4, 328 nm)…………………………………………………………………………..63 

Anexo 63. Chromatogram of ketone 2 synthesized in crude glycerol from corn oil (Cycle 

5, 328 nm)…………………………………………………………………………..63 

Anexo 64. Proposed mechanism of aldol reaction for synthesis of 1 via carbanion 

elimination (E1cB)………………………………………………………………….64 

Anexo 65. Chromatogram of ketones 2 and 2.a from soybean, obtained from HPLC-MS 
experiment……………………………………………………………………..........65 

Anexo 66. Mass Spectrum of ketone 2.a……………………………………............65 

Anexo 67. Mass Spectrum of ketone 2……………………………………………...66 

Anexo 68. UV-Vis spectrum of by-product 2.a from HPLC-PAD experiment…….66 



12 

Sumário 
INTRODUCTION ..................................................................................................................... 13 

2.    EXPERIMENTAL .............................................................................................................. 15 

2.1.  Materials and reagents .................................................................................................. 15 

2.2. Instrumentation and methods ....................................................................................... 15 

2.3. Synthesis, identity and purity of reference samples of ketones 1 and 2 .................... 16 

2.4.  Synthesis of ketones 1 and 2 using glycerol and other protic solvents ..................... 16 

2.5. Theoretical calculations ................................................................................................. 17 

2.6. Synthesis of ketones 1 and 2 using crude glycerol ....................................................... 18 

3. RESULTS AND DISCUSSION ............................................................................................ 19 

3.1. Synthesis, identity and purity of reference samples of ketones 1 and 2 .................... 19 

3.2. Synthesis of ketones 1 and 2 using glycerol and other protic solvents ...................... 21 

3.3. Synthesis of ketones 1 and 2 using crude glycerol ....................................................... 24 

4. CONCLUSION ...................................................................................................................... 27 

5. AKNOWLEDGMENTS ....................................................................................................... 28 

6. REFERENCES ...................................................................................................................... 28 

SUPLEMENTARY MATERIALS .......................................................................................... 32 



13 

INTRODUCTION  

α,β-Unsaturated ketones are versatile structural subunits useful to heterocycle 

synthesis, due to reactivity of carbonyl and its behavior as Michael’s acceptors, 

undergoing 1,2- and 1,4- nucleophilic additions, respectively (AGARWAL et al., 2009; 

MARZINZIK; FELDER, 1998; SAMSHUDDIN; NARAYANA; KUNHANNA, 2012). 

Furthermore, these ketones are present in bioactive natural and synthetic products. 

Among these, compounds containing (2E,4E)-1,5-diphenylpenta-2,4-dien-1-one (1) and 

(2E,6E)-2,6-dibenzylidenecyclohexanone (2) skeletons have demonstrated several 

bioactivities: antibacterial, antitubercular, antiviral, anti-cancer, and anti-helmintic 

(AGUILERA et al., 2016; GE et al., 2013; LAMBERT et al., 2013; MOHD FAUDZI et 

al., 2015; POLAQUINI et al., 2017; WEI et al., 2012; WELDON et al., 2014) (Figure 1). 

Figure 1. Structures of ketones 1 and 2 

OO

1 2

Aldol reactions have been extensively used for (E)-α,β-unsaturated ketones 

synthesis, which involves condensation between aldehydes and ketones, under acid or 

basis catalysis as well as protic solvents. Although, required use of solvents possess 

disadvantages, including flammability, low biodegrability and toxicity (MESTRES, 

2004), the selection by suitable solvent is a crucial step for organic synthesis procedures. 

Several solvents has been developed, which are related to principles of green chemistry 

(or suitanable chemistry), including water, liquid ionics, polyethylenoglycol (PEG), 

perfluorinated solvents and glycerol (JESSOP, 2011; LENARDÃO et al., 2003). 

 Glycerol (or 1,2,3-propanetriol) is a versatile solvent and has been used in 

organic reactions due to several properties, including high boiling point, negligible vapor 

pressure, high polarity (able to solve organic and inorganic solutes), low-toxicity,  high 

avaibility, biodegradability and biocompatibility (WOLFSON; DLUGY; SHOTLAND, 

2007). It has been used in condensation reactions for synthesis of several compounds, 

including sulfanyl ketones (PERIN et al., 2014), bis(indolyl)methanes and n-



14 

valeraldehyde (SILVEIRA et al., 2009; WOLFSON et al., 2009). Furthermore, glycerol 

has been studied as recyclable solvent by green procedures due to immiscibility in 

hydrophobic solvents, allowing removal of products by simple liquid-liquid extraction 

and successive reactions (PERIN et al., 2010; SILVEIRA et al., 2009). 

Glycerol is the main co-product from transesterification reactions of 

acylglicerides from oils and fats (UMPIERRE; MACHADO, 2013). This reaction has 

been extensively used by biodiesel production, which displays rapid development, 

generating tremendous ammount of waste glycerol (million tons per year). Thus, 

reasonable solutions for utilization of waste glycerol are urgent topics from an 

environmental, social and economical point of view (QUISPE; CORONADO; 

CARVALHO JR., 2013; TAN; ABDUL AZIZ; AROUA, 2013). 

Herein, we investigated effects of glycerol, crude glycerol from biodiesel 

production and other protic solvents, including ethanol, methanol, PEG-400 and water in 

synthesis of ketones 1 and 2. Yields of aldol condensation reactions were calculated by 

gravimetry and chromatography measurements. In order to investigate comparisons 

between glycerol and water yields, theoretical investigations on mechanism of aldol 

condensation for synthesis of 1 were proposed using density functional theory 

calculations. In addition, crude glycerol from corn and sunflower oils were selected for 

re-use studies for synthesis of 1 and 2, respectively. 



27 
 

 

 

4. CONCLUSION 
 

In conclusion, glycerol and crude glycerol from biodiesel production have 

proved to be an efficient and ecologically preferable reaction medium for synthesis of 

α,β-unsaturated ketones 1 and 2, complying with the requirements of green chemistry, 

such as safe synthesis and the use of source renewable raw materials. Gravimetry and 

chromatography yields in glycerol and crude glycerol were higher than other protic 

solvents, including ethanol, methanol, PEG-400 and water. Theoretical investigations 

were able to suggest the mechanism of aldol reaction as E1cB, as well as make a detailed 

energetic comparison between glycerol and water role as a solvent on determining step 

of reactions.  In addition, crude glycerol from corn and sunflower oils can be easily 

recovered and used for further mono- and dicondensation reactions and is notably relevant 

to green chemistry concept.  

 

 

 

 

 

 

 

 

 

 

 

 

 



28 
 

 

 

5. AKNOWLEDGMENTS  
 

We would like to thank National Institute for Science and Technology of 

Biodiversity and Natural Products (INCT-BioNat) for MS experiments, as well as Center 

for Scientific Computing (NCC/GridUNESP) of São Paulo State University (UNESP) for 

theoretical calculations. 

 

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